Another meta-analysis observed an increased risk in those with the homozygous S allele, but found the LS genotype to be inversely associated with OCD.A genome-wide association study found OCD to be linked with single-nucleotide polymorphisms (SNPs) near BTBD3, and two SNPs in DLGAP1 in a trio-based analysis, but no SNP reached significance when analyzed with case-control data.One meta-analysis found a small but significant association between a polymorphism in SLC1A1 and OCD.The relationship between OCD and Catechol-O-methyltransferase (COMT) has been inconsistent, with one meta-analysis reporting a significant association, albeit only in men, and another meta analysis reporting no association.It has been postulated by evolutionary psychologists that moderate versions of compulsive behavior may have had evolutionary advantages. Examples would be moderate constant checking of hygiene, the hearth, or the environment for enemies. Similarly, hoarding may have had evolutionary advantages. In this view, OCD may be the extreme statistical tail of such behaviors, possibly the result of a high number of predisposing genes. Brain structure and functioning
Imaging studies have shown differences in the frontal cortex and subcortical structures of the brain in patients with OCD. There appears to be a connection between the OCD symptoms and abnormalities in certain areas of the brain, but such a connection is not clear.
It has been reported in some studies that there is a connection between childhood trauma and obsessive-compulsive symptoms. More research is needed to understand this relationship better. Mechanisms
Neuroimaging
Functional neuroimaging during symptom provocation has observed abnormal activity in the orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (dlPFC), right premotor cortex, left superior temporal gyrus, globus pallidus externus, hippocampus, and right uncus. Weaker foci of abnormal activity were found in the left caudate, posterior cingulate cortex, and superior parietal lobule. However, an older meta-analysis of functional neuroimaging in OCD reported that the only consistent functional neuroimaging finding was increased activity in the orbital gyrus and head of the caudate nucleus, while anterior cingulate cortex (ACC) activation abnormalities were too inconsistent.A meta-analysis comparing affective and nonaffective tasks observed differences with controls in regions implicated in salience, habit, goal-directed behavior, self-referential thinking, and cognitive control. For nonaffective tasks, hyperactivity was observed in the insula, ACC, and head of the caudate/putamen, while hypoactivity was observed in the medial prefrontal cortex (mPFC) and posterior caudate. Affective tasks were observed to relate to increased activation in the precuneus and posterior cingulate cortex, while decreased activation was found in the pallidum, ventral anterior thalamus, and posterior caudate. The involvement of the cortico-striato-thalamo-cortical loop in OCD, as well as the high rates of comorbidity between OCD and ADHD, have led some to draw a link in their mechanism. Observed similarities include dysfunction of the anterior cingulate cortex and prefrontal cortex, as well as shared deficits in executive functions.