White Matter Correlates of Early-Onset Bipolar Illness and Predictors of One-Year Recurrence of Depression in Adults with Bipolar Disorder.

Diffusion Magnetic Resonance Imaging (dMRI) studies have reported abnormalities in emotion regulation circuits in BD; however, no study has examined the contribution of previous illness on these mechanisms. Using global probabilistic tractography, we aimed to identify neural correlates of previous BD illness and the extent to which these can help predict one-year recurrence of depressive episodes. dMRI data were collected in 70 adults with early-onset BD who were clinically followed for up to 18 years and 39 healthy controls. Higher number of depressive episodes during childhood/adolescence and higher percentage of time with syndromic depression during longitudinal follow-up was associated with lower fractional anisotropy (FA) in focal regions of the forceps minor (left, F = 4.4, p = 0.003; right, F = 3.1, p = 0.021) and anterior cingulum bundle (left, F = 4.7, p = 0.002; right, F = 7.0, p < 0.001). Lower FA in these regions was also associated with higher depressive and anxiety symptoms at scan. Remarkably, those having higher FA in the right cluster of the forceps minor (AOR = 0.43, p = 0.017) and in a cluster of the posterior cingulum bundle (right, AOR = 0.50, p = 0.032) were protected against the recurrence of depressive episodes. Previous depressive symptomatology may cause neurodegenerative effects in the forceps minor that are associated with worsening of BD symptomatology in subsequent years. Abnormalities in the posterior cingulum may also play a role.

White Matter Correlates of Suicidality in Adults With Bipolar Disorder Who Have Been Prospectively Characterized Since Childhood.

BACKGROUND: Prevention of suicide in individuals with early-onset bipolar disorder (BD) remains a challenge. Diffusion magnetic resonance imaging studies in BD have identified neural correlates of emotional dysregulation implicated in BD and suicide. Using diffusion magnetic resonance imaging, we sought to identify neural signatures of suicide attempts in adults with childhood-onset BD who have been clinically followed for up to 19 years as part of the COBY (Course and Outcome of Bipolar Youth) study. METHODS: Diffusion magnetic resonance imaging data were collected in 68 adults with BD: 20 in the suicide attempter (SA+) group and 48 in the non-suicide attempter (SA-) group. Multivariate analysis of covariance was used to identify the effect of group (SA+, SA-) on mean fractional anisotropy (indirect index of fiber collinearity) in key white matter tracts of emotional regulation. The effect of suicidal ideation and other clinical factors was further explored. False discovery rate was used to account for multiple comparison. Forty healthy control subjects were included. RESULTS: Analyses revealed a main effect of group on fractional anisotropy (F5,59 = 3.0, p = .017). Specifically, the SA+ group showed lower fractional anisotropy than the SA- and healthy control groups in the middle portion of the forceps minor (FMIN) (F1,63 = 8.5, p = .010) and in the anterior (F1,63 = 7.8, p = .010) and posterior (F1,63 = 8.7, p = .006) portion of the right cingulum bundle (CB). Abnormalities in the FMIN, but not CB, were also associated with suicidal ideation (F1,64 = 10.6, p = .002) and levels of emotional distress at scan. CONCLUSIONS: FMIN and CB abnormalities have been associated with emotional dysregulation in BD. Our findings suggest that the FMIN may represent a generic marker of suicidal ideation and, more broadly, emotional distress, while CB may represent a specific marker of attempted suicide.

Psychometrics of the screen for adult anxiety related disorders (SCAARED)- A new scale for the assessment of DSM-5 anxiety disorders.

OBJECTIVE: To examine the psychometrics of the Screen for Adult Anxiety Related Disorders (SCAARED). METHODS: The SCAARED was adapted from the Screen for Child Anxiety Related Emotional Disorders. Participants (N=336) ages 18-27 years old were evaluated using the Structured Clinical Interview for DSM-IV Disorders (SCID). The SCAARED was completed at or within two-weeks before the SCID. The psychometrics of the SCAARED were analyzed using standard statistical analyses including principal components, and Receiver Operant Curve analyses. A replication was performed in an age/sex matched independent sample (N=158). RESULTS: The SCAARED showed four factors: somatic/panic/agoraphobia, generalized anxiety, separation anxiety, and social anxiety. The total and each factor scores demonstrated good internal consistency (α=0.86-0.97) and good discriminant validity between anxiety and other disorders and within anxiety disorders for generalized and social anxiety. Area Under the Curve for the total and each of the factor scores ranged between 0.72 and 0.84 (p<0.0001). These results were replicated in the independent sample. CONCLUSIONS: The SCAARED showed excellent psychometric properties supporting its use to screen adults for anxiety disorders, longitudinal studies following youth into adulthood and studies comparing child and adult populations. Further replication studies in larger community and clinical samples are indicated.

