Vascular Endothelial Growth Factor Polymorphism rs699947 Is Associated with Neurostructural Phenotypes in Youth with Bipolar Disorder.

Background: Vascular endothelial growth factor (VEGF) may be relevant to bipolar disorder (BD) and brain structure. We evaluated VEGF rs699947 single-nucleotide polymorphism in relation to structural neuroimaging phenotypes in youth BD. Methods: We collected 3 T anatomical magnetic resonance images from 154 youth (79 BD and 75 healthy control [HC]) genotyped for VEGF rs699947. The participants were age (BD = 17.28 ± 1.40 and HC = 17.01 ± 1.83, t = -1.02, p = 0.31) and sex (BD = 63.3% females and HC = 52.0% females, χ2 = 2.01, p = 0.16) matched. Cortical thickness, surface area (SA), and volume were examined by region-of-interest (ROI) and vertex-wise analyses using general linear models (GLMs). ROI investigations selected for the prefrontal cortex (PFC), amygdala, and hippocampus. Vertex-wise analyses controlled for age, sex, and intracranial volume. Results: ROI results found lower PFC SA (p = 0.003, ηp2 = 0.06) and volume (p = 0.04, ηp2 = 0.03) in BD and a main effect of rs699947 on hippocampal volume (p = 0.03, ηp2 = 0.05). The latter two findings did not survive multiple comparisons. Vertex-wise analyses found rs699947 main effects on left postcentral gyrus volume (p < 0.001), right rostral anterior cingulate SA (p = 0.004), and right superior temporal gyrus thickness (p = 0.004). There were significant diagnosis-by-genotype interactions in the left superior temporal, left caudal middle frontal, left superior frontal, right fusiform, and right lingual gyri, and the left insular cortex. Posthoc analyses revealed the AA allele was associated with larger brain structures among HC, but smaller brain structures in BD for most clusters. Conclusions: Overall, we found preliminary evidence of divergent associations between BD and HC youth in terms of neurostructural correlates of VEGF rs699947 encompassing highly relevant frontotemporal regions.

Comorbid Eating Disorders in a Sample of Youth With Bipolar Disorder: Elevated Burden of Dimensional and Categorical Psychopathology.

Objective: There is growing recognition of the importance of comorbid eating disorders (ED) among individuals with bipolar disorder (BD). However, most studies on this topic have focused on adult samples, and little is known regarding comorbid ED among youth with BD.Methods: The sample included 197 youth with DSM-IV BD (BD-I, BD-II, or BD-NOS [not otherwise specified]), aged 13-20 years and recruited from a subspecialized clinic within a tertiary academic health sciences center from 2009 to 2017. Univariate analyses examined demographic and clinical variables among participants with versus without lifetime DSM-IV ED. Variables significant at P < .10 were entered into a backward stepwise regression.Results: Fifty-six participants (28.4%) had lifetime DSM-IV ED (3.6% anorexia nervosa, 8.1% bulimia nervosa, 16.8% ED not otherwise specified). Significant correlates of lifetime ED were female sex (P < .001), BD-II subtype (P = .03), suicidal ideation (P = .006), suicide attempts (P = .004), non-suicidal self-injury (P < .001), sexual abuse (P = .02), cigarette smoking (P = .001), anxiety disorders (P = .004), posttraumatic stress disorder (P = .004), substance use disorders (P = .006), history of individual therapy (P = .01), and family history of anxiety (P = .01). Significant correlates of no lifetime ED were BD-I subtype (P < .001) and lifetime lithium use (P = .01). The ED group had significantly more severe lifetime depression (P < .001) and significantly more self-reported affective lability (P < .001) and borderline personality traits (P < .001). In multivariate analysis, the most robust predictors of lifetime ED were female sex (odds ratio [OR] = 4.61, P = .004), BD-I subtype (OR = 0.21, P = .03), cigarette smoking (OR = 2.78, P = .02), individual therapy (OR = 3.92, P = .03), family history of anxiety (OR = 2.86, P = .02), and borderline personality traits (OR = 1.01, P = .009).Conclusions: ED are common among youth with BD and associated with adverse clinical characteristics, many of which converge with prior adult literature. Future studies evaluating specific ED subtypes are warranted, as are treatment studies targeting comorbid ED in youth with BD.

Inflammatory markers, brain-derived neurotrophic factor, and the symptomatic course of adolescent bipolar disorder: A prospective repeated-measures study.

BACKGROUND: Numerous studies have found elevated pro-inflammatory markers and reduced brain-derived neurotrophic factor (BDNF) during symptomatic episodes of bipolar disorder (BD) in adults. There is a paucity of research examining these markers in youth with BD, or longitudinally in any BD age group. METHODS: 79 adolescents, ages 13-19 years, were enrolled, including 43 symptomatic adolescents with BD and 36 age-matched healthy controls (HC). Blood samples were collected from all participants at intake, and repeatedly from BD participants at pre-specified intervals over the course of two years. Serum was assayed for levels of pro-inflammatory markers (c-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor alpha [TNF-α]), BDNF and the anti-inflammatory marker, IL-10. Week-by-week severity of mood symptoms was assessed using semi-structured interviews. RESULTS: Adolescents with BD provided an average of 4.6 blood samples, on average every 5.0 months. During the most severe symptomatic interval (i.e., highest sum of mood symptom scores) among BD adolescents, levels of CRP (p = 0.01) and pro- to anti-inflammatory ratios (CRP/IL-10; p < 0.001 and IL-6/IL-10; p = 0.046) were significantly greater, and IL-10 levels (p = 0.004) were significantly lower, vs. HC. There were no differences between BD and HC in IL-6, TNF-α or BDNF. Within BD participants, higher BDNF (p = 0.01) and IL-10 levels (p = 0.001) significantly predicted greater burden of mood symptoms over the subsequent epoch. Moreover, higher CRP levels (p = 0.009) at intake predicted greater time to recovery from the index symptomatic episode. CONCLUSIONS: In the first repeated-measures study on this topic in adolescents with BD, we found evidence that CRP, an inexpensive and ubiquitous blood test, may be useful in predicting the prospective course of BD symptoms. Future larger studies are warranted.