liu.seSearch for publications in DiVA
Change search
Refine search result
12 51 - 88 of 88
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Kalafateli, Aimilia Lydia
    et al.
    Univ Gothenburg, Sweden.
    Vallof, Daniel
    Univ Gothenburg, Sweden.
    Jornulf, Julia Winsa
    Univ Gothenburg, Sweden.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Jerlhag, Elisabet
    Univ Gothenburg, Sweden.
    A cannabinoid receptor antagonist attenuates ghrelin-induced activation of the mesolimbic dopamine system in mice2018In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 184, p. 211-219Article in journal (Refereed)
    Abstract [en]

    Ghrelin has been attributed various physiological processes including food intake and reward regulation, through activation of the mesolimbic dopamine system. Reward modulation involves the mesolimbic dopamine system, consisting of the ventral tegmental area (VTA) dopamine neurons targeting nucleus accumbens (NAc), a system that ghrelin activates through VTA-dependent mechanisms. In the first study, we found that systemic intraperitoneal (ip) administration of rimonabant attenuated intracerebroventricular (icv) ghrelins ability to cause locomotor stimulation and NAc dopamine release in mice. Ghrelin-induced (icv) chow intake was not altered by rimonabant administration (ip). Finally, we showed that bilateral VTA administration of rimonabant blocks the ability of intra-VTA administered ghrelin to increase locomotor activity, but does not affect food intake in mice. Collectively, these data indicate clear dissociation between regulation of food intake and activation of the mesolimbic dopamine system.

  • 52.
    Karlsson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Aziz, Abdul Maruf Asif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rehman, Faazal
    NIAAA, MD USA.
    Pitcairn, Caleb
    Laboratory of Clinical and Translational Studies, NIAAA, NIH, Bethesda, Maryland, USA.
    Barchiesi, Riccardo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Barbier, Estelle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Wendel Hansen, Mikaela
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gehlert, Don
    CNS Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
    Steensland, Pia
    Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Melanin-Concentrating Hormone and Its MCH-1 Receptor: Relationship Between Effects on Alcohol and Caloric Intake2016In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 40, no 10, p. 2199-2207Article in journal (Refereed)
    Abstract [en]

    Background: Reward and energy homeostasis are both regulated by a network of hypothalamic neuropeptide systems. The melanin-concentrating hormone (MCH) and its MCH-1 receptor (MCH1-R) modulate alcohol intake, but it remains unknown to what extent this reflects actions on energy balance or reward. Here, we evaluated the MCH1-R in regulation of caloric intake and motivation to consume alcohol in states of escalated consumption.

    Methods: Rats had intermittent access (IA) to alcohol and were divided into high- and low-drinking groups. Food and alcohol consumption was assessed after administration of an MCH1-R antagonist, GW803430. Next, GW803430 was evaluated on alcohol self-administration in protracted abstinence induced by IA in high-drinking rats. Finally, the effect of GW803430 was assessed on alcohol self-administration in acute withdrawal in rats exposed to alcohol vapor. Gene expression of MCH and MCH1-R was measured in the hypothalamus and nucleus accumbens (NAc) in both acute and protracted abstinence.

    Results: High-drinking IA rats consumed more calories from alcohol than chow and GW803430 decreased both chow and alcohol intake. In low-drinking rats, only food intake was affected. In protracted abstinence from IA, alcohol self-administration was significantly reduced by pretreatment with GW803430 and gene expression of both MCH and the MCH1-R were dysregulated in hypothalamus and NAc. In contrast, during acute withdrawal from vapor exposure, treatment with GW803430 did not affect alcohol self-administration, and no changes in MCH or MCH1-R gene expression were observed.

    Conclusions: Our data suggest a dual role of MCH and the MCH1-R in regulation of alcohol intake, possibly through mechanisms involving caloric intake and reward motivation. A selective suppression of alcohol self-administration during protracted abstinence by GW803430 was observed and accompanied by adaptations in gene expression of MCH and MCH1-R. Selective suppression of escalated consumption renders the MCH1-R an attractive target for treatment of alcohol use disorders.

  • 53.
    Karlsson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rehman, Faazal
    NIAAA, MD USA.
    Damadzic, Ruslan
    NIAAA, MD USA.
    Atkins, Alison Lynn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Schank, Jesse R.
    University of Georgia, GA 30602 USA.
    Gehlert, Donald R.
    Lilly Research Labs, IN USA.
    Steensland, Pia
    Karolinska Institute, Sweden.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Correction: The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation (vol 233, nr 12, pp. 2355–2363, 2016)2016In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 21-22, p. 3825-3825Article in journal (Other academic)
    Abstract [en]

    n/a

  • 54.
    Karlsson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rehman, Faazal
    NIH, MD 20892 USA.
    Damdazic, Ruslan
    NIH, MD 20892 USA.
    Atkins, Alison Lynn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Schank, Jesse R.
    University of Georgia, GA 30602 USA.
    Gehlert, Donald R.
    Eli Lilly and Co, IN 46285 USA.
    Steensland, Pia
    Karolinska Institute, Sweden.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation2016In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 12, p. 2355-2363Article in journal (Refereed)
    Abstract [en]

    Melanin-concentrating hormone (MCH) is involved in the regulation of food intake and has recently been associated with alcohol-related behaviors. Blockade of MCH-1 receptors (MCH1-Rs) attenuates operant alcohol self-administration and decreases cue-induced reinstatement, but the mechanism through which the MCH1-R influences these behaviors remains unknown. MCH1-Rs are highly expressed in the nucleus accumbens shell (NAcSh) where they are co-expressed with dopamine (DA) receptors. MCH has been shown to potentiate responses to dopamine and to increase phosphorylation of DARPP-32, an intracellular marker of DA receptor activation, in the NAcSh. In the present study, we investigated the role of the MCH1-R in alcohol reward using the conditioned place preference (CPP) paradigm. We then used immunohistochemistry (IHC) to assess activation of downstream signaling after administration of a rewarding dose of alcohol. We found that alcohol-induced CPP was markedly decreased in mice with a genetic deletion of the MCH1-R as well as after pharmacological treatment with an MCH1-R antagonist, GW803430. In contrast, an isocaloric dose of dextrose did not produce CPP. The increase in DARPP-32 phosphorylation seen in wildtype (WT) mice after acute alcohol administration in the NAcSh was markedly reduced in MCH1-R knock-out (KO) mice. Our results suggest that MCH1-Rs regulate the rewarding properties of alcohol through interactions with signaling cascades downstream of DA receptors in the NAcSh.

  • 55.
    Karlsson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Schank, Jesse R.
    Department of Physiology and Pharmacology, University of Georgia, Athens, GA.
    Rehman, Faazal
    Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
    Stojakovic, Andrea
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Björk, Karl
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Barbier, Estelle
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Solomon, Matthew
    Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
    Tapocik, Jenica
    Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Proinflammatory signaling regulates voluntary alcohol intake and stress-induced consumption after exposure to social defeat stress in mice2017In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 22, no 5, p. 1279-1288Article in journal (Refereed)
    Abstract [en]

    Proinflammatory activity has been postulated to play a role in addictive processes and stress responses, but the underlying mechanisms remain largely unknown. Here, we examined the role of interleukin 1 (IL-1) and tumor necrosis factor-a (TNF-a) in regulation of voluntary alcohol consumption, alcohol reward and stress-induced drinking. Mice with a deletion of the IL-1 receptor I gene (IL-1RI KO) exhibited modestly decreased alcohol consumption. However, IL-1RI deletion affected neither the rewarding properties of alcohol, measured by conditioned place preference (CPP), nor stress-induced drinking induced by social defeat stress. TNF-a signaling can compensate for phenotypic consequences of IL1-RI deletion. We therefore hypothesized that double deletion of both IL-1RI and TNF-1 receptors (TNF-1R) may reveal the role of these pathways in regulation of alcohol intake. Double KOs consumed significantly less alcohol than control mice over a range of alcohol concentrations. The combined deletion of TNF-1R and IL-1RI did not influence alcohol reward, but did prevent increased alcohol consumption resulting from exposure to repeated bouts of social defeat stress. Taken together, these data indicate that IL-1RI and TNF-1R contribute to regulation of stress-induced, negatively reinforced drinking perhaps through overlapping signaling events downstream of these receptors, while leaving rewarding properties of alcohol largely unaffected.

  • 56.
    Lee, Ji Soo
    et al.
    NIAAA, MD USA.
    Sorcher, Jill L.
    NIAAA, MD USA.
    Rosen, Allison D.
    NIAAA, MD USA.
    Damadzic, Ruslan
    NIAAA, MD USA.
    Sun, Hui
    NIAAA, MD USA.
    Schwandt, Melanie
    NIAAA, MD USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Kelly, John
    Johns Hopkins Univ, MD 21205 USA.
    Mauro, Kelsey L.
    NIAAA, MD USA.
    Luo, Audrey
    NIAAA, MD USA.
    Rosoff, Daniel
    NIAAA, MD USA.
    Muench, Christine
    NIAAA, MD USA.
    Jung, Jeesun
    NIAAA, MD USA.
    Kaminsky, Zachary A.
    Johns Hopkins Univ, MD 21205 USA.
    Lohoff, Falk W.
    NIAAA, MD USA.
    Genetic Association and Expression Analyses of the Phosphatidylinositol-4-Phosphate 5-Kinase (PIP5K1C) Gene in Alcohol Use DisorderRelevance for Pain Signaling and Alcohol Use2018In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 42, no 6, p. 1034-1043Article in journal (Refereed)
    Abstract [en]

