Objectives Vascular‐brain associations are well established in adults but neglected in youth and psychiatric populations, who are at greater cardiovascular risk. We therefore examined the association of retinal vascular caliber with regional brain structure in adolescents with and without bipolar disorder (BD). Methods One hundred and three adolescents (n = 51 BD, n = 52 healthy control [HC]) completed retinal fundus imaging, yielding arteriolar and venular diameters, followed by T1‐weighted 3‐Tesla MRI. Region of interest (ROI) analyses examined ventrolateral prefrontal cortex (vlPFC) and ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, and hippocampus, complemented by vertex‐wise analyses. Linear regression assessed the association between retinal measures and brain structure, adjusting for covariates including age, sex, BMI, and intracranial volume (ICV). Results In the overall sample, arteriolar caliber was negatively associated with ACC volume (β = −0.20, puncorrected = .046) and surface area (β = −0.19, puncorrected = .049). There were no other significant ROI findings. Vertex‐wise analyses detected several significant positive bilateral associations of arteriovenous ratio (AVR) with volume and surface area in regions including rostral middle frontal gyrus (left p = .001; right p = .006), isthmus cingulate cortex (left and right p < .001), and left precuneus (p < .001). Significant negative associations were also observed for AVR (p = .03) and arteriolar caliber (p = .01), including a cluster encompassing the left rostral middle frontal gyrus and orbitofrontal cortical thickness. In the sole retinal‐by‐diagnosis interaction, greater AVR was more strongly associated with lower volume in the left middle temporal and fusiform gyri in BD versus HC (p = .004). Conclusion This study provides evidence that vascular‐brain associations are already evident in adolescence, suggesting that optimizing cardiovascular health may benefit the brain. This may be particularly relevant in BD and other brain disorders. Future research focusing on subpopulations where vascular‐brain associations may be especially strong, for whom vascular‐related interventions may be most indicated, is warranted.

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Objective: The increased prevalence rate of white matter hyperintensities is one of the most consistently reported brain abnormalities in adults with bipolar disorder. However, findings in children and adolescents with bipolar disorder are less consistent. Prior studies have been constrained by small sample sizes and/or poor age-and sex-matching of healthy controls. We examined this topic in the largest sample of adolescents with bipolar disorder to date. Methods: T 2-weighted 3-Tesla magnetic resonance imaging data were acquired for 83 adolescents with bipolar disorder diagnosed via the Kiddie Schedule for Affective Disorders and the Schizophrenia, Present and Lifetime version semi-structured interview and 64 age-and sex-matched healthy controls. All acquired scans were examined by neuroradiologists and the presence or absence of white matter hyperintensities was determined for each participant. Results: The prevalence of white matter hyperintensities did not differ between adolescents with bipolar disorder (13.3%) and controls (21.9%; w 2 = 1.90; p = 0.168). Conclusion: In contrast to the study hypothesis, the prevalence of white matter hyperintensities was not higher in adolescents with bipolar disorder than controls. The large sample size and good matching for age and sex bolster the reliability of this negative finding. Future studies are warranted to evaluate the prevalence, incidence, and predictors of white matter hyperintensities in early-onset bipolar disorder prospectively.

Objective: Numerous studies have examined the association of antimanic medications with neurocognition in adults with bipolar disorder (BD). However, few studies have examined this topic in youth. Thus, we aimed to examine the association of lithium and second-generation antipsychotics (SGAs), the first-line antimanic medications for youth with BD, with neurocognition in a relatively large sample of youth with BD. Methods: Participants included 91 youth with BD-I, -II, or -Not Otherwise Specified, aged 13–20 years ( n = 14 current lithium use, n = 51 current SGA use). We examined four tests from the Cambridge Neuropsychological Test Automated Battery: Intra/Extra Dimensional Set-Shifting Task (IED), Rapid Visual Information Processing Task (RVP), Stockings of Cambridge Test (SOC), and Affective Go/No-Go (AGN). Within-sample Z-scores were computed, and a global neurocognitive composite score and g factor derived from these tests comprised the primary outcomes. Multivariable analyses controlled for age, sex, and IQ. Results: Current lithium use was significantly associated with poorer cognitive flexibility/set-shifting (IED). After further controlling for lifetime comorbid attention-deficit/hyperactivity disorder and current depression symptoms in sensitivity analyses, the lithium finding was no longer significant. Current SGA use was significantly associated with greater affective processing bias (AGN). No significant findings survived correction for multiple comparisons. All other cognitive outcomes were not significantly associated with current lithium use, current SGA use, or total number of current medications. Conclusions: Treatment with lithium or SGAs was associated with minimal neurocognitive impairments, with small effect sizes in primary multivariable analyses. This study adds to the limited body of literature examining medication use in relation to neurocognition in youth with BD. While the current study cannot rule out associations of smaller effect size, present findings suggest that leading mood-stabilizing medications are not associated with frank neurocognitive impairments in youth with BD.

Aim: Early-onset bipolar disorder (BD) is associated with a more severe illness as well as a number of clinical factors among adults. Early-onset can be categorized as childhood-(age < 13) or adolescent-(age ≥ 13) onset, with the two displaying different clinical profiles. We set out to examine differences in clinical, and familial characteristics among adolescents with childhood-versus adolescent-onset BD. Methods:The study included 195 adolescents with BD, ages 14-18 years. Age of onset was determined retrospectively by self-report. Participants completed the semi-structured K-SADS-PL diagnostic interviews along with self-reported dimensional scales. Analyses examined between-group differences for clinical and familial variables. Variables associated with age of onset at p < 0.1 in univariate analyses were evaluated in a logistic regression model.Results: Approximately one-fifth of participants had childhood-onset BD (n = 35; 17.9%). A number of clinical and familial factors were significantly associated with childhood-onset BD. However, there were no significant differences in depressive and manic symptom severity. In multivariate analyses, the variables most strongly associated with childhood-onset were police contact, and family history of suicidal ideation. Smoking and psychiatric hospitalization were associated with adolescentonset. Conclusions:In this large clinical sample of adolescents with BD, one-fifth reported childhood-onset BD. Correlates of childhood-onset generally aligned with those observed in the literature. Future research is warranted to better understand the genetic and environmental implications of high familial loading of psychopathology associated with childhood-onset, and to integrate age-related treatment and prevention strategies.

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