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.

Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood.

Individuals born in Sweden 1985–1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems.

Among 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43–2.70) and females (HR 5.39; 95% CI 4.97–5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06–1.51) and females (HR 1.69; 95% CI 1.21–2.36).

Females with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.

Familial co-aggregation studies of eating disorders (EDs) and schizophrenia reveal shared genetic and environment factors, yet their etiological and clinical relationship remains unclear. We evaluate the influence of schizophrenia family history on clinical outcomes of EDs.

We conducted a cohort evaluation of the association between family history of schizophrenia and ED clinical features, psychiatric comorbidities, and somatic and mental health burden in individuals born in Sweden 1977–2003 with anorexia nervosa (AN) or other EDs (OED: bulimia nervosa, binge-eating disorder, and ED not otherwise specified).

Of 12 424 individuals with AN and 20 716 individuals with OED, 599 (4.8%) and 1118 (5.4%), respectively, had a family history of schizophrenia (in up to third-degree relatives). Among individuals with AN, schizophrenia in first-degree relatives was significantly associated with increased comorbid attention-deficit/hyperactivity disorder (ADHD) [HR(95% CI) 2.26 (1.27–3.99)], substance abuse disorder (SUD) [HR (95% CI) 1.93 (1.25–2.98)], and anxiety disorders [HR (95% CI) 1.47 (1.08–2.01)], but higher lowest illness-associated body mass index (BMI) [1.14 kg/m2, 95% CI (0.19–2.10)]. Schizophrenia in any relative (up to third-degree) in AN was significantly associated with higher somatic and mental health burden, but lower ED psychopathology scores [−0.29, 95% CI (−0.54 to −0.04)]. Schizophrenia in first-degree relatives in individuals with OED was significantly associated with increased comorbid ADHD, obsessive-compulsive disorder, SUD, anxiety disorders, somatic and mental health burden, and suicide attempts.

We observed different patterns of ED-related outcomes, psychiatric comorbidity, and illness burden in individuals with EDs with and without family histories of schizophrenia and provide new insights into the diverse manifestations of EDs.

Genetically informed studies have provided mixed findings as to what extent parental substance misuse is associated with offspring substance misuse and antisocial behavior due to shared environmental and genetic factors.

We linked data from nationwide registries for a cohort of 2 476 198 offspring born in Sweden 1958–1995 and their parents. Substance misuse was defined as International Classification of Diseases diagnoses of alcohol/drug use disorders or alcohol/drug-related criminal convictions. Quantitative genetic offspring-of-siblings analyses in offspring of monozygotic and dizygotic twin, full-sibling, and half-sibling parents were conducted.

Both maternal and paternal substance misuse were robustly associated with offspring substance misuse [maternal adjusted hazard ratio (aHR) = 1.83 (95% confidence interval (CI) 1.80–1.87); paternal aHR = 1.96 (1.94–1.98)] and criminal convictions [maternal aHR = 1.56 (1.54–1.58); paternal aHR = 1.66 (1.64–1.67)]. Additive genetic effects explained 42% (95% CI 25–56%) and 46% (36–55%) of the variance in maternal and paternal substance misuse, respectively, and between 36 and 44% of the variance in substance misuse and criminality in offspring. The associations between parental substance misuse and offspring outcomes were mostly due to additive genetic effects, which explained 54–85% of the parent-offspring covariance. However, both nuclear and extended family environmental factors also contributed to the associations, especially with offspring substance misuse.

Our findings from a large offspring-of-siblings study indicate that shared genetic influences mostly explain the associations between parental substance misuse and both offspring substance misuse and criminality, but we also found evidence for the contribution of environmental factors shared by members of nuclear and extended families.

There is converging evidence of gray matter (GM) structural alterations in different limbic structures in Post-Traumatic Stress Disorder (PTSD) patients. The aim of this study was to evaluate GM density in PTSD in relation to trauma load.