    BackgroundThe gene encoding phosphatidylinositol-4-phosphate 5-kinase (PIP5K1C) has been recently implicated in pain regulation. Interestingly, a recent cross-tissue and cross-phenotypic epigenetic analysis identified the same gene in alcohol use disorder (AUD). Given the high comorbidity between AUD and chronic pain, we hypothesized that genetic variation in PIP5K1C might contribute to susceptibility to AUD. MethodsWe conducted a case-control association study of genetic variants in PIP5K1C. Association analyses of 16 common PIP5K1C single nucleotide polymorphisms (SNPs) were conducted in cases and controls of African (427 cases and 137 controls) and European ancestry (488 cases and 324 controls) using standard methods. In addition, given the prominent role of the opioid system in pain signaling, we investigated the effects of acute alcohol exposure on PIP5K1C expression in humanized transgenic mice for the -opioid receptor that included the OPRM1 A118G polymorphism, a widely used mouse model to study analgesic response to opioids in pain. PIP5K1C expression was measured in the thalamus and basolateral amygdala (BLA) in mice after short-term administration (single 2g/kg dose) of alcohol or saline using immunohistochemistry and analyzed by 2-way analysis of variance. ResultsIn the case-control association study using an NIAAA discovery sample, 8 SNPs in PIP5K1C were significantly associated with AUD in the African ancestry (AA) group (pamp;lt;0.05 after correction; rs4807493, rs10405681, rs2074957, rs10432303, rs8109485, rs1476592, rs10419980, and rs4432372). However, a replication analysis using an independent sample (N=3,801) found no significant associations after correction for multiple testing. In the humanized transgenic mouse model with the OPRM1 polymorphism, PIP5K1C expression was significantly different between alcohol and saline-treated mice, regardless of genotype, in both the thalamus (pamp;lt;0.05) and BLA (pamp;lt;0.01). ConclusionsOur discovery sample shows that genetic variants in PIP5K1C are associated with AUD in the AA group, and acute alcohol exposure leads to up-regulation of PIP5K1C, potentially explaining a mechanism underlying the increased risk for chronic pain conditions in individuals with AUD.

  • 57.
    Lexne, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Strain, James J.
    Icahn School of Medicine at Mount Sinai Mount Sinai Medical Center, New York, USA.
    Nylander, Per-Olof
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Marteinsdottir, Ina
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Temperament and character in patients with acute abdominal pain2018In: Comprehensive Psychiatry, ISSN 0010-440X, E-ISSN 1532-8384, Vol. 87, p. 128-133Article in journal (Refereed)
    Abstract [en]

    Background

    Several conditions presenting with abdominal pain are associated with specific personality factors although it is unclear if this is true also in emergency clinic settings.

    Objective

    To study personality factors among patients with acute abdominal pain in an emergency ward.

    Methods

    Consecutive patients (N = 165) with abdominal symptoms at an emergency clinic were administrated the Temperament and Character Inventory (TCI). Three main groups were identified; specific abdominal diagnoses, (N = 77), non-specific abdominal pain, (N = 67) and organic dyspepsia (N = 21). TCI results were compared between clinical groups and a control group (N = 122).

    Results

    As compared to individuals with specific abdominal diagnoses and controls, those with organic dyspepsia were significantly more anxious (harm avoidance), (p = 0.003), and had lower ability to cooperate (cooperativeness) (p = 0.048 and p = 0.004 respectively). They were also significantly more unpretentious (self-transcendence) compared to individuals with specific abdominal diagnoses (p = 0.048), non-specific abdominal pain (p = 0.012) and controls (p = 0.004) and evidenced less mature character (sum of self-directedness and cooperativeness) compared to those with specific abdominal diagnoses and controls (p = 0.003).

    Conclusion

    Individuals seeking care at an emergency clinic with organic dyspepsia showed a distinguishable pattern of personality features that distinguished them from the other comparison groups. Therefore an evaluation of personality factors may add a new dimension to the diagnostic investigation in the emergency care of abdominal pain and contribute to the optimization of the treatment of organic dyspepsia.

  • 58.
    Lindell, S. G.
    et al.
    Laboratory of Comparative Behavioral Genomics, NIH/NIAAA/LNG, USA; Laboratory of Clinical and Translational Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center, USA.
    Schwandt, M. L.
    Laboratory of Clinical and Translational Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center, USA.
    Suomi, S. J.
    Laboratory of Comparative Ethology, National Institutes of Health/National Institute of Child Health and Human Development, NIH Animal Center, USA.
    Rice, K. C.
    Chemical Biology Research Branch, National Institute on Drug Abuse, Bethesda, USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Laboratory of Clinical and Translational Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center, USA.
    Barr, C. S.
    Laboratory of Comparative Behavioral Genomics, NIH/NIAAA/LNG, USA; Laboratory of Clinical and Translational Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center, USA.
    Intermittent Access to Ethanol Induces Escalated Alcohol Consumption in Primates2017In: Journal of addictive behaviors, therapy and rehabilitation, ISSN 2324-9005, Vol. 6, no 1Article in journal (Refereed)
    Abstract [en]

    Escalation of voluntary alcohol drinking is characteristic of alcohol addiction and can be induced in rodents using intermittent access to alcohol. This model has been used to evaluate candidate therapeutics, but key systems involved in the transition into alcohol addiction, such as CRF, differ in their organization between rodents and primates. We examined the ability of an intermittent access schedule to induce escalation of voluntary alcohol drinking in non-human primates and used this model to assess the role of corticotropin releasing hormone (CRF) signaling in this process.

  • 59.
    Malik, Saima
    et al.
    Ctr Addict and Mental Hlth, Canada.
    Jacobs, Mark
    Ctr Addict and Mental Hlth, Canada; Univ Toronto, Canada.
    Cho, Sang-Soo
    Ctr Addict and Mental Hlth, Canada; Univ Toronto, Canada.
    Boileau, Isabelle
    Ctr Addict and Mental Hlth, Canada.
    Blumberger, Daniel
    Univ Toronto, Canada; Ctr Addict and Mental Hlth, Canada; Ctr Addict and Mental Hlth, Canada.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Wilson, Alan
    Ctr Addict and Mental Hlth, Canada.
    Daskalakis, Zafiris J.
    Univ Toronto, Canada; Ctr Addict and Mental Hlth, Canada; Ctr Addict and Mental Hlth, Canada.
    Strafella, Antonio P.
    Ctr Addict and Mental Hlth, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Univ Toronto, Canada.
    Zangen, Abraham
    Ben Gurion Univ Negev, Israel.
    Le Foll, Bernard
    Ctr Addict and Mental Hlth, Canada; Univ Toronto, Canada; Ctr Addict and Mental Hlth, Canada; Ctr Addict and Mental Hlth, Canada.
    Deep TMS of the insula using the H-coil modulates dopamine release: a crossover [C-11] PHNO-PET pilot trial in healthy humans2018In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 12, no 5, p. 1306-1317Article in journal (Refereed)
    Abstract [en]

    Modulating the function of the insular cortex could be a novel therapeutic strategy to treat addiction to a variety of drugs of abuse as this region has been implicated in mediating drug reward and addictive processes. The recent advent of the H-coil has permitted the targeting of deeper brain structures which was not previously feasible. The goal of this study was to bilaterally target the insular region using the H-coil with repetitive Transcranial Magnetic Stimulation (rTMS) and subsequently measure changes in dopamine levels using Positron Emission Tomography (PET) with [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO). This was a within-subject, crossover, blinded and sham-controlled pilot study. Eight healthy, right-handed subjects, aged 19-45, participated in the investigation. All subjects underwent 3 PHNO-PET scans preceded by rTMS (sham, 1Hz or 10Hz), on 3 separate days. Low frequency rTMS (1Hz), targeting the insular cortex, significantly decreased dopamine levels in the substantia nigra, sensorimotor striatum and associative striatum. Replicating this study in tobacco smokers or alcoholics would be a logical follow-up to assess whether H-coil stimulation of the bilateral insula can be employed as a treatment option for addiction. Trial registration: NCT02212405

  • 60.
    Marteinsdottir, Ina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Garvin, Peter
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Psychological Resources Are Independently Associated with Markers of Inflammation in a Middle-Aged Community Sample2016In: International Journal of Behavioral Medicine, ISSN 1070-5503, E-ISSN 1532-7558, Vol. 23, no 5, p. 611-620Article in journal (Refereed)
    Abstract [en]

    Purpose To elucidate possible independent associations of psychological resources with inflammatory markers, all linked with coronary heart disease (CHD). Method In a middle-aged general population (n = 944), psychological resources (coping, self-esteem, and sense of coherence (SOC)), a global measure of quality of life (Cantrils self-anchoring ladder, also called "ladder of life"), and psychological risk factors (hopelessness, vital exhaustion, and depressive symptoms) were used in linear regression models to evaluate associations with the inflammatory markers interleukin (IL)-6, C-reactive protein (CRP), and matrix metalloproteinase (MMP)-9. Adjustments were done for age, sex, medical conditions, and cardiovascular risk factors. Results After full adjustments, self-esteem was independently associated with all three biomarkers. Ladder of life was associated with IL-6 and log-CRP; coping, vital exhaustion, and depressive symptoms with IL-6; and SOC with MMP-9 (p amp;lt; 0.05 for all associations). Conclusion Numerous significant associations of psychological resources and risk factors with IL-6, CRP, and MMP-9 were found in a community-based sample. The associations of psychological resources were mostly independent, while the psychological risk factors seemed preferentially dependent on lifestyle factors as smoking, physical activity, and body mass index (BMI). This suggests that the psychological resources (in particular self-esteem) protective effects on CHD are linked to inflammatory markers.

