Clinical correlates of suicidality and self-injurious behaviour among Canadian adolescents with bipolar disorder.

There is high risk of suicidality in bipolar disorder (BD), particularly in early onset cases. The literature regarding correlates and putative predictors of suicide attempts (SA), non-suicidal self-injury (NSSI) and suicidal ideation (SI) among youth with BD remains sparse. Participants included 197 adolescents with BD, divided into 4 groups: SA (with or without NSSI), NSSI (with or without SI), SI only, and comparison group (CG; no SA/NSSI/SI). Diagnoses, treatment, and suicidality measures were determined via semi-structured interviews, conducted between 2009 and 2017. Univariate analyses were followed by multinomial regression. Overall, 73.6% of participants had history of SA, NSSI, and/or SI. In comparison to CG, SA and NSSI were each associated with BD-II/-NOS (odds ratio [OR] = 15.99, p = 0.002; OR = 16.76, p = 0.003), female sex (OR = 6.89, p = 0.006; OR = 3.76, p = 0.02), and emotion dysregulation (OR = 1.10, p < 0.001; OR = 1.07, p = 0.004). NSSI and SI were each associated with most severe lifetime depression (OR = 1.10, p = 0.01; OR = 1.10, p = 0.01). SA and SI were associated with psychiatric hospitalization (OR = 19.45, p = 0.001; OR = 6.09, p = 0.03). SA was associated with poorer global functioning at most severe episode (OR = 0.88, p = 0.008). NSSI was associated with not living with both natural parents (OR = 0.22, p = 0.009). Study limitations include cross-sectional and retrospective design, stringent cut-offs for SA and NSSI, and recruitment from a tertiary clinical setting. Three quarters of adolescents with BD have had suicidality and/or self-injury. SA and NSSI were most similar to one another, and most different from CG, supporting the broader construct of self-harm. Future research should address the gap in knowledge regarding how sex differences and neurobiology are associated with the observed clinical differences.

Prevalence of white matter hyperintensities is not elevated in a large sample of adolescents and young adults with bipolar disorder

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: T2-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%; χ2 = 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.

Clinical and neurostructural characteristics among youth with familial and non-familial bipolar disorder: Family history and youth bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is highly heritable and often severe, particularly when illness onset occurs early in life. There is limited knowledge regarding the clinical and neurostructural correlates of family history of BD among youth with BD. METHODS: Clinical characteristics were evaluated in 197 youth with BD, ages 13-20 years, including 87 with familial BD and 110 with non-familial BD. Structural neuroimaging was examined in a subsample of familial BD (n=39), non-familial BD (n=42), and healthy control (HC, n=58) youth. Region of interest (ROI) analyses of anterior cingulate cortex (ACC), inferior frontal gyrus (IFG), and amygdala were complemented by whole-brain vertex-wise analyses. RESULTS: Youth with familial BD had more family history of other psychiatric disorders, less severe worst manic episode, and less treatment with lithium, selective serotonin reuptake inhibitor (SSRI) antidepressants, and any lifetime psychiatric medications. None of these findings survived after correction for multiple comparisons. There were no significant between-group differences in ROI analyses. In whole-brain analyses, significant differences in cortical thickness were as follows: familial and non-familial BD < HC in left precentral gyrus and right inferior parietal lobe; familial BD < HC in left superior frontal gyrus; non-familial BD < HC in right precentral gyrus. LIMITATIONS: Relatives did not complete full diagnostic interviews. CONCLUSIONS: There were relatively few differences in clinical and neurostructural correlates related to family history of BD in youth with BD. Current findings suggest that family history of BD is not a strong contributor to the clinical or neuroimaging phenotypes in youth with BD.

Prevalence and correlates of police contact amongst youth with bipolar disorder.

