The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.

Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10–25 (N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions.

We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01–1.11) and persistent contact (1.12, 1.03–1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03–1.21).

We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM.

We linked 659 906 individuals born in Denmark 1990–2000 to their parents, grandparents, and aunts/uncles using population-based registers. We compared rates of T2DM in relatives of children with and without a diagnosis of any or one of 11 specific psychiatric disorders, including neuropsychiatric and neurodevelopmental disorders, using Cox regression. In a genotyped sample (iPSYCH2015) of individuals born 1981–2008 (n = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders.

Among 5 235 300 relative pairs, relatives of individuals with a psychiatric disorder had an increased risk for T2DM with stronger associations for closer relatives (parents:hazard ratio = 1.38, 95% confidence interval 1.35–1.42; grandparents: 1.14, 1.13–1.15; and aunts/uncles: 1.19, 1.16–1.22). In the genetic sample, one standard deviation increase in T2DM-PRS was associated with an increased risk for any psychiatric disorder (odds ratio = 1.11, 1.08–1.14). Both familial T2DM and T2DM-PRS were significantly associated with seven of 11 psychiatric disorders, most strongly with attention-deficit/hyperactivity disorder and conduct disorder, and inversely with anorexia nervosa.

Our findings of familial co-aggregation and higher T2DM polygenic liability associated with psychiatric disorders point toward shared familial risk. This suggests that part of the comorbidity is explained by shared familial risks. The underlying mechanisms still remain largely unknown and the contributions of genetics and environment need further investigation.

Although several types of risk factors for anorexia nervosa (AN) have been identified, including birth-related factors, somatic, and psychosocial risk factors, their interplay with genetic susceptibility remains unclear. Genetic and epidemiological interplay in AN risk were examined using data from Danish nationwide registers. AN polygenic risk score (PRS) and risk factor associations, confounding from AN PRS and/or parental psychiatric history on the association between the risk factors and AN risk, and interactions between AN PRS and each level of target risk factor on AN risk were estimated.

Participants were individuals born in Denmark between 1981 and 2008 including nationwide-representative data from the iPSYCH2015, and Danish AN cases from the Anorexia Nervosa Genetics Initiative and Eating Disorder Genetics Initiative cohorts. A total of 7003 individuals with AN and 45 229 individuals without a registered AN diagnosis were included. We included 22 AN risk factors from Danish registers.

Risk factors showing association with PRS for AN included urbanicity, parental ages, genitourinary tract infection, and parental socioeconomic factors. Risk factors showed the expected association to AN risk, and this association was only slightly attenuated when adjusted for parental history of psychiatric disorders or/and for the AN PRS. The interaction analyses revealed a differential effect of AN PRS according to the level of the following risk factors: sex, maternal age, genitourinary tract infection, C-section, parental socioeconomic factors and psychiatric history.

Our findings provide evidence for interactions between AN PRS and certain risk-factors, illustrating potential diverse risk pathways to AN diagnosis.

Machine learning (ML) approaches are a promising venue for identifying vocal markers of neuropsychiatric disorders, such as schizophrenia. While recent studies have shown that voice-based ML models can reliably predict diagnosis and clinical symptoms of schizophrenia, it is unclear to what extent such ML markers generalize to new speech samples collected using a different task or in a different language: the assessment of generalization performance is however crucial for testing their clinical applicability.

In this research, we systematically assessed the generalizability of ML models across contexts and languages relying on a large cross-linguistic dataset of audio recordings of patients with schizophrenia and controls.

We trained ML models of vocal markers of schizophrenia on a large cross-linguistic dataset of audio recordings of 231 patients with schizophrenia and 238 matched controls (>4.000 recordings in Danish, German, Mandarin and Japanese). We developed a rigorous pipeline to minimize overfitting, including cross-validated training set and Mixture of Experts (MoE) models. We tested the generalizability of the ML models on: (i) different participants, speaking the same language (hold-out test set); (ii) different participants, speaking a different language. Finally, we compared the predictive performance of: (i) models trained on a single language (e.g., Danish) (ii) MoE models, i.e., ensemble of models (experts) trained on a single language whose predictions are combined using a weighted sum (iii) multi-language models trained on multiple languages (e.g., Danish and German).

Model performance was comparable to state-of-the art findings (F1: 70%-80%) when trained and tested on participants speaking the same language (out-of-sample performance). Crucially, however, the ML models did not generalize well - showing a substantial decrease of performance (close to chance) - when trained in a language and tested on new languages (e.g., trained on Danish and tested on German). MoE and multi-language models showed a better increase of performance (F1: 55%-60%), but still far from those requested for achieving clinical applicability.

Our results show that the cross-linguistic generalizability of ML models of vocal markers of schizophrenia is very limited. This is an issue if our first goal is to translate these vocal markers into effective clinical applications. We argue that more emphasis needs to be placed on collecting large open datasets to test the generalizability of voice-based ML models, for example, across different speech tasks or across the heterogeneous clinical profiles that characterize schizophrenia spectrum disorder.

None Declared

Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record phenotypes.

Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations.

Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex.

Our BMI-stratified results provide potential avenues of functional mechanism for AN-genes to investigate further.

In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.

Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.

Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.

These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.

Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.

The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.

Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.

Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.

High rate of non-attendance in mental health treatment is a major problem in terms of lost economic resources and deteriorated quality of life for the patients.

The aim of the present study was to conduct an analysis of the influence of demographic and clinical variables on treatment attendance.

A naturalistic study of 2473 non-psychotic consecutive patients offered psychotherapeutic treatment. Demographic and clinical variables were registered at assessment. Bivariate and multiple logistic regression analyses of the associations between these variables and attendance were conducted.

675 (27.3%) did not show up and 289 (11.7%) dropped out of treatment. Regression analysis showed that younger age, few years of school, taking an education, unemployment, no sick leave, personality disorder, low or high GAF, no earlier treatment, no use of psychoactive medicine, and substance abuse were significant predictors for non-attendance.

No-show was predicted mainly by clinical factors, whereas drop-out was predicted by demographic variables. Results and strategies to reduce non-attendance were discussed.

In a previous study women with long-term sequalae of child sexual abuse (CSA) were randomly assigned to analytic (Group A) or systemic group psychotherapy (Group S). Pre-post-analysis indicated that both therapies led to significant improvement, but overall Group S had significantly better outcome than Group A. As gains tended to rise in Group A during follow-up and decline in Group S, no statistically significant difference was detected in gains between the two treatment modalities after one year.

This study investigates if gains are maintained five year following termination, and if the groups differ in gains.

106 women started on allocated intervention. Psychological distress (GSI from SCL-90R), psycho-social functioning (GAF), and global life quality (GLQ), were assessed before and after treatment and one and five years following termination.

86 patients (81%) completed group therapy, 68 (64%) completed the one-year follow-up and 64 (60%) the five-year follow-up. At five year follow-up ANOVA was performed using treatment group as a between factor and the four time points as repeated measures. Intention to treat analysis demonstrated that improvement were significant on all measures (P < 0.000). Independent samples t-test on gains was NS for all measures.

Women with a history of CSA who were treated with Group A or Group S treatment maintained statistical significant improvement on GSI, GAF and GLQ five years post-treatment. No significant difference was found in gains between groups.

Psychotherapeutic treatment is associated with significant reduction of symptoms in patients, and it is generally assumed that treatment improves health and decreases the need for additional health care. The present study investigates the long-term changes in utilization of health care services for patients referred to psychotherapeutic treatment in 2004 and 2005.

The study was a matched control study, which included 716 consecutive patients and 15,220 matched controls. Data from a comprehensive set of health care services were collected from central registries for an observation period of four years before intake and four years after ended treatment. Changes in utilization of health care services in eight health parameters were analyzed with t-test and with ANCOVA one and four year pre-post treatment.

Of the 761 patients, 216 patients did not show up for treatment, while 545 patients completed treatment; 228 responded and 201 did not respond to treatment. Data on treatment response was missing for the remaining 116 patients. Completer patients increased their use of all health care services with 296% (ES = 0.58) in the four year pre-post comparison, while the control group only increased with 99% (ES = 0.23). Four years after ended treatment completer patients still showed a consumption of health care services significantly above the control group on five out of eight health care parameters. Response status only affected one health care parameter.

Over a long-term period psychotherapy patients increased their utilization of health care services with a factor 3 compared to a control group.

Mental disorders are a primary cause of occupational impairments. This study investigated long-term changes in occupational functioning for patients referred to psychotherapeutic treatment at a Danish mental healthcare centre in 2004 and 2005.

We recruited 761 consecutive patients and 15,220 matched-control subjects. Data on number of days per year on sick leave, unemployment, and disability pension were collected from central registries over a 5-year observation period from 2002–2007. Differences in number of days with occupational impairments between and within groups were analyzed with t-test and with ANCOVA one and two year pre-post treatment.

Of the 761 patients, 216 patients did not show up for treatment, while 545 patients completed treatment; 228 responded and 201 did not respond to treatment. Data on treatment response was missing for the remaining 116 patients. Completer patients’ days on sick leave increased significantly from 15.7 days two years before treatment to 23.1 days two years after treatment (p < 0.000) and significant more than the control group (5.4days : 7.5 days). Similar results were found for days on disability pension (p = 0.013). Unemployment did not show any significant change for completer patients compared to the control group (p = 0.569). Variations in results were seen, depending on treatment status as no-show, responder or non-responder.

Patients that received psychotherapeutic intervention showed long-term increases in days on sick leave and disability pension.

Several studies have found that women who have experienced child sexual abuse (CSA) develop Post-Traumatic Stress Disorder (PTSD) related to their victimization experiences. The current study evaluated the presence of PTSD symptoms five years after discharge among adult women suffering from sequalae from CSA.

This randomized prospective 5-year follow-up study included 106 women: 52 assigned to psychodynamic group psychotherapy and 54 assigned to systemic group psychotherapy. PTSD symptoms were evaluated at baseline, discharge and 1 and 5 years after discharge, using the crime-related post-traumatic stress disorder scale (CR-PTSD) from the Symptom Checklist-90-Revised (SCL-90-R). ANOVA was performed using treatment group as a between factor and the four time points as repeated measures.

PTSD symptoms were significantly reduced during therapy for both groups (P < 0.000), but the systemic group exhibited significantly more reduction of PTSD symptoms than the analytic group (P < 0.002) at discharge. Difference in trajectories was found for the two groups (P > 0.005). No difference in reduction of PTSD symptoms was found between groups at 1 and 5 year follow-up.

Symptoms of PTSD were reduced in women with a history of CSA participating in both analytic and systemic specialized incest group psychotherapy. Improvement was maintained for both groups at 5-year-follow-up. The trajectories of PTSD symptoms for the two groups differed significantly, however. Implications of the difference in trajectories for treatment planning will be discussed. The findings in the present study stress the importance of long-term follow-up studies in evidence-based research.

To estimate the risk of schizophrenia in adulthood among children and adolescents with ADHD compared to the background population.

Two hundred and eight youths with ADHD (183 boys; 25 girls) were followed prospectively. Diagnoses of schizophrenia were obtained from The Danish Psychiatric Central Register. The relative risk (RR) of schizophrenia for cases with ADHD, compared to the normal population, was calculated as risk ratios. Hazard ratios (HR's) by Cox regression were calculated in the predictor analyses.

Mean age for ADHD cases at follow-up was 31.1 years. Schizophrenia diagnoses were given to 3.8% of these cases. Compared to the general population, RR of schizophrenia in cases with ADHD was 4.3 (95% CI 1.9–8.57).

This prospective follow-up study found children with ADHD to be at higher risk of later schizophrenia than controls. If replicated, these results warrant increased focus on the possible emergence symptoms of schizophrenia or schizophreniform psychosis during clinical follow-up of patients with ADHD.

There is a lack of evidence regarding which kind of psychotherapy that is the most effective when treating traumatized refugees. Studies on the effect of psychotherapy among other patient groups with PTSD suggest a good effect using cognitive behavioural therapy (CBT). The competence center for transcultural psychiatry (CTP) has specialized in the treatment of traumatized refugees. The objectives were to study the effect of CBT with a focus on either stress management or cognitive restructuring in a clinical sample of traumatized refugees with PTSD and to identify predictors for the treatment effect.

All patients (n = 143) referred to CTP from June 2011–March 2012 and fulfilling the inclusion criteria were offered to participate in the study. Participants were offered combined treatment with a psychiatrist (psycho-education and psychopharmacological treatment when needed) and a psychologist (CBT). The duration of the treatment was 6–7 months. The participants were randomized to either CBT with a focus on stress management or cbt with focus on cognitive restructuring. The primary outcome was PTSD measured by the Harvard Trauma Questionnaire.

The results are presently being analyzed and will be presented at the congress.

Both research results and the clinical experience at CTP suggest, that cognitive restructuring is not always a useful tool and that stress reducing techniques could be more useful. This hypothesis was tested in the present study.

The authors have not supplied their declaration of competing interest.

Population-based cohort study with childhood anthropometric measures obtained annually from the age of 7 to 13 years in 253,353 Danes born 1930–1976 and followed to 31 December 2010. During this period, 4936 were registered with schizophrenia. The associations of childhood BMI with risk of schizophrenia were estimated with Cox regression models.

Childhood BMI was significantly inversely associated with risk of schizophrenia, however with different patterns among boys and girls. In boys, childhood BMI had an inverse non-linear association with schizophrenia risk dependent on age at diagnosis; in particular, a surprisingly strong association was found between leanness and later onset of schizophrenia. In girls, the risk of schizophrenia decreased linearly with increasing BMI z-score (HR: 0.93; 95% CI: 0.88–0.98). In both boys and girls, birth weight was inversely associated with later risk. In girls, but not in boys, birth weight appeared to significantly modify the associations; there was a somewhat stronger inverse association in the lowest birth weight category.

Birth weight as well as childhood BMI at ages 7 through 13 years is associated with risk of schizophrenia in both genders, but with a particular high risk of late-onset in lean boys irrespective of birth weight, and in lean girls with low birth weight. If replicated, these observations may inform preventive efforts build on schizophrenia trajectories rooted in early life.