  • 61.
    Mayo, Leah
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    A Hippocampal Signature of Posttraumatic Stress Disorder Vulnerability2018In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 84, no 2, p. 78-79Article in journal (Other academic)
    Abstract [en]

    n/a

  • 62.
    Mayo, Leah
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Lindé, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Morrison, India
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Putting a good face on touch: Facial expression reflects the affective valence of caress-like touch across modalities2018In: Biological Psychology, ISSN 0301-0511, E-ISSN 1873-6246, Vol. 137, p. 83-90Article in journal (Refereed)
    Abstract [en]

    Touch plays a central role in interpersonal behavior, especially in its capacity to convey-and induce- changes in affect. Previous research has established that slow, caress-like stroking over the skin elicits positive subjective affective responses, with higher ratings of "pleasantness" compared to a faster-moving touch stimulus. Ratings of pleasantness are associated with increased activity of a distinct class of nerve fibers: C-tactile (CT) afferents. Here, we used facial electromyography (EMG) to determine if touch that optimally activates CT afferents also influences facial muscle activity believed to reflect changes in affect. We found that less pleasant, fast-moving stroking (30 cm/s) elicited robustly negative facial EMG responses, as indexed by stronger contraction of the corrugator muscle. In contrast, pleasant, slow-moving stroking (3 cm/s) that optimally activates CT afferents resulted in decreased negative facial affective responses, manifested as significant corrugator relaxation compared to fast stroking. Moreover, the facial tracking of affective valence during touch was supra-modal, with similar effects during both directly-experienced touch and viewing of touch videos. The results of this EMG study imply that touch that fails to optimally activate CT afferent produces a negative affective response, whereas pleasant, caress-like touch has not only subjective but expressive correlates, reflected in net positive affective changes in facial expression.

  • 63.
    Mayo, Leah M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Asratian, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Lindé, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Holm, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Nätt, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Augier, Gaëlle
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Stensson, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Vecchiarelli, Haley A.
    Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Canada.
    Balsevich, Georgia
    Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Canada.
    Aukema, Robert J.
    Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Canada.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Spagnolo, Primavera A.
    National Institute on Alcohol Abuse and Alcoholism and National Institute of Neurological Disorders and Stroke, NIH, Bethesda, USA.
    Lee, Francis S.
    Institute for Developmental Psychobiology, Weill Cornell Medical College of Cornell University, New York, USA.
    Hill, Matthew N.
    Hotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Canada.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Article in journal (Refereed)
    Abstract [en]

    Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinction, suggesting that FAAH inhibitors may aid fear extinction-based treatments. A human FAAH 385C-greater thanA substitution encodes an FAAH enzyme with reduced catabolic efficacy. Individuals homozygous for the FAAH 385A allele may therefore offer a genetic model to evaluate the impact of elevations in AEA signaling in humans, helping to inform whether FAAH inhibitors have the potential to facilitate fear extinction therapy for PTSD. To overcome the challenge posed by low frequency of the AA genotype (appr. 5%), we prospectively genotyped 423 individuals to examine the balanced groups of CC, AC, and AA individuals (n = 25/group). Consistent with its loss-of-function nature, the A allele was dose dependently associated with elevated basal AEA levels, facilitated fear extinction, and enhanced the extinction recall. Moreover, the A-allele homozygotes were protected against stress-induced decreases in AEA and negative emotional consequences of stress. In a humanized mouse model, AA homozygous mice were similarly protected against stress-induced decreases in AEA, both in the periphery, and also in the amygdala and prefrontal cortex, brain structures critically involved in fear extinction and regulation of stress responses. Collectively, these data suggest that AEA signaling can temper aspects of the stress response and that FAAH inhibition may aid the treatment for stress-related psychiatric disorders, such as PTSD.

  • 64.
    Nennig, S. E.
    et al.
    Univ Georgia, GA 30602 USA.
    Fulenwider, H. D.
    Univ Georgia, GA 30602 USA.
    Chimberoff, S. H.
    Univ Georgia, GA 30602 USA.
    Smith, B. M.
    Univ Georgia, GA 30602 USA.
    Eskew, J. E.
    Univ Georgia, GA 30602 USA.
    Sequeira, M. K.
    Univ Georgia, GA 30602 USA.
    Karlsson, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Liang, C.
    Univ Georgia, GA 30602 USA.
    Chen, J. F.
    Univ Southern Calif, CA USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Schank, J. R.
    Univ Georgia, GA 30602 USA.
    Selective Lesioning of Nuclear Factor-kappa B Activated Cells in the Nucleus Accumbens Shell Attenuates Alcohol Place Preference2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 5, p. 1032-1040Article in journal (Refereed)
    Abstract [en]

    Nuclear factor.-light chain enhancer of activated B cells (NF-kappa B) is a transcription factor commonly associated with innate immunity and is activated by infection and inflammation. NF-kappa B has recently gained attention as a mediator of complex psychiatric phenomena such as stress and addiction. In regards to alcohol, most research on NF-kappa B has focused on neurotoxicity and few studies have explored the role of NF-kappa B in alcohol reward, reinforcement, or consumption. In these studies, we used conditioned place preference to assess the activity of NF-kappa B in response to rewarding doses of alcohol. To measure NF-kappa B activity we used a line of transgenic mice that express the LacZ gene under the control of an NF-kappa B-regulated promoter. In these animals, staining for beta-galactosidase (beta-gal) identifies cells in which NF-kappa B has been activated. We then used the Daun02 inactivation method to specifically silence NF-kappa B-expressing cells during place preference conditioning. Daun02 is an inactive prodrug that is converted to the inhibitory molecule daunorubicin by beta-gal. After alcohol place conditioning, we observed increased beta-gal staining in the nucleus accumbens (NAC) shell and dorsal raphe nucleus, and found that disruption of NF-kappa B-expressing cells using Daun02 attenuated the development of alcohol place preference when infused into the NAC shell following conditioning sessions. We found this effect to be regionally and temporally specific. These results suggest that, in addition to its role in alcohol-induced neurotoxicity, NF-kappa B mediates the development of alcohol place preference via its actions in the NAC shell.

  • 65.
    Nordanskog, Pia
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    On electroconvulsive therapy in depression: Clinical, cognitive and neurobiological aspects2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Electroconvulsive therapy (ECT) is used worldwide to treat severe mental disorders. The most common mental disorder, and the third leading cause of disease burden in the world is depression. The clinical efficacy of ECT for severe depression is well-established. However, both the pathophysiology of depression and the mechanism of action of ECT remain elusive.

    The main aims of this thesis are to address the following issues: 1) the use and practice of ECT in Sweden has not been systematically evaluated since 1975, 2) cognitive side-effects (memory disturbances) are a major concern with ECT and 3) the mechanism of action of ECT remain elusive. The neurobiological aspects of ECT focus on two hypotheses. First, the recent years´ preclinical studies that have provided evidence that ECT induces hippocampal cell proliferation, including neurogenesis. Second, that enhanced functional inhibition of neuronal activity is a key feature.

    Current use and practice of ECT in Sweden (paper I) is based on data from the national quality register for ECT, the mandatory patient register of the National Board of Health and Welfare and a survey. Treated person rate (TPR) in Sweden 2013 was found to be 41 individuals / 100 000, and thus unchanged since the latest systematic investigation in Sweden 1975. In more than 70% of treatment series the indication was a depressive episode. The selection of patients for ECT and treatment technique in Sweden was similar to that in other western countries, but the consent procedure and the involvement of nurses and nursing assistants in the delivery of ECT differ. Data also shows that there is room for improvement in both the specificity of use and availability of ECT.

    The second study in this thesis is a longitudinal observational trial where 12 (paper II and III) and 14 (paper IV) patients with depression referred for ECT were investigated. Patients underwent a 3 T MRI structural scanning and DSC-MRI perfusion, a neuropsychological test battery and clinical ratings before ECT, within one to two weeks after ECT and after 6 and 12 months.  In line with preclinical findings and the plasticity hypothesis of mechanism of action of ECT, the hippocampal volume increased after ECT in patients with depression. However, this increase was transient and returned to baseline levels within 6 months. No correlation was found between volumetric changes and clinical effect or cognitive outcome. Instead our results suggested an association to the number of treatments, without relation to the side of stimulation. A right-sided decrease in frontal blood flow distinguished remission from non-remission after ECT. There were significant impairments in verbal episodic memory and verbal fluency within one week after ending the ECT course, but these impairments were transient and no persistent cognitive impairments were seen during the follow-up.

    In summary, this thesis present the first update on the use and practice of ECT in Sweden in the last 40 years as well as a pioneering MRI-study on the hippocampal volume increase in the treatment of depression with ECT. Supportive to earlier findings we also found the cognitive side-effects that are measurable after ECT to be transient. Furthermore, we found that a decreased frontal blood flow is of importance for the anti-depressive response to ECT.

    List of papers
    1. Electroconvulsive Therapy in Sweden 2013: Data From the National Quality Register for ECT
    Open this publication in new window or tab >>Electroconvulsive Therapy in Sweden 2013: Data From the National Quality Register for ECT
    Show others...
    2015 (English)In: The Journal of ECT, ISSN 1095-0680, Vol. 31, no 4, p. 263-267Article in journal (Refereed) Published
    Abstract [en]

    Objectives: The use of electroconvulsive therapy (ECT) varies across countries. The aim of this study was to describe and explore the use of ECT in Sweden in 2013.

    Methods: The Swedish mandatory patient register of the National Board of Health and Welfare includes information on diagnoses and treatments, including ECT. All 56 hospitals that provide ECT in Sweden also report to the nonmandatory national quality register for ECT, which contains information on patient and treatment characteristics. In this study, we combined data from both registers. In addition, all hospitals responded to a survey concerning equipment and organization of ECT.

    Results: We identified 3972 unique patients who received ECT in Sweden in 2013. This translates into 41 ECT-treated individuals per 100,000 inhabitants. Of these patients, 85% opted to participate in the quality register. The median age was 55 years (range, 15-94 years), and 63% were women. The indication was depression in 78% of the treatment series. Of 4 711 hospitalized patients with severe depression, 38% received ECT. The median number of treatments per index series was 7. Unilateral treatment was used in 86% of the series.

    Conclusions: In Sweden, ECT is used at a relatively high rate as compared with other western countries, and the rate was unchanged from the last survey in 1975. However, there is room for improvement in the specificity of use and availability of ECT for disorders where ECT is considered a first-line treatment.

