The G72/G30 gene complex and cognitive abnormalities in schizophrenia
Terry E Goldberg1, Richard E Straub, Joseph H Callicott
1Clinical Brain Disorders Branch, IRP, NIMH, NIH, Bethesda, MD, USA. tgoldber@nshs.edu
Summary
Genetic variations in the G72 gene region (DAOA) are linked to cognitive impairments in schizophrenia, particularly affecting working memory and attention. While not directly associated with clinical diagnosis, these G72 gene variations impact neurophysiology.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- The G72/G30 gene complex (DAOA) is implicated in schizophrenia and bipolar disorder, potentially through NMDA neurotransmission.
- NMDA signaling is crucial for cognitive functions and neurophysiology, making it a plausible target for G72's effects.
Purpose of the Study:
- To investigate the association between G72 gene variations and cognitive/neurophysiological functions in schizophrenia.
- To examine the relationship between G72 single nucleotide polymorphisms (SNPs) and cognitive measures (attention, working memory, episodic memory) and brain activity (fMRI BOLD response).
Main Methods:
- Two independent family-based association studies were conducted using over 600 participants (controls, schizophrenia patients, siblings).
- Mixed model ANOVAs analyzed the relationship between G72 SNPs and cognitive measures.
- fMRI BOLD response during memory tasks assessed genotype effects on neurophysiology in normal controls.
Main Results:
- No significant association was found between single G72 SNPs and clinical diagnosis.
- Significant diagnosis-by-genotype interactions for G72 SNP 10 were observed for working memory and attention, with an exaggerated allele load effect in schizophrenia patients.
- G72 SNP 10 genotype significantly affected hippocampal BOLD activation during episodic memory tasks in fMRI studies.
Conclusions:
- SNP variations in the G72 gene region contribute to cognitive impairment in schizophrenia.
- G72 gene variations influence specific cognitive domains and associated neurophysiological functions, independent of direct clinical diagnosis association.
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