Obsessive Compulsive Disorder and Serotonin

Author: Alessandra Cultrera
Date: 19/01/2014


Alessandra Cultrera


Definition and Symptoms

OCD is a mental disorder characterized by the presence of obsessions and/or compulsions. Obsessions are recurrent and persistent thoughts, urges, or images that are experienced as intrusive and unwanted, whereas compulsions are repetitive behaviors or mental acts that an individual feels driven to perform in response to an obsession or according to rules that must be applied rigidly. While the specific content of obsessions and compulsions varies among individuals, certain symptom dimensions are common in OCD, including those of cleaning (contamination obsessions and cleaning compulsions); symmetry (symmetry obsessions and repeating, ordering and counting compulsions); forbidden or taboo thoughts (e.g. , aggressive, sexual and religious obsessions and related compulsions); and harm (e.g., fears of harm to oneself or others and related checking compulsions). Most individuals with OCD have both obsessions and compulsions. Compulsions are typically performed in reasponse to an obsession (e. g., thoughts of contamination leading to washing rituals or that somthing is incorrect leading to repeating rituals until it fells "just right"). The aim is to reduce the distress triggered by obsessions or to prevent a feared event (e. g., becoming ill). However, these compulsions either are not connected in a realistic way to the feared event (e. g., arranging items symmetrically to prevent harm to a loved one) ore are clearly excessive (e. g., showering for hours each day). Compulsions are not done for pleasure, although some individuals experience relief from anxiety or distress.

• Some related to OCD disorders are body dysmorphic disorder and hoarding disorder, trichotillomania and excoriation.


The 12-month prevalence of OCD in the United States is 1.2%, with a similar prevalence internationally (1.1%-1.8%). Females are affected at a shghtly higher rate than males in adulthood, although males are more commonly affected in childhood.

Development and Course

In the United States, the mean age at onset of OCD is 19.5 years, and 25% of cases start by age 14 years. Onset after age 35 years is unusual but does occur. Males have an earlier age at onset than females: nearly 25% of males have onset before age 10 years. The onset of symptoms is typically gradual; however, acute onset has also been reported.
If OCD is untreated, the course is usually chronic, often with waxing and waning symptoms. Some individuals have an episodic course, and a minority have a deteriorating course. Without treatment, remission rates in adults are low (e.g., 20% for those reevaluated 40 years later). Onset in childhood or adolescence can lead to a lifetime of OCD. However, 40% of individuals with onset of OCD in childhood or adolescence may experience remission by early adulthood.

More about Pediatric OCD

Neurobiological basis

The mechanism of action of the drugs effective in treating OCD ( clomipramine , a non-selective serotonin reuptake inhibitor, and the selective serotonin reuptake inhibitors [SSRIs]: citalopram, fluoxetine, fluvoxamine, sertraline and paroxetine) has given rise to the hypothesis that deficient serotonin function is a key element in the pathophysiology of OCD. These drugs block serotonin reuptake by the pre-synaptic neuron, thereby increasing serotonin availability at post-synaptic receptors. The serotonin hypothesis is also supported by the observation that m-CPP (a metabolite of trazodone), which is a partial agonist at serotonin receptor types 1A, 1D (with inhibitory function) and 2C, exacerbates OCD.


Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS) of animals, including humans.

The neurons of the Raphei nuclei are the principal source of 5-HT release in the brain. Axons of neurons in the lower raphe nuclei terminate in the spinal cord as well as the cerebellum's deep nuclei and cortex. Axons of neurons in the higher raphe nuclei terminate in 1) subcortical nuclei including the centrally located thalami; the surrounding corpus striata including the nucleus accumbens; the hypothalamus, hippocampus, and amygdala, 2) the cingulate cortex, including the cingulum, a tract of association fibers connecting the corpus callosum with the hippocampus, and 3) the neocortex.

