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

Most mental disorders, when examined individually, are associated with an increased risk of cardiometabolic complications. However, these associations might be attributed to a general liability toward psychopathology or confounded by unmeasured familial factors.

To examine whether the associations between psychiatric diagnoses and increased risk of cardiometabolic complications are attributable to a general liability toward psychopathology, or confounded by unmeasured familial factors.

We conducted a cohort study in Sweden and identified all individuals and their siblings born in Sweden 1955-1962 with follow-up through 2013. After excluding individuals who died or emigrated before 1987, the final sample consisted 672 823 individuals. We extracted ICD-coded diagnoses (recorded 1973-1987) for ten psychiatric conditions and criminal convictions when participants were aged 18-25 years, and ICD-coded diagnoses (recorded 1987-2013) for five cardiometabolic complications (obesity, hypertensive diseases, hyperlipidemia, type 2 diabetes mellitus, and cardiovascular diseases) when the participants were 51-58 years old. Logistic regression models were used to estimate the bivariate associations between psychiatric conditions or criminal convictions and cardiometabolic complications in individuals. A general factor model was used to identify general, internalizing, externalizing, and psychotic factors based on the psychiatric conditions and criminal convictions. We then regressed the cardiometabolic complications on the latent general factor and three uncorrelated specific factors within a structural equation modeling framework in individuals and across sibling pairs.

Each psychiatric conditions significantly increased the risk of cardiometabolic complications; however, most of these associations were attributable to the general factor of psychopathology, rather than to specific psychiatric conditions. There were no or only small associations between individuals’ general psychopathology and their siblings’ cardiometabolic complications, suggesting that the associations were not attributable to genetic or environmental confounding factors shared within families. The same pattern was evident for the specific internalizing and psychotic factors.

Individuals with mental disorders in early life had an increased long term risk of cardiometabolic complications, which appeared attributable to a general liability toward psychopathology. Sibling analyses suggested that the elevated risk could not be attributed to confounds shared within families.This highlights the importance of transdiagnostic and lifestyle based interventions to reduce the risk of cardiometabolic complications, particularly in patients with several mental disorders.

None Declared

Intellectual disability (ID) has been linked to substance use-related problems (SUP). However, previous research is limited by the small sample sizes, lack of general population comparison and have not accounted for familial confoundings. The role of other psychiatric comorbidities also remains unknown.

To examine the risk of SUP in individuals with mild-ID and assess whether the associations depend on other psychiatric comorbidities, controlling for potential familial confounding.

Population-based cohort study of individuals born in Sweden 1973-2003. We identified 19,078 individuals with mild-ID, 953,900 reference individuals from the general population, and 20,722 full-siblings of individuals with mild-ID. Conditional logistic regression models were used to compare individuals with mild-ID to the general population and their full-siblings regarding the risk of SUP, including alcohol and substance use disorders, alcohol and substance-related somatic diseases, substance-related crime, and substance-related death. Analyses were repeated stratified by the presence of psychiatric comorbidities.

Individuals with mild-ID had increased risks of any SUP (adjusted OR [95%CI]: 1.41 [1.35, 1.47]), compared to the general population, including alcohol-related somatic diseases (3.27 [1.92, 5.59]), alcohol (2.05 [1.91, 2.22]) and drug-use disorder (1.79 [1.69, 1.91]), and alcohol (1.36 [1.19, 1.49]) and drug-related crime (1.27 [1.19, 1.36]). The risk of SUP for individuals with mild ID was particularly elevated with comorbid mood (3.74 [3.47, 4.04]), anxiety (3.30 [3.09, 3.53]) and attention-deficit/hyperactivity disorders (2.61 [2.44, 2.80]). Increased risk of SUP remained significant when controlling for familial confounding.

Individuals with mild-ID, especially those with other psychiatric comorbidities, are at increased risks of SUP.

No significant relationships.

To study associations between intellectual disability (ID) and sexual and violent offending among individuals subject to pre-trial forensic psychiatric assessment. To investigate sentences following pre-trial forensic psychiatric assessment in offenders with and without ID.

A population-based observational study using data from pre-trial forensic psychiatric assessments in Sweden (1997–2013), the Swedish National Crime Register and several other Swedish national registers. The study population consisted of 7450 offenders (87% men, 13% women) who were subject to forensic psychiatric assessment in 1997–2013, of whom 481 (6.5%) were clinically assessed as having ID.

