The serotonin hypothesis of obsessive compulsive disorder: Implications of pharmacologic challenge studies

Department of Psychiatry, Yale University, New Haven, CT 06519.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 05/1992; 53 Suppl(4):17-28.
Source: PubMed


Demonstration of the efficacy of serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors such as clomipramine in the treatment of obsessive compulsive disorder has fueled interest in the neurobiological basis of this illness. Results of treatment studies, investigations of biological markers, and pharmacologic challenges are reviewed and implications for a 5-HT theory of obsessive compulsive disorder discussed. While the nature of the dysregulation in serotonin transmission that may attend obsessive compulsive disorder has yet to be fully elucidated, evidence accumulates that 5-HT function in part modulates obsessive compulsive symptoms. Development of more specific probes and new brain imaging techniques will further enhance understanding of the pathophysiology of obsessive compulsive disorder.

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    • "Clinical expression of OCD is heterogeneous in terms of symptomatology and comorbid conditions, suggesting heterogeneity in the underlying pathology [4]. Although OCD pathophysiology remains unclear, accumulating evidence implicates contributions of the serotonergic and dopaminergic systems [5] [6] and the cortico–striato–thalamocortical circuitry which includes the orbitofrontal cortex [4,7–9]. "
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    ABSTRACT: Objective: The serotonergic system is implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, the distinct role of serotonin (5-HT) receptor subtypes remains unclear. This study investigates the contribution of 5-HT2A and 5-HT2C receptors in the modulation of persistence in the reinforced spatial alternation model of OCD. Methods: Male Wistar rats were assessed for spontaneous and pharmacologically induced (by m-chlorophenylpiperazine: mCPP) directional persistence in the reinforced alternation OCD model. Systemic administration of mCPP (non-specific 5-HT agonist, 2.5mg/kg), M100907 (selective 5-HT2A receptor antagonist, 0.08 mg/kg), SB242084 (selective 5-HT2C receptor antagonist, 0.5 mg/kg) and vehicle was used. Experiment 1 investigated M100907 and SB242084 effects in animals spontaneously exhibiting high and low persistence during the early stages of alternation training. Experiment 2 investigated M100900 and SB242084 effects on mCPP-induced persistence. Results: Under the regime used in Experiment 1, 5-HT2A or 5-HT2C receptor antagonism did not affect spontaneous directional persistence in either high or low persistence groups. In Experiment 2, 5-HT2C but not 5-HT2A receptor antagonism significantly reduced, but did not abolish, mCPP-induced directional persistence. Conclusions: These findings suggest that 5-HT2C but not 5-HT2A receptors contribute to the modulation of mCPP-induced persistent behaviour, raising the possibility that the use of 5-HT2C antagonists may have a therapeutic value in OCD.
    Full-text · Article · Jan 2013 · Behavioural brain research
    • "A serotonergic hypothesis of OCD was suggested originally by the observed differential efficacy of SRIs in alleviating OCD symptoms.[55] Since then, numerous studies of peripheral receptor binding in the blood or concentrations of serotonin metabolites in cerebrospinal fluid have been performed but have yielded inconsistent results.[56] Pharmacological challenge studies provide another indirect approach. "
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    ABSTRACT: Obsessive-compulsive disorder (OCD) was considered a relatively rare disorder until about two decades ago. Since then, considerable advance has been made in understanding the various aspects of OCD that include epidemiology, clinical features, comorbidity, biology and treatment. In the last one decade, there has also been interest in a group of related disorders called obsessive-compulsive spectrum disorders. There is substantial research from India on various aspects of OCD, particularly from the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore. We attempt to review all the relevant Indian data on OCD.
    No preview · Article · Jan 2010 · Indian Journal of Psychiatry
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    • "It has been suggested that OCD might be related to the functioning of brain serotonin systems. This hypothesis is based largely on the notion that SSRIs possess antiobsessional efficacy [29-31]. Neuroimaging studies have been very influential in shaping neurobiological models of OCD. "
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    ABSTRACT: Alterations in ceruloplasmin are currently assumed as one of the mechanisms underlying the development of a number of neurodegenerative disorders. Several studies indicate that elevated serum ceruloplasmin levels may play a role in schizophrenia by exacerbating or perpetuating dopaminergic dysregulation. No study investigating the relationship between ceruloplasmin and obsessive-compulsive disorder (OCD) has been published to date. Nowadays OCD is increasingly speculated to be a different disorder than other anxiety disorders, and rather is considered to be more similar to psychotic disorders. The objective of this study to explore whether there is an association of ceruloplasmin with OCD as in schizophrenia. 26 pure OCD and 9 co-morbid OCD patients from Gaziantep University Sahinbey Research Hospital, Psychiatry Clinics, diagnosed according to the DSM IV and 40 healthy controls were included in the study. Blood samples were collected; ceruloplasmin levels were measured. The mean ceruloplasmin level in pure OCD patients, co-morbid OCD patients, and control group persons were 544.46 +/- 26.53, 424.43 +/- 31.50 and 222.35 +/- 8.88 U/L respectively. Results of all 3 groups differ significantly. Positive predictive value of ceruloplasmin for that cut-off point is 31/31 (100%) and negative predictive value is 40/44 (91%) in our group. Although the nature of relationship is not clear there was an association between ceruloplasmin levels and OCD in our study.
    Full-text · Article · Dec 2008 · Behavioral and Brain Functions
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