Serotonin is natural ligand of 5-HT receptors. With the exception of the 5-HT3 receptor, a ligand-gated ion channel, all other serotonin receptors are G protein-coupled receptors that activate an intracellular second messenger cascade to produce an excitatory or inhibitory response.

Functional brain imaging studies have produced a model for pathophysiology of OCD which involves hyperactivity in certain subcortical and cortical regions. On the basis of imaging studies, it has been proposed that inappropriately increased activity in the head of the caudate nucleus inhibits globus pallidus fibers that ordinarily dampen thalamic activity. The resulting increase in thalamic activity produces increased activity in orbitofrontal cortex, which, via the cingulate gyrus, completes the circuit to the caudate and produces increased activity in the head of the caudate. This hypothesis is supported by evidence from MRI (magnetic resonance imaging) studies, which have found an abnormally small caudate in some OCD patients, and by positron emission tomography ( PET scan) studies, which have found increased metabolism in orbital frontal cortex, cingulate gyrus, and caudate, with decreases following successful treatment.

It has been hypotezised that two differents circuits, integrating each other in globus pallidus, are involved in OCD:
1) Serotoninergic hypersensitivity, due to 5-HT deficiency, causes reducted function in hippocampus, that results in hyperactivity of inhibitory transmission from paleostriatus (inhibited by hippocampus) to globus pallidus
2) Caudate hyperactivity results in an increase of inhibitory activity on globus pallidus.
The consequence of these two phenomena should be a loss of inhibition on thalamus, with activation of positive feedback on motory cortex (probably resulting in abnormal motor behaviour) and on frontal-orbital cortex (probably resulting in an increase of worries, anxiety and obsessions).

More about OCD Biological Basis and Genetics


The goals of therapy are to diminish symptoms and to ameliorate or reverse their effects on the patient's interpersonal, work place and social functioning. A modest proportion of patients will achieve freedom from significant symptoms.
A comprehensive treatment plan evolves as one gets to know the patient. Experienced clinicians will exercise their clinical judgement in tailoring the plan to their patients' needs, preferences, capacities, situation and history. For a patient with isolated, mild to moderate OCD, a combination of an SRI and exposure and response prevention in vivo is a reasonable initial strategy in most cases. In certain situations, such as the patient with low motivation or anergia secondary to major depression, medications alone may be preferable. In still other cases, medications may be needed to decrease the intensity of symptoms so that the patient can subsequently comply with behavioral treatment. There is insufficient data to draw any conclusions about the relative efficacy of medications alone, exposure and response prevention alone, and their combination, but many experienced clinicians believe that the combination offers more rapid improvement and greater protection against relapse. All patients should be guided to educate themselves through various OCD related resources.


Only one form of psychotherapy has been found in multiple controlled trials to be effective in treating OCD. It is termed exposure and response prevention (ERP). Both components, exposure to feared situations or thoughts, and the prevention of rituals, whether physical or mental, are necessary to maximize the treatment response. Clinicians can easily learn the basic principles from published sources. Most of the behavior therapy literature concerns patients with cleaning or checking rituals. Whether other OCD symptoms respond as well is yet to be determined. About 50% of patients presenting for treatment can benefit from behavior therapy without medications. About 20% to 30% are resistant to therapy and 20% drop out of treatment before achieving much benefit. At follow-up six months to three or more years after treatment, 65-75% of patients are much improved or improved, but 25% show no lasting benefit.


OCD patients are believed to have a lower level of serotonin in neural synapses than healthy persons. Given this, seretonergic agents, such as clomipramine (Anafranil), citalopram (Celexa), fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine (Luvox) have been used extensively to treat OCD in both adults and youths. The Food and Drug Administration (FDA) has approved only clomipramine, fluoxetine, fluvoxamine, and sertraline for use in youth.
More about clomipramine and its 3D structure.
More about fluoxetine and its 3D structure.

More about Pharmacological treatment

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2014-01-19T17:40:11 - Alessandra Cultrera
2014-01-19T15:59:05 - Alessandra Cultrera
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