Anxiety Disorders: Mundo E

Bareggi SR, Mundo E, Dell'Osso B, Altamura AC. · University of Milan, Department of Pharmacology, Via Vanvitelli 32, 20129 Milano, Italy. · Expert Opin Drug Metab Toxicol. · Pubmed #17916059 No free full text.

Abstract: Escitalopram, the active (S)-enantiomer of citalopram, has been approved in many countries throughout the world for the treatment of depression and anxiety disorders. It is more potent and selective than citalopram in inhibiting serotonin re-uptake in the CNS, and less potent than various other selective serotonin re-uptake inhibitors in relation to other transporter proteins and receptors: in particular, it is six times less potent than citalopram in binding to the histamine H1 and muscarinic receptors. Escitalopram has favourable pharmacokinetics: it is rapidly absorbed, has a bioavailability of 80% and is not affected by food intake. It has little potential for drug interactions: it has low protein binding and, as it is metabolised by three CYP isozymes, any impairment in the activity of one is unlikely to have a significant effect on metabolic clearance. Caution is necessary only when it is coadministered with drugs metabolised by CYP2D6, such as metoprolol, or administered to the elderly or patients with severe hepatic or renal impairment. The multiple-dose pharmacokinetics of oral escitalopram are proportional at a range of doses including its therapeutic doses. Escitalopram is approved for the treatment of a number of anxiety disorders. It seems to be well tolerated and induces few or no discontinuation symptoms, and may be considered a first-line agent for the pharmacotherapy of obsessive-compulsive disorder, generalised anxiety disorder, panic disorder and social phobia. Further studies are needed to define its activity in impulse control disorders.

Dell'Osso B, Altamura AC, Mundo E, Marazziti D, Hollander E. · Department of Psychiatry, Compulsive, Impulsive and Anxiety Disorders Program, Mount Sinai School of Medicine, New York, NY, USA. · Int J Clin Pract. · Pubmed #17229184 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) is currently recognised as one of the most common psychiatric disorders as well as one of the most disabling of all medical disorders. Obsessive-compulsive related disorders (OCRDs), often comorbid with OCD, include many distinct psychiatric conditions (i.e. some somatoform disorders, eating disorders, impulse control disorders and some neurological conditions) which have overlapping symptoms and compulsive qualities with OCD. Although effective treatments exist, OCD and related disorders are often underdiagnosed and undertreated. Serotonin reuptake inhibitors (SRIs) and cognitive behavioural therapy (CBT) represent the first-line treatment for OCD and related disorders. However, the time and the doses of the medications used in the treatment of OCD and related disorders differ from those recommended in depressive disorders. In addition, remission is not common for patients with OCD and related disorders in clinical practice, and poor responders as well as refractory cases may benefit from different treatment strategies including integrated treatment, pharmacological augmentation and brain stimulation techniques.

Altamura AC, Montresor C, Salvadori D, Mundo E. · Department of Psychiatry, Department of Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy. · Int J Neuropsychopharmacol. · Pubmed #15469668 No free full text.

Abstract: The aim of this study was to evaluate the effects of comorbid subthreshold anxiety on the course and the treatment of Depressive Disorders. The sample studied comprised four groups defined by the DSM-IV Axis I diagnosis: (1) Patients with a Major Depressive Disorder (MDD) and an Anxiety Disorder (DA); (2) patients with MDD and a subthreshold Anxiety Disorder (Da); (3) patients with subthreshold depression and an Anxiety Disorder (dA); (4) patients with subthreshold depression and subthreshold anxiety (da). HAMD, HAMA and CGI rating scales were administered monthly for 12 months while patients were treated with different antidepressants. Significant differences were found among the four groups with respect to the baseline depressive symptoms: Da presented more frequently suicidal ideation (chi2=9.568, d.f.=3, p=0.023), psychomotor retardation (chi2=12.568, d.f.=3, p=0.006), sexual dysfunctions (chi2=7.761, d.f.=3, p=0.05), hypochondriacal ideation (chi2=13.633, d.f.=3, p=0.003), weight loss (chi2=9.520, d.f.=3, p=0.023), and diurnal variation of symptoms (chi2=13.258, d.f.=3, p=0.004). With respect to the treatment response Da patients showed an overall worse response to antidepressants, having a longer latency and a lower reduction of symptoms. These results suggest that patients with Major Depression and subthreshold anxiety present with a more severe baseline clinical picture and seem to have a less efficient response to antidepressants.

