PubMed Health⌕ Search

PubMed · 12607204

Obsessive compulsive disorder: serotonin and beyond.

Abstract

OCD was considered a rare, treatment refractory disorder of psychological origin, up until 20 years ago. Research in the last two decades has altered the perspectives regarding OCD. It is now clear that OCD is a prevalent disorder--about 2% of the population suffer from OCD--and that it is amenable both to psychological (cognitive-behavioural approach) and pharmacological intervention (with serotonergic medication). The biochemical and neuroanatomical (the frontal basal-thalamo cortical circuit) pathophysiology of OCD is also beginning to emerge. OCD is unique with regards to its specific response to serotonergic medication that blocks reuptake. Clomiprimine, fluoxetine, fluvoxemine, paroxetine, sertraline and citalopram were all found to be effective treatments for OCD based on large, multicentre, double-blind, placebo-controlled studies. As only serotonergic medications appear to be effective in OCD, the serotonergic hypothesis has been formulated and tested. Indeed, pharmacological challenges with specific serotonin agonists such as mCPP and sumatriptan, which were associated with transient exacerbation of OCD symptoms, are in line with the specific role of 5HT in the pathogenesis of OCD. However, this serotonergic hypothesis, while necessary, is not sufficient. It is clear that the dopaminergic and autoimmune mechanism are also implicated in the pathogenesis of OCD. Further studies are required to understand the relevance of the serotonergic and non-serotonergic systems in OCD, and to highlight the various possible subtypes of this intriguing disorder.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J Zohar, M Chopra, Y Sasson, R Amiaz, D Amital. 2000. Obsessive compulsive disorder: serotonin and beyond.. https://doi.org/10.3109/15622970009150571

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Dynamics of tyrosine hydroxylase mediated regulation of dopamine synthesis.

Tyrosine hydroxylase's catalysis of tyrosine to dihydroxyphenylalanine (DOPA) is the highly regulated, rate-limiting step catalyzing the synthesis of the catecholamine neurotransmitter dopamine. Phosphorylation, cofactor-mediated regulation, and the cell's redox status, have been shown to regulate the enzyme's activity. This paper incorporates these regulatory mechanisms into an integrated dynamic model that is capable of demonstrating relative rates of dopamine synthesis under various physiological conditions. Most of the kinetic equations and substrate parameters used in the model correspond with published experimental data, while a few which were not available in literature have been optimized based on explicit assumptions. This kinetic pathway model permits a comparison of the relative regulatory contributions made by variations in substrate, phosphorylation, and redox status on enzymatic activity and permits predictions of potential disease states. For example, the model correctly predicts the recent observation that individuals with haemochromatosis and having excessive iron accumulation are at increased risk for acquiring Parkinsonism, a defect in neuronal dopamine synthesis (Bartzokis et al., 2004; Costello et al., 2004). Alpha synuclein mediated regulation of tyrosine hydroxylase has also been incorporated in the model, allowing an insight into the overexpression and aggregation of alpha synuclein in Parkinson's disease.

Dopamine↗

The n-3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia.

The dopamine hypothesis of schizophrenia has been the most influential since the 1970s. Normally, the prefrontal dopamine system suppressively controls the limbic dopamine system. Since the activities of prefrontal dopaminergic neurons are reduced in schizophrenia, the suppressive effect of the prefrontal area on the limbic system is reduced, and activities of the limbic dopamine system are enhanced. Reduced activities of the prefrontal dopamine system contribute to negative symptoms and cognitive disorders, and increased activities of the limbic dopamine system induce positive symptoms. While the dopamine hypothesis explains the relationship between dopamine kinetics and psychiatric symptoms in schizophrenia, it is not a direct explanation of its etiology. The cause of the abnormal activities of dopaminergic neurons in schizophrenia and its resultant symptoms are unknown. Since the late 1980s, it has been revealed that the n-3 fatty acid concentration is reduced in the plasma and erythrocyte membranes of schizophrenic patients and that the administration of n-3 fatty acids may be effective for the treatment of schizophrenia. Whether or not n-3 fatty acid deficiency plays a direct role in schizophrenia etiology, and the mechanisms underlying their therapeutic effect have yet to be clarified. Recently, the dopamine hypothesis and n-3 fatty acid hypothesis have been suggested to represent different aspects of the same pathology of schizophrenia. In schizophrenia, the brain concentrations of certain n-3 fatty acids are decreased. In rodents, n-3 fatty acid deficiency has been shown to cause decreases in dopamine concentration, number of vesicles and D2 receptors at prefrontal presynaptic terminals. The following minireview provides a summary of findings from n-3 fatty acid deficient animal models and their relevance to schizophrenia pathology is discussed.

Dopamine↗

Phase contrast radiography of Lewy bodies in Parkinson disease.

Parkinson's disease (PD), defined as a neurodegenerative disorder, is characterized by the loss of dopaminergic neurons and the presence of Lewy bodies in neurons. Morphological study of Lewy bodies is important to identify the causes and the processes of PD. Here, we investigate a possibility of phase contrast radiography using coherent synchrotron X-rays to explore the microscopic details of Lewy bodies in thick (approximately 3 mm) midbrain tissues. Autopsied midbrain tissues of a PD patient were sliced in 3 mm thickness and then examined using synchrotron X-rays from the 7B2 beamline of the Pohang Light Source. Refraction-enhanced phase contrast radiography and microtomography were adopted to identify dark core and dim edge of Lewy bodies in neurons. The morphology of Lewy bodies was clearly revealed by the phase contrast radiography in very thick (3 mm) midbrain tissues without any staining treatment. Three-dimensional volume rendered microtomography of the autopsied midbrain tissues demonstrates striking evidence that several Lewy bodies are agglomerated by dim edges in a neuron. We suggest that the phase contrast radiography could be a useful tool to morphologically investigate the causes or the processes in PD.

Dopamine↗