Platelet Serotonin Transporter in Children and Adolescents with Obsessive-Compulsive Disorder or Tourette's Syndrome

Sallee, Floyd R.; Richman, Harvey; Beach, Kevin; Sethuraman, Gopalan; Nesbitt, Lori A.

doi:10.1097/00004583-199612000-00017

Cited by 49 publications

(26 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As expected, the reduction in the number of 5-HTTbinding sites in OCD patients described in previous works (Bastani et al, 1991;Delorme et al, 2004;Marazziti et al, 1992Marazziti et al, , 1997Marazziti et al, , 1999Sallee et al, 1996;Weizman et al, 1992) was confirmed in our study. This appears to be the most consistent abnormality of the peripheral serotonergic system observed to date in OCD.…”

Section: Discussionsupporting

confidence: 93%

“…The 5-HT transporter (5-HTT) is a critical component of the serotonergic system and the principal site of action of the widely prescribed 5-HT reuptake inhibitors (Blier and de Montigny, 1999). Untreated OCD patients exhibit either reduced (YaryuraTobias et al, 1979) or normal (Cath et al, 2001;Delorme et al, 2004;Flament et al, 1987;Hanna et al, 1991;Insel and Winslow, 1992) whole blood or platelet 5-HT levels, whereas the binding capacity (B max ) of the platelet 5-HTT is consistently reduced, both for [ 3 H]-paroxetine (Marazziti et al, 1999;Sallee et al, 1996) and [ 3 H]-imipramine (Bastani et al, 1991;Marazziti et al, 1992;Marazziti et al, 1997;Weizman et al, 1992). Treatment with 5-HT reuptake inhibitors lowers whole blood 5-HT concentration and further decreases the number of 5-HTT-binding sites, and the magnitude of the decrease is correlated with clinical improvement (Black et al, 1990;Delorme et al, 2004;Flament et al, 1987;Hanna et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Platelet Serotonergic Markers as Endophenotypes for Obsessive-Compulsive Disorder

Delorme

Betancur

Crinon

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Although compelling evidence has shown that obsessive-compulsive disorder (OCD) has a strong genetic component, its genetic basis remains to be elucidated. Identifying biological abnormalities in nonaffected relatives is one of the strategies advocated to isolate genetic vulnerability factors in complex disorders. Since peripheral serotonergic disturbances are frequently observed in OCD patients, the aim of this study was to investigate if they could represent endophenotypes, by searching for similar abnormalities in the unaffected parents of OCD patients. We assessed whole blood serotonin (5-HT) concentration, platelet 5-HT transporter (5-HTT) and 5-HT 2A receptorbinding characteristics, and platelet inositol trisphosphate (IP 3 ) content in a sample of OCD probands (n ¼ 48) and their unaffected parents (n ¼ 65), and compared them with sex-and age-matched controls (n ¼ 113). Lower whole blood 5-HT concentration, fewer platelet 5-HTT-binding sites, and higher platelet IP 3 content were found in OCD probands and their unaffected parents compared to controls. Whole blood 5-HT concentration showed a strong correlation within families (po0.001). The only parameter that appeared to discriminate affected and unaffected subjects was 5-HT 2A receptor-binding characteristics, with increased receptor number and affinity in parents and no change in OCD probands. The presence of peripheral serotonergic abnormalities in OCD patients and their unaffected parents supports a familial origin of these disturbances. These alterations may serve as endophenotypic markers in OCD, and could contribute to the study of the biological mechanisms and genetic underpinnings of the disorder.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Platelet Serotonergic Markers as Endophenotypes for Obsessive-Compulsive Disorder

Delorme

Betancur

Crinon

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Our data also replicated previous findings of a decreased density of 3 H-Par binding sites suggestive of a presynaptic serotonergic dysfunction in OCD [25,[28][29][30][31][32][33][34]. According to our working hypothesis, a 5-HT dysfunction might determine both OCD and aggression; however, we were unable to detect any correlation between platelet 3 HPar binding and aggression in OCD.…”

Section: Discussionsupporting

confidence: 91%

“…Further evidence of alterations in the serotonergic system in OCD is provided by challenge tests with m-CPP or MK 212 [25,26], by cerebrospinal fluid measurement of 5-hydroxyindoleacetic acid, the major 5-HT metabolite [27], and platelet studies on the 5-HT transporter [25,[28][29][30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

No Correlation between Aggression and Platelet <sup>3</sup>H-Paroxetine Binding in Obsessive-Compulsive Disorder Patients

et al. 2001

View full text Add to dashboard Cite

Different findings suggest that the serotonin (5-HT) system may be involved in both the regulation of aggression and the pathophysiology of obsessive-compulsive disorder (OCD). Our study aimed to evaluate the aggressive features of a group of OCD patients and to explore possible correlations with a serotonergic marker, namely platelet 5-HT transporter. Psychopathological and biological patterns were compared with those of a group of healthy controls and those of patients with major depression. Twenty-one patients affected by OCD, 21 by depression and 21 healthy controls were included in the study. Aggressive features were measured by means of the Buss and Durkee Hostility Inventory (BDHI). The platelet 5-HT transporter was evaluated by means of the ³H-paroxetine binding parameters (maximum binding capacity, B_max and dissociation constant, K_d). The OCD patients showed a total score on the BDHI not significantly different from that of healthy controls and lower than that of depressed patients. The factor profile was similar in the 3 groups, but higher in the depressed patients. The irritability, resentment, guilt, negativism and suspiciousness factors were significantly more pronounced in depressed patients. Some sex-related difference in single factors were also observed. The B_max of ³H-paroxetine binding was lower in OCD patients than in depressives or healthy controls. OCD patients were more similar to healthy controls than to depressed patients with regard to aggressive features measured by means of the BDHI. This suggests that aggression in OCD is a complex phenomenon that probably requires specific instruments of evaluation.

