Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

The two major subtypes of bipolar disorder (BD), BD-I and BD-II, are distinguished based on the presence of manic or hypomanic episodes. Historically, BD-II was perceived as a less severe form of BD-I. Recent research has challenged this concept of a severity continuum. Studies in large samples of unrelated patients have described clinical and genetic differences between the subtypes. Besides an increased schizophrenia polygenic risk load in BD-I, these studies also observed an increased depression risk load in BD-II patients. The present study assessed whether such clinical and genetic differences are also found in BD patients from multiplex families, which exhibit reduced genetic and environmental heterogeneity. Comparing 252 BD-I and 75 BD-II patients from the Andalusian Bipolar Family (ABiF) study, the clinical course, symptoms during depressive and manic episodes, and psychiatric comorbidities were analyzed. Furthermore, polygenic risk scores (PRS) for BD, schizophrenia, and depression were assessed. BD-I patients not only suffered from more severe symptoms during manic episodes but also more frequently showed incapacity during depressive episodes. A higher BD PRS was significantly associated with suicidal ideation. Moreover, BD-I cases exhibited lower depression PRS. In line with a severity continuum from BD-II to BD-I, our results link BD-I to a more pronounced clinical presentation in both mania and depression and indicate that the polygenic risk load of BD predisposes to more severe disorder characteristics. Nevertheless, our results suggest that the genetic risk burden for depression also shapes disorder presentation and increases the likelihood of BD-II subtype development.

Due to the exponential increase of autism spectrum disorders’ prevalence in Western countries, it is necessary to improve early detection and intervention to enhance developmental milestones. This systematic review identified the most effective screening instrument, which can be used at an early age and which identifies the maximum number of autism cases. We identified several instruments with adequate predictive properties—the Autism Parent Screen for Infants (APSI), Battelle Development Inventory, second edition (BDI-2); Brief Infant-Toddler Social and Emotional Assessment (BITSEA); First Year Inventory (FYI); Infant-Toddler Checklist/Communication and Symbolic Behavior Scales Developmental Profile (ITC/CSBS-DP); Program of Research and Studies on AUTISM (PREAUT-Grid); Checklist for Early Signs of Developmental Disorders (CESDD); Social Attention and Communication Study (SACS); and the Screening Tool for Autism in Toddlers and Young Children (STAT)—that can be applied from 12 months of age in Western countries. The ITC/CSBS-DP has been proposed for universal screening from 12 months of age onwards, complemented by the Modified Checklist for Autism in Toddlers, Revised/Revised with Follow-Up (M-CHAT-R/F), which can be used from 15 months of age onwards. This strategy could improve early detection in at-risk children within the current health system, thus allowing for early intervention.

Introduction: Social anxiety in gender dysphoria is still under investigation. Aim: To determine the prevalence and associated factors of social anxiety in a sample of individuals with gender dysphoria. Methods: A cross-sectional design was used in a clinical sample attending a public gender identity unit in Spain. The sample consisted of 210 individuals (48% trans female and 52% trans male). Main outcome measures: Mini-International Neuropsychiatric Interview (MINI) for diagnosis of social anxiety disorder, Structured Clinical Interview, Exposure to Violence Questionnaire (EVQ), Beck Depression Inventory (BDI-II), and Functional Social Support Questionnaire (Duke-UNC-11). Results: Of the total sample, 31.4% had social anxiety disorder. Social anxiety disorder was highly correlated with age (r = −0.181; CI = 0.061–0.264; P = .009) and depression (r = 0.345; CI = 0.213–0.468; P < .001); it is strongly associated to current cannabis use (relative risk [RR] = 1.251; CI = 1.070–1.463; P = .001) and lifetime suicidal ideation (RR = 1.902; CI 1.286–2.814; P < .001). Moreover, it is significantly associated to lifetime nonsuicidal self-injury (RR = 1.188; CI 1.018–1.386; P = .011), nationality (RR = 7.792; CI 1.059–57.392; P = .013), perceived violence at school during childhood and adolescence (r = 0.169; CI = 0.036–0.303; P = .014), unemployment (RR = 1.333; CI 1.02–1.742; P = .021), and hospitalization of parents in childhood (RR = 1.146; CI = 1.003–4.419; P = .046). Using multivariable analysis, the highly significant variables within the model were depression score (odds ratio [OR] = 1.083; CI = 1.045–1.123; P < .001) and current cannabis use (OR = 3.873; CI = 1.534–9.779, P = .004), also age (OR = 0.948; CI = 0.909–0.989; P = .012), hospitalization of parents during childhood (OR = 2.618; CI = 1.107–6.189; P = .028), and nationality (OR = 9.427; CI = 1.065–83.457; P = .044) were associated with social anxiety disorder. Conclusion: This study highlights the necessity of implementing actions to prevent and treat social anxiety in this high-risk population.

Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF‐κB‐p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1‐knockout and wild‐type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF‐κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1‐KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF‐κB‐p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1‐knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.