    Place, publisher, year, edition, pages
    Wolters Kluwer, 2015
    Keywords
    electroconvulsive therapy, depression, epidemiology
    National Category
    Psychiatry Neurology Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:liu:diva-121477 (URN)10.1097/YCT.0000000000000243 (DOI)000365687200013 ()25973769 (PubMedID)
    Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2016-05-04Bibliographically approved
    2. Increase in Hippocampal Volume After Electroconvulsive Therapy in Patients With Depression: A Volumetric Magnetic Resonance Imaging Study
    Open this publication in new window or tab >>Increase in Hippocampal Volume After Electroconvulsive Therapy in Patients With Depression: A Volumetric Magnetic Resonance Imaging Study
    Show others...
    2010 (English)In: JOURNAL OF ECT, ISSN 1095-0680, Vol. 26, no 1, p. 62-67Article in journal (Refereed) Published
    Abstract [en]

    Background: Major depression has traditionally been regarded as a neurochemical disease, but findings of a decreased hippocampal volume in patients with depression have turned the pathophysiological focus toward impairments in structural plasticity. The mechanisms of action of the most effective antidepressive treatment, electroconvulsive therapy (ECT), still remains elusive, but recent animal research has provided evidence for a cell proliferative effect in the hippocampus. The aim of this prospective study was to determine if hippocampal volume changes after ECT in patients with depression.

    Methods: Twelve patients with depression and ongoing antidepressive pharmacological treatment were investigated with clinical ratings and 3 T magnetic resonance imaging within 1 week before and after the ECT series. Each hippocampus was manually outlined on coronal slices, and the volume was calculated.

    Results: The left as well as the right hippocampal volume increased significantly after ECT.

    Conclusions: The hippocampal volume increases after ECT, supporting the hypothesis that hippocampus may play a central role in the treatment of depression.

    Keywords
    ECT, depression, hippocampus, MRI, neurogenesis
    National Category
    Psychiatry Neurology
    Identifiers
    urn:nbn:se:liu:diva-54702 (URN)10.1097/YCT.0b013e3181a95da8 (DOI)000275571000017 ()
    Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2015-09-22Bibliographically approved
    3. Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression
    Open this publication in new window or tab >>Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression
    2014 (English)In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 129, no 4, p. 303-311Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE:

    In a previous magnetic resonance imaging (MRI) study, we found a significant increase in hippocampal volume immediately after electroconvulsive therapy (ECT) in patients with depression. The aim of this study was to evaluate hippocampal volume up to 1 year after ECT and investigate its possible relation to clinical and cognitive outcome.

    METHOD:

    Clinical and cognitive outcome in 12 in-patients with depression receiving antidepressive pharmacological treatment referred for ECT were investigated with the Montgomery-Asberg Depression Rating Scale (MADRS) and a broad neuropsychological test battery within 1 week before and after ECT. The assessments were repeated 6 and 12 months after baseline in 10 and seven of these patients, respectively. Hippocampal volumes were measured on all four occasions with 3 Tesla MRI.

    RESULTS:

    Hippocampal volume returned to baseline during the follow-up period of 6 months. Neither the significant antidepressant effect nor the significant transient decrease in executive and verbal episodic memory tests after ECT could be related to changes in hippocampal volume. No persistent cognitive side effects were observed 1 year after ECT.

    CONCLUSION:

    The immediate increase in hippocampal volume after ECT is reversible and is not related to clinical or cognitive outcome.

    Place, publisher, year, edition, pages
    United States: Wiley-Blackwell, 2014
    Keywords
    hippocampus, magnetic resonance imaging, depression, electroconvulsive therapy, cognition, longitudinal
    National Category
    Psychiatry Neurology
    Identifiers
    urn:nbn:se:liu:diva-104959 (URN)10.1111/acps.12150 (DOI)000332684900006 ()23745780 (PubMedID)
    Available from: 2014-03-04 Created: 2014-03-04 Last updated: 2017-12-05
    4. Relative decrease of frontal blood flow after electroconvulsive therapy in depression distinguishes remission: a perfusion MRI study
    Open this publication in new window or tab >>Relative decrease of frontal blood flow after electroconvulsive therapy in depression distinguishes remission: a perfusion MRI study
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Understanding electroconvulsive therapy (ECT) is of importance not only for optimizing treatment, but could also provide important information about key features of the healing process in depression. Enhanced inhibition (the anticonvulsant hypothesis) is one of several suggested mechanisms of action of ECT. Earlier studies on cerebral blood flow during ECT have given diverging results. Our aim was to study changes in cerebral blood flow in depression treated with ECT and their relation to treatment outcome.

    Methods: We obtained MRI scans in 14 depressed subjects referred for ECT. Cerebral blood flow (CBF) was measured using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) within 1 week before and 2 weeks after a course of ECT. The relative CBF was calculated from mean values in predefined regions of interest in relation to the mean value in the whole brain.

    Results: A significant relative CBF increase in the occipital region (p < 0.05) and a significant relative decrease in the right lateral temporal lobe (p < 0.05) were found in the entire study group. A significant decrease in the right frontal lobe, with a significant anteriorposterior and right-left gradient shift in relative CBF, was a distinguishing feature in patients with ECT-induced remission (n = 8).

    Limitations: This observational study is limited by the risk of random bias and its low number of participants.

    Conclusions: Our results suggest that a decreased relative blood flow in frontal regions may be a hallmark of treatment efficacy in depression treated with ECT.

    National Category
    Public Health, Global Health, Social Medicine and Epidemiology Psychiatry Neurology
    Identifiers
    urn:nbn:se:liu:diva-121478 (URN)
    Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2015-09-21Bibliographically approved
  • 66.
    Nordanskog, Pia
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Hultén, Martin
    Psychiatric Neuromodulation Unit (PNU), Dept of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.
    Landén, Mikael
    Psychiatric Neuromodulation Unit (PNU), Dept of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.
    Lundberg, Johan
    Department of Clinical Neuroscience, Karolinska Institutet and Section for Affective Disorders, Northern Stockholm Psychiatry, Stockholm, Sweden.
    von Knorring, Lars
    Department of Neuroscience, Psychiatry, Uppsala university, Uppsala, Sweden.
    Nordenskjöld, Axel
    Department of Psychiatry, Faculty ofMedicine and Health, Örebro University, Örebro, Sweden.
    Electroconvulsive Therapy in Sweden 2013: Data From the National Quality Register for ECT2015In: The Journal of ECT, ISSN 1095-0680, Vol. 31, no 4, p. 263-267Article in journal (Refereed)
    Abstract [en]

    Objectives: The use of electroconvulsive therapy (ECT) varies across countries. The aim of this study was to describe and explore the use of ECT in Sweden in 2013.

    Methods: The Swedish mandatory patient register of the National Board of Health and Welfare includes information on diagnoses and treatments, including ECT. All 56 hospitals that provide ECT in Sweden also report to the nonmandatory national quality register for ECT, which contains information on patient and treatment characteristics. In this study, we combined data from both registers. In addition, all hospitals responded to a survey concerning equipment and organization of ECT.

    Results: We identified 3972 unique patients who received ECT in Sweden in 2013. This translates into 41 ECT-treated individuals per 100,000 inhabitants. Of these patients, 85% opted to participate in the quality register. The median age was 55 years (range, 15-94 years), and 63% were women. The indication was depression in 78% of the treatment series. Of 4 711 hospitalized patients with severe depression, 38% received ECT. The median number of treatments per index series was 7. Unilateral treatment was used in 86% of the series.

    Conclusions: In Sweden, ECT is used at a relatively high rate as compared with other western countries, and the rate was unchanged from the last survey in 1975. However, there is room for improvement in the specificity of use and availability of ECT for disorders where ECT is considered a first-line treatment.

  • 67.
    Nordanskog, Pia
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Knutsson, Linda
    Department of Medical Radiation Physics, Lund University, Lund, Sweden.
    Larsson, Elna-Marie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
    Johanson, Aki
    Department of Psychiatry, Lund University, Lund, Sweden.
    Relative decrease of frontal blood flow after electroconvulsive therapy in depression distinguishes remission: a perfusion MRI studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Understanding electroconvulsive therapy (ECT) is of importance not only for optimizing treatment, but could also provide important information about key features of the healing process in depression. Enhanced inhibition (the anticonvulsant hypothesis) is one of several suggested mechanisms of action of ECT. Earlier studies on cerebral blood flow during ECT have given diverging results. Our aim was to study changes in cerebral blood flow in depression treated with ECT and their relation to treatment outcome.

    Methods: We obtained MRI scans in 14 depressed subjects referred for ECT. Cerebral blood flow (CBF) was measured using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) within 1 week before and 2 weeks after a course of ECT. The relative CBF was calculated from mean values in predefined regions of interest in relation to the mean value in the whole brain.

    Results: A significant relative CBF increase in the occipital region (p < 0.05) and a significant relative decrease in the right lateral temporal lobe (p < 0.05) were found in the entire study group. A significant decrease in the right frontal lobe, with a significant anteriorposterior and right-left gradient shift in relative CBF, was a distinguishing feature in patients with ECT-induced remission (n = 8).

    Limitations: This observational study is limited by the risk of random bias and its low number of participants.

    Conclusions: Our results suggest that a decreased relative blood flow in frontal regions may be a hallmark of treatment efficacy in depression treated with ECT.

  • 68.
    Ole, Brus
    et al.
    Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro.
    Nordanskog, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Ullvi, Båve
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Yang, Cao
    Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro; Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Åsa, Hammar
    Department of Biological and Medical Psychology, University of Bergen, Bergen Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
    Mikael, Landén
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Gothenburg.
    Johan, Lundberg
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm.
    Axel, Nordenskjöld
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Subjective Memory Immediately Following Electroconvulsive Therapy2017In: Journal of ECT, ISSN 1095-0680, E-ISSN 1533-4112, Vol. 33, no 2, p. 96-103Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES

    The aims of the present study were to describe the short-term rate of subjective memory worsening (SMW) and identify factors of importance for SMW in a large clinical sample treated for depression with electroconvulsive therapy (ECT).