OBJECTIVES: While multiple studies have examined prevalence and correlates of police contact in adults with bipolar disorder (BD), literature on this topic in youth is sparse. We therefore examined the prevalence and correlates of police contact amongst youth with BD. METHODS: The study included 197 youth with BD and 127 healthy controls, ages 14-20 years. Semi-structured interviews were used to determine diagnoses, treatment and police contact. The Life Problems Inventory examined self-reported trait impulsivity and emotional dysregulation. Analyses examined demographic and clinical variables among youth with versus without lifetime police contact. Variables that were associated with police contact at p<0.1 in univariate analyses were evaluated in a logistic regression model. Specific reasons for police contact, determined based on chart review, are reported descriptively. RESULTS: Lifetime prevalence of police contact was significantly higher amongst youth with BD versus healthy controls (36% versus. 3%; χ 2 = 47.58, p =<0.001). In multivariate analyses, age of BD onset, living with both natural parents, comorbid substance use disorder and conduct disorder, and psychiatric hospitalization were associated with police contact. Common reasons for police contact included shoplifting/theft and suicidality/self-harm . LIMITATIONS: The cross-sectional and retrospective study design precludes conclusions regarding directionality of the observed associations and/or causal inferences. CONCLUSIONS: One third of youth with BD experienced police contact. Correlates generally aligned with those observed with adults. Future longitudinal research is warranted to understand distal and proximal antecedents of police contact, with the goal of developing strategies to prevent police contact, incarceration, and related consequences.

Severe anhedonia among adolescents with bipolar disorder is common and associated with increased psychiatric symptom burden.

BACKGROUND: Anhedonia, a deficit in the ability to experience pleasure, is a cardinal symptom of major depressive episodes. In contrast to adolescent major depressive disorder, there is limited research examining anhedonia in the context of depression among adolescents with bipolar disorder (BD). We therefore examined clinical characteristics of anhedonia in a large sample of adolescents with BD. METHODS: Participants were 197 adolescents, aged 13-20 years old, with BD type I, II or not otherwise specified. Diagnoses were determined using a semi-structured interview. Anhedonia severity was rated from one to six on the Depression Rating Scale (DRS). Adolescents were divided into "severe" and "non-severe" anhedonia groups based on the DRS item scoring. The association of anhedonia with clinical and demographic variables was evaluated in univariate analyses followed by logistic regression analyses for variables with p ≤ 0.1. RESULTS: Threshold anhedonia was evident among 90.9% during their most severe depressive episode. Significant factors associated with severe most severe lifetime anhedonia ("lifetime anhedonia") included: female sex, lifetime history of self-injurious behavior, physical abuse, affective lability, higher lifetime depression severity, comorbid anxiety disorders, family history of ADHD, and second-generation antipsychotic use. In regression analyses, severe lifetime anhedonia was independently associated with female sex, comorbid anxiety disorders, most severe lifetime mania severity, and lifetime second-generation antipsychotic use. CONCLUSION: The vast majority of adolescents with BD experience anhedonia. More severe anhedonia is associated with indicators of greater illness severity. Future research is warranted to evaluate the neurobiological underpinnings of anhedonia among adolescents with BD.

Prevalence of white matter hyperintensities is not elevated in a large sample of adolescents and young adults with bipolar disorder.

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: T2-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%; χ2 = 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.

Markedly increased prevalence of migraine headaches in adolescents with bipolar disorder.

OBJECTIVE: There is substantial evidence of increased prevalence of migraines, and negative psychiatric correlates of migraines, in adults with bipolar disorder (BD). Given the paucity of data on this topic in youth, we investigated the prevalence and correlates of migraine in a large sample of adolescents with BD. METHOD: The study included 165 adolescents with BD-I, -II, or -not otherwise specified (NOS), diagnosed via the KSADS-PL semi-structured interview, and 89 healthy controls (HCs). Non-migraine headache and migraine headache was evaluated using the validated ID-Migraine 3-item screener. RESULTS: Although the prevalence of non-migraine headaches did not differ between adolescents with BD (24.2%) and HCs (32.6%; P = .15), migraine was significantly more prevalent among adolescents with BD (38.2%) compared to HCs (3.4%; adjusted odds ratio 14.76, 95% confidence interval 4.39-49.57; P < .001). Within BD, migraine was associated with female sex, BD-II/-NOS subtype, less severe worst past functioning, higher past depression severity, higher self-reported affective lability, higher body mass index, and less use of lithium and second-generation antipsychotics. DISCUSSION: Migraine is much more prevalent among adolescents with BD compared to HCs; the magnitude of this association exceeds what has been reported in adult samples. Correlates of migraine in youth BD are similar to those found for adults, including the link with the depressive polarity of BD. Future prospective studies are warranted to evaluate temporal associations between migraine and mood symptoms, and to evaluate neurobiological and cardiovascular underpinnings of these associations.

