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.

Behavioral (externalizing) and emotional (internalizing) problems were showed to be associated with the prenatal environment. Changes in placental DNA methylation was identified as a relevant potential mechanism of such association.

We aimed to explore the associations between placental DNA methylation and child behavior in order to explore pathways that could link prenatal exposures to child behavior.

Data including 441 children of 3 years of age from the EDEN mother-child cohort. Child behavior assessed using the Strengths and Difficulties Questionnaire (SDQ). Both hypotheses-driven and exploratory analyses (including epigenome-wide association studies (EWAS) and differentially methylated regions (DMR) analyses) were conducted. The analyses were adjusted for confounding and technical factors and estimated placental cell composition. All the p-values were corrected using a false discovery rate (FDR) procedure for multiple tests.

In the hypothesis-driven analysis, cg26703534 (AHRR), was significantly associated with emotional problems (pFDR = 0.03). In the exploratory analyses, cg09126090 (pFDR = 0.04) and cg10305789 (PPP1R16B; pFDR < 0.01) were significantly associated with peer-relationship problems and 33 DMRs were significantly associated with at least one of the SDQ subscales. Placental DNA methylation showed more associations with internalizing than externalizing symptoms, especially among girls. DMRs tented to include highly methylated CpGs.

This study investigated for the first time the associations between placental DNA methylation and internalizing and externalizing symptoms in preschoolers. Further analyses, such as consortium meta-analyses would be necessary to confirm and extend our results.

None Declared

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

Insomnia in depression is common and difficult to resolve. Music is commonly used as a sleep aid, and clinical trials pointing to positive effects of music as a sleep aid are increasing adding to the evidence base. There is little knowledge on the effectiveness of music for depression related insomnia.

A recent RCT study conducted in psychiatry at Aalborg University Hospital examined effects of a music intervention for insomnia in depression. The intervention group listened to music at bedtime for four weeks, controls were offered music intervention post-test. Primary outcome measure was Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes included Actigraphy, The Hamilton depression Rating Scale (HAMD-17) and World Health Organisation well-being questionnaires (WHO-5, WHOQOL-BREF).

A two-armed randomized controlled trial (n=112) and a qualitative interview study (n=4)

The RCT study showed signficant improvements for the music intervention group in sleep quality and quality of life at four weeks according to global PSQI scores (effect size= -2.1, 95%CI -3.3; -0.9) and WHO-5 scores (effect size 8.4, 95%CI 2.7; 14.0). Actigraphy measures showed no changes and changes in depression symptoms (HAMD-17) were not detected.

The interview study unfolded examples of the influences of music on sleep and relaxation. Music distracted, affected mood and arousal positively and supported formation of sleep habits.

Results from the trial are discussed and merged with findings from the interview study. The results from the trial suggested moderate effects of music listening for the population while findings from the interview study showed examples of individual and highly varying outcomes.

Music is suggested as a low-cost, side-effect free and safe intervention in supplement to existing treatments improving sleep in depression.

None Declared

Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression.

This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs.

We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR = 1.71, 95% confidence interval [CI]: 1.55–1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR = 1.05, 95% CI: 1.01–1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR = 1.18, 95% CI: 1.12–1.25). No significant association were observed among adult OC users who had previously used OCs (HR = 1.00, 95% CI: 0.95–1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression.

Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk–benefit assessments should be conducted.

Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane synaptic vesicle glycoprotein 2A (SV2A) of pre-synaptic vesicles is commonly used to measure synaptic density, as a novel approach to the detection of synaptic changes. We do not know if a single dose of cocaine suffices to affect pre-synaptic SV2A density, especially during adolescence when synapses undergo intense maturation. Here, we explored potential changes of pre-synaptic SV2A density in target brain areas associated with the cocaine-induced boost of dopaminergic neurotransmission, specifically testing if the effects would last after the return of dopamine levels to baseline.

We administered cocaine (20 mg/kg i.p.) or saline to rats in early adolescence, tested their activity levels and removed the brains 1 hour and 7 days after injection. To evaluate immediate and lasting effects, we did autoradiography with [3H]UCB-J, a specific tracer for SV2A, in medial prefrontal cortex, striatum, nucleus accumbens, amygdala, and dorsal and ventral areas of hippocampus. We also measured the striatal binding of [3H]GBR-12935 to test cocaine’s occupancy of the dopamine transporter at both times of study.

We found a significant increase of [3H]UCB-J binding in the dorsal and ventral sections of hippocampus 7 days after the cocaine administration compared to saline-injected rats, but no differences 1 hour after the injection. The [3H]GBR-12935 binding remained unchanged at both times.

Cocaine provoked lasting changes of hippocampal synaptic SV2A density after a single exposure during adolescence

Mismatch negativity (MMN) amplitude is reduced in psychotic disorders and associated with symptoms and functioning. Due to these robust associations, it is often considered a biomarker for psychotic illness. The relationship between MMN and clinical outcomes has been examined well in early onset psychotic illness; however, its stability and predictive utility in chronic samples are not clear.

We examined the five-year stability of MMN amplitude over two timepoints in individuals with established psychotic disorders (cases; N = 132) and never-psychotic participants (NP; N = 170), as well as longitudinal associations with clinical symptoms and functioning.

MMN amplitude exhibited good temporal stability (cases, r = 0.53; never-psychotic, r = 0.52). In cases, structural equation models revealed MMN amplitude to be a significant predictor of worsening auditory hallucinations (β = 0.19), everyday functioning (β = −0.13), and illness severity (β = −0.12) at follow-up. Meanwhile, initial IQ (β = −0.24), negative symptoms (β = 0.23), and illness severity (β = −0.16) were significant predictors of worsening MMN amplitude five years later.

These results imply that MMN measures a neural deficit that is reasonably stable up to five years. Results support disordered cognition and negative symptoms as preceding reduced MMN, which then may operate as a mechanism driving reductions in everyday functioning and the worsening of auditory hallucinations in chronic psychotic disorders. This pattern may inform models of illness course, clarifying the relationships amongst biological mechanisms of predictive processing and clinical deficits in chronic psychosis and allowing us to better understand the mechanisms driving such impairments over time.

There is a concern that the COVID-19 pandemic will lead to an increase in suicides. Several reports from the first months of the pandemic showed no increase in suicide rates while studies with longer observation times report contrasting results. In this study, we explore the suicide rates in Norway during the first year of the pandemic for the total population as well as for relevant subgroups such as sex, age, geographical areas, and pandemic phases.

This is a cohort study covering the entire Norwegian population between 2010 and 2020. The main outcome was age-standardized suicide rates (per 100,000 inhabitants) in 2020 according to the Norwegian Cause of Death Registry. This was compared with 95% prediction intervals (95% PI) based on the suicide rates between 2010 and 2019.

In 2020, there were 639 suicides in Norway corresponding to a rate of 12.1 per 100,000 (95% PI 10.2–14.4). There were no significant deviations from the predicted values for suicides in 2020 when analyzing age, sex, pandemic phase, or geographical area separately. We observed a trend toward a lower than predicted suicide rate among females (6.5, 95% PI 6.0–9.2), and during the two COVID-19 outbreak phases in 2020 (2.8, 95% PI 2.3–4.3 and 2.8, 95% CI 2.3–4.3).

There is no indication that the COVID-19 pandemic led to an increase in suicide rates in Norway in 2020.

Music therapy is frequently provided to patients at the end of life, and studies have shown a benefit in relief of symptoms and a positive impact on quality of life (QoL), but little is known regarding the effect of music therapy (MT) on caregivers. Caregivers are at risk for anxiety, emotional distress and experience anticipatory grief as the patient nears death. Caregivers are present with patients and may also benefit from MT.

To assess the impact of MT on caregivers for hospice patients and determine the feasibility of research in this population.

Twenty caregivers of patients hospitalized for general inpatient hospice care were enrolled. MT was provided by a board-certified music therapist, and sessions included pre-MT assessment, 20-45 minutes of MT, and post-MT assessment. Caregiver stress was measured with the Pearlin Role Overload Measure (ROM), QoL was measured with the Linear Analogue Self-Assessment (LASA), and depression and anxiety were measured with the Patient Health Questionnaire for Depression and Anxiety (PHQ-4). These three measures were taken pre-MT, post-MT and 6 months post-MT. Caregivers were also asked to complete a Music Therapy Program Survey post-MT.

The MT intervention was completed for 15/20 caregivers (75%). Of those who did not complete MT, 2 withdrew prior, 1 was not available, 1 patient passed during the MT session, and 1 patient died prior to MT. 14 caregivers completed pre-MT and post-MT assessments, and 9 caregivers completed assessments at all 3 timepoints. The MT Program Survey (post-MT assessment, n=14) showed 100% of caregivers were very satisfied with MT and would recommend to others, 78% found MT effective for stress relief, 69% for relaxation, 71% for spiritual support, 86% for emotional support, and 71% for feeling of wellness.

Research on MT is feasible for acute hospice care caregivers with a majority of caregivers consenting to research and about half completing surveys pre-MT, post-MT, and 6-months post-MT (9/20). Future larger studies should be conducted to better assess the impact of MT on caregivers.

A subgroup of patients with anorexia nervosa (AN) undergoing involuntary treatment (IT) seems to account for most of the IT events. Little is known about these patients and their treatment including the temporal distribution of IT events and factors associated with subsequent utilization of IT. Hence, this study explores (1) utilization patterns of IT events, and (2) factors associated with subsequent utilization of IT in patients with AN.

In this nationwide Danish register-based retrospective exploratory cohort study patients were identified from their first (index) hospital admission with an AN diagnosis and followed up for 5 years. We explored data on IT events including estimated yearly and total 5-year rates, and factors associated with subsequent increased IT rates and restraint, using regression analyses and descriptive statistics.

IT utilization peaked in the initial few years starting at or following the index admission. A small percentage (1.0%) of patients accounted for 67% of all IT events. The most frequent measures reported were mechanical and physical restraint. Factors associated with subsequent increased IT utilization were female sex, lower age, previous admissions with psychiatric disorders before index admission, and IT related to those admissions. Factors associated with subsequent restraint were lower age, previous admissions with psychiatric disorders, and IT related to these.

High IT utilization in a small percentage of individuals with AN is concerning and can lead to adverse treatment experiences. Exploring alternative approaches to treatment that reduce the need for IT is an important focus for future research.