    METHODS

    This register-based study included 1212 patients from the Swedish National Quality Register for ECT. Subjective memory worsening was defined as a 2-point worsening on the memory item of the Comprehensive Psychopathological Rating Scale from before to within 1 week after treatment. Associations between patient characteristics and treatment factors were examined using logistic regression.

    RESULTS

    Subjective memory worsening was experienced in 26%. It was more common in women than in men (31% vs 18%; P < 0.001) and more common in patients aged 18 to 39 years than in patients 65 years or older (32% vs 22%; P = 0.008). Patients with less subjective memory disturbances before ECT had a greater risk of SMW. Patients in remission after ECT had a lower risk of SMW. A brief pulse width stimulus gave higher risk of SMW compared with ultrabrief pulse (odds ratio, 1.61; 95% confidence interval, 1.05-2.47).

    CONCLUSIONS

    Subjective memory worsening is reported by a minority of patients. However, young women are at risk of experiencing SMW. Ultrabrief pulse width stimulus could be considered for patients treated with unilateral electrode placement who experience SMW. Each patient should be monitored with regard to symptoms and adverse effects, and treatment should be adjusted on an individual basis to maximize the clinical effect and with efforts to minimize the cognitive adverse effects.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  • 69.
    Oltedal, Leif
    et al.
    University of Bergen, Norway; University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA; Haukeland Hospital, Norway.
    Bartsch, Hauke
    University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA.
    Evjenth Sorhaug, Ole Johan
    University of Bergen, Norway.
    Kessler, Ute
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Abbott, Christopher
    University of New Mexico, NM 87131 USA.
    Dols, Annemieke
    VUmc Amsterdam, Netherlands.
    Stek, Max L.
    VUmc Amsterdam, Netherlands.
    Ersland, Lars
    Haukeland Hospital, Norway.
    Emsell, Louise
    Katholieke University of Leuven, Belgium.
    van Eijndhoven, Philip
    Donders Institute Brain Cognit and Behav, Netherlands.
    Argyelan, Miklos
    Feinstein Institute Medical Research, NY USA.
    Tendolkar, Indira
    Donders Institute Brain Cognit and Behav, Netherlands.
    Nordanskog, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Hamilton, Paul J.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Balslev Jorgensen, Martin
    Psychiat Centre Copenhagen, Denmark.
    Sommer, Iris E.
    University of Medical Centre, Netherlands.
    Heringa, Sophie M.
    University of Medical Centre, Netherlands.
    Draganski, Bogdan
    University of Lausanne, Switzerland; Max Planck Institute Human Brain and Cognit Neurosci, Germany.
    Redlich, Ronny
    Department of Psychiatry, University of Münster, Germany.
    Dannlowski, Udo
    University of Munster, Germany; University of Marburg, Germany.
    Kugel, Harald
    University of Munster, Germany.
    Bouckaert, Filip
    Katholieke University of Leuven, Belgium.
    Sienaert, Pascal
    Katholieke University of Leuven, Belgium.
    Anand, Amit
    Cleveland Clin, OH 44106 USA.
    Espinoza, Randall
    University of Calif Los Angeles, CA USA.
    Narr, Katherine L.
    University of Calif Los Angeles, CA 90024 USA.
    Holland, Dominic
    University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA.
    Dale, Anders M.
    University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA.
    Oedegaard, Ketil J.
    University of Bergen, Norway; Haukeland Hospital, Norway; KG Jebsen Centre Research Neuropsychiat Disorders, Norway.
    The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 14, p. 422-432Article in journal (Refereed)
    Abstract [en]

    Major depression, currently the worlds primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches. (C) 2017 The Author(s). Published by Elsevier Inc.

  • 70.
    Perini, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Hamilton, Paul
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Kämpe, Robin
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Zetterqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    The salience of self, not social pain, is encoded by dorsal anterior cingulate and insula2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6165Article in journal (Refereed)
    Abstract [en]

    The human neural correlates of social rejection have attracted significant research interest, but remain subject to vigorous debate. Specifically, it has been proposed that a matrix of brain regions overlapping with the classical pain matrix, and including the dorsal anterior cingulate cortex (dACC) and the anterior insular cortex (AI) is critical for processing of social rejection. The present study expands on this conceptualization, by showing that these areas are involved in processing of self-relevant social evaluation, irrespective of valence. Forty healthy adolescents (N = 20 females) were tested in a magnetic resonance imaging (MRI) scanner. We used a novel paradigm that balanced participants experience of rejection and acceptance. In addition, the paradigm also controlled for whether the social judgment was towards the participants or towards other fictitious players. By creating a "self" and "other" distinction, we show that right AI and dACC are involved in processing the salience of being judged by others, irrespective of the quality of this judgment. This finding supports the idea that these regions are not specific to social rejection or even to pain or metaphorically painful experiences, but activate to self-relevant, highly salient information.

  • 71.
    Persson, Anna
    et al.
    Karolinska Institute, Sweden; Stockholm Centre Dependency Disorders, Sweden.
    Back, Sudie E.
    Medical University of South Carolina, USA; Ralph H Johnson Vet Affairs VA Medical Centre, SC USA.
    Killeen, Therese K.
    Medical University of South Carolina, SC 29425 USA.
    Brady, Kathleen T.
    Medical University of South Carolina, SC 29425 USA; Ralph H Johnson Vet Affairs VA Medical Centre, SC USA.
    Schwandt, Melanie L.
    NIAAA, MD USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Magnusson, Åsa
    Karolinska Institute, Sweden; Stockholm Centre Dependency Disorders, Sweden.
    Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure ( COPE): A Pilot Study in Alcohol-dependent Women2017In: Journal of addiction medicine, ISSN 1932-0620, E-ISSN 1935-3227, Vol. 11, no 2, p. 119-125Article in journal (Refereed)
    Abstract [en]

    Objectives: Posttraumatic stress disorder (PTSD) and substance use disorders are highly comorbid. Effective treatments are largely lacking. This pilot study evaluated the safety and feasibility of a novel intervention, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), in preparation for a randomized controlled trial. Methods: Twenty-two treatment-seeking women with current DSM-IV-TR PTSD and alcohol dependence (AD) were recruited. Participants received COPE. Safety and feasibility were evaluated, as were efficacy-related outcomes: PTSD and depression symptom severity, alcohol use, craving, and dependence severity. Results: No adverse events occurred. COPE was implemented in routine clinical practice. Among the assessed women, 95.8% were eligible to participate. Treatment attendance and completion were higher than in previous studies. Post treatment, all efficacy-related outcomes, including PTSD and depression symptom severity, alcohol use, craving, and dependence severity, were significantly reduced. Conclusions: COPE was safe and feasible to use. Concerns that trauma-focused, exposure-based therapy might promote relapse in this population appear unwarranted. Our findings provide initial evidence suggestive of COPE efficacy for comorbid PTSD and AD in women. These results provide a strong rationale for investigating the efficacy of COPE for comorbid PTSD and AD in women in a randomized controlled trial.

  • 72.
    Popiolek, Katarzyna
    et al.
    Örebro University, Sweden.
    Brus, Ole
    Örebro University, Sweden.
    Elvin, Tove
    Örebro University, Sweden.
    Landen, Mikael
    Karolinska Institute, Sweden; Gothenburg University, Sweden.
    Lundberg, Johan
    Karolinska Institute, Sweden; Stockholm County Council, Sweden.
    Nordanskog, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Nordenskjold, Axel
    Örebro University, Sweden.
    Rehospitalization and suicide following electroconvulsive therapy for bipolar depression-A population-based register study2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 226, p. 146-154Article in journal (Refereed)
    Abstract [en]

    Background: Electroconvulsive therapy (ECT) is effective in bipolar depression, but relapse is common. The aim of the study was (i) to identify prognostic factors (ii) and to determine the impact of pharmacological approaches on the risk for rehospitalization or suicide. Methods: This register study analyzed data from individuals treated with inpatient ECT for bipolar depression. Subjects were identified using the Swedish National Patient Register between 2011 and 2014 and the Swedish National Quality Register for ECT. Other national registers provided data on psychopharmacotherapy, socio-demographic factors, and causes of death. The endpoint was the composite of rehospitalization for any psychiatric disorder, suicide attempt or completed suicide (RoS). Cox regression was used to calculate hazard ratios in univariate and multivariate models. Results: Data from 1255 patients were analyzed. The mean period of follow-up was 346 days. A total of 29%, 41%, and 52% of patients reached RoS at 3, 6, and 12 months post-discharge. A history of multiple psychiatric admissions, lower age, and post-discharge treatment with antipsychotics or benzodiazepines was associated with RoS. Limitations: Indication bias may have affected the results. Conclusions: A history of multiple hospital admissions and lower age are key predictors of the composite of rehospitalization or suicide in patients treated with ECT for bipolar depression. Lithium might be effective. By contrast, antipsychotics and benzodiazepines were associated with increased risk, but possibly this finding was influenced by indication bias.

