Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Psychiatric conditions in parents are associated not only with the same condition in offspring, but also with virtually all other psychiatric conditions. However, it remains unknown whether this intergenerational transmission of psychiatric conditions was attributable to broader psychopathology comorbidity or to specific conditions.

To estimate associations between general and specific factors of psychopathology in parents, and a wide range of register-based outcomes in their offspring.

Based on Swedish national registers, we linked 2 947 703 individuals born in Sweden between 1970 and 2000 to their biological parents (1 705 780 pairs of parents) and followed them to December 31, 2013. First, we estimated one general and three unrelated (specific) psychopathology factors (capturing internalizing, externalizing, and psychotic problems, respectively, independently of general psychopathology) based on nine parental register-based psychiatric diagnoses and violent criminal court convictions. Second, we regressed each offspring outcome on the latent general and three specific factors simultaneously.

The general psychopathology factor in parents was significantly associated with all 31 offspring outcomes (mean Odds Ratio (OR) = 1.22; range: 1.08–1.40), which means that children whose parents scored one standard deviation above the mean on general psychopathology had, on average, a 23% higher probability of all outcomes. The specific psychotic factor in parents was primarily associated with psychotic-like outcomes (mean OR = 1.17; range: 1.05–1.25), and the specific internalizing factor in parents was primarily associated with offspring internalizing (mean OR = 1.11; range: 1.11–1.13) and neurodevelopmental outcomes (mean OR = 1.07; range: 1.02–1.10). The specific externalizing factor in parents was associated with externalizing (mean OR = 1.27; range: 1.21–1.32) and internalizing outcomes (mean OR = 1.10; range: 1.01–1.13).

The intergenerational transmission of psychiatric conditions across different types of spectra appeared largely attributable to a parental general factor of psychopathology, whereas specific factors were primarily responsible for within-spectrum associations between parents and their offspring. Service providers (e.g., child psychologists, psychiatrists, teachers, and social workers) might benefit from taking the total number of parental mental health problems into account, regardless of type, when forecasting child mental health and social functions.

None Declared

Children with parents with psychiatric diagnoses have an increased probability for not only the same condition as their parent, but also for other conditions and behavioral and psychosocial problems. Whereas many studies have focused on parental severe mental illness due to their significant impairment, less attention has been paid to more common disorders despite their higher prevalence. In addition, because most past research only included one exposure or one outcome at a time, it remains difficult to examine and compare broad patterns of intergenerational transmission.

To examine associations between six parental psychiatric diagnoses in parents, and a broad range of psychiatric diagnoses, psychotropic medications, criminality, suicide, violent victimization, accidents, and school and labor performance in their offspring.

Based on Swedish national registers, we linked all individuals born in Sweden between 1970 and 2000 to their biological parents (N = 3 286 293). We used a matched cohort design, analyzed with stratified Cox regression and conditional logistic regressions to examine associations between six psychiatric diagnoses in the parents, and 32 outcomes in their offspring. All exposed and unexposed children were followed from their date of birth to the date of emigration from Sweden, the death, or 31 December 2013 when the offspring were 14-44 years old.

In terms of absolute risk, most children who had parents with psychiatric diagnoses were not diagnosed in specialist care themselves, as the proportion of having any of the 16 types of psychiatric conditions ranged from 22.17% (exposed to parental depression) to 25.05% (exposed to parental drug-related disorders) at the end of follow-up. Nevertheless, in terms of relative risk, all six parental psychiatric diagnoses increased the probability of all 32 outcomes in their offspring, with the Hazard Ratio ranging from 1.04 to 8.91 for time-to-event outcomes, and the Odds Ratio ranging from 1.29 to 3.36 for binary outcomes. Some specificities were observed for parental psychotic and substance misuse diagnoses, which strongly predicted offspring psychotic-like and externalizing-related outcomes, respectively.

The intergenerational transmission of parental psychiatric conditions appeared largely transdiagnostic, even for non-psychiatric outcomes in offspring. Given the broad spectrum of associations with the outcomes, service providers (e.g., psychiatrists, teachers, and social workers) should consider clients’ broader psychiatric family history when predicting prognosis and planning interventions/treatment.

None Declared

We investigated how well a visual associative learning task discriminates Alzheimer’s disease (AD) dementia from other types of dementia and how it relates to AD pathology.