Mundo E, Maina G, Uslenghi C. · Department of Neuropsychiatric Sciences, San Raffaele Hospital, University of Milan, School of Medicine, Italy. · Int Clin Psychopharmacol. · Pubmed #10759337 No free full text.

Abstract: The aim of this prospectively randomized, double-blind, parallel group, multicentre study was to compare the efficacy and tolerability of fluvoxamine and clomipramine in patients suffering from obsessive-compulsive disorder (OCD) (DSM-III-R). Fourteen centres participated in this trial. Sixty-eight patients were randomized to receive fluvoxamine and 65 to receive clomipramine. The duration of the study was 10 weeks. The two treatment groups showed a marked improvement of obsessive-compulsive symptomatology, as determined by the Yale-Brown Obsessive-Compulsive Scale, the National Institute of Mental Health Obsessive-Compulsive Global Scale and Clinical Global Impression. No statistically significant differences were found between fluvoxamine and clomipramine in terms of efficacy during the study. A similar number of patients in each group withdrew from the study prematurely, but there were more dropouts due to adverse events in the clomipramine group. Concerning tolerability, there were significantly more reports of constipation and dry mouth in the clomipramine group. The results show that fluvoxamine and clomipramine have similar efficacy in the treatment of patients suffering from OCD, but fluvoxamine is better tolerated. In view of the superior safety profile of fluvoxamine compared to clomipramine in terms of a risk-benefit assessment, the use of fluvoxamine would appear to be advantageous for this patient population.

Mundo E, Bareggi SR, Pirola R, Bellodi L. · Department of Neuropsychiatric Sciences, San Raffaele Hospital, University of Milan School of Medicine, Italy. · Biol Psychiatry. · Pubmed #10023504 No free full text.

Abstract: BACKGROUND: Previous studies on serotonergic responsivity in obsessive-compulsive disorder (OCD) showed about 50% of patients experiencing an acute worsening of OC symptoms when administered meta-chlorophenylpiperazine or i.v. clomipramine. The aim of this study was to determine what variables influence the response to acute i.v. clomipramine. Could this response be predictive of the response to chronic treatment with two serotonergic drugs with differing selectivity profiles: clomipramine and fluvoxamine? METHODS: Fifty OC patients were consecutively recruited. All underwent a challenge with 25 mg i.v. clomipramine and placebo and were administered 10-week oral clomipramine or fluvoxamine according to a double-blind design. The efficacy of the antiobsessional treatment was evaluated by Yale-Brown Obsessive-Compulsive Scale and Clinical Global Impression scale scores. RESULTS: Obsessions worsened in 42% patients as rated by change values in 100-mm visual analogue scale scores for the clomipramine vs. placebo infusion. There was a significant difference in gender distribution between "worsened" and "unchanged" patients, since female subjects were more frequently "unchanged." Thirty-one patients completed the 10-week treatment. According to both qualitative and quantitative evaluations, female subjects showed a better antiobsessional response, and this difference was enhanced in the clomipramine-treated group. CONCLUSIONS: Results suggest a role for reproductive hormones in the pathophysiology or treatment of OC patients.

Altamura AC, Dell'Osso B, Buoli M, Zanoni S, Mundo E. · Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy. · J Clin Psychopharmacol. · Pubmed #18626267 No free full text.

Abstract: The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%, respectively, compared with pretreatment scores) were selected and randomized to citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous augmentation. The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs. Analyses of variance with repeated measures on HAM-D(21), collected daily in blind-raters design, were performed to detect any change of depressive symptoms between the 3 groups. In addition, the number of responders and remitters was computed in the 3 groups of treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo, with a superiority of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on anxiety-somatization symptoms (P = 0.027). The number of responders was significantly superior in the active treatment groups versus the placebo group ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to anxiety-somatization symptoms. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results, and larger randomized controlled trials are warranted to confirm the present findings.

