Effects of prenatal nutrient supplementation and early life exposures on neurodevelopment at age 10: a randomised controlled trial - the COPSYCH study protocol.

INTRODUCTION: Nutrient deficiency and immune and inflammatory disturbances in early life may compromise neurodevelopment and be implicated in the aetiology of psychiatric disorders. However, current evidence is limited by its predominantly observational nature. COpenhagen Prospective Study on Neuro-PSYCHiatric Development (COPSYCH) is a research alliance between Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research with the overall aim to investigate effects of prenatal and early life exposures on neurodevelopment at 10 years. COPSYCH will investigate the impact of prenatal n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) and high-dose vitamin D supplementation on neurodevelopment reflected by brain development, neurocognition and psychopathology. Moreover, the neurodevelopmental impact of early life exposures such as infections, low grade inflammation and the gut microbiome will be scrutinised. METHODS AND ANALYSIS: COPSYCH is based on the prospective and ongoing COPSAC2010 birth cohort of 700 mother-child pairs. Randomised controlled trials of supplementation with n-3 LCPUFA and/or high-dose vitamin D or placebo in the third trimester were embedded in a factorial 2×2 design (ClinicalTrials.gov: NCT01233297 and NCT00856947). This unique cohort provides deep phenotyping data from 14 previous clinical follow-up visits and exposure assessments since birth. The ongoing 10-year visit is a 2-day visit. Day 1 includes a comprehensive neurocognitive examination, and assessment of psychopathological dimensions, and assessment of categorical psychopathology. Day 2 includes acquisition of brain structural, diffusion and functional sequences using 3 Tesla MRI. Study outcomes are neurocognitive, psychopathological and MRI measures. ETHICS AND DISSEMINATION: This study has been approved by the Danish National Committee on Health Research Ethics and The Danish Data Protection Agency. The study is conducted in accordance with the guiding principles of the Declaration of Helsinki. Parents gave written informed consent before enrolment.

Hippocampal volume and memory impairment after electroconvulsive therapy in patients with depression.

OBJECTIVE: Patients hesitate to consent to electroconvulsive therapy (ECT) because of the fear of memory impairment. The mechanisms underlying this impairment are unclear, but several observations suggest hippocampal alterations may be involved. We investigated whether ECT-induced change in hippocampal volume correlates with memory impairment. METHODS: Using a 3 T MRI scanner, we acquired brain images and assessed cognitive performance in 22 severely depressed patients at three time points: (1) before ECT series, (2) within one week after the series, and (3) at six-month follow-up. The hippocampus was segmented into subregions using FreeSurfer. The dentate gyri (DG) were the primary regions of interest (ROIs) and major hippocampal subregions secondary ROIs. Cognitive performance was assessed using the Screen for Cognitive Impairment in Psychiatry and verbal memory using the Verbal Learning subtest. The linear mixed model and the repeated-measures correlation were used for statistical analyses. RESULTS: ECT induced an increase in the right and left DG volume with co-occurring worsening in verbal memory, and these changes were within-patients negatively correlated (right DG, rrm  = -0.85, df = 18, p = 0.0000002; left DG, rrm  = -0.58, df = 18, p = 0.008). At a six-month follow-up, the volume of both DG decreased with a co-occurring improvement in verbal memory, and these changes were negatively correlated in the right DG (rrm  = -0.64, df = 15, p = 0.005). Volume increases in 14 secondary ROIs were also negatively correlated with memory impairment. CONCLUSION: ECT-related transient increases in the volume of major hippocampal subregions within-patients are associated with memory impairment. Hippocampal alterations following ECT should be the focus in searching for causes of the cognitive side effects.