ID offenders were more likely than non-ID offenders to have a sexual crime as an index crime [26.2 v. 11.5%, adjusted odds ratio (OR) 2.7, 95% confidence interval (CI) 2.02–3.58] as well as previous convictions regarding sexual offending (10.4 v. 5.6%, adj OR 2.3, 95% CI 1.70–3.12). These associations were restricted to male offenders; sexual offending was uncommon among women. Comorbid attention-deficit hyperactivity disorder reduced the association between ID and sexual offending (adj OR 2.7 v. 3.1, p = 0.017), while comorbid autism spectrum disorder had no significant influence on the association (adj OR 2.7 v. 3.0, p = 0.059). Violent crime was equally common among ID and non-ID offenders. Offenders with ID were more likely than non-ID offenders to be sentenced to forensic psychiatric care or community sanctions and measures (such as probation, conditional sentences or fines) than to prison; however, 15% of individuals who received an ID diagnosis during the forensic psychiatric assessment were sentenced to prison. Previous criminal convictions, concurrent antisocial personality disorders and substance use disorders were associated with a higher probability of a prison sentence among offenders with ID.

Sexual crime is overrepresented among offenders with ID compared to offenders with other mental disorders than ID in forensic psychiatric contexts. ID offenders become subject to forensic psychiatric care and forensic psychiatric services need evidence-based treatment programmes for offenders with ID. In addition, there is a need for early intervention strategies suitable for disability services and special education schools, in order to address the complex needs of individuals with ID and prevent sexual and violent offending.

The aim of this study was to investigate the distribution of the regional cerebral blood flow (rCBF) in occupational related PTSD subjects and to seek for possible correlations between brain perfusion and self-rating scales (SRSs) in order to cross-check their diagnostic value and to look for their neural correlates.

Sixteen traumatized underground and long-distance train drivers developing (S) and 17 not developing (NS) PTSD after having experienced a “person-under-train” accident underwent clinical assessment and 99mTc-HMPAO-SPECT during trauma scripts. Statistical parametric mapping (SPM2) was applied to analyse rCBF changes in S as compared to NS, and to search for correlations between rCBF and SRSs scores, modeling age, months since trauma and the ratio ‘gray matter/intra-cranial volume’ as nuisance variables.

Significantly higher activity was observed during trauma script in left posterior insula, posterior cingulate, inferior parietal lobule, precuneus, and caudate in S as compared to NS. Impact of Event Scale (IES) and World Health Organisation (ten) Well-Being Index (WHO-10) scores highly correlated with tracer uptake to a great extent in the same regions in which rCBF differences between S and NS were found.

These findings support the involvement of posterior insular, cingulated, and parietal cortices (as well as the caudate) in the pathogenesis of PTSD and in the processing of related subjective well-being and distress. Our findings seem to provide a cross-validation for IES and WHO-10 scales by means of SPECT data, supporting their validity in the diagnosis of PTSD, and suggesting their use in future works.

Functional studies in Autism Spectrum Disorder (ASD) have shown localised focal hypoperfusion and abnormalities in the anatomo-functional connectivity of limbic-striatal “social” brain. However, no common regional abnormalities have been found across studies.

The aim of this study was to investigate the cerebral blood flow (CBF) at rest in subjects with ASD as compared to a group of healthy controls.

In this preliminary investigation six normal intelligence patients with ASD and 5 age and sex matched healthy controls (HC) were examined using PET/CT camera and, as CBF tracer, 11C-butanol, a radiopharmaceutical produced on-site. The combination of these two methodologies reduced the whole examination time to less than 10 minutes. Statistical Parametric Mapping was implemented to analyse the data.

As compared to HC, ASD showed a highly significant CBF increase (height threshold p=0.001, p< 0.0001 at voxel-level), bilaterally, in large portions of the cerebellum, of the visual associative cortex and of the posterior parietal lobe.

This preliminary study was performed by the state-of-the-art neuroimaging methodologies that reduced considerably the examination time and resulted in less stress and more reliable investigations. The occipital and parietal associative cortex as well as the cerebellum showed an increased CBF in ASD, underscoring their involvement in the disease and raising methodological and diagnostic issues to be considered when exploring the neuroanatomy of ASD.

The monoamine systems have been suggested to play a role for the biological background of ADHD symptoms. Thus, polymorphisms in e.g. the serotonin transporter (5HTT) gene have been associated with ADHD like phenotypes.

Furthermore, platelet MAOB activity has frequently been linked to impulsiveness-related traits.

Biological markers and candidate genes for psychiatric problems are often studied separately. We study ADHD symptoms with regard to the combination of platelet MAOB activity and 5HTT genotype.

To test the hypothesis that associations between ADHD like behavior problems and 5HTT-LPR polymorphism, would be more robust if calculations were done in combination with platelet MAOB enzyme activity.

The study group consisted of 156 adolescent twin pairs, i.e. 312 individuals. ADHD symptoms were scored with a structured clinical interview of both the twin and a parent using Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL).