3,599 patients (63.9 ± 8.9 years old, 41% female) from the Amsterdam Dementia Cohort completed two sets of the Visual Association Test (VAT) in a single test session and underwent magnetic resonance imaging. We performed receiver operating curve analysis to investigate the VAT’s discriminatory ability between AD dementia and other diagnoses and compared it to that of other episodic memory tests. We tested associations between VAT performance and medial temporal lobe atrophy (MTA), and amyloid status (n = 2,769, 77%).

Patients with AD dementia performed worse on the VAT than all other patients. The VAT discriminated well between AD and other types of dementia (area under the curve range 0.70–0.86), better than other episodic memory tests. Six-hundred forty patients (17.8%) learned all associations on VAT-A, but not on VAT-B, and they were more likely to have higher MTA scores (odds ratios range 1.63 (MTA 0.5) through 5.13 for MTA ≥ 3, all p < .001) and to be amyloid positive (odds ratio = 3.38, 95%CI = [2.71, 4.22], p < .001) than patients who learned all associations on both sets.

Performance on the VAT, especially on a second set administered immediately after the first, discriminates AD from other types of dementia and is associated with MTA and amyloid positivity. The VAT might be a useful, simple tool to assess early episodic memory deficits in the presence of AD pathology.

Postpartum psychosis is a rare psychiatric emergency, occurring days to weeks after 1-2 per 1000 deliveries. Its low prevalence makes it difficult to recruit enough participants to investigate the underlying pathophysiology. It is epidemiologically linked to bipolar disorder, which one study also found it to resemble in genetic susceptibility for psychiatric disorders (Di Florio et al. Lancet Psych 2021; 8: 1045–52).

In this study we aim to investigate polygenic liability for psychiatric disorders in two new Swedish postpartum psychosis cohorts.

Cases with postpartum psychosis, defined as a psychiatric hospitalization within 6 weeks after delivery, and/or receiving a diagnosis of F53.1 (ICD 10) or 294.40 (ICD 8.), parous women with severe mental illness without postpartum psychosis, and healthy parous controls were identified in two Swedish genetic studies: the Swedish bipolar collection (SWEBIC) and Predictors for ECT (PREFECT). Polygenic risk scores (PRS) were calculated from summary statistics from genome wide studies on bipolar disorder (Mullins et al. Nat Genet 2021; 53 817-829), schizophrenia (Trubetskoy et al. Nature 2022; 604 502-508) and major depression (Wray et al. Nat Genet. 2018; 50 668-681). The p-value thresholds best predicting their respective phenotype were used in logistic regression analyses with the first six principal components and genotyping platform as confounders.

We identified 176 patients with postpartum psychosis and genetic information (N(SWEBIC)=126, N(PREFECT)=50). Compared with healthy parous women, patients with postpartum psychosis had significantly higher PRS for bipolar disorder (SWEBIC: odds ratio [OR] 2.6 (95% confidence interval [CI] 1.9-3.5), PREFECT: OR 2.4 (95% CI 1.8-3.2), Figure 1.) and schizophrenia (SWEBIC: OR 1.6 (95% CI 1.2-2.2), PREFECT: OR 1.8 (95%; CI 1.3-2.5)). Patients with postpartum psychosis had significantly higher PRS for bipolar disorder (SWEBIC: OR 1.4 (95% CI 1.2-1.8), PREFECT: OR 1.5 (95% CI 1.1-2)) compared with parous women with severe mental illness without postpartum psychosis. We found no associations with major depression PRS in either cohort.

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We replicated previous findings of significantly higher PRS for bipolar disorder and schizophrenia in postpartum psychosis compared with healthy controls. In contrast to previous research, we find postpartum psychosis cases to have higher PRS for bipolar disorder than bipolar disorder cases. Our findings highlight the genetic influence in postpartum psychosis and support previous genetic and epidemiological evidence that postpartum psychosis lies on the bipolar spectrum.

None Declared

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

The term “neuroprogression” imply that bipolar disorder (BD) progressively worsens for some patients and accompanying neuroanatomical changes. BD has indeed been associated with cortical and subcortical brain abnormalities. But cross-sectional studies cannot determine whether the observed brain alterations reflect static premorbid traits or whether they result from progressive changes during the course of illness.

The aims of this series of studies were to determine if progressive brain changes occur in bipolar disorder, and if so, what the drivers of these changes are.

We addressed these questions in the St. Göran cohort – a longitudinal study where patients and controls undergo structural magnetic resonance imaging (MRI) scans at baseline and after 7 years. We have also conducted a longitudinal multicenter study within the ENIGMA consortium including 307 patients and 925 healthy controls scanned at two time points.

