Elevation of C-reactive protein in adolescent bipolar disorder vs. anxiety disorders.

Bipolar disorder (BD) largely begins in adolescence, but diagnosis lags for years, causing significant morbidity and mortality, and demonstrating the need for better diagnostic tools. Suggesting an association between BD and immune activity, elevated levels of peripheral inflammatory markers, including C-reactive protein (CRP), have been found in adults with BD. As similar data are extremely limited in adolescents, this study examined CRP levels in adolescents with BD (n = 37) compared to those with anxiety disorders (ADs, n = 157) and healthy controls with no psychiatric diagnoses (HCs, n = 2760). CRP blood levels for patients aged 12-17 years were retrieved from a nationwide repository of deidentified clinical data. After excluding patients with inflammatory conditions, differences in CRP were examined using multivariate and weighted regressions (covariates: demographics and BMI). Mean CRP levels were significantly elevated in adolescents with BD relative to those with ADs and HCs. Mean CRP levels were lower in the ADs cohort versus HCs. Although CRP levels were significantly higher in males and younger patients, the significant between-cohort differences in CRP remained after controlling for multiple confounders. To our knowledge, our study is the first to compare CRP levels between adolescent BD, ADs, and HCs, comprising a novel and essential contribution. Our results suggest the presence of a unique immune process in adolescents with BD and indicate that CRP may represent a biomarker with a crucial role in the diagnostic assessment of adolescent BD.

Narrative Analyses: Cognitive Behavior Group Therapy for Women with Menopause and Bipolar or Major Depressive Disorders.

Background: Bipolar and depressive disorders (bipolar disorder [BD], major depressive disorder [MDD]), as well as menopause affect millions of women. Although there are three known cognitive behavioral group treatment (CBGT) protocols to help women with problematic menopause symptoms, they do not target women on the BD or MDD spectrum. The purpose of this qualitative study was to learn more about the treatment needs and group experiences of women with problematic menopause symptoms and diagnosed on the BD and MDD spectrum, who participated in a CBGT intervention for menopausal symptoms. Methods: Narrative data recorded by clinicians (Interventionists' notes) and participants (Evaluation of Groups Survey) were analyzed using content analyses. Results: Several themes emerged from (n = 11 BD; n = 48 MDD) what women wanted help with (specific symptoms and general aspects of menopause), what women liked about CBGT (specific and general aspects of the program), and changes needed in the CBGT intervention (things wished for and barriers that interfered with the program). The two diagnostic groups differed in their responses, although both groups identified content and delivery gaps they wished would be addressed. Specifically related to their diagnosis, women most commonly talked about problems with worsening mood and mood instability and multiple stressors interfering with their ability to follow through with the intervention. Conclusions: These findings can help refine existing CBGT protocols for women diagnosed on the BD and MDD spectrum seeking help for menopause symptoms. Trial Registry: Parent study ClinicalTrials.gov [identifier: NCT02860910].

Adult Brain Serotonin Deficiency Causes Hyperactivity, Circadian Disruption, and Elimination of Siestas.

UNLABELLED: Serotonin (5-HT) is a crucial neuromodulator linked to many psychiatric disorders. However, after more than 60 years of study, its role in behavior remains poorly understood, in part because of a lack of methods to target 5-HT synthesis specifically in the adult brain. Here, we have developed a genetic approach that reproducibly achieves near-complete elimination of 5-HT synthesis from the adult ascending 5-HT system by stereotaxic injection of an adeno-associated virus expressing Cre recombinase (AAV-Cre) into the midbrain/pons of mice carrying a loxP-conditional tryptophan hydroxylase 2 (Tph2) allele. We investigated the behavioral effects of deficient brain 5-HT synthesis and discovered a unique composite phenotype. Surprisingly, adult 5-HT deficiency did not affect anxiety-like behavior, but resulted in a robust hyperactivity phenotype in novel and home cage environments. Moreover, loss of 5-HT led to an altered pattern of circadian behavior characterized by an advance in the onset and a delay in the offset of daily activity, thus revealing a requirement for adult 5-HT in the control of daily activity patterns. Notably, after normalizing for hyperactivity, we found that the normal prolonged break in nocturnal activity (siesta), a period of rapid eye movement (REM) and non-REM sleep, was absent in all animals in which 5-HT deficiency was verified. Our findings identify adult 5-HT as a requirement for siestas, implicate adult 5-HT in sleep-wake homeostasis, and highlight the importance of our adult-specific 5-HT-synthesis-targeting approach in understanding 5-HT's role in controlling behavior. SIGNIFICANCE STATEMENT: Serotonin (5-HT) is a crucial neuromodulator, yet its role in behavior remains poorly understood, in part because of a lack of methods to target specifically adult brain 5-HT synthesis. We developed an approach that reproducibly achieves near-complete elimination of 5-HT synthesis from the adult ascending 5-HT system. Using this technique, we discovered that adult 5-HT deficiency led to a novel compound phenotype consisting of hyperactivity, disrupted circadian behavior patterns, and elimination of siestas, a period of increased sleep during the active phase. These findings highlight the importance of our approach in understanding 5-HT's role in behavior, especially in controlling activity levels, circadian behavior, and sleep-wake homeostasis, behaviors that are disrupted in many psychiatric disorders such as attention deficit hyperactivity disorder.