  • 73.
    Ree, Anbjorn
    et al.
    Univ Oslo, Norway.
    Morrison, India
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Sailer, Uta
    Univ Oslo, Norway.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Mayo, Leah
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Using Facial Electromyography to Assess Facial Muscle Reactions to Experienced and Observed Affective Touch in Humans2019In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 145, article id e59228Article in journal (Refereed)
    Abstract [en]

    Affective

  • 74.
    Rundgren, Sara
    et al.
    Orebro Univ, Sweden.
    Brus, Ole
    Orebro Univ, Sweden.
    Bave, Ullvi
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Landen, Mikael
    Karolinska Inst, Sweden; Gothenburg Univ, Sweden.
    Lundberg, Johan
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Nordanskog, Pia
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience.
    Nordenskjold, Axel
    Orebro Univ, Sweden.
    Improvement of postpartum depression and psychosis after electroconvulsive therapy: A population-based study with a matched comparison group2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 235, p. 258-264Article in journal (Refereed)
    Abstract [en]

    Introduction: Electroconvulsive therapy (ECT) is used to treat postpartum depression and psychosis based on clinical experience and small observational studies. Aims: The primary aim was to test the hypothesis that the response rate to ECT for depression and psychosis is higher during the postpartum period than outside this period. The secondary aim was to identify predictors of a response to ECT during the postpartum period. Materials and methods: Cases with postpartum depression and/or psychosis received ECT within 6 months of delivery. A matched comparison group with depression and/or psychosis (not within the postpartum period) was identified from the Swedish National Quality Register for ECT. The improvement 1 week after ECT was classified according to the Clinical Global Impressions Scale - Improvement scale (CGI-I) as responder (CGI-I score 1-2) or non-responder (CGI-I score 3-7). Results: 185 cases and 185 comparison group subjects were included (46% with psychosis in each groups). More cases (87.0%) than comparison group subjects (73.5%) responded to ECT (p = 0.001). Adjusted binary regression analysis revealed that more severe symptoms prior to treatment were the only statistically significant predictor of response. Limitations: There was no control group without ECT treatment. Conclusion: The response rate of those with postpartum depression and/or psychosis to ECT was high. The response rate of patients with psychosis or depression was higher during the postpartum period than outside it. This study supports the use of ECT for severe forms of postpartum depression and/or psychosis.

  • 75.
    Sarchiapone, Marco
    et al.
    University of Molise, Italy; NIHMP, Italy.
    Iosue, Miriam
    University of Molise, Italy.
    Carli, Vladimir
    Karolinska Institute, Sweden.
    Amore, Mario
    University of Genoa, Italy.
    Baca-Garcia, Enrique
    Autonomous University of Madrid, Spain.
    Batra, Anil
    University Hospital Tuebingen, Germany.
    Cosman, Doina
    Iuliu Hatieganu University of Medical and Pharm, Romania.
    Courtet, Philippe
    University Hospital Montpellier, France.
    Di Sciascio, Guido
    University of Bari, Italy.
    Gusmao, Ricardo
    CHLO, Portugal.
    Parnowski, Tadeusz
    Institute Psychiat and Neurol, Poland.
    Pestality, Peter
    National Institute Psychiat and Addict, Hungary.
    Saiz, Pilar
    University of Oviedo, Spain.
    Thome, Johannes
    University of Rostock, Germany.
    Tingstrom, Anders
    Lund University, Sweden; Malmö University Hospital, Sweden.
    Wojnar, Marcin
    Medical University of Warsaw, Poland.
    Zeppegno, Patrizia
    University of Piemonte Orientale Amedeo Avogadro, Italy.
    Thorell, Lars-Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. EMOTRA AB, Sweden.
    EUDOR-A multi-centre research program: A naturalistic, European Multi-centre Clinical study of EDOR Test in adult patients with primary depression2017In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 17, article id 108Article in journal (Refereed)
    Abstract [en]

    Background: Electrodermal reactivity has been successfully used as indicator of interest, curiosity as well as depressive states. The measured reactivity depends on the quantity of sweat secreted by those eccrine sweat glands that are located in the hypodermis of palmar and plantar regions. Electrodermal hyporeactive individuals are those who show an unusual rapid habituation to identical non-significant stimuli. Previous findings suggested that electrodermal hyporeactivity has a high sensitivity and a high specificity for suicide. The aims of the present study are to test the effectiveness and the usefulness of the EDOR (ElectroDermal Orienting Reactivity) Test as a support in the suicide risk assessment of depressed patients and to assess the predictive value of electrodermal hyporeactivity, measured through the EDOR Test, for suicide and suicide attempt in adult patients with a primary diagnosis of depression. Methods and design: 1573 patients with a primary diagnosis of depression, whether currently depressed or in remission, have been recruited at 15 centres in 9 different European countries. Depressive symptomatology was evaluated through the Montgomery-Asberg Depression Scale. Previous suicide attempts were registered and the suicide intent of the worst attempt was rated according to the first eight items of the Beck Suicide Intent Scale. The suicide risk was also assessed according to rules and traditions at the centre. The EDOR Test was finally performed. During the EDOR Test, two fingers are put on gold electrodes and direct current of 0.5 V is passed through the epidermis of the fingers according to standards. A moderately strong tone is presented through headphones now and then during the test. The electrodermal responses to the stimuli represent an increase in the conductance due to the increased number of filled sweat ducts that act as conductors through the electrically highly resistant epidermis. Each patient is followed up for one year in order to assess the occurrence of intentional self-harm. Discussion: Based on previous studies, expected results would be that patients realizing a suicide attempt with a strong intent or committing suicide should be electrodermally hyporeactive in most cases and non-hyporeactive patients should show only few indications of death intent or suicides.

  • 76.
    Schank, Jesse R.
    et al.
    University of Georgia, GA 30602 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Substance P and the Neurokinin-1 Receptor: The New CRF2017In: ROLE OF NEUROPEPTIDES IN ADDICTION AND DISORDERS OF EXCESSIVE CONSUMPTION, ISSN 0074-7742, Vol. 136, p. 151-175Article, review/survey (Refereed)
    Abstract [en]

    Substance P (SP) is an 11-amino acid neuropeptide of the tachykinin family that preferentially activates the neurokinin-1 receptor (NK1R). First isolated 85 years ago and sequenced 40 years later, SP has been extensively studied. Early studies identified a role for SP and the NK1R in contraction of intestinal smooth muscle, central pain processing, and neurogenic inflammation. An FDA-approved NK1R antagonist, aprepitant, is used clinically for the treatment of chemotherapy-induced nausea, as the NK1R influences the activity of the brain stem emesis centers. More recently, SP and the NK1R have gained attention for their role in complex psychiatric processes including stress, anxiety, and depression. However, clinical development of NK1R antagonists for these indications has so far been unsuccessful. Several preclinical studies have also demonstrated a role of the NK1R in drug taking and drug seeking, especially as it relates to escalated consumption and stress-elicited seeking. This line of research developed in parallel with findings supporting a role of corticotropin-releasing factor (CRF) in stress-induced drug seeking. Over this time, CRF arguably gained more attention as a target for development of addiction pharmacotherapies. However, this effort has not resulted in a viable drug for use in human populations. Given promising clinical findings for the efficacy of NK1R antagonists on craving in alcoholics, along with recent data suggesting that a number of negative results from NK1R trials were likely due to insufficient receptor occupancy, the NK1R merits being revisited as a target for the development of novel pharmacotherapeutics for addiction.

  • 77.
    Schroeder, Jennifer R.
    et al.
    Johns Hopkins Bayview Med Ctr, MD 21224 USA.
    Phillips, Karran A.
    NIDA, MD 21224 USA.
    Epstein, David H.
    NIDA, MD 21224 USA.
    Jobes, Michelle L.
    NIDA, MD 21224 USA.
    Furnari, Melody A.
    NIDA, MD 21224 USA.
    Kennedy, Ashley P.
    NIDA, MD 21224 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Preston, Kenzie L.
    NIDA, MD 21224 USA.
    Assessment of pioglitazone and proinflammatory cytokines during buprenorphine taper in patients with opioid use disorder2018In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 235, no 10, p. 2957-2966Article in journal (Refereed)
    Abstract [en]

    Background Preliminary evidence suggested that the PPAR gamma agonist pioglitazone reduces opioid-withdrawal symptoms, possibly by inhibiting increases in proinflammatory cytokines. Methods A randomized, placebo-controlled clinical trial was conducted utilizing two different study designs (entirely outpatient, and a combination of inpatient and outpatient) to evaluate the safety and efficacy of pioglitazone as an adjunct medication for people with opioid physical dependence undergoing a buprenorphine taper. Participants were stabilized on buprenorphine/naloxone (sublingual, up to 16/4 mg/day), then randomized to receive oral pioglitazone (up to 45 mg/day) or placebo before, during, and after buprenorphine taper. Outcome measures included the Subjective Opiate Withdrawal Scale (SOWS) and Clinical Opiate Withdrawal Scale, use of rescue medications to alleviate opioid withdrawal symptoms, and opioid-positive urine specimens. Cerebrospinal fluid (CSF) and plasma were collected during the taper in a subset of participants for measurement of proinflammatory cytokines. Results The clinical trial was prematurely terminated due to slow enrollment; 40 participants per group were required for adequate statistical power to test study hypotheses. Twenty-four participants enrolled; 17 received at least one dose of study medication (6 pioglitazone, 11 placebo). SOWS scores were higher in the pioglitazone arm than in the placebo arm after adjusting for use of rescue medications; participants in the pioglitazone arm needed more rescue medications than the placebo arm during the post-taper phase. SOWS scores were positively correlated with monocyte chemoattractant protein-1 (MCP-1) in CSF (r = 0.70, p = 0.038) and plasma (r = 0.77, p = 0.015). Participants having higher levels of plasma MCP-1 reported higher SOWS, most notably after the buprenorphine taper ended. Conclusions Results from this study provide no evidence that pioglitazone reduces opioid withdrawal symptoms during buprenorphine taper. High correlations between MCP-1 and opioid withdrawal symptoms support a role of proinflammatory processes in opioid withdrawal.

