Body mass index and variability in hippocampal volume in youth with major depressive disorder.

BACKGROUND: The hippocampus has been implicated in major depressive disorder (MDD), in both adults and youth. However, possible sources of variability for the hippocampus have not been well delineated. Here, we explored the relationship between body mass index (BMI) and hippocampal volume in youth with MDD. METHODS: Twenty-two controls (9 male, 13 female, 12-24 years), 24 youth with MDD and normal BMI (12 male, 12 female, 14-24 years), and 20 youth with MDD and high BMI (14 male, 6 female, 13-22 years) underwent magnetic resonance (MR) imaging and spectroscopy (1H-MRS). Hippocampal volume was determined through manual tracing of high-resolution anatomical T1 scans, and LCModel quantified neurochemical concentrations. Intracranial volume was used as a covariate in analysis to control for effects of brain volume on hippocampus. RESULTS: In youth with MDD and normal BMI, right hippocampal volume was reduced (p = 0.006, Bonferroni) and a trend for reduced left hippocampal volume was noted when compared to healthy controls (p = 0.054, Bonferroni). Left hippocampal volumes were negatively associated with BMI in youth with MDD and high BMI group (r = -0.593, p = 0.006). No associations were found between the right hippocampus and BMI and there were no group differences for metabolite concentrations. LIMITATIONS: Larger sample sizes would enable researchers to explore overweight vs obese groups and effect of sex in MDD-BMI groups. CONCLUSIONS: BMI may account for some of the variability observed in previous studies of hippocampal volume in MDD, and therefore BMI impacts should be considered in future analyses.

National Analysis of Risk Assessment Content in Prenatal Records Across Canada.

Each Canadian province/territory has a distinct prenatal record form to guide maternity health care. Because there is no national oversight of these forms, little is known about how they compare regarding content on risk assessment for adverse perinatal outcomes. We cataloged and compared the risk factors that are captured on prenatal record forms across Canada. Nine out of 12 records included risk sections, with an average of 35 risk items. We identified 100 prenatal risk factors and categorized them as medical (73%), lifestyle (11%), psychosocial (11%), or personal (5%). Where present, clinical definitions for risk factors often varied. The substantial differences in risk assessment content in the prenatal record forms may contribute to differences in health care quality among provinces. The development of standardized national guidelines for prenatal risk assessment may be a valuable goal.

Repetitive Transcranial Magnetic Stimulation in Youth With Treatment Resistant Major Depression.

Background: Major depressive disorder (MDD) is common in youth and treatment options are limited. We evaluated the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) in adolescents and transitional aged youth with treatment resistant MDD. Methods: Thirty-two outpatients with moderate to severe, treatment-resistant MDD, aged 13-21 years underwent a three-week, open-label, single center trial of rTMS (ClinicalTrials.gov identifier NCT01731678). rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) using neuronavigation and administered for 15 consecutive week days (120% rest motor threshold; 40 pulses over 4 s [10 Hz]; inter-train interval, 26 s; 75 trains; 3,000 pulses). The primary outcome measure was change in the Hamilton Depression Rating Scale (Ham-D). Treatment response was defined as a >50% reduction in Ham-D scores. Safety and tolerability were also examined. Results: rTMS was effective in reducing MDD symptom severity (t = 8.94, df = 31, p < 0.00001). We observed 18 (56%) responders (≥ 50% reduction in Ham-D score) and 14 non-responders to rTMS. Fourteen subjects (44%) achieved remission (Ham-D score ≤ 7 post-rTMS). There were no serious adverse events (i.e., seizures). Mild to moderate, self-limiting headaches (19%) and mild neck pain (16%) were reported. Participants ranked rTMS as highly tolerable. The retention rate was 91% and compliance rate (completing all study events) was 99%. Conclusions: Our single center, open trial suggests that rTMS is a safe and effective treatment for youth with treatment resistant MDD. Larger randomized controlled trials are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01731678.

Pannexin 1 regulates postnatal neural stem and progenitor cell proliferation.

BACKGROUND: Pannexin 1 forms ion and metabolite permeable hexameric channels and is abundantly expressed in the brain. After discovering pannexin 1 expression in postnatal neural stem and progenitor cells we sought to elucidate its functional role in neuronal development. RESULTS: We detected pannexin 1 in neural stem and progenitor cells in vitro and in vivo. We manipulated pannexin 1 expression and activity in Neuro2a neuroblastoma cells and primary postnatal neurosphere cultures to demonstrate that pannexin 1 regulates neural stem and progenitor cell proliferation likely through the release of adenosine triphosphate (ATP). CONCLUSIONS: Permeable to ATP, a potent autocrine/paracine signaling metabolite, pannexin 1 channels are ideally suited to influence the behavior of neural stem and progenitor cells. Here we demonstrate they play a robust role in the regulation of neural stem and progenitor cell proliferation. Endogenous postnatal neural stem and progenitor cells are crucial for normal brain health, and their numbers decline with age. Furthermore, these special cells are highly responsive to neurological injury and disease, and are gaining attention as putative targets for brain repair. Therefore, understanding the fundamental role of pannexin 1 channels in neural stem and progenitor cells is of critical importance for brain health and disease.