Numerous studies have examined the role of this
polymorphism in risk of
neuropsychiatric disorders, including (but not limited to)
schizophrenia and
depression. It is generally thought that some variants of the polymorphism lead to memory impairment and susceptibility to neuropsychiatric disorders, and a 2007
meta-analysis of
case-control studies found a relationship between the SNP and
substance-related disorders,
eating disorders, and
schizophrenia. Another 2007
meta-analysis could, however, find no association between the SNP and
schizophrenia or
bipolar disorder. Meta-analyses of
Alzheimer's disease and
Parkinson's disease also indicate that the SNP has little or no association with these diseases. Also inconsistencies in association studies with depression have been noted. The reason for these inconsistent results have been suggested to stem from several sources, with one recent review arguing that statistical artefact, sampling bias, population stratification and uncontrolled gene-environment interactions are likely to underscore this effect. As hippocampal function is a core component of several psychiatric conditions, and stress is a non-specific but substantial risk factor for affective, anxiety, eating and psychotic disorders, Notaras et al. argue that "
there is a long-term effect of glucocorticoids in 66Met carriers that potentiates the fear circuitry into adulthood, which may increase susceptibility to trauma, events with negative emotional valence and related psychopathology". where it has been shown that 66Met variant perturbs extinction learning in both man and mouse. The Val66Met polymorphism alters vulnerability to stress in mice and humans, which likely contributes to PTSD risk. In treatment response studies val/val homozygotes may respond better than met allele carriers with drug resistant depression treated with
repetitive transcranial magnetic stimulation. == Subject variables in healthy humans ==