In vivo PET study of 5HT2A serotonin and D2 dopamine dysfunction in drug-naive obsessive-compulsive disorder

Perani, Daniela; Garibotto, Valentina; Gorini, Alessandra; Moresco, Rosa María; Henin, Marta; Panzacchi, A.; Matarrese, Mario; Carpinelli, A.; Bellodi, Laura; Fazio, Ferruccio

doi:10.1016/j.neuroimage.2008.04.233

Cited by 175 publications

(118 citation statements)

References 52 publications

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Section: Aims Of the Studymentioning

confidence: 99%

“…Whereas resistant OCD is typically explained by serotonin mechanisms, another neurobiological mechanisms are involved [5]. For example, in some patients, dopaminergic hyperactivity modulated by an underlying serotonergic hypo activity has been suggested [6].Antipsychotics have been suggested as second-line treatment in resistant OCD with a controversial effectiveness [7]. At first sight, risperidone's effectiveness in resistant OCD [8] seems paradoxical: if OCD is conceived as a serotonin deficiency, the coprescription of a 5-HT antagonist with a SSRI should worsen OCD symptomatology.…”

mentioning

confidence: 99%

“…part of the striatum, involved in the maintainance of an inhibitor tone of dopaminergic transmission which regulates the balance between the direct and indirect dopaminergic pathways described above [6].…”

mentioning

confidence: 99%

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Neurobiology and Effectiveness of Antipsychotic Drugs in Resistant Obsessive-Compulsive Disorder: A Systematic Review

Ducasse¹,

Fond²,

Mondor³

2013

J Depress Anxiety

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Aims of the StudyTo synthesize in a comprehensive review, the mechanistic hypotheses of antipsychotic potential activity in OCD and to summarize clinical trials on the effectiveness of antipsychotic drugs in OCD, in monotherapy or in combination with SSRIs.A systematic review of the literature was conducted using PRISMA criteria. The paradigm search was "obsessive compulsive disorder and antipsychotic agents". Medline, Cochrane and Web of science databases were explored without date or language restriction. Case reports, open label studies and randomized double-blind controlled trials were included in the qualitative review.Unlike the classical serotonergic hypothesis, OCD may result from striatal dopaminergic hyperactivity, modulated in some patients by an underlying serotonergic hypo activity. In the treatment of resistant OCD, most studies report the effectiveness of first-generation antipsychotic (haloperidol, amisulpride) and some second-generation antipsychotics (risperidone, olanzapine, aripiprazole, quetiapine) in combination with an SSRI. Moreover, in case reports, recrudescence or onset of OCD symptoms in patients with schizophrenia have been described in a switch from first generation antipsychotic medication to olanzapine, risperidone, aripiprazole or clozapine, but not within a switch to amisulpride or quetiapine.These preliminary results on the use of antipsychotic medication in OCD deserve further investigation for potential guideline updates.Obsessive-Compulsive Disorder (OCD) is "the presence of recurrent ego-dystonic and intrusive thoughts or images (obsessions), with ritualized behaviors (compulsions) performed in order to neutralize obsessive thoughts" [1]. The lifetime prevalence of OCD in France in 2006 was 2 to 3%, its prevalence over a period of 6 months was 1 to 2% and the sex ratio is 1 [2]. In the USA, in 2005, OCD was recognized as a fairly common psychological disorder with reported lifetime prevalence between 1.6 and 3.3%, and 1 year prevalence between 1.0 and 2.1% "Resistant OCD" may be defined as OCD whose symptoms persist after treatment by SSRIs in high doses for at least 8 weeks [2]. The SSRI response-rate is only 40% to 60% of patients [4]. Whereas resistant OCD is typically explained by serotonin mechanisms, another neurobiological mechanisms are involved [5]. For example, in some patients, dopaminergic hyperactivity modulated by an underlying serotonergic hypo activity has been suggested [6].Antipsychotics have been suggested as second-line treatment in resistant OCD with a controversial effectiveness [7]. At first sight, risperidone's effectiveness in resistant OCD [8] seems paradoxical: if OCD is conceived as a serotonin deficiency, the coprescription of a 5-HT antagonist with a SSRI should worsen OCD symptomatology. Moreover, low doses of risperidone (<3 mg/d) have found to be the best effective where the anti-5-HT2A activity is optimal with a very low anti-D2 activity [9,10]. Finally, some second-generation antipsychotics have been involved in de novo OCD genesis in psyc...

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Section: Aims Of the Studymentioning

confidence: 99%

mentioning

confidence: 99%

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Neurobiology and Effectiveness of Antipsychotic Drugs in Resistant Obsessive-Compulsive Disorder: A Systematic Review

Ducasse¹,

Fond²,

Mondor³

2013

J Depress Anxiety

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“…Several evidences of dopamine dysregulation in OCD have also been found in humans. An indirect strong evidence of the role of dopamine in OCD is provided by some neurological diseases associated with dopaminergic dysfunction such as Tourette's syndrome, Sydenham's chorea and Parkinson disease, which often show obsessive-compulsive symptoms in their clinical presentation (Lochner et al, 2005;Pauls et al, 1986Pauls et al, , 1995; in addition, Tourette's Syndrome and OCD are supposed to share common neurobiological underpinnings and genetic factors, due to the fact that they are described as comorbid, mainly in the childhood-onset forms (Perani et al 2008). Moreover, the increase in synaptic dopamine levels due to the effect of drugs such as cocaine and amphetamines h a v e b e e n r e p o r t e d t o e x a c e r b a t e o r i n d u c e a s w e l l a s t o i m p r o v e O C D s y m p t o m s (Westemberg et al 2007).…”

Section: Dopaminergic Agentsmentioning

confidence: 99%

“…Also neuroimaging studies provide interesting data about the dopamine involvement in OCD. Recently Perani et al (Perani et al 2008) conducted a positron emission tomography (PET) study in drug-naïve OCD patients, measuring both serotonin (5HT2A) and dopamine (D2) receptors distribution in vivo. The observed reduction of D2 receptors binding potential suggests a dopaminergic dysfunction, in particular in the ventral portion of striatum.…”

Section: Dopaminergic Agentsmentioning

confidence: 99%

The Treatment of Obsessive-Compulsive Disorder and the Approaches to Treatment Resistance

Pallanti¹,

Grassi²,

Cantisani³

2011

Different Views of Anxiety Disorders

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Influence of Compulsivity of Drug Abuse on Dopaminergic Modulation of Attentional Bias in Stimulant Dependence

Ersche

Bullmore²,

Craig³

et al. 2010

Arch Gen Psychiatry

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Context There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges. Objective To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D2/D3 receptor antagonist and agonist challenges. Design Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging. Setting Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England. Participants Stimulant-dependent individuals (n=18) and healthy volunteers (n=18). Interventions Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions. Main Outcome Measures Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire. Results Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups. Conclusions Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation by dopaminergic challenges.

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In vivo PET study of 5HT2A serotonin and D2 dopamine dysfunction in drug-naive obsessive-compulsive disorder

Cited by 175 publications

References 52 publications

Neurobiology and Effectiveness of Antipsychotic Drugs in Resistant Obsessive-Compulsive Disorder: A Systematic Review

Neurobiology and Effectiveness of Antipsychotic Drugs in Resistant Obsessive-Compulsive Disorder: A Systematic Review

The Treatment of Obsessive-Compulsive Disorder and the Approaches to Treatment Resistance

Influence of Compulsivity of Drug Abuse on Dopaminergic Modulation of Attentional Bias in Stimulant Dependence

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