Clinical correlates of socioeconomic status in adolescent bipolar disorder.

BACKGROUND: Lower socioeconomic status (SES) is associated with symptomatic severity, comorbidity, and functional impairment in adults with bipolar disorder (BD). Little is known about clinical correlates of SES in adolescents with BD. METHODS: Participants included 195 adolescents, 13-20 years old, with BD type I, II or not otherwise specified (NOS). Diagnoses were determined by standardized semi-structured interviews. Based on the Hollingshead scale, participants were divided into "low" (SES 1-3) and the "high" (SES 4-5) SES groups. Demographic and clinical correlates of SES were evaluated in univariate analyses; significant variables were evaluated in a logistic regression model. RESULTS: Compared to participants in the high SES group (n = 150), participants in the low SES group (n = 45) were significantly younger, less likely to be of Caucasian race and living with natural parents. In the logistic regression model, controlling for age and race, the low SES group had higher risk of police contact or arrest (OR = 2.41, 95% CI:1.14-5.11, p = 0.022), less treatment with stimulants(OR = 0.20 95% CI: 0.06-0.67, p = 0.009), and more post-traumatic stress disorder (PTSD) (OR = 4.08, 95% CI:1.33-12.46, p = 0.014) compared to the high SES group. In sensitivity analyses that further controlled for intact family, the finding of higher rates of police contact or arrest was no longer significant. LIMITATIONS: Cross-sectional design; higher-skewed SES sample. CONCLUSIONS: Lower SES in adolescent BD is associated with higher legal risk, increased PTSD, and under-treatment of attention-deficit/hyperactivity disorder (ADHD). Future studies are needed to evaluate the inter-relationships of these correlates, using prospective designs that can evaluate the direction of these associations. Further studies incorporating neurobiological markers are also needed to explore mechanisms underlying SES-related differences in BD.

Proof-of-concept study of a multi-gene risk score in adolescent bipolar disorder.

BACKGROUND: Few studies have examined multiple genetic variants concurrently for the purpose of classifying bipolar disorder (BD); the literature among youth is particularly sparse. We selected 35 genetic variants, previously implicated in BD or associated characteristics, from which to identify the most robustly predictive group of genes. METHODS: 215 Caucasian adolescents (114 BD and 101 healthy controls (HC), ages 13-20 years) were included. Psychiatric diagnoses were determined based on semi-structured diagnostic interviews. Genomic DNA was extracted from saliva for genotyping. Two models were used to calculate a multi-gene risk score (MGRS). Model 1 used forward and backward regressions, and model 2 used a PLINK generated method. RESULTS: In model 1, GPX3 rs3792797 was significant in the forward regression, DRD4 exonIII was significant in the backward regression; IL1ß rs16944 and DISC1 rs821577 were significant in both the forward and backward regressions. These variants are involved in dopamine neurotransmission; inflammation and oxidative stress; and neuronal development. Model 1 MGRS did not significantly discriminate between BD and HC. In model 2, ZNF804A rs1344706 was significantly associated with BD; however, this association did not predict diagnosis when entered into the weighted model. LIMITATIONS: This study was limited by the number of genetic variants examined and the modest sample size. CONCLUSIONS: Whereas regression approaches identified four genetic variants that significantly discriminated between BD and HC, those same variants no longer discriminated between BD and HC when computed as a MGRS. Future larger studies are needed evaluating intermediate phenotypes such as neuroimaging and blood-based biomarkers.