Magnetic Resonance Imaging (MRI) scans of 21 subjects exposed to occupational trauma, who developed PTSD (S), and of 22 who did not (NS), were performed. The self-rated Trauma Antecedent Questionnaire (TAQ) was administered to assess lifelong trauma load and resilience. TAQ includes two scales (“trauma and neglect” TAQ−, and “resilience factors” TAQ+) further divided into four subscales measuring trauma load and resilience in four different age periods: zero to six, seven to twelve, thirteen to eighteen and adult. Regression analyses between the two sub-scales and GM density were performed on all 43 subjects by means of an optimized Voxel-Based Morphometry (VBM) analysis as implemented in SPM2.

The analyses showed that GM density negatively correlated only with adult TAQ- in bilateral posterior cingulate, left anterior insula, and right anterior parahippocampal gyrus.

Irrespective of the PTSD diagnosis, trauma load was found to correlate with GM density in several limbic structures suggesting a high vulnerability of these structures to the effects of stress and trauma, These regions are implicated in integration, encoding and retrieval of autobiographical and episodic memories, emotional processing, interoceptive awareness and self-referential conscious experience. Thus, our study supports lower GM densities in limbic and paralimbic cortices as a potential structural basis for memory and dissociative dysfunction in PTSD.

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.

Several studies have reported limbic structures volume decrease in Post-Traumatic Stress Disorder (PTSD). However, in PTSD the effect of therapy on brain structures has seldom been investigated. the aim of the study was to evaluate the grey matter (GM) loss in occupational related PTSD and to assess the volumetric differences between patients responding (R) and non-responding (NR) to psychotherapy.

Pre-EMDR MRI data of 21 train drives who did develop PTSD (S) and 22 who did not develop PTSD (NS) after person-under-the-train accidents were compared. Within S further comparisons were made between 10 R to Eye Movement Desensitisation Reprocessing (EMDR) therapy and 5 NR. Data were analysed by optimised voxel-based morphometry as implemented in Statistical Parametric Mapping.

As compared to NS, S showed a significant GM volume reduction in precuneus, lingual gyrus, posterior cingulate and parahippocampal cortex. the R>NR comparison highlighted a significant GM reduction in NR in bilateral posterior cingulate, left middle frontal cortex and right parahippocampal, insular and temporal cortices.

Comparing two large groups of subjects significant GM volumetric reductions were found in PTSD in posterior limbic structures. NR showed, as compared to R, volume reduction in cortical structures including posterior cingulate and parahippocampal cortex. These latter two structures seem to be the hallmark for both PTSD diagnosis and therapy outcome prediction.

Several studies have reported limbic structures volume decrease in Post-Traumatic Stress Disorder (PTSD). However, in PTSD the effect of therapy on brain structures has seldom been investigated. The aim of the study was to evaluate the grey matter (GM) loss in occupational related PTSD and to assess the volumetric differences between patients responding (R) and non-responding (NR) to psychotherapy.

Pre-EMDR MRI data of 21 train drives who did develop PTSD (S) and 22 who did not develop PTSD (NS) after person-under-the-train accidents were compared. Within S further comparisons were made between 10 R to Eye Movement Desensitisation Reprocessing (EMDR) therapy and 5 NR. Data were analysed by optimised voxel-based morphometry as implemented in Statistical Parametric Mapping.

As compared to NS, S showed a significant GM volume reduction in precuneus, lingual gyrus, posterior cingulate and parahippocampal cortex. The R>NR comparison highlighted a significant GM reduction in NR in bilateral posterior cingulate, left middle frontal cortex and right parahippocampal, insular and temporal cortices.

Comparing two large groups of subjects significant GM volumetric reductions were found in PTSD in posterior limbic structures. NR showed, as compared to R, volume reduction in cortical structures including posterior cingulate and parahippocampal cortex. These latter two structures seem to be the hallmark for both PTSD diagnosis and therapy outcome prediction.

This study examined low episodic memory scores as a potential risk factor for developing depression by using longitudinal data from the PART project in Stockholm, Sweden.