We addressed these questions in the St. Göran cohort – a longitudinal study where patients and controls undergo structural magnetic resonance imaging (MRI) scans at baseline and after 7 years. We have also conducted a longitudinal multicenter study within the ENIGMA consortium including 307 patients and 925 healthy controls scanned at two time points.

BD is associated with some (accelerated ventricular enlargement) but not global progressive brain changes (change in cortical structures do not differ from controls). Occurrence of manic episodes is, however, associated with accelerated cortical thinning over time. These results highlight the importance of preventing the potentially toxic effects of manic episodes and might explain why some patients experience worsening cognitive function.

ML has received lecture honoraria (unrelated to this topic) from Lundbeck pharmaceuticals.

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.

Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.

The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.

Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Cross-sectional studies have found impaired cognitive functioning in patients with bipolar disorder, but long-term longitudinal studies are scarce.

The aims of this study were to examine the 6-year longitudinal course of cognitive functioning in patients with bipolar disorder and healthy controls. Subsets of patients were examined to investigate possible differences in cognitive trajectories.

Patients with bipolar I disorder (n = 44) or bipolar II disorder (n = 28) and healthy controls (n = 59) were tested with a comprehensive cognitive test battery at baseline and retested after 6 years. We conducted repeated measures ANCOVAs with group as a between-subject factor and tested the significance of group and time interaction.

By and large, the change in cognitive functioning between baseline and follow-up did not differ significantly between participants with bipolar disorder and healthy controls. Comparing subsets of patients, for example those with bipolar I and II disorder and those with and without manic episodes during follow-up, did not reveal subgroups more vulnerable to cognitive decline.

Cognitive performance remained stable in patients with bipolar disorder over a 6-year period and evolved similarly to healthy controls. These findings argue against the notion of a general progressive decline in cognitive functioning in bipolar disorder.

Bipolar Disorder type 1 (BP-1) is a severe and common psychiatric disorder with a strong genetic contribution to increased disease risk. Heritability is around 60% and at least a dozen different genes seems to be involved in the etiology. The DAOA-G72/G30) locus on chromosome 13p22-34 has been associated with BP-1 in at least six independent datasets, although there are different SNPs and haplotypes associated with increased disease risk in these studies.

276 Swedish patients with BP-1, diagnosed according to DSM-IV, and 940 controls were analyzed with 36 SNPs from eight previously reported candidate genes for bipolar disorder (DAOA-G72/G30, P2RX7, COMT, BDNF, CAMKK2, GRK3, SLC6A4 and S100A10). Genotyping was carried out with Applied Biosystems TaqMan® using ABI PRISM® 7900HT Sequence Detecting System. Statistical analysis was performed with the Unphased program.

None of the SNPs showed a significant association by itself. However, three SNPs in different haplotype blocks in the DAOA-G72/G30 genes were together associated to bipolar disorder (p=0.0009). The association remained when different SNPs in each haplotype block were analyzed.

This is the first study of the G72/30 gene in a homogeneous Swedish BP-1 sample. We found a strong association, which required SNPs from three different haplotype blocks. Thus, the association between the DAOA-G72/G30 genes and Swedish patients with BP-1 disorder was more complex than previous findings.

Even though 0.3-0.8% percent of the male population are born with hypospadias, it is not known if this is associated with an increased risk for psychiatric morbidity later in life.

The aim of this study was to assess the association between hypospadias and risk of psychiatric disorders in affected individuals.

The association between hypospadias and psychiatric disorders was examined in a population-based cohort study using Swedish registers. Individuals born in Sweden between 1973 and 2009 were included in the study. Among them, 11,156 patients with hypospadias were identified and matched with 1,098,714 distinct controls by year of birth and county. The following outcomes were evaluated: 1- suicide attempt, 2- psychotic, 3- mood, 4-anxiety, 5- eating, 6- personality disorders, 7- disorders due to psychoactive substance use, 8- ADHD, 9- pervasive developmental disorders, 10- intellectual disabilities, and 11- other childhood emotional disorders.

After adjusting for socio-economic and perinatal factors, malformations and/or genetic syndromes, patients with hypospadias were more likely to be diagnosed with pervasive developmental disorders (OR 1.4; 95% CI 1.1-1.6), intellectual disabilities (OR 1.8; 95% CI 1.6-2.1), ADHD (OR 1.2; 95% CI 1.0-1.4) and other childhood emotional disorders (OR 1.3; 95% CI 1.1-1.4) compared to the controls. No relation between other psychiatric diagnosis and hypospadias was found.