Altamura AC, Dell'osso B, D'Urso N, Russo M, Fumagalli S, Mundo E. · Department of Psychiatry, University of Milan, Milan, Italy. · CNS Spectr. · Pubmed #18496479 links to  free full text

Abstract: INTRODUCTION: The aim of the present study was to investigate the impact of the duration of untreated illness (DUI)-defined as the time elapsing between the onset of generalized anxiety disorder (GAD) and the first adequate pharmacologic treatment-on treatment response and clinical course in a sample of subjects with GAD. METHODS: One hundred patients with GAD, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria, were enrolled and their main demographic and clinical features collected. Patients were then treated with selective serotonin reuptake inhibitors or venlafaxine for 8 weeks in open-label conditions. Treatment response and other clinical variables were analyzed after dividing the sample into two groups according to DUI (DUI <or=12 months and DUI >12 months). RESULTS: When the DUI was computed with respect to the first antidepressant treatment (DUI-AD), a higher improvement (Clinical Global Impressions-Severity of Illness scale) after the pharmacologic treatment was found in the group with a shorter DUI (analysis of variance with repeated measures: time effect F=654.975, P<.001; group effect: F=4.369, P=.039). When computed with respect to the first treatment with benzodiazepines (DUI-BDZ), the two groups did not show any significant difference in treatment response (time effect: F=652.183, P<.001; group effect: F=0.009, P=.924). In addition, patients with a longer DUI (DUI-BDZ or DUI-AD) showed an earlier age at onset, a longer duration of illness and a higher rate of comorbid psychiatric disorders with onset later than GAD. CONCLUSION: Results from this preliminary study seem to suggest that a shorter DUI-AD may determine a better response to pharmacologic treatment in patients with GAD, and that a longer DUI (DUI-BDZ and DUI-AD) may be associated to a worse clinical course. Further investigation on the relationship between DUI and GAD is needed.

Dell'osso B, Mundo E, Marazziti D, Altamura AC. · Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy. · J Psychopharmacol. · Pubmed #18208931 No free full text.

Abstract: Obsessive compulsive disorder (OCD) is a chronic disorder, currently recognized as one of the most common psychiatric disorder as well as one of the most disabling of all medical disorders. OCD is characterized by high rates of partial and/or absent response to standard, recommended treatments (serotonin reuptake inhibitors and psychotherapy). Recent investigation showed that Venlafaxine, a dual serotonin and norepinephrine reuptake inhibitor (SNRI), may be a valid alternative for some treatment-refractory patients. We present the cases of four OCD patients with comorbid mood or anxiety disorders, who were treated with serotonin reuptake inhibitors (SRIs) at adequate doses for at least 12 weeks, showing partial/no response. Patients were then switched to Duloxetine up to 120 mg/day and followed up for 12 weeks. Three out of four patients showed a Yale-Brown Obsessive Compulsive Scale(Y-BOCS) score reduction >or=35%. Duloxetine may be helpful in patients with treatment-resistant OCD, although larger and controlled studies are warranted to confirm this preliminary observation.

Dell'Osso B, Mundo E, Altamura AC. · Department of Psychiatry and Clinical Sciences "Luigi Sacco", University of Milan, Milano, Italy. bernardo.dell' · CNS Spectr. · Pubmed #17075559 links to  free full text

Abstract: Obsessive-compulsive disorder (OCD) is a relatively common, often chronic and disabling disorder with high rates of partial and/or absent response to standard, recommended treatments, such as selective serotonin reuptake inhibitors (SSRIs) and psychotherapy. This article presents the cases of four patients suffering from OCD and comorbid mood or anxiety disorders, who were treated with SSRIs at adequate doses for at least 12 weeks, showing a partial response. Quetiapine treatment was added to SSRIs