Platelet [3H]paroxetine binding in patients with OCD-related disorders

Marazziti, Donatella; Dell’Osso, Liliana; Presta, S.; Pfanner, Chiara; Rossi, Alessandra; Masala, I.; Baroni, Stefano; Giannaccini, Gino; Lucacchini, Antonio; Cassano, Giovanni Battista

doi:10.1016/s0165-1781(99)00102-x

Cited by 39 publications

(18 citation statements)

References 25 publications

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“…Marazziti et al (1999) studied platelet 5-HT transporter binding density in a group of 6 patients with BDD, 5 with impulse dyscontrol, 5 with kleptomania, 6 with Tourette's syndrome, and 1 with trichotillomania ("OCD-related disorders") and compared them to 20 patients with OCD and 20 healthy subjects (Marazziti, Dell'Osso, & Presta, 1999). They found significantly lower platelet 5-HT transporter binding density in the OCD and OCD-related disorders compared to controls, suggesting a shared abnormality at the level of the presynaptic 5-HT transporter.…”

Section: Neurochemistry Of Bddmentioning

confidence: 99%

The pathophysiology of body dysmorphic disorder

2008

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Body dysmorphic disorder (BDD) is an often severe and disabling condition, affecting up to 2% of the population. Despite its prevalence and clinical significance, very little is known about the pathophysiology of BDD. However, clues to its possible neurobiological substrates and abnormalities in information processing are starting to emerge. This article reviews findings from genetic, brain lesion, neuroimaging, neuropsychological, and psychopharmacological studies that have allowed us to develop a tentative model of the functional neuroanatomy of BDD. There is likely a complex interplay of dysfunctions in several brain networks underlying the pathophysiology of BDD. A combination of dysfunctions in frontal-subcortical circuits, temporal, parietal, and limbic structures, and possibly involving hemispheric imbalances in information processing, may produce both the characteristic symptoms and neurocognitive deficits seen in BDD. An improved understanding of the pathophysiology of BDD will be crucial to guide the development of better treatments.

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Section: Neurochemistry Of Bddmentioning

confidence: 99%

The pathophysiology of body dysmorphic disorder

2008

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“…These findings seem somewhat disparate but can be accommodated by overarching theories of corticostriatal circuitry dysfunction [56]. Neurochemical and neuroendocrine findings in OCD have been weaker and more inconsistent [57] and generally are understudied in other OC spectrum conditions, with some notable exceptions [58]. Whereas research on the neurobiology of the OCSDs is increasing [59], until more systematic studies are conducted, neurobiologic support for membership in the OC spectrum remains qualified.…”

Section: Neurobiologymentioning

confidence: 99%

The obsessive-compulsive spectrums

Phillips

2002

Psychiatric Clinics of North America

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The obsessive-compulsive (OC) spectrum is a fascinating concept that has captured the interest of researchers and clinicians alike. Although it has compelling merits, it is also controversial and bedeviled by many unresolved questions. For example, what disorders should be included in this spectrum? Should the Diagnostic and Statistical Manual of Mental Disorders (DSM) be reorganized to include a section of OC spectrum disorders (OCSDs) that includes obsessivecompulsive disorder (OCD) and putative spectrum disorders? How should we treat these disorders' delusional variants?This article addresses treatment approaches implied by this spectrum concept and the pros and cons of including this putative grouping of disorders in future editions of DSM. It also addresses two hypothesized spectrums that might be considered "subspectrums" of this OC spectrum. One spectrum, the compulsive/impulsive spectrum, views the OC spectrum along a dimension that ranges from compulsivity to impulsivity. The other is the delusionality spectrum, which is highly relevant to conceptualizations of the OC spectrum and other disorders (eg, the mood disorders). It has received far less attention than the OC spectrum itself or the compulsivity/ impulsivity spectrum, however. The delusionality spectrum poses particularly interesting classification dilemmas that will be addressed during the DSM-V process, and it has important and surprising implications for the treatment of OCD and certain OCSDs. Although other OC spectrums and subspectrums have been proposed, such as a "cognitive-motoric" dimension, which is a subspectrum that conceptualizes OCSDs as ranging from primarily obsessional to primarily motoric [1], these spectrums and subspectrums have received less attention than the others and are not discussed in this article.The following case highlights the clinical relevance of the spectrum concepts on which this article focuses and some of the theoretical and scientific issues they raise. CaseMr. A., a 47-year-old divorced white man, was obsessed with minor acne scars on his face, especially those on the bridge of his nose. Although he looked normal, he believed that the marks made him look like a monster and "as ugly as the Elephant Man." Mr. A. was occasionally able to acknowledge that his skin might look normal and that his view of his appearance might be distorted, but he was usually "100% convinced" that his belief was accurate. In addition to thinking about these perceived flaws for at least 10 hours a day, he performed repetitive behaviors, such as mirror checking and applying makeup to cover the marks. Mr. A. also had time-consuming and distressing obsessions that focused on whether he had placed various objects in exactly the right place, and he spent hours every day rearranging them. Mr. A. also had vocal and motor tics that consisted of repetitive hand movements,

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“…After release from synaptic terminals, serotonin (5-HT) is removed from the synaptic cleft by the serotonin transporter (5-HTT), which is encoded by the SLC6A4 gene. Some studies have found reduced 5-HTT binding activity on the platelets of patients with OCD relative to normal controls [Flament et al, 1987;Sallee et al, 1996;Marazziti et al, 1999], suggesting a possible role for this transporter in OCD.A well-characterized 44-bp insertion/deletion polymorphism (5-HTTLPR) in the promoter region of the SLC6A4 gene has been found to influence transcriptional activity in platelet studies and thence the amount of protein made and presumably efficiency with which 5-HT is removed from the synaptic cleft. The long variant (l-allele) of the gene is more than twice as efficiently transcribed as the short variant (s-allele) and therefore leads to more efficient reuptake of 5-HT Lesch et al, 1996;Cavallini et al, 2002].…”

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confidence: 99%

Association of the serotonin transporter polymorphism and obsessive‐compulsive disorder: Systematic review

Bloch

Landeros-Weisenberger

Sen

et al. 2008

American J of Med Genetics Pt B

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We investigated the association between the long (l) and short (s) alleles of the serotonin transporter polymorphism (5-HTTLPR) in the promoter region of the SLC6A4 gene and obsessive-compulsive disorder (OCD) using meta-analysis to combine all published data from case-control and family based association studies (2,283 cases). In stratified meta-analysis we investigated whether age of sample (child and adult), ethnicity (Caucasian and Asian) and study design (case-control and family-based association studies) moderated any association. In the overall meta-analysis we found no evidence of association between genetic variation at the 5-HTTLPR locus and OCD. We did find significant heterogeneity between studies. In the stratified meta-analyses, we demonstrated a significant association between the l-allele and OCD in family-based association studies and in studies involving children and Caucasians. Our meta-analysis suggests the possibility that the l-allele may be associated with OCD in specific OCD subgroups such as childhood-onset OCD and in Caucasians. Further meta-analyses based on individual patient data would be helpful in determining whether age of OCD onset, gender and the presence of comorbid illness (e.g., tics) moderates the relationship between 5-HTTLPR and OCD.

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Platelet [3H]paroxetine binding in patients with OCD-related disorders

Cited by 39 publications

References 25 publications

The pathophysiology of body dysmorphic disorder

The pathophysiology of body dysmorphic disorder

The obsessive-compulsive spectrums

Association of the serotonin transporter polymorphism and obsessive‐compulsive disorder: Systematic review

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