Hypospadias is associated with an increased risk of neurodevelopmental disorders.

Rapid cycling (RC) is a severe form of bipolar disorder (BD) with an increased rate of episodes. Circadian disturbances are common in BD, and those with RC might be even more vulnerable.

To investigate if the P2RX7 gene would be involved in the circadian rhythm and in part thereby be implicated in RC.

Gene expression was analyzed in peripheral mononuclear cells (PBMCs) from healthy volunteers (n=8) at the sleep research center, University of California, Irvine Medical Center, USA. Swedish outpatients recruited from psychiatric clinics for BD, diagnosed with BD type 1(n=569; RC: n=121) and anonymous blood donor controls (n=1,044) was investigated in case-case and case-control SNP/haplotype association analyses.

P2RX7 RNA levels were dramatically increased during sleep deprivation in PBMCs from the healthy volunteers (p=2.3*10-9). The P2RX7 rs 2230912 _A allele was more common (OR=2.2, p=0.002) and the ACGTTT haplotype in P2RX7 containing the protective rs2230912_G allele was less common, among RC cases compared to nonRC bipolar patients and blood donor controls.

Sleep deprivation activates P2RX7 expression in healthy persons which suggests that P2RX7 is involved in, or downstream, circadian rhythm regulation. The putatively low-activity P2RX7 rs2230912 allele A variant was associated with RC in BD which supports earlier findings of P2RX7 associations to affective disorder.

Electroconvulsive therapy (ECT) effectively treats severe depression, but not all patients remit. The aim of the study was to identify clinical factors that associate with ECT-induced remission in a community setting.

Depressed patients who underwent ECT in 2011–2014 were identified from the Swedish National Quality Register for ECT. Remission was defined as self-rated Montgomery-Åsberg Depression Rating Scale scores of 0–10 after ECT. Other registers provided data on previous antidepressant use, comorbidities, and demographics.

Of 1671 patients fulfilling the inclusion criteria, 42.8% achieved remission. Older age, education length over 9 years, psychotic symptoms, shorter duration of preceding antidepressant use, pulse width stimulus ≥ 0.50 ms, absence of substance use disorders, anxiety diagnosis, lamotrigine, and benzodiazepines, were associated with remission.

This study shows that psychotic subtype of depression and older age are clinically relevant predictors of a beneficial ECT effect. Additionally, ECT outcomes can be further improved by optimizing the treatment technique and concomitant medication.

Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences.

A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models.

PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31–1.99), ASD: aHR = 2.02 (95% CI 1.45–2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19–1.57), ASD: aHR = 1.46 (95% CI 1.21–1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys.

Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.

Clinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however, their design often limits generalisation to routine clinical practice.

To estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder.

We used national registers to identify 35022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine and olanzapine treatment from 2006 to 2009. The main outcome was psychiatric hospital admissions. We used stratified cox regression to compare periods on and off medication within the same individual.

Medication with lithium, valproate, lamotrigine, olanzapine and quetiapine was associated with reduced rates of admission to hospital. Lithium was more effective than quetiapine and olanzapine. The effects of specific drugs depended on the polarity of the mood episode.

Our findings complement results from randomised controlled trails, but suggest that lithium is more effective than both quetiapine and olanzapine in routine clinical practice.

Advanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age's relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence.

Data for 2 276 809 individuals born in Sweden 1979–2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987–2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history.

Even after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25–29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14–1.53] for AN and 1.26 (95% CI 1.13–1.40) for AED.

In this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline.

The concept of cognitive reserve (CR) hypothesizes that intellectually stimulating activities provide resilience against brain pathology/disease. Whereas brain abnormalities and cognitive impairment are frequently reported in bipolar disorder (BD), it is unknown whether the impact of brain alterations can be lessened by higher CR in BD.

We tested if higher CR would reduce the influence of total volumes of deep white matter hypointensities (WMH), ventricular cerebrospinal fluid (CSF), and prefrontal cortex on memory, executive, and attention/speed functions in patients with BD (n = 75). Linear regression models with interaction terms for CR and brain volumes were applied to directly test if CR reduces the influence of brain pathology on cognitive domains.

CR reduced the influence of total volumes of deep WMH (β = −0.38, Q = 0.003) and ventricular CSF (β = −41, Q = 006) on executive functions.

The interactions between CR and total volumes of deep WMH/ventricular CSF appear to account for executive functioning in BD. The results suggest that the concept of CR is applicable in BD. Higher reserve capacity in BD alters the relationship between brain pathology and clinical presentation.