Presence of a short 5HTT-LPR allele, in combination with high levels of platelet MAOB enzyme activity was associated with higher scores of ADHD like problems and disruptive behavior in boys. No such associations were found in girls.

This examination of ADHD scores in a non-clinical sample suggests that the effects of the 5HTT-LPR are moderated by platelet MAOB activity.

Current approaches to assess violence risk in secure hospitals are resource intensive, limited by accuracy and authorship bias and may have reached a performance ceiling. This study seeks to develop scalable predictive models for violent offending following discharge from secure psychiatric hospitals.

We identified all patients discharged from secure hospitals in Sweden between January 1, 1992 and December 31, 2013. Using multiple Cox regression, pre-specified criminal, sociodemographic, and clinical risk factors were included in a model that was tested for discrimination and calibration in the prediction of violent crime at 12 and 24 months post-discharge. Risk cut-offs were pre-specified at 5% (low vs. medium) and 20% (medium vs. high).

We identified 2248 patients with 2933 discharges into community settings. We developed a 12-item model with good measures of calibration and discrimination (area under the curve = 0.77 at 12 and 24 months). At 24 months post-discharge, using the 5% cut-off, sensitivity was 96% and specificity was 21%. Positive and negative predictive values were 19% and 97%, respectively. Using the 20% cut-off, sensitivity was 55%, specificity 83% and the positive and negative predictive values were 37% and 91%, respectively. The model was used to develop a free online tool (FoVOx).

We have developed a prediction score in a Swedish cohort of patients discharged from secure hospitals that can assist in clinical decision-making. Scalable predictive models for violence risk are possible in specific patient groups and can free up clinical time for treatment and management. Further evaluation in other countries is needed.

Wellcome Trust (202836/Z/16/Z) and the Swedish Research Council. The funding sources had no involvement in writing of the manuscript or decision to submit or in data collection, analysis or interpretation or any aspect pertinent to the study.

Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).

Thirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.

Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.

Glutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

Studies on the individual gender-specific risk and familial co-aggregation of suicidal behaviour in autism spectrum disorder (ASD) are lacking.

We conducted a matched case-cohort study applying conditional logistic regression models on 54 168 individuals recorded in 1987–2013 with ASD in Swedish national registers: ASD without ID n = 43 570 (out of which n = 19035, 43.69% with ADHD); ASD + ID n = 10 598 (out of which n = 2894 individuals, 27.31% with ADHD), and 270 840 controls, as well as 347 155 relatives of individuals with ASD and 1 735 775 control relatives.

The risk for suicidal behaviours [reported as odds ratio OR (95% confidence interval CI)] was most increased in the ASD without ID group with comorbid ADHD [suicide attempt 7.25 (6.79–7.73); most severe attempts i.e. requiring inpatient stay 12.37 (11.33–13.52); suicide 13.09 (8.54–20.08)]. The risk was also increased in ASD + ID group [all suicide attempts 2.60 (2.31–2.92); inpatient only 3.45 (2.96–4.02); suicide 2.31 (1.16–4.57)]. Females with ASD without ID had generally higher risk for suicidal behaviours than males, while both genders had highest risk in the case of comorbid ADHD [females, suicide attempts 10.27 (9.27–11.37); inpatient only 13.42 (11.87–15.18); suicide 14.26 (6.03–33.72); males, suicide attempts 5.55 (5.10–6.05); inpatient only 11.33 (9.98–12.86); suicide 12.72 (7.77–20.82)]. Adjustment for psychiatric comorbidity attenuated the risk estimates. In comparison to controls, relatives of individuals with ASD also had an increased risk of suicidal behaviour.

Clinicians treating patients with ASD should be vigilant for suicidal behaviour and consider treatment of psychiatric comorbidity.

Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.

We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.

Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.

Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.

Many studies have addressed the question of whether mental disorder is associated with creativity, but high-quality epidemiological evidence has been lacking.

To test for an association between studying a creative subject at high school or university and later mental disorder.

In a case–control study using linked population-based registries in Sweden (N = 4 454 763), we tested for associations between tertiary education in an artistic field and hospital admission with schizophrenia (N = 20 333), bipolar disorder (N = 28 293) or unipolar depression (N = 148 365).

Compared with the general population, individuals with an artistic education had increased odds of developing schizophrenia (odds ratio = 1.90, 95% CI = [1.69; 2.12]) bipolar disorder (odds ratio = 1.62 [1.50; 1.75]) and unipolar depression (odds ratio = 1.39 [1.34; 1.44]. The results remained after adjustment for IQ and other potential confounders.

Students of artistic subjects at university are at increased risk of developing schizophrenia, bipolar disorder and unipolar depression in adulthood.

None.