  • 78.
    Schwandt, Melanie L.
    et al.
    NIAAA, MD USA.
    Cortes, Carlos R.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. NIAAA, MD USA.
    Kwako, Laura E.
    NIAAA, MD USA.
    George, David T.
    NIAAA, MD USA.
    Momenan, Reza
    NIAAA, MD USA.
    Sinha, Rajita
    Yale University, CT 06520 USA.
    Grigoriadis, Dimitri E.
    Neurocrine Bioscience, CA USA.
    Merlo Pich, Emilio
    Imperial Coll London, England.
    Leggio, Lorenzo
    NIAAA, MD USA; NIDA, MD 20892 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. NIAAA, MD USA.
    The CRFI Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects2016In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 41, no 12, p. 2818-2829Article in journal (Refereed)
    Abstract [en]

    Blockade of corticotropin-releasing factor receptor I (CRFI) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRFI antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients. Anxious, alcohol-dependent women (age 21-65 years, n = 39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test Craving was evaluated using two established protocols, one that combines a social stressor with physical alcohol cue exposure, and one that uses guided imagery to present personalized stress, alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and alcohol cues. In contrast to our recent observations with another CRFI antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left alcohol craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRFI antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRFI blockade in stress-induced alcohol craving and relapse.

  • 79.
    Schwieler, Lilly
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Markus K
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Skogh, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Kegel, Magdalena E
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Orhan, Funda
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Abdelmoaty, Sally
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Finn, Anja
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Bhat, Maria
    AstraZeneca, Research & Development, Innovative Medicines, Personalised Healthcare & Biomarkers, Science for Life Laboratory, Solna, Sweden / Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Samuelsson, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Lundberg, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dahl, Marja-Liisa
    Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Sellgren, Carl
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Schuppe-Koistinen, Ina
    AstraZeneca, Research & Development, Innovative Medicines, Personalised Healthcare & Biomarkers, Science for Life Laboratory, Solna, Sweden / Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Svensson, Camilla
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Erhardt, Sophie
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Engberg, Göran
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia - significance for activation of the kynurenine pathway.2015In: Journal of Psychiatry & Neuroscience, ISSN 1180-4882, E-ISSN 1488-2434, Vol. 40, no 2, p. 126-13Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway.

    METHODS: We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry.

    RESULTS: We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA.

    LIMITATIONS: The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age.

    CONCLUSION: We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-D-aspartate receptor antagonist KYNA in patients with schizophrenia.

  • 80.
    Schwieler, Lilly
    et al.
    Karolinska Institute, Sweden.
    Samuelsson, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Frye, Mark A.
    Mayo Clin, MN USA.
    Bhat, Maria
    AstraZeneca, Sweden; Karolinska Institute, Sweden.
    Schuppe-Koistinen, Ina
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Jungholm, Oscar
    Karolinska Institute, Sweden.
    Johansson, Anette G.
    Karolinska Institute, Sweden.
    Landen, Mikael
    Gothenburg University, Sweden; Karolinska Institute, Sweden.
    Sellgren, Carl M.
    Karolinska Institute, Sweden; Broad Institute MIT and Harvard, MA USA; Harvard University, MA 02115 USA.
    Erhardt, Sophie
    Karolinska Institute, Sweden.
    Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients2016In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 13, no 51Article in journal (Refereed)
    Abstract [en]

    Background: Neuroinflammation is increasingly recognized as contributing to the pathogenesis of depression. Key inflammatory markers as well as kynurenic acid (KYNA) and quinolinic acid (QUIN), both tryptophan metabolites, have been associated with depressive symptoms and suicidality. The aim of the present study is to investigate the peripheral concentration of cytokines and tryptophan and kynurenine metabolites in patients with unipolar treatment-resistant depression before and after electroconvulsive therapy (ECT), the most effective treatment for depression. Methods: Cytokines in plasma from patients with major depressive disorder (MDD; n = 19) and healthy volunteers (n = 14) were analyzed with electrochemiluminescence detection. Tryptophan and kynurenine metabolites were detected with high-performance liquid chromatography (HPLC) and LC/MS. KYNA was analyzed in a second healthy control cohort (n = 22). Results: Patients with MDD had increased plasma levels of interleukin (IL)-6 compared to healthy volunteers (P &lt; 0.05). We also found an altered kynurenine metabolism in these patients displayed by decreased plasma levels of KYNA (P &lt; 0.0001) as well as a significantly increased QUIN/KYNA ratio (P &lt; 0.001). Plasma levels of tryptophan, kynurenine, and QUIN did not differ between patients and controls. Treatment with ECT was associated with a significant decrease in the plasma levels of tryptophan (P &lt; 0.05), kynurenine (P &lt; 0.01), and QUIN (P &lt; 0.001), whereas plasma levels of KYNA did not change. The QUIN/KYNA ratio was found to significantly decrease in ECT-treated patients (P &lt; 0.05). There was a significant inverse correlation between symptom severity and kynurenine levels at baseline (r = -0.67, P = 0.002). Conclusions: This study confirms an imbalanced kynurenine pathway in MDD supporting the hypothesis of a netstimulation of N-methyl-D-aspartic acid (NMDA) receptors in the disorder. Treatment with ECT profoundly decreased QUIN, an NMDA-receptor agonist previously suggested to be implicated in the pathogenesis of depression, an effect that might have bearing for the good clinical outcome of ECT.

  • 81.
    Sells, Joanna R.
    et al.
    NIAAA, MD 20892 USA; Uniformed Serv University of Health Science, MD 20814 USA.
    Waters, Andrew J.
    Uniformed Serv University of Health Science, MD 20814 USA.
    Schwandt, Melanie L.
    NIAAA, MD 20814 USA.
    Kwako, Laura E.
    NIAAA, MD 20814 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    George, David T.
    NIAAA, MD 20814 USA.
    Ramchandani, Vijay A.
    NIAAA, MD 20892 USA.
    Characterization of comorbid PTSD in treatment-seeking alcohol dependent inpatients: Severity and personality trait differences2016In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 163, p. 242-246Article in journal (Refereed)
    Abstract [en]

    Background: Post-traumatic stress disorder (PTSD) is often comorbid with alcohol dependence (AD), but little is known about the characteristics of AD treatment-seeking inpatients with PTSD. We examined differences between treatment-seeking alcohol dependent inpatients with and without comorbid PTSD. We hypothesized that those with AD and PTSD would have higher levels of: (1) alcohol use and AD severity; (2) anxiety and mood disorders; (3) neuroticism. Methods: Individuals (N = 411, mean age = 41.7 +/- 10.0 years) with AD were monitored over 30 days in a suburban inpatient alcohol treatment setting. Patients were evaluated to identify AD and comorbid PTSD, mood and anxiety disorders, alcohol use and dependence severity, personality, and aggression. Results: Those with PTSD (19% of the sample) did not differ in the amount of alcohol consumed, but had greater: (1) severity of AD (p = 0.001, d = 0.44); (2) diagnosis of anxiety (p = 0.000, OR = 3.64) and mood (p = 0.000, OR = 4.83) disorders; and (3) levels of neuroticism (p amp;lt; 0.001, d = 0.67) and aggression (p amp;lt; 0.001, d = 0.81). Conclusions: AD patients with comorbid PTSD present a more severe phenotype across AD severity, frequency of anxiety and mood disorders, and levels of neuroticism and aggression. This group may benefit from concurrent treatment of both AD and PTSD. Future research can investigate neuroticism as a potential treatment target. Published by Elsevier Ireland Ltd.

  • 82.
    Spagnolo, Primavera A.
    et al.
    NIAAA, MD USA.
    Ramchandani, Vijay A.
    NIAAA, MD USA.
    Schwandt, Melanie L.
    NIAAA, MD USA.
    Kwako, Laura E.
    NIAAA, MD USA.
    George, David T.
    NIAAA, MD USA.
    Mayo, Leah
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN).
    Hillard, Cecilia J.
    Medical Coll Wisconsin, WI 53226 USA; Medical Coll Wisconsin, WI 53226 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence2016In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 40, no 11, p. 2426-2434Article in journal (Refereed)
    Abstract [en]

    BackgroundA common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses. MethodsForty-nine patients with PTSD and AD were admitted for 4weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity. ResultsFAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain. ConclusionsThis is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics.

  • 83.
    Stojakovic, Andrea
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Walczak, Magdalena
    Jagiellonian Univ, Poland.
    Cieslak, Przemyslaw E.
    Polish Acad Sci, Poland.
    Trenk, Aleksandra
    Jagiellonian Univ, Poland.
    Sköld, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Mirrasekhian, Elahe
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Parkitna, Jan Rodriguez
    Polish Acad Sci, Poland.
    Blasiak, Tomasz
    Jagiellonian Univ, Poland.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Several behavioral traits relevant for alcoholism are controlled by gamma 2 subunit containing GABA(A) receptors on dopamine neurons in mice2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 7, p. 1548-1556Article in journal (Refereed)
    Abstract [en]

    The risk factors for developing alcohol addiction include impulsivity, high sensitivity to the rewarding action of ethanol, and low sensitivity to its sedative and intoxicating effects. Genetic variation in GABA(A) receptor subunits, including the gamma 2 subunit (Gabrg2), affects the risk for developing alcoholism. Alcohol directly potentiates GABA(A) receptors and activates the mesolimbic dopamine system. Here, we deleted Gabrg2 selectively in dopamine cells of adult mice. The deletion resulted in elevated firing of dopamine neurons and made them less sensitive to drugs acting at GABA(A) receptors. At the behavioral level, the deletion increased exploratory behavior and augmented both correct and incorrect responding in the go/no-go task, a test often used to assay the response inhibition component of impulsivity. In addition, conditioned place preference to alcohol, but not to cocaine or morphine, was increased. Ethanol-induced locomotor activation was enhanced in the mice lacking Gabrg2 on dopaminergic cells, whereas the sedative effect of alcohol was reduced. Finally, the alcohol drinking, but not the alcohol preference, at a high concentration was increased in the mutant mice. In summary, deletion of Gabrg2 on dopamine cells induced several behavioral traits associated with high risk of developing alcoholism. The findings suggest that mice lacking Gabrg2 on dopaminergic cells could be used as models for individuals at high risk for developing alcoholism and that GABA(A) receptors on dopamine cells are protective against the development of excessive alcohol drinking.

