Comorbid obsessive-compulsive symptoms in schizophrenia: contributions of pharmacological and genetic factors

Abstract

A large subgroup of around 25% of schizophrenia patients suffers from obsessive-compulsive symptoms (OCS) and about 12% fulfill the diagnostic criteria of an obsessive-compulsive disorder (OCD). The additional occurrence of OCS is associated with high subjective burden of disease, additional neurocognitive impairment, poorer social and vocational functioning, greater service utilization and high levels of anxiety and depression. Comorbid patients can be assigned to heterogeneous subgroups. One hypothesis assumes that second generation antipsychotics (SGAs), most importantly clozapine, might aggravate or even induce second-onset OCS. Several arguments support this assumption, most importantly the observed chronological order of first psychotic manifestation, start of treatment with clozapine and onset of OCS. In addition, correlations between OCS-severity and dose and serum levels and duration of clozapine treatment hint toward a dose-dependent side effect. It has been hypothesized that genetic risk-factors dispose patients with schizophrenia to develop OCS. One study in a South Korean sample reported associations with polymorphisms in the gene SLC1A1 (solute carrier family 1A1) and SGA-induced OCS. However, this finding could not be replicated in European patients. Preliminary results also suggest an involvement of polymorphisms in the BDNF gene (brain-derived neurotrophic factor) and an interaction between markers of SLC1A1 and the gene DLGAP3 (disc large associated protein 3) as well as GRIN2B (N-methyl-D-aspartate receptor subunit 2B). Further research of well-defined samples, in particular studies investigating possible interactions of genetic risk-constellations and pharmacodynamic properties, are needed to clarify the assumed development of SGA-induced OCS. Results might improve pathogenic concepts and facilitate the definition of at risk populations, early detection and monitoring of OCS as well as multimodal therapeutic interventions.

Relationship of obsessive compulsive symptoms/disorder with clozapine: A retrospective study from a multispeciality tertiary care centre

“…The sample sizes of these studies have varied from 41 to 200 and these studies suggest that 0-28.4% of patients have new symptoms of OCS/OCD while receiving clozapine (Ertugrul et al, 2005;de Haan et al, 1999de Haan et al, , 2004Ghaemi et al, 1995;Baker et al, 1992;Mahendran et al, 2007;Lin et al, 2006;Mukhopadhaya et al, 2009;Sa et al, 2009;Bleakley et al, 2011;Doyle et al, 2014). Some studies suggest that presence of OCS/OCD may be related to the severity of primary illness, higher doses of clozapine administered and the longer duration of clozapine use (Lin et al, 2006;Schirmbeck et al, 2011;Schirmbeck and Zink, 2013); however, others have reported no such association (Ertugrul et al, 2005;Kim et al, 2012). Some studies suggest that development of OCS/OCD may be related to plasma concentration of clozapine (Lin et al, 2006) and motoric impairment (Mukhopadhaya et al, 2009).…”

Increased orbitofrontal cortex activation associated with “pro-obsessive” antipsychotic treatment in patients with schizophrenia

“…Furthermore, the development of SGA-associated OCS within a so far incompletely understood interaction of genetic disposition and environmental factors needs to be addressed. 6 …”

“…[3][4][5] The clinical presentation of OCS in patients with schizophrenia is diverse, with manifestations of OCS before, concurrent with or subsequent to the first onset of psychosis and a persisting, remitting or fluctuating course. 6 This phenotypic heterogeneity suggests that a variety of causal factors have to be considered. Progress in understanding underlying neurobiological mechanisms will most likely be achieved if defined homogeneous subgroups within the comorbid sample are investigated.…”

“…Progress in understanding underlying neurobiological mechanisms will most likely be achieved if defined homogeneous subgroups within the comorbid sample are investigated. 6 One of these homogeneous subgroups comprises patients who experience a de novo onset or a marked aggravation of OCS after treatment initiation with secondgeneration antipsychotic agents (SGAs). Clozapine in particu lar has been associated with a risk of inducing OCS.…”

New frontiers in the neuropsychopharmacology of mental illness

“…This could be relevant and/or potentially translatable to the etiology and treatment of major depression and anxiety. Schirmbeck and Zink (2013) review the contributions of pharmacological and genetic factors in schizophrenia patients with comorbid obsessive-compulsive symptoms (OCS). In this article, they present an in-depth and very detailed coverage of the concepts explaining the co-occurrence of OCS in schizophrenia.…”