Objective Identify diagnostic risk factors of mania/hypomania in the offspring of parents with bipolar disorder (“high-risk offspring”). Method High-risk offspring aged 6-18 years (n=391) and demographically-matched offspring (n=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean interval 2.5 years; mean duration 6.8 years). Results High-risk offspring, as compared to community offspring, had significantly higher rates of subthreshold (hypo)manic (13.3% vs. 1.2%, p<.0001), manic/hypomanic (9.2% vs. 0.8%, p=.0003) and major depressive episodes (32.0% vs. 14.9%, p<.0001). They also had higher rates of attention-deficit hyperactivity (30.7% vs. 18.2%, p=.01), disruptive behavior (27.4% vs. 15.3%, p=.03), anxiety (39.9% vs. 21.8%, p=.0002), and substance use disorders (20.0% vs. 10.1%, p=.008), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% vs. 13.7%; p=.10). Multivariate Cox regressions in the high-risk offspring showed that subthreshold (hypo)manic episodes (Hazard Ratio 2.29, p=.03), major depressive episodes (Hazard Ratio 1.99, p=.05), and disruptive behavior disorders (Hazard Ratio 2.12, p=.03) were associated with subsequent mania/hypomania. Only subthreshold (hypo)manic episodes (Hazard Ratio 7.57, p<.0001) were associated when analyses were restricted to prospective data. Conclusions Subthreshold (hypo)manic episodes were a diagnostic risk factor for the development of mania/hypomania in the offspring of parents with bipolar disorder, and should be a target for clinical assessment and future treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.

Objective We aimed to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorder in youth at familial risk of bipolar disorder (“at-risk” youth). Method Offspring aged 6–18 of parents with bipolar-I/II disorder (n=391) and offspring of community controls (n=248) were recruited without regard to non-bipolar psychopathology. At baseline, 8.4% (33/391) of offspring of bipolar parents had bipolar spectrum; 14.7% (44/299) of offspring with follow-up developed new-onset bipolar spectrum (15 with bipolar-I/II) over eight years. Scales collected at baseline and follow-up were reduced using factor analyses; factors (both at baseline and visit proximal to conversion or last contact) were then assessed as predictors of new-onset bipolar spectrum. Results Relative to community control offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsydromal manic, and affective lability symptoms (p<.05). The strongest predictors of new-onset bipolar spectrum were: baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed bipolar spectrum, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesized model that affective lability at baseline predicted new-onset bipolar spectrum, in part, through increased manic symptoms at the visit prior to conversion; earlier parental age of mood disorder onset also significantly increased risk of conversion (p<.001). While youth without anxiety/depression, affective lability, and mania (and with a parent with older age of mood disorder onset) had a 2% predicted chance of conversion to bipolar spectrum, those with all risk factors had a 49% predicted chance of conversion. Conclusions Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum in this population of at-risk youth. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings.

The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.

This risk calculator provides a practical tool for assessing the probability that a youth at familial risk for BPSD will develop new-onset BPSD within the next 5 years. Such a tool may be used by clinicians to inform frequency of monitoring and treatment options and for research studies to better identify potential participants at ultra high risk of conversion.

Objective-To evaluate lifetime prevalence and specificity of DSM-IV psychiatric disorders and severity of depressive and manic symptoms at intake in preschool offspring of parents with Disorder I-II.Methods-121 offspring ages 2-5 years old of 83 parents with Bipolar Disorder and 102 offspring of 65 demographically matched control parents (29 with non-Bipolar psychiatric disorders and 36 without any lifetime psychopathology) were recruited. Parents with Bipolar Disorder were recruited through advertisement and adult outpatient clinics and control parents were ascertained at random from the community. Subjects were evaluated with standardized instruments. All staff were blind to parental diagnoses.Results-After adjusting for within-family correlations and both biological parents' non-Bipolar psychopathology, compared to the offspring of the control parents, offspring of parents with Bipolar Disorder, particularly those older than 4 years old, showed an 8-fold increased life-time prevalence of Attention Deficit Hyperactive Disorder (ADHD) and significantly higher rates of ≥ 2 psychiatric disorders. While only 3 offspring of parents with Bipolar Disorder had mood disorders, offspring of parents with Bipolar Disorder, especially those with ADHD and Oppositional-Defiant Disorder, had significantly more severe current manic and depressive symptomatology than the offspring of the controls.Conclusions-Preschool offspring of parents with Bipolar Disorder are at increased risk for ADHD and demonstrate increased subthreshold manic and depressive symptomatology. Longitudinal follow-up is warranted to evaluate whether these children are at high-risk to develop mood and other psychiatric disorders.