  • 84.
    Theorell, Töres
    et al.
    Stockholm University, Sweden; Karolinska Institute, Sweden.
    Hammarström, Anne
    Umeå University Hospital, Sweden.
    Aronsson, Gunnar
    Stockholm University, Sweden.
    Träskman Bendz, Lil
    Lund University, Sweden.
    Grape, Tom
    South Health Care Centre, Sweden.
    Hogstedt, Christer
    Karolinska Institute, Sweden.
    Marteinsdottir, Ina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Skoog, Ingmar
    University of Gothenburg, Sweden.
    Hall, Charlotte
    Swedish Council Health Technology Assessment, Sweden.
    A systematic review including meta-analysis of work environment and depressive symptoms2015In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 15, no 738Article, review/survey (Refereed)
    Abstract [en]

    Background: Depressive symptoms are potential outcomes of poorly functioning work environments. Such symptoms are frequent and cause considerable suffering for the employees as well as financial loss for the employers. Accordingly good prospective studies of psychosocial working conditions and depressive symptoms are valuable. Scientific reviews of such studies have pointed at methodological difficulties but still established a few job risk factors. Those reviews were published some years ago. There is need for an updated systematic review using the GRADE system. In addition, gender related questions have been insufficiently reviewed. Method: Inclusion criteria for the studies published 1990 to June 2013: 1. European and English speaking countries. 2. Quantified results describing the relationship between exposure (psychosocial or physical/chemical) and outcome (standardized questionnaire assessment of depressive symptoms or interview-based clinical depression). 3. Prospective or comparable case-control design with at least 100 participants. 4. Assessments of exposure (working conditions) and outcome at baseline and outcome (depressive symptoms) once again after follow-up 1-5 years later. 5. Adjustment for age and adjustment or stratification for gender. Studies filling inclusion criteria were subjected to assessment of 1.) relevance and 2.) quality using predefined criteria. Systematic review of the evidence was made using the GRADE system. When applicable, meta-analysis of the magnitude of associations was made. Consistency of findings was examined for a number of possible confounders and publication bias was discussed. Results: Fifty-nine articles of high or medium high scientific quality were included. Moderately strong evidence (grade three out of four) was found for job strain (high psychological demands and low decision latitude), low decision latitude and bullying having significant impact on development of depressive symptoms. Limited evidence (grade two) was shown for psychological demands, effort reward imbalance, low support, unfavorable social climate, lack of work justice, conflicts, limited skill discretion, job insecurity and long working hours. There was no differential gender effect of adverse job conditions on depressive symptoms Conclusion: There is substantial empirical evidence that employees, both men and women, who report lack of decision latitude, job strain and bullying, will experience increasing depressive symptoms over time. These conditions are amenable to organizational interventions.

  • 85.
    Ulrich, Roger S.
    et al.
    Chalmers Univ Technol, Sweden; Chalmers Univ Technol, Sweden.
    Bogren, Lennart
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Sahlgrens Univ Hosp, Sweden.
    Gardiner, Stuart K.
    Legacy Hlth, OR 97232 USA.
    Lundin, Stefan
    Chalmers Univ Technol, Sweden; White Arkitekter AB, Sweden.
    Psychiatric ward design can reduce aggressive behavior2018In: Journal of Environmental Psychology, ISSN 0272-4944, E-ISSN 1522-9610, Vol. 57, p. 53-66Article in journal (Refereed)
    Abstract [en]

    The article describes a conceptual model proposing that aggression in psychiatric facilities may be reduced by designing the physical environment with ten evidence-grounded stress-reducing features. The model was tested in a newer hospital in Sweden having wards with nine of the ten features. Data on two clinical markers of aggressive behavior, compulsory injections and physical restraints, were compared with data from an older facility (replaced by the newer hospital) that had only one stress-reducing feature. Another hospital with one feature, which did not change during the study period, served as a control. The proportion of patients requiring injections declined (p amp;lt; 0.0027) in the new hospital compared to the old facility but did not change in the control hospital. Among patients who received injections, the average number of injections declined marginally in the new hospital compared to the old facility, but increased in the control hospital by 19%. The average number of physical restraints (among patients who received at least one) decreased 50% in the new hospital compared to the old. These findings suggest that designing better psychiatric buildings using reasoned theory and the best available evidence can reduce the major patient and staff safety threat posed by aggressive behavior.

  • 86.
    Van Hedger, Kathryne
    et al.
    Univ Chicago, IL 60637 USA.
    Keedy, Sarah K.
    Univ Chicago, IL 60637 USA.
    Mayo, Leah M.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    de Wit, Harriet
    Univ Chicago, IL 60637 USA.
    Neural responses to cues paired with methamphetamine in healthy volunteers2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 8, p. 1732-1737Article in journal (Refereed)
    Abstract [en]

    Drug cues, or conditioned responses to stimuli paired with drugs, are widely believed to promote drug use. The acquisition of these conditioned responses has been well characterized in laboratory animals: neutral stimuli paired with drugs elicit conditioned responses resembling the motivational and incentive properties of the drug itself. However, few studies have examined acquisition of conditioning, or the nature of the conditioned response, in humans. In this study, we used fMRI to examine neural responses to stimuli that had been paired with methamphetamine or placebo in healthy young adults. Participants first underwent four conditioning sessions in which visual-auditory stimuli were paired with either methamphetamine (20 mg, oral) or placebo. Then on a drug-free test day, the stimuli were presented during an fMRI scan to assess neural responses to the stimuli. We hypothesized that the stimuli would elicit drug-like brain activity, especially in regions related to reward. Instead, we found that the methamphetamine-paired stimuli, compared to placebo-paired stimuli, produced greater activation in regions related to visual and auditory processing, consistent with the drugs unconditioned effects on sensory processing. This is the first study to demonstrate conditioned neural responses to drug-paired stimuli after just two pairings of methamphetamine in healthy adults. The study also illustrates that conditioned responses may develop to unexpected components of the drugs effects.

  • 87.
    Ventorp, F.
    et al.
    Lund University, Sweden; Michigan State University, MI USA.
    Barzilay, R.
    Tel Aviv University, Israel; Geha Mental Health Centre, Israel.
    Erhardt, S.
    Karolinska Institute, Sweden.
    Samuelsson, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Linköping University, Faculty of Medicine and Health Sciences.
    Traskman-Bendz, L.
    Lund University, Sweden.
    Janelidze, S.
    Lund University, Sweden.
    Weizman, A.
    Geha Mental Health Centre, Israel; Tel Aviv University, Israel.
    Offen, D.
    Tel Aviv University, Israel.
    Brundin, L.
    Lund University, Sweden; Michigan State University, MI USA; Van Andel Research Institute, MI USA.
    The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood-brain barrier permeability2016In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 193, p. 349-354Article in journal (Refereed)
    Abstract [en]

    Background: The glycosaminoglycan hyaluronic acid (HA) is an important component of the extracellular matrix (ECM) in the brain. CD44 is a cell adhesion molecule that binds to HA in the ECM and is present on astrocytes, microglia and certain neurons. Cell adhesion molecules have been reported to be involved in anxiety and mood disorders. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in brain GWAS studies as a possible risk gene for suicidal behavior. Method: We measured the CSF levels of HA and the soluble CD44 (sCD44) in suicide attempters (n=94) and in healthy controls (n=45) using ELISA and electrochemiluminescence assays. We also investigated other proteins known to interact with CD44, such as osteopontin and the matrix metalloproteinases MMP1, MMP3 and MMP9. Results: The suicide attempters had higher CSF levels of HA (p=.003) and MMP9 (p=.004). The CSF levels of HA correlated with BBB-permeability (rho=0.410, p&lt;.001) and MMP9 correlated with sCD44 levels (rho=0.260, p=.005). Limitations: Other relevant biological contributors to suicidal behavior is not addressed in parallel to the specific role of CD44-HA signaling. The gender distribution of the patients from whom CSF was analyzed was uneven. Conclusions: Increased BBB-permeability and HA levels might be a results of increased neuroinflammation and can play a role in the pathobiology of suicidal behavior. The CD44 signaling pathway might be considered a novel target for intervention in mood disorders. (C) 2016 Elsevier B.V. All rights reserved.

  • 88.
    Zetterqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Fredlund, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Priebe, Gisela
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden.
    Wadsby, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Jonsson, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Self-reported nonsuicidal self-injury (NSSI) and sex as self-injury (SASI): Relationship to abuse, risk behaviors, trauma symptoms, self-esteem and attachment2018In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 265, p. 309-316Article in journal (Refereed)
    Abstract [en]

    This study focuses on a conceptually unexplored behavior among adolescents who report deliberately using sex as a means of self-injury. In a large high school-based sample (n = 5743), adolescents who engaged in sex as self injury (SASI, n = 43) were compared to adolescents who reported direct nonsuicidal self-injury (NSSI, n = 933) and those who reported both NSSI and SASI (n = 82). Re.sults showed that significantly more adolescents with SASI had experience of penetrating sexual abuse, as well as more sexual partners compared to those with NSSI. The SASI group also had higher levels of self-reported trauma symptoms, such as dissociation, posttraumatic stress and sexual concerns compared to those with NSSI, suggesting a distinct relationship between sexual abuse, trauma symptoms and engaging in sex as self-injury. There was no difference between the SASI and NSSI groups regarding experiences of emotional and physical abuse, self-esteem, parental care or overprotection or symptoms of depression, anxiety and anger. Adolescents who engaged in both NSSI + SASI stood out as a more severe and burdened group, with more experience of abuse, risk behaviors and impaired psychosocial health. Adolescents with traumatic experiences such as sexual abuse need to be assessed for SASI and vice versa.

12 51 - 88 of 88
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf