Hippocampal volume and the brain-derived neurotrophic factor Val66Met polymorphism in first episode psychosis.
ABSTRACT Small hippocampi and impaired memory are common in patients with psychosis and brain-derived neurotrophic factor (BDNF) plays a critical role in hippocampal neuroplasticity and memory. A common BDNF allele (Val66Met) has been the focus of numerous studies but results from the few BDNF-imaging studies are complex and contradictory. The objective of this study was to determine the association between Val66Met and hippocampal volume in patients with first episode psychosis. Secondary analyses explored age-related associations and the relationship between Val66Met and memory.
Hippocampal volume and BDNF genotyping were obtained for 58 patients with first-episode psychosis and 39 healthy volunteers. Patients were recruited from an early psychosis program serving a catchment-area population.
Hippocampal volume was significantly smaller in patients than controls (F(1,92)=4.03, p<0.05) and there was a significant group-by-allele interaction (F(1,92)=3.99, p<0.05). Hippocampal volume was significantly smaller in patients than controls who were Val-homozygotes but no group differences were found for Met carriers. Findings were not affected by diagnosis, antipsychotic medication, or age, and there was no change in hippocampal volume during a one-year follow-up. Val-homozygous patients had worse immediate and delayed memory than their Met counterparts.
Results suggest the effects of the BDNF Val66Met allele may be different in patients with psychosis than in healthy adults. Hippocampal volume in patient and control Met allele carriers was very similar suggesting that illness-related factors have minimal influence in this group. In contrast, Val homozygosity was related to smaller hippocampi and poorer memory functioning only in patients with psychosis.
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ABSTRACT: Brain-derived neurotrophic factor (BDNF), a neurotrophin known to be responsible for development, regeneration, survival and maintenance of neurons has been implicated in the pathophysiology of schizophrenia. This review seeks to complement previous reviews on biological roles of BDNF and summarizes evidence on the involvement of BDNF in the pathophysiology of schizophrenia with an emphasis on clinical relevance. The expressions of BDNF were altered in patients with schizophrenia and were found to be correlated with psychotic symptomatology. Antipsychotics appeared to have differential effects on expression of BDNF but did not restore BDNF expression of patients with schizophrenia to normal levels. In addition, evidence suggests that BDNF is involved in the major neurotransmitter systems and is associated with disruptions in brain structure, neurodevelopmental process, cognitive function, metabolic and immune systems commonly associated with schizophrenia. Besides that, BDNF has been demonstrated to be tightly regulated with estrogen which has also been previously implicated in schizophrenia. Evidence gathered in this review confirms the relevance of BDNF in the pathophysiology of schizophrenia and the potential utility of BDNF as a suitable biomarker for diagnostic and prognostic purposes for disease outcome and other co-morbidities. However, further investigations are warranted to examine the specificity of BDNF in schizophrenia compared to other neurodegenerative disorders and other neuropsychiatric illness. Longitudinal prospective studies will also be of added advantage for evaluation of prognostic utility of BDNF in schizophrenia.Clinical Psychopharmacology and Neuroscience 08/2012; 10(2):61-70.
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ABSTRACT: Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val(66)Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis. Functional magnetic resonance imaging was used to assess how the Brain Derived Neurotrophic Factor Val(66)Met polymorphism modulated brain regional activity and functional connectivity in 26 cognitively unimpaired Multiple Sclerosis patients and 25 age- and education-matched healthy controls while performing an episodic memory task that included encoding and retrieving visual scenes. We found a highly significant group by genotype interaction in the left posterior hippocampus, bilateral parahippocampus, and left posterior cingulate cortex. In particular, Multiple Sclerosis patients homozygous for the Val(66) allele, relative to Met(66) carriers, showed greater brain responses during both encoding and retrieval while the opposite was true for healthy controls. Furthermore, a robust group by genotype by task interaction was detected for the functional connectivity between the left posterior hippocampus and the ipsilateral posterior cingulate cortex. Here, greater hippocampus-posterior cingulate cortex connectivity was observed in Multiple Sclerosis Met(66) carriers relative to Val(66) homozygous during retrieval (but not encoding) while, again, the reverse was true for healthy controls. The Val(66)Met polymorphism has opposite effects on hippocampal circuitry underlying episodic memory in Multiple Sclerosis patients and healthy controls. Enhancing the knowledge of how genetic factors influence cognitive functions may improve the clinical management of memory deficits in patients with Multiple Sclerosis.PLoS ONE 01/2013; 8(4):e61063. · 3.73 Impact Factor