Background Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation is associated with increased risk for suicidal behavior. However, it is not clear whether such dysregulation exists prior to or is a consequence of attempt. Studies also show an activation of inflammatory responses in suicidal behavior but often combine attempters with those with ideation. Methods The sample consisted of psychiatric inpatients, aged 15-30 years, admitted for suicide attempt (SA, n=38), inpatients admitted for suicidal ideation with no prior history of attempts (SI, n=40), and healthy controls (n=37). We compared SA, SI, and controls on hair cortisol concentrations (HCC), which provides retrospective levels of cortisol and thus prior to the attempt in SA. We also compared them on the expression of genes in the HPA axis and inflammatory pathways previously implicated in suicidal behavior (GR or NR3C1, SKA2, FKBP5, IL-1β, TNF-α); plasma C-Reactive Protein (CRP); and cellular measures of glucocorticoid receptor (GR) sensitivity and stimulated production of IL-6. Results We found lower HCC [β=−0.55, 95% CI (−0.96, −0.13), p=0.01, ES=−0.54] in first-time SA compared to SI and controls. In addition, SA showed lower GR or NR3C1 (α isoform) mRNA [β=−5.11, 95% CI (−10.9, 0.73), p=0.09, ES=−0.46], higher CRP [β=0.94, 95% CI (−0.004, 1.9), p=0.05, ES=0.60], and higher TNF-α mRNA [β=26.4, 95% CI (7.7, 45.2), p=0.006, ES=0.73]. Conclusions This is the first study to differentiate youth who attempt suicide from those with suicidal ideation on HCC and to show that low HCC precedes suicide attempt. Suicide attempters also showed a distinct biological profile on several markers in both the HPA axis and inflammatory pathways. Future longitudinal studies are needed to examine the ability of these biomarkers to predict suicidal behavior.

Objective The authors sought to identify and evaluate longitudinal mood trajectories and associated baseline predictors in youths with bipolar disorder. Method A total of 367 outpatient youths (mean age, 12.6 years) with bipolar disorder with at least 4 years of follow-up were included. After intake, participants were interviewed on average 10 times (SD=3.2) over a mean of 93 months (SD=8.3). Youths and parents were interviewed for psychopathology, functioning, treatment, and familial psychopathology and functioning. Results Latent class growth analysis showed four different longitudinal mood trajectories: “predominantly euthymic” (24.0%), “moderately euthymic” (34.6%), “ill with improving course” (19.1%), and “predominantly ill” (22.3%). Within each class, youths were euthymic on average 84.4%, 47.3%, 42.8%, and 11.5% of the follow-up time, respectively. Multivariate analyses showed that better course was associated with higher age at onset of mood symptoms, less lifetime family history of bipolar disorder and substance abuse, and less history at baseline of severe depression, manic symptoms, suicidality, subsyndromal mood episodes, and sexual abuse. Most of these factors were more noticeable in the “predominantly euthymic” class. The effects of age at onset were attenuated in youths with lower socioeconomic status, and the effects of depression severity were absent in those with the highest socioeconomic status. Conclusions A substantial proportion of youths with bipolar disorder, especially those with adolescent onset and the above-noted factors, appear to be euthymic over extended periods. Nonetheless, continued syndromal and subsyndromal mood symptoms in all four classes underscore the need to optimize treatment.

Objectives Previous studies have suggested that the sum of Attention, Aggression, and Anxious/Depressed subscales of Child Behavior Checklist (CBCL-PBD; pediatric bipolar disorder phenotype) may be specific to pediatric bipolar disorder (BP). The purpose of this study was to evaluate the usefulness of the CBCL and CBCL-PBD to identify BP in children <12 years old. Methods A sample of children with BP I, II, and not otherwise specified (NOS) (n=157) ascertained through the Course and Outcome for Bipolar Disorder in Youth (COBY) study were compared with a group of children with major depressive/anxiety disorders (MDD/ANX; n=101), disruptive behavior disorder (DBD) (n=127), and healthy control (HC) (n=128). The CBCL T-scores and area under the curve (AUC) scores were calculated and compared among the above-noted groups. Results Forty one percent of BP children did not have significantly elevated CBCL-PBD scores (≥2 standard deviations [SD]). The sensitivity and specificity of CBCL-PBD≥2 SD for diagnosis of BP was 57% and 70–77%, respectively, and the accuracy of CBCL-PBD for identifying a BP diagnosis was moderate (AUC=0.72–0.78). Conclusion The CBCL and the CBCL-PBD showed that BP children have more severe psychopathology than HC and children with other psychopathology, but they were not useful as a proxy for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BP.