Prescription of psychiatric medications and polypharmacy in the LAMS cohort.

OBJECTIVE: This study evaluated demographic and clinical correlates and predictors of polypharmacy at baseline assessment in the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a cohort of children age six to 12 years at their first outpatient mental health visit at university-affiliated clinics. METHODS: Use of medications in four classes (mood stabilizers, antidepressants, antipsychotics, and stimulants) was assessed, and the Service Assessment for Children and Adolescents classified lifetime and current use of various services. Analyses examined correlates of the number of medications prescribed and odds of polypharmacy, defined as use of two or more concurrent medications. RESULTS: In the total sample, 201 of 698 participants (29%) were prescribed two or more medications. These participants had lower Children's Global Assessment Scale scores, more comorbid disorders, and higher baseline parent-reported mood symptoms than those prescribed no or one medication. White youths were three times as likely as nonwhite youths to be receiving two or more psychotropics, even after adjustment for other demographic and clinical characteristics. Of 262 participants (38% of sample) not being treated with medications, 252 (96%) had a diagnosis of at least one psychiatric disorder (74% had two or more). CONCLUSIONS: Findings suggest that patients with greater severity and comorbidity were more likely to receive two or more medications. However, 38% of these children with serious disorders were not receiving psychotropic medication at the time of this assessment. Results counter findings suggesting overtreatment with medications of children with psychiatric disorders in the community.

Preliminary findings regarding proinflammatory markers and brain-derived neurotrophic factor among adolescents with bipolar spectrum disorders.

Mood symptoms in adult bipolar disorder are associated with increased proinflammatory markers and decreased brain-derived neurotrophic factor (BDNF). We examined serum interleukin-6, high-sensitivity C-reactive protein (hsCRP), and BDNF among 30 bipolar disorder adolescents. Hypomanic/manic symptoms were positively associated with hsCRP. BDNF levels were negatively associated with interleukin-6. Forty percent had cardiovascular high-risk hsCRP levels. Larger longitudinal studies are warranted.

Irritability without elation in a large bipolar youth sample: frequency and clinical description.

OBJECTIVE: To determine whether some children with bipolar disorder (BP) manifest irritability without elation and whether these children differ on sociodemographic, phenotypic, and familial features from those who have elation and no irritability and from those who have both. METHOD: Three hundred sixty-one youths with BP recruited into the three-site Course and Outcome of Bipolar Illness in Youth study were assessed at baseline and for most severe past symptoms using standardized semistructured interviews. Bipolar disorder subtype was identified, and frequency and severity of manic symptoms were quantified. The subjects were required to have episodic mood disturbance to be diagnosed with BP. The sample was then reclassified and compared based on the most severe lifetime manic episode into three subgroups: elated only, irritable only, and both elated and irritable. RESULTS: Irritable-only and elated-only subgroups constituted 10% and 15% of the sample, respectively. Except for the irritable-only subjects being significantly younger than the other two subgroups, there were no other between-group sociodemographic differences. There were no significant between-group differences in the BP subtype, rate of psychiatric comorbidities, severity of illness, duration of illness, and family history of mania in first- or second-degree relatives and other psychiatric disorders in first-degree relatives, with the exception of depression and alcohol abuse occurring more frequently in the irritability-only subgroup. The elated-only group had higher scores on most DSM-IV mania criterion B items. CONCLUSIONS: The results of this study support the DSM-IV A criteria for mania in youths. Irritable-only mania exists, particularly in younger children, but similar to elated-only mania, it occurs infrequently. The fact that the irritable-only subgroup has similar clinical characteristics and family histories of BP, as compared with subgroups with predominant elation, provides support for continuing to consider episodic irritability in the diagnosis of pediatric BP.

The Child Behavior Checklist (CBCL) and the CBCL-bipolar phenotype are not useful in diagnosing pediatric bipolar disorder.

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 (>or=2 standard deviations [SD]). The sensitivity and specificity of CBCL-PBD >or= 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, 4(th) edition (DSM-IV) diagnosis of BP.