Editorial: Combining Genetic and Clinical Predictors of Bipolar Disorder: Towards Improving Diagnostic Precision in Youth.

Bipolar disorder (BD) is a complex, heterogeneous illness, with 60% to 85% of its variance attributed to genetic factors.1 Adolescence marks the first peak period of risk for the onset of BD, with the initial (hypo)manic episode often preceded by childhood psychopathology, including anxiety and sleep disorders, as well as internalizing symptoms.2 Given the non-specific nature of childhood antecedents, combined with the prominence of depressive episodes in the early illness course, accurate diagnosis is often delayed by 8 to 10 years from onset.3 Yet, the early course of BD in youth is already associated with significant morbidity and mortality. Therefore, more accurate and timely diagnosis is a priority. One way forward could be to combine biomarkers with clinical variables to help validate diagnoses, improve individual risk prediction and treatment, and advance discovery research into pathogenesis.

Systematic Review and Meta-Analysis: Risks of Anxiety Disorders in Offspring of Parents With Mood Disorders.

OBJECTIVE: To examine the risk of anxiety disorders in offspring of parents with mood disorders. METHOD: We conducted a systematic review and meta-analysis. We searched 4 electronic databases (Medline, Embase, PsycINFO, and Web of Science [core collection]) to identify cross-sectional and cohort studies that examined the association between parental mood disorders (including bipolar disorder and unipolar depression) and risk of anxiety disorders in offspring. Pooled risk ratios (RRs) of overall and specific anxiety disorders were synthesized using a random effects model. Subgroup analyses and meta-regression were performed to identify moderation factors. RESULTS: A total of 35 studies were included in the final analysis. Our results showed higher risks of all types of anxiety disorders in the offspring of parents with mood disorders (any anxiety disorder, RR = 1.82, 95% CI = 1.47-2.26), except for agoraphobia (RR = 1.08, 95% CI = 0.56-2.08), and with an especially elevated risk of panic disorder (RR = 3.07, 95% CI = 2.19-4.32). Subgroup analysis demonstrated no significant difference between the risks of anxiety disorders across the offspring of parents with bipolar disorder as opposed to unipolar depression. The absence of anxiety disorders in control parents, younger offspring age, and specific parent/offspring sex were associated with higher RRs for some anxiety disorders in offspring of parents with mood disorders. CONCLUSION: Our findings suggest a robust relationship between parental mood disorders and offspring anxiety disorders, and highlight the potential value of prevention and early intervention for anxiety disorders in this context. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. STUDY PREREGISTRATION INFORMATION: Anxiety Disorders in Offspring of Parents with Mood Disorders: A Systematic Review; https://www.crd.york.ac.uk/prospero/; CRD42021215058.

White matter microstructural and morphometric alterations in autism: implications for intellectual capabilities.

BACKGROUND: Neuroimage literature of autism spectrum disorder (ASD) has a moderate-to-high risk of bias, partially because those combined with intellectual impairment (II) and/or minimally verbal (MV) status are generally ignored. We aimed to provide more comprehensive insights into white matter alterations of ASD, inclusive of individuals with II (ASD-II-Only) or MV expression (ASD-MV). METHODS: Sixty-five participants with ASD (ASD-Whole; 16.6 ± 5.9 years; comprising 34 intellectually able youth, ASD-IA, and 31 intellectually impaired youth, ASD-II, including 24 ASD-II-Only plus 7 ASD-MV) and 38 demographic-matched typically developing controls (TDC; 17.3 ± 5.6 years) were scanned in accelerated diffusion-weighted MRI. Fixel-based analysis was undertaken to investigate the categorical differences in fiber density (FD), fiber cross section (FC), and a combined index (FDC), and brain symptom/cognition associations. RESULTS: ASD-Whole had reduced FD in the anterior and posterior corpus callosum and left cerebellum Crus I, and smaller FDC in right cerebellum Crus II, compared to TDC. ASD-IA, relative to TDC, had no significant discrepancies, while ASD-II showed almost identical alterations to those from ASD-Whole vs. TDC. ASD-II-Only had greater FD/FDC in the isthmus splenium of callosum than ASD-MV. Autistic severity negatively correlated with FC in right Crus I. Nonverbal full-scale IQ positively correlated with FC/FDC in cerebellum VI. FD/FDC of the right dorsolateral prefrontal cortex showed a diagnosis-by-executive function interaction. LIMITATIONS: We could not preclude the potential effects of age and sex from the ASD cohort, although statistical tests suggested that these factors were not influential. Our results could be confounded by variable psychiatric comorbidities and psychotropic medication uses in our ASD participants recruited from outpatient clinics, which is nevertheless closer to a real-world presentation of ASD. The outcomes related to ASD-MV were considered preliminaries due to the small sample size within this subgroup. Finally, our study design did not include intellectual impairment-only participants without ASD to disentangle the mixture of autistic and intellectual symptoms. CONCLUSIONS: ASD-associated white matter alterations appear driven by individuals with II and potentially further by MV. Results suggest that changes in the corpus callosum and cerebellum are key for psychopathology and cognition associated with ASD. Our work highlights an essential to include understudied subpopulations on the spectrum in research.

School Functions in Unaffected Siblings of Youths with Autism Spectrum Disorders.

This study investigated school functioning among unaffected siblings of youths with autistic spectrum disorder (ASD) and identified the correlates for school maladjustment. We recruited 66 youths with a clinical diagnosis of ASD, aged 8-19, their unaffected siblings and 132 typically developing controls (TD). We found that ASD youths had poorer school functions than unaffected siblings and TD. Unaffected siblings had poorer attitude toward schoolwork and more severe behavioral problems at school than TD. Several associated factors for different scholastic functional domains (i.e., academic performance, attitude toward school work, social interactions, behavioral problems) in the siblings included IQ, autistic traits, inattention/oppositional symptoms, sibling relationships, etc. Our findings suggest the need of assessing school functions in unaffected siblings of ASD. TRIAL REGISTRATION: Clinical trial registration identifier: NCT01582256.