show abstract

“…Similarly, results from selective breeding experiments with rats have demonstrated that platelet 5-HT content has a Serotonin Transporter and Blood Serotonin 103 marked heritable component (Jernej and Cicin-Sain 1990). Studies characterizing the platelet 5-HTT with paroxetine, a selective 5-HT transporter inhibitor, have found reduced binding capacity in OCD (Marazziti et al 1996;Sallee et al 1996). Some data have also suggested that the normal seasonal variation in platelet 5-HT content is disrupted in OCD (Brewerton et al 1993).…”

mentioning

confidence: 99%

Serotonin Transporter and Seasonal Variation in Blood Serotonin in Families with Obsessive-Compulsive Disorder

Hanna

Himle

Curtis

et al. 1998

Neuropsychopharmacology

142

View full text Add to dashboard Cite

The serotonin transporter (HTT) is a candidate gene for obsessive-compulsive disorder (OCD) that has been associated with anxiety-related traits. The long (1) and short (s) variants of theThe serotonin transporter (HTT = SLC6A4) is a plausible candidate gene for obsessive-compulsive disorder (OCD) and several other psychiatric disorders (Altemus et al. 1996;Lesch et al. 1995;Ogilvie et al. 1996). It has been associated with anxiety-related traits in two predominantly male samples (Gelernter et al. 1995;Ramamoorthy et al. 1993). A complementary deoxyribose nucleic acid (cDNA) encoding the 5-HTT in the human midbrain raphe complex has been isolated, and its identity with the human platelet serotonin (5-HT) transporter site has been demonstrated (Lesch et al. 1993a,b).HTT gene transcription is regulated by a deletion/ insertion polymorphism in the promoter (Heils et al. 1995). The long (I) and short (s) variants of this polymorphic region have different transcriptional efficiencies in transfection assays and lymphoblastoid cell lines Lesch et al. 1996). The short allele reduces the transcriptional efficiency of the HTT gene promoter, resulting in decreased 5-HTT binding and 5-HT uptake in lymphoblasts . Studies of HIT gene expression in lymphoblast cell lines from 10 subjects with different genotypes suggested that the polymorphism has more of a dominant-recessive than a codominant-additive effect, with the short variant ap-0893-133X/98/$19.00 PII S0893-133X(97)00097-3 NEUROPSYCHOPHARMACOLOGY 1998-VOL. 18, NO. 2 pearing dominant to the long variant. However, the dominant mode of action of the short allele has been questioned (Goldman 1996).Because of the small sample size in that study and the importance of the HTT, we examined the relationship between the HTT promoter variant and whole blood 5-HT concentration in 70 individuals from 20 families ascertained through children and adolescents between 10 and 17 years of age with a DSM-III-R diagnosis of OCD. Sampling through early-onset cases can be a useful strategy in identifying a more clearly genetic or homogeneous form of a disorder (Lander and Schork 1994). Family studies have demonstrated that OCD is often familial and that the morbid risk of the disorder is higher among the relatives of early-onset probands than among the relatives of late-onset probands (Bellodi et al. 1992;Pauls et al. 1995).The selective response of OCD to potent 5-HT transporter inhibitors (serotonin reuptake inhibitors, SRis) has suggested that a serotonergic abnormality may be involved in OCD (Goodman et al. 1990;Leonard et al. 1989). The 5-HTT is an initial site of action for those drugs and is crucial to the termination of serotonergic neurotransmission (Amara and Kuhar 1993). Two treatment studies of childhood OCD using clomipramine, a potent 5-HT transporter inhibitor, have demonstrated a significant correlation between clinical improvement and a marked reduction in either platelet 5-HT or whole blood 5-HT content, reflecting the effect of the drug on the platelet uptake site (F...

show abstract

Platelet Serotonin Transporter in Children and Adolescents with Obsessive-Compulsive Disorder or Tourette's Syndrome

Cited by 49 publications

References 54 publications

Platelet Serotonergic Markers as Endophenotypes for Obsessive-Compulsive Disorder

Platelet Serotonergic Markers as Endophenotypes for Obsessive-Compulsive Disorder

No Correlation between Aggression and Platelet <sup>3</sup>H-Paroxetine Binding in Obsessive-Compulsive Disorder Patients

Serotonin Transporter and Seasonal Variation in Blood Serotonin in Families with Obsessive-Compulsive Disorder

Contact Info

Product

Resources

About