Objective: The aim of the present study was to assess the validity of the Ease of Language Understanding (ELU) model through a statistical assessment of the relationships among its main parameters: processing speed, phonology, working memory (WM), and dB Speech Noise Ratio (SNR) for a given Speech Recognition Threshold (SRT) in a sample of hearing aid users from the n200 database.

Methods: Hearing aid users were assessed on several hearing and cognitive tests. Latent Structural Equation Models (SEMs) were applied to investigate the relationship between the main parameters of the ELU model while controlling for age and PTA. Several competing models were assessed.

Results: Analyses indicated that a mediating SEM was the best fit for the data. The results showed that (i) phonology independently predicted speech recognition threshold in both easy and adverse listening conditions and (ii) WM was not predictive of dB SNR for a given SRT in the easier listening conditions (iii) processing speed was predictive of dB SNR for a given SRT mediated via WM in the more adverse conditions.

Conclusion: The results were in line with the predictions of the ELU model: (i) phonology contributed to dB SNR for a given SRT in all listening conditions, (ii) WM is only invoked when listening conditions are adverse, (iii) better WM capacity aids the understanding of what has been said in adverse listening conditions, and finally (iv) the results highlight the importance and optimization of processing speed in conditions when listening conditions are adverse and WM is activated.

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported beta = 0.120). For the second research question, this was the case for 65% of the teams (median reported beta = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates.

Introduction

Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR.

Methods

We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction.

Results

Our sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %).

Implications

Our findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR.

Importance  About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts.

Objective  To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples.

Design, Setting, and Participants  Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]).

Main Outcomes and Measures  GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition.

Results  The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04).

Conclusions and Relevance  In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.

Touch is a powerful communication tool, but we have a limited understanding of the role played by particular physical features of interpersonal touch communication. In this study, adults living in Sweden performed a task in which messages (attention, love, happiness, calming, sadness, and gratitude) were conveyed by a sender touching the forearm of a receiver, who interpreted the messages. Two experiments (N = 32, N = 20) showed that within close relationships, receivers could identify the intuitive touch expressions of the senders, and we characterized the physical features of the touches associated with successful communication. Facial expressions measured with electromyography varied by message but were uncorrelated with communication performance. We developed standardized touch expressions and quantified the physical features with 3D hand tracking. In two further experiments (N = 20, N = 16), these standardized expressions were conveyed by trained senders and were readily understood by strangers unacquainted with the senders. Thus, the possibility emerges of a standardized, intuitively understood language of social touch.

A major problem with longitudinal studies is the bias generated due to attrition, particularly apparent amongst patients suffering from psychotic disorders. Factors associated with study-participation were investigated as part of a larger research collaboration (STRATA). Out of 479 eligible participants, only 50 (10,4%) were successfully followed up. The present study investigated whether study participation differed depending on baseline characteristics. Results indicated that individuals who did not participate were more likely to report an alcohol use disorder while those who did respond were more likely to have been in full-time education for longer and be of white ethnicity. Participation did not differ depending on diagnosis, symptoms, GAF, age of onset or depression.

Purpose The aim of the present study was to contribute to the inconsistent literature on the comorbid relationship of alcohol problems and depressive symptoms from late adolescent to emerging adulthood by accounting for their trajectories and their conjoint relationship while controlling for the influence of externalising symptoms. Methods We utilised data, from a longitudinal school cohort from Northern Ireland (Belfast Youth Developmental Study), over three time points where the participants were 16, 17 and 21 years of age. A total of 3118 participants were included, 1713 females and 1405 males. Second-order latent growth models were applied to examine growth trajectories. Parallel process growth models were used to assess whether growth trajectories of the symptoms were associated. Externalising symptoms were subsequently added as a covariate. Results Alcohol problems among males significantly increased over time but decreased in females. Depressive symptoms initially increased then decreased in both genders. Results indicated associations of the alcohol problems and depression, both initially and with time. Accounting for externalising symptoms only somewhat diminished this effect in males but not in females. An increase of initial levels of depression was associated with a decrease in alcohol problems over time. This association was only true among females. After controlling for externalising symptoms, the relationship was no longer observed. Conclusions The present study provides further evidence of a significant relationship of alcohol problems and depression in adolescents and further supports a small literature indicating that depression may have protective effects of alcohol problems. Finally, the study shows the importance of accounting for externalising symptoms.

