Obsessive–compulsive disorder: an integrative genetic and neurobiological perspective

Abstract

Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviours that are experienced as unwanted. Family and twin studies have demonstrated that OCD is a multifactorial familial condition that involves both polygenic and environmental risk factors. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuit in the pathophysiology of the disorder, which is supported by the observation of specific neuropsychological impairments in patients with OCD, mainly in executive functions. Genetic studies indicate that genes affecting the serotonergic, dopaminergic and glutamatergic systems, and the interaction between them, play a crucial part in the functioning of this circuit. Environmental factors such as adverse perinatal events, psychological trauma and neurological trauma may modify the expression of risk genes and, hence, trigger the manifestation of obsessive-compulsive behaviours.

Obsessive–compulsive disorder in children and adolescents

“…In particular, genes within the serotonergic, dopaminergic and glutamatergic system appear to influence OCD. 15 Neuropsychological models of OCD propose that OCD arises from alterations to frontostriatal circuitry. Hyperactivation of the orbitofrontal cortex has been proposed to mediate persistent thoughts about threat and harm (ie, obsessions), which in turn lead to attempts to neutralise the perceived threat (ie, compulsions).…”

Overactive Performance Monitoring as an Endophenotype for Obsessive-Compulsive Disorder: Evidence From a Treatment Study

“…OCD leads to an enormous reduction in life quality and often follows a chronic course when not treated. There is increasing evidence from twin and family studies for small to moderate genetic effects (2). However, reliable evidence of specific genetic alterations has not yet emerged.…”

“…However, reliable evidence of specific genetic alterations has not yet emerged. Overall, data point to the involvement of gene variants in the serotonergic, dopaminergic, and glutamate systems (2). Combined, evidence suggests that OCD is genetically complex, with multiple genetic and environmental factors contributing to its development (2).…”

Participant Characteristics as Modifiers of Response to N-Acetyl Cysteine (NAC) in Obsessive-Compulsive Disorder

“…For example, although disturbed glutamate activity is becoming an increasingly regarded feature of OCD, it may be limited to a subset of people with polymorphisms in glutamate genes (Pauls, Abramovitch, Rauch, & Geller, 2014). Thus, NAC may be more suitable in these cases, only a handful of which may have been randomized into the current study.…”