A Homer 1 gene variant influences brain structure and function, lithium effects on white matter, and antidepressant response in bipolar disorder: A multimodal genetic imaging study

Autor: Andrea Falini, S. Brioschi, Andrea de Bartolomeis, Veronica Aggio, Francesco Benedetti, M. Riberto, Elena Mazza, Sara Poletti, Benedetta Vai, Clara Locatelli, Elisa M T Melloni, Alice Vitali, Irene Bollettini, Cristina Colombo, Cristina Lorenzi
Přispěvatelé: Benedetti, Francesco, Poletti, Sara, Locatelli, Clara, Mazza, Elena, Lorenzi, Cristina, Vitali, Alice, Riberto, Martina, Brioschi, Silvia, Vai, Benedetta, Bollettini, Irene, Melloni, Elisa, Aggio, Veronica, Falini, Andrea, De Bartolomeis, Andrea, Colombo, Cristina
Rok vydání: 2018
Předmět:
Male
Bipolar Disorder
Emotions
Antidepressant
Neuropsychological Tests
Multimodal Imaging
0302 clinical medicine
Homer Scaffolding Proteins
Gray Matter
Prefrontal cortex
Major depressive episode
Brain Mapping
Depression
fMRI
White matter
Brain
Middle Aged
White Matter
Antidepressive Agents
Diffusion Tensor Imaging
Treatment Outcome
medicine.anatomical_structure
Cerebrovascular Circulation
Lithium Compounds
Female
Glutamate
medicine.symptom
Psychology
Grey matter
Bipolar disorder
Brain imaging
White People
03 medical and health sciences
Neuroplasticity
medicine
Humans
Biological Psychiatry
Anterior cingulate cortex
Pharmacology
Depressive Disorder
Major
Genetic Variation
Phototherapy
medicine.disease
030227 psychiatry
Oxygen
Homer
Mood disorders
Sleep Deprivation
Neuroscience
030217 neurology & neurosurgery
Zdroj: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 81:88-95
ISSN: 0278-5846
DOI: 10.1016/j.pnpbp.2017.10.011
Popis: Background The Homer family of postsynaptic scaffolding proteins plays a crucial role in glutamate-mediated synaptic plasticity, a phenotype associated with Bipolar Disorder (BD). Homer is a target for antidepressants and mood stabilizers. The AA risk genotype of the Homer rs7713917 A > G SNP has been associated with mood disorders and suicide, and in healthy humans with brain function. Despite the evidence linking Homer 1 gene and function to mood disorder, as well as its involvement in animal models of depression, no study has yet investigated the role of Homer in bipolar depression and treatment response. Methods We studied 199 inpatients, affected by a major depressive episode in course of BD. 147 patients were studied with structural MRI of grey and white matter, and 50 with BOLD functional MRI of emotional processing. 158 patients were treated with combined total sleep deprivation and light therapy. Results At neuroimaging, patients with the AA genotype showed lower grey matter volumes in medial prefrontal cortex, higher BOLD fMRI neural responses to emotional stimuli in anterior cingulate cortex, and lower fractional anisotropy in bilateral frontal WM tracts. Lithium treatment increased axial diffusivity more in AA patients than in G*carriers. At clinical evaluation, the same AA homozygotes showed a worse antidepressant response to combined SD and LT. Conclusions rs7713917 influenced brain grey and white matter structure and function in BD, long term effects of lithium on white matter structure, and antidepressant response to chronotherapeutics, thus suggesting that glutamatergic neuroplasticity and Homer 1 function might play a role in BD psychopathology and response to treatment.
Databáze: OpenAIRE
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