Obsessive-Compulsive Symptoms in Schizophrenia by Lieuwe de Haan & Frederike Schirmbeck & Mathias Zink

Author:Lieuwe de Haan & Frederike Schirmbeck & Mathias Zink
Language: rus
Format: mobi
Tags: Internal Medicine, Medical, Specialties, Nonfiction, Psychiatry, Neurology, Health & Well Being
ISBN: 9783319129525
Publisher: Springer
Published: 2015-03-22T22:00:00+00:00

128

K.S. Hong

GRIN2B is the third glutamate-related gene which was associated with SGA-

induced OCSs in a previous study (Cai et al. 2013 ). It encodes the NR2B subunit of NMDA receptors and plays an important role in glutamate synaptic function.

Variants of this gene were reported to be associated with OCD (Arnold et al. 2004 ) and the orbital frontal cortex and anterior cingulate cortex volume of pediatric

patients with OCD (Arnold et al. 2009 ). The SNP associated with SGA-induced

OCSs in the study by Cai et al. ( 2013 ) (rs890) is located in the 3’ untranslated region (3’-UTR). Although variants in the 3’-UTR might be related to messenger RNA

processing of the gene, the exact role of rs890 in the function of the protein is not

yet known (Cai et al. 2013 ).

The susceptibility to SGA-induced OCSs might be induced by multiple genes.

Considering the hypothetical mechanism of OCD and pharmacodynamic profi les of

SGAs, candidate genes involved in serotonergic, dopaminergic, and GABAergic

systems as well as more glutamatergic genes should be tested in future studies. The

susceptibility might be due to an interactive effect of these genes causing dysregula-

tion of the cortico-striato-thalamo-cortical (CSTC) circuitry, a candidate brain net-

work related to OCD (Milad and Rauch 2012 ; Pauls et al. 2014 ). The CSTC circuitry uses both glutamate and GABA as its primary neurotransmitters (Pittenger et al.

2011 ).

Gene–environment interactions also seemed to play an etiologic role for OCD or

OCSs (Monzani et al. 2014 ). Adverse perinatal events (Geller et al. 2008 ), psychosocial stressors and traumatic life events (Grisham et al. 2011 ; Lafl eur et al. 2011 ;

Landau et al. 2011 ), and streptococcal infections (Murphy et al. 2010 ) have been suggested as environmental triggers for OCD or related phenotypes. These events

could trigger the expression of genes involved in the CSTC circuitry through epi-

genetic mechanisms (Pauls et al. 2014 ). However, biological mechanisms of gene–

environment interactions remain to be elucidated. Furthermore, valid methods for

the assessment of environmental factors have not yet been well established (Pauls

et al. 2014 ). Compared to the abovementioned environmental factors, substances and medications including SGAs would be a more straightforward environmental

factor that can be reliably measured. Therefore, genetic studies on the SGA-induced

OCSs could provide an important early insight into the complete genetic architec-

ture of OCSs or OCD in schizophrenia.

Conclusions

It is well known that a signifi cantly higher rate of OCSs or OCD is demonstrated

in schizophrenia patients compared to the general population. As genetic factors

play a major role in the development of both schizophrenia and OCD, the mecha-

nism underlying their link and combination could also be elucidated through

genetic studies. Until now, only a limited number of genetic studies have been

performed on OCSs or comorbid OCD in schizophrenia. Recently, pharmacoge-

netic studies generated stimulating fi ndings suggesting the role of glutamatergic

genes in the development of SGA-induced OCSs. They seem to be a relatively

homogeneous phenotype having a unique environmental triggering factor (the

drug). Investigation of this phenotype would be an important starting point,

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