RESUMO
OBJECTIVE: In major depressive disorder (MDD), single nucleotide polymorphisms (SNPs) in monoaminergic genes may impact disease susceptibility, treatment response, and brain volume. The objective of this study was to examine the effect of such polymorphisms on hippocampal volume in patients with treatment-resistant MDD and healthy controls. Candidate gene risk alleles were hypothesised to be associated with reductions in hippocampal volume. METHODS: A total of 26 outpatients with treatment-resistant MDD and 27 matched healthy controls underwent magnetic resonance imaging and genotyping for six SNPs in monoaminergic genes [serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), serotonin 1A and 2A receptors (HTR1A and HTR2A), catechol-O-methyltransferase (COMT), and brain-derived neurotrophic factor (BDNF)]. Hippocampal volume was estimated using an automated segmentation algorithm (FreeSurfer). RESULTS: Hippocampal volume did not differ between patients and controls. Within the entire study sample irrespective of diagnosis, C allele-carriers for both the NET-182 T/C [rs2242446] and 5-HT1A-1019C/G [rs6295] polymorphisms had smaller hippocampal volumes relative to other genotypes. For the 5-HTTLPR (rs25531) polymorphism, there was a significant diagnosis by genotype interaction effect on hippocampal volume. Among patients only, homozygosity for the 5-HTTLPR short (S) allele was associated with smaller hippocampal volume. There was no association between the 5-HT2A, COMT, and BDNF SNPs and hippocampal volume. CONCLUSION: The results indicate that the volume of the hippocampus may be influenced by serotonin- and norepinephrine-related gene polymorphisms. The NET and 5-HT1A polymorphisms appear to have similar effects on hippocampal volume in patients and controls while the 5-HTTLPR polymorphism differentially affects hippocampal volume in the presence of depression.
Assuntos
Transtorno Depressivo Maior/genética , Transtorno Depressivo Resistente a Tratamento/genética , Hipocampo/patologia , Adulto , Algoritmos , Alelos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Catecol O-Metiltransferase/genética , Catecol O-Metiltransferase/metabolismo , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/patologia , Transtorno Depressivo Resistente a Tratamento/metabolismo , Transtorno Depressivo Resistente a Tratamento/patologia , Feminino , Genótipo , Hipocampo/metabolismo , Homozigoto , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Polimorfismo de Nucleotídeo Único , Receptor 5-HT1A de Serotonina/genética , Receptor 5-HT1A de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismoRESUMO
Intact episodic memory requires the ability to make associations between the contextual features of an event, referred to as contextual binding. Binding processes combine different contextual elements into a complete memory representation. It has been proposed that binding errors during the encoding process are responsible for the episodic memory impairments reported in schizophrenia. Since the hippocampus is critical for contextual binding and episodic memory, it was hypothesized that patients with schizophrenia would show a deficit in information processing in the hippocampus, measured with functional magnetic resonance imaging (fMRI). In the current experiment, 21 patients with schizophrenia and 22 healthy control participants were scanned while being tested on navigating in a virtual town (i.e. find the grocery store from the school), a task that was shown to be critically dependent on the hippocampus. Between-group comparisons revealed significantly less activation among patients relative to controls in the left middle frontal gyrus, and right and left hippocampi. We propose that the context and the content are not appropriately linked, therefore affecting the formation of a cognitive map representation in the patient group and eliciting a contextual binding deficit.
