The neural bases of obsessive–compulsive disorder in children and adults

Abstract

Functional imaging studies have reported with remarkable consistency hyperactivity in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus of patients with Obsessive-Compulsive Disorder (OCD). These findings have often been interpreted as evidence that abnormalities in cortico-basal ganglia-thalamo-cortical loops involving the OFC and ACC are causally related to OCD. This interpretation remains controversial, however, because such hyperactivity may represent either a cause or a consequence of the symptoms. This article analyzes the evidence for a causal role of these loops in producing OCD in children and adults. The article first reviews the strong evidence for anatomical abnormalities in these loops in patients with OCD. These findings are not sufficient to establish causality, however, because anatomical alterations may themselves be a consequence rather than a cause of the symptoms. The article then reviews three lines of evidence that, despite their own limitations, permit stronger causal inferences: the development of OCD following brain injury, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, and neurosurgical lesions that attenuate OCD. Converging evidence from these various lines of research supports a causal role for the cortico-basal ganglia-thalamo-cortical loops that involve the OFC and ACC in the pathogenesis of OCD in children and adults.

Investigation of Cortical Glutamate–Glutamine and γ-Aminobutyric Acid in Obsessive–Compulsive Disorder by Proton Magnetic Resonance Spectroscopy

“…Thus, decreased GABA levels could reflect fewer GABAergic interneurons and result in reduced MPFC inhibitory tone, consistent with reports of cortical inhibitory dysfunction in OCD (Greenberg et al, 2000;Richter et al, 2012). Reduced MPFC inhibitory tone is also consistent with current OCD models that posit abnormal frontostriatal activation (Maia et al, 2008;Pittenger et al, 2011;Ting and Feng, 2011;Wu et al, 2012), as reduced MPFC inhibitory tone could generate abnormal striatal activation either directly due to ACC projections to the striatum or indirectly due to ACC projections to the OFC (Price and Drevets, 2010;Schmahmann and Pandya, 2006). On the other hand, acute psychological stress has recently been shown to decrease MPFC GABA levels in healthy controls (Hasler et al, 2010).…”

“…Studies measuring blood flow or glucose metabolism by positron emission tomography and hemodynamic response by functional magnetic resonance imaging find increased activity in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and striatum in people with OCD (reviewed in Maia et al, 2008). This increased activity may reflect primary abnormalities in glutamatergic neurotransmission (Carlsson, 2001;Pittenger et al, 2011;Rosenberg and Keshavan, 1998;Wu et al, 2012).…”

Quality of life in children with OCD before and after treatment

“…Functional neuroimaging studies have consistently shown hyperactivity in the orbitofrontal cortex, the anterior cingulate cortex, the thalamus and the striatum of patients with OCD. Various lines of research support a causal role for the cortico-basal ganglia-thalamo-cortical loops that involve the orbitofrontal cortex and the anterior cingulate cortex in the pathogenesis of OCD in children as well as in adults (Brem et al, 2012;Maia, Cooney, & Peterson, 2008).…”

Gender differences in obsessive-compulsive disorder: a literature review

“…Because the development of the caudate nucleus and the orbitofrontal cortex (OFC) -two central components of the OFC/ACC (anterior cingulate cortex) loop -is different for boys and girls, this could explain, at least in part, the higher prevalence of early-onset OCD among boys. 32 Sobin et al 33 found some indirect indicators of a higher negative impact of OCD among male sufferers. For example, two thirds remain single versus only one third of women.…”

“…This finding indicates that abnormal development of these structures could be related to early onset of symptoms. 32 As the PFC continues to mature throughout adult life, abnormalities in later maturation processes could be related to late-onset OCD. Because the development of the caudate nucleus and the orbitofrontal cortex (OFC) -two central components of the OFC/ACC (anterior cingulate cortex) loop -is different for boys and girls, this could explain, at least in part, the higher prevalence of early-onset OCD among boys.…”