A population-based sample of non-depressed participants (20-64 years) were re-examined three years after the initial screening (n=708). At baseline, a neuropsychological test battery including tests of episodic memory was administered. Also, information about demographic and socioeconomic factors, alcohol use, and anxiety diagnoses was collected. The psychiatric data for depression diagnoses were collected both at baseline and follow-up.

Logistic regressions were conducted on three separate study groups that were defined according to three different assessments of episodic memory (i.e., free + cued recall, free recall or cued recall) among individuals who scored in the 25 lowest or highest percentiles in the memory tests. The results suggest that low episodic memory performance defined as the sum of free and cued recall of organizable words, constitute a risk for depression diagnosis three years later, even after controlling for differences in demographic, socioeconomic, alcohol use and anxiety levels. Also, female gender, low educational level, and financial strain constituted significant risk factors for developing depression.

This study indicates that low episodic memory performance predates depressive diagnosis and might be considered as a premorbid marker of incipient depression.

Anorexia nervosa and bulimia nervosa are two severe eating disorders associated with high premature mortality, suicidal risk and serious medical complications. Transition between anorexia nervosa and bulimia nervosa over the illness course and familial co-aggregation of the two eating disorders imply aetiological overlap. However, genetic and environmental liabilities to the overlap are poorly understood. Quantitative genetic research using clinical diagnosis is needed.

We acquired a clinical diagnosis of anorexia nervosa (prevalence = 0.90%) and bulimia nervosa (prevalence = 0.48%) in a large population-based sample (N = 782 938) of randomly selected full-sisters and maternal half-sisters born in Sweden between 1970 and 2005. Structural equation modelling was applied to quantify heritability of clinically diagnosed anorexia nervosa and bulimia nervosa and the contributions of genetic and environmental effects on their overlap.

The heritability of clinically diagnosed anorexia nervosa and bulimia nervosa was estimated at 43% [95% confidence interval (CI) (36–50%)] and 41% (31–52%), respectively, in the study population, with the remaining variance explained by variance in unique environmental effects. We found statistically significant genetic [0.66, 95% CI (0.49–0.82)] and unique environmental correlations [0.55 (0.43–0.66)] between the two clinically diagnosed eating disorders; and their overlap was about equally explained by genetic and unique environmental effects [co-heritability 47% (35–58%)].

Our study supports shared mechanisms for anorexia nervosa and bulimia nervosa and extends the literature from self-reported behavioural measures to clinical diagnosis. The findings encourage future molecular genetic research on both eating disorders and emphasize clinical vigilance for symptom fluctuation between them.

Causes of the comorbidity of substance misuse with anxiety-related and depressive disorders (anxiety/depression) remain poorly known. We estimated associations of substance misuse and anxiety/depression in the general population and tested them while accounting for genetic and shared environmental factors.

We studied individuals born in Sweden 1968–1997 (n = 2 996 398) with follow-up in nationwide register data for 1997–2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Substance misuse was defined as ICD-10 alcohol or drug use disorder or an alcohol/drug-related criminal conviction. Three dimensions of ICD-10 anxiety and depressive disorders and a substance misuse dimension were identified through exploratory factor analysis.

Substance misuse was associated with a 4.5-fold (95% CI 4.50–4.58) elevated risk of lifetime generalized anxiety/depression, 4.7-fold (95% CI 4.63–4.82) elevated risk of panic disorder and agora/social phobia, and 2.9-fold elevated risk of phobias/OCD (95% CI 2.82–3.02) as compared to those without substance misuse. The associations were attenuated in within-family analyses but we found elevated risks in monozygotic twin pairs discordant for substance misuse as well as significant non-shared environmental correlations. The association between anxiety/depression and substance misuse was mainly driven by generalized anxiety/depression, whereas other anxiety/depression dimensions had minor or no independent associations with substance misuse.

Substance misuse and anxiety/depression are associated at the population level, and these associations are partially explained by familial liabilities. Our findings indicate a common genetic etiology but are also compatible with a potential partially causal relationship between substance misuse and anxiety/depression.