Xiaoyu Men, Victoria Marshe, Samar S Elsheikh, George S Alexopoulos, Patricia Marino, Barnett S Meyers, Benoit H Mulsant, Anthony J Rothschild, Aristotle N Voineskos, Ellen M Whyte, James Lowery Kennedy, Alastair J Flint, Daniel J Müller
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引用次数: 0
Abstract
Introduction: Little is known regarding genetic factors associated with treatment outcome of psychotic depression. We explored genomic associations of remission and relapse of psychotic depression treated with pharmacotherapy.
Methods: Genomic analyses were performed in 171 men and women aged 18-85 years with an episode of psychotic depression who participated in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). Participants were treated with open-label sertraline plus olanzapine for up to 12 weeks; those who achieved remission or near-remission and maintained it following 8 weeks of stabilization were eligible to participate in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse.
Results: There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31 kb from SYNPO2) in the whole sample and rs6844137 (within the intronic region of SYNPO2) in the European ancestry subsample were associated with a decreased likelihood of remission. In polygenic risk analyses, participants who had greater improvement after antidepressant treatments showed a higher likelihood of reaching remission. Those who achieved remission and had a higher polygenic risk for Alzheimer's disease had a significantly decreased likelihood of relapse.
Conclusion: Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression.
期刊介绍:
The biological approach to mental disorders continues to yield innovative findings of clinical importance, particularly if methodologies are combined. This journal collects high quality empirical studies from various experimental and clinical approaches in the fields of Biological Psychiatry, Biological Psychology and Neuropsychology. It features original, clinical and basic research in the fields of neurophysiology and functional imaging, neuropharmacology and neurochemistry, neuroendocrinology and neuroimmunology, genetics and their relationships with normal psychology and psychopathology. In addition, the reader will find studies on animal models of mental disorders and therapeutic interventions, and pharmacoelectroencephalographic studies. Regular reviews report new methodologic approaches, and selected case reports provide hints for future research. ''Neuropsychobiology'' is a complete record of strategies and methodologies employed to study the biological basis of mental functions including their interactions with psychological and social factors.