Mephedrone (4-methylmethcathinone; 4-MMC) is a novel recreational drug similar to methylenedioxymethamphetamine (MDMA) and amphetamine. Several adverse effects have been reported, but little is known about its sub-acute effects. To study sub-acute effects of mephedrone over a period of 9 days. Recreational mephedrone users were recruited and followed over a time period of 9 days. It was recorded whether participants consumed mephedrone or not within the period of testing; those who did were compared to those who did not. Forty-six regular mephedrone users (22 males, 24 females) participated, 21 participants voluntarily opted to consume mephedrone 1-3 days after baseline and 25 opted to abstain. Participants were assessed at baseline on a multitude of measures and provided daily reports on cognition, sleep, mood, physical problems, mephedrone cravings and substance use on each subsequent day of the study. The study controlled for psychopathology, sleep, past and current substance use, impulsivity and demographics. Those who consumed mephedrone reported persistent negative mood, physical problems and fatigue, compared to those who did not-after controlling for baseline group differences in sleep and subsequent alcohol and cannabis use. The results provide the first prospective evidence of the duration and extent of specific undesirable sub-acute effects of mephedrone in regular recreational users and indicate sub-acute effects of mephedrone on mood, fatigue and physical symptoms.

Background: Alcohol problems and internalizing symptoms are consistently found to be associated but how they relate to each other is unclear. Objective: The present study aimed to address limitations in the literature of comorbidity of alcohol problems and internalizing symptoms by investigating the direction of effect between the phenotypes and possible gender differences in college students. Method: We utilized data from a large longitudinal study of college students from the United States (N = 2607). Three waves of questionnaire-based data were collected over the first two years of college (in 2011–2013). Cross-lagged models were applied to examine the possible direction of effect of internalizing symptoms and alcohol problems. Possible effects of gender were investigated using multigroup modeling. Results: There were significant correlations between alcohol problems and internalizing symptoms. A direction of effect was found between alcohol problems and internalizing symptoms but differed between genders. A unidirectional relationship varying with age was identified for males where alcohol problems initially predicted internalizing symptoms followed by internalizing symptoms predicting alcohol problems. For females, a unidirectional relationship existed wherein alcohol problems predicted internalizing symptoms. Conclusions/Importance: We conclude that the relationship between alcohol problems and internalizing symptoms is complex and differ between genders. In males, both phenotypes are predictive of each other, while in females the relationship is driven by alcohol problems. Importantly, our study examines a population-based sample, revealing that the observed relationships between alcohol problems and internalizing symptoms are not limited to individuals with clinically diagnosed mental health or substance use problems.

Background: Longitudinal studies are essential for understanding the trajectory and prognosis of patients diagnosed with schizophrenia, in particular those who are treatment resistant as this outcome is difficult to predict. However, follow-up is challenging within this patient population due to high relapse rates, difficulties recontacting participants due to regular change of address, and patients’ symptoms leading to their refusal to take part.

Methods: We describe one of the work packages of STRATA (Schizophrenia: Treatment Resistance and Therapeutic Advances) as an example of the challenges facing follow-up studies in schizophrenia research. The main aim of STRATA is to identify differences between treatment-resistant and treatment-responsive patients with schizophrenia and create a method for early identification of treatment resistant patients; thereby allowing earlier transition to more suitable treatments such as clozapine. Cohorts of patients from pre-existing studies of first-episode psychosis are presently being recontacted. Three studies across the UK (“AESOP,” Nottingham and London samples; “RPGI” and “NIFEPS,” Belfast samples) were included in STRATA. In total, 484 participants were eligible for recontact; 157 participants from AESOP, 85 from the RPGI; and 242 from the NIFEPS study. Participants were contacted via their clinical team, letter, or phone. Participants were invited to take part in a 40-minute interview in which demographic, substance use, medication history, and symptomatology (PANSS) data was collected. Participants were also asked to provide a blood and urine sample. Ethical permission was obtained to contact participants using information collected at previous visits and to obtain up to date contact addresses.

Results: Out of the 484 participants who were recontacted, 13 were deceased, 9 were excluded, 23 requested information after the first contact but then ceased to respond, 47 declined to participate, and addresses were not identified for 63 participants. Thirty-four consented and completed all the assessments. The remaining 295 participants have yet to respond. Clozapine had been prescribed to 8.82% of completed participants and 47.06% have been prescribed 3 or more antipsychotics.

Conclusion: The present study confirms the difficulties in longitudinal studies of patients diagnosed with schizophrenia. More research is needed in order to identify the attitudes and practices, which keep patients from participating in research. Additionally, in the general population, it is estimated that about two-third of individuals diagnosed with schizophrenia are treatment resistant. We can therefore conclude that treatment resistance is somewhat over-represented in the present sample.

The literature supports a relationship between alcohol use disorders and internalising disorders, but how they relate to each other is unclear. Both disorders, as well as their comorbidity increase in adolescence, making adolescence of particular interest. The main objective of the present thesis was to investigate the relationship between alcohol use disorders and internalising disorders in longitudinal cohorts of adolescents. I was interested in the relationship in terms of causality, developmental growth relationships, latent growth trajectories, gender differences, whether the relationship differs with age and whether externalising disorders had an impact on the relationship. To assess these aims, two longitudinal, self-reported, prospective cohorts of adolescents were available for the present thesis. Several models addressing different issues were applied to assess the relationship of alcohol use disorders and internalising disorders. The direction of effect between the phenotypes was assessed using cross-lagged models. Latent growth models were applied in order to investigate the development of each phenotype across time. Parallel growth models of the latent growth curves assessed whether the development of one phenotype was predictive of the other phenotype. Growth mixture models were used in order to establish whether latent trajectory classes of each phenotype were present and whether trajectories of each phenotype were associated with the other phenotype. Finally, externalising symptoms were added as a covariate to the cross-lagged models in order to assess whether externalising symptoms impacted the relationship between alcohol use/problems and internalising symptoms. Additionally, all analysis assessed for gender differences as well as differences between alcohol use and alcohol problems in their relationship to internalising symptoms. Moreover, all analysis was performed on both samples in order to test whether the results were consistent across different age groups, different settings and different geographical locations. Results did indicate a significant relationship between alcohol use disorders and internalising disorder, but the relationship differed by age, gender and sample. However, when growth of the traits was accounted for, a bidirectional relationship was observed. In addition, a weak or a negative relationship was indicated between alcohol use and internalising disorders. Our final most comprehensive model of latent trajectories indicated similar relationships of alcohol use disorders and internalising disorders in both the samples. Evidence for latent trajectories varying with severity was indicated for alcohol use, alcohol use disorders and internalising symptoms. Evidence indicated a significant relationship between alcohol use disorders and internalising disorders. Several different pathways explained the association between alcohol problems and internalising symptoms; there was not one pathway which accounts for the relationship. The two main pathways observed were a model of self-medication (consistent in both samples) and one of a bidirectional relationship, driven by alcohol problems in some individuals and internalising symptoms in other individuals. In a sample of US college students, internalising symptoms and alcohol problems indicated a bidirectional relationship. In a school cohort of mid to late adolescents in Northern Ireland, depression predicted alcohol problems in males while alcohol problems acted as the main driver of a comorbid relationship of the phenotypes in females. Pathway presented tended to depend on factors such as age, gender, whether anxiety was assessed or not, and characteristics of the sample. Finally, externalising symptoms did not significantly account for the relationship between alcohol problems and internalising symptoms but did account for the positive relationships between alcohol use and internalising symptoms and enhanced the negative. Our results provided a possible explanation to the inconsistencies in the literature, either by suggesting that several pathways are present between the two disorders or that the association is so weak that it is hard to pick up on.