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

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

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

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.

1. (1) Self-tracking with the One Button Tracker is a novel symptom registration method, particularly suited for use in psychotherapeutic treatment and research.

2. (2) Rumination and intrusions appear to the participants as distinct cognitive phenomena and treatment targets in PTSD.

3. (3) Registering rumination and intrusions in real-time could reveal important temporal relations between them and the contexts in which they occur.

4. (4) The data obtained with this self-tracking method can potentially be used as a tool in, and for the further development of psychotherapy for PTSD.

During the last decades we have seen a new focus on early treatment of psychosis. Several reviews have shown that duration of untreated psychosis (DUP) is correlated to better outcome. However, it is still unknown whether early treatment will lead to a better long term outcome. This study reports the effects of reducing DUP on 5-year course and outcome.

During 1997-2000 a total of 281 consecutive patients aged > 17 years with first episode non-affective psychosis were recruited of which 192 participated in the 5-year follow-up. A comprehensive early detection (ED) program with public information campaigns and low-threshold psychosis detection teams was established in one health-care area (ED-area), but not in a comparable area (No-ED area). Both areas ran equivalent treatment programs during the first 2 years and need-adapted treatment thereafter.

At the start of treatment ED-patients had shorter DUP and less symptoms than No-ED-patients. There were no significant differences in treatment (psychotherapy and medication) for the 5 years. Mixed-effects modeling showed better scores for the ED-group on PANSS negative, depressive and cognitive factors and for GAF social functioning at 5 year follow-up. The ED-group also had more contacts with friends. Regression analysis did not find that these differences could be explained by confounders.

Early treatment had positive effects on clinical and functional status at 5 year follow-up in first episode psychosis.

Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.

The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.

There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.

These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

Mounting evidence has suggested a pivotal role of immune dysfunction in the pathophysiology of autism spectrum disorders (ASD). In this study, levels of inflammatory cytokines were measured intrauterinely in amniotic fluid (AF) samples and postnatally in dried blood spots samples (DBSS) of children diagnosed later in life with ASD and their controls.

Study population was retrieved from a historic birth cohort (HBC) kept at Statens Serum Institute (SSI) in Copenhagen, Denmark. The HBC comprises AF and maternal serum samples collected during antenatal screening/diagnostic tests since 1980. All singleton ASD cases who had a corresponding AF sample in the HBC and born 1982–2000 were identified utilizing Danish nation-wide health registers. Controls were selected from the HBC and frequency-matched to cases on gender and year of birth. Corresponding DBSS were indentified in the Danish Newborn Screening Biobank. Levels of selected inflammatory cytokines in AF samples and DBSS were analyzed at SSI using Luminex xMAP technology. Case-control differences were assessed as categories (logistic regression) or continuous measures (tobit regression).

Total of 414 cases and 820 controls were included in the study. Measurements performed on AF showed elevated levels of TNF, IL-4, and IL-10 in ASD. Discrepant pattern was seen in DBSS with elevated levels of IL-8 and sIL-6rα. While findings in this study show that immune dysfunction in ASD starts intrauterinly, the discrepant intrauterine/neonatal patterns are of a special interest. Finally, further studies to examine the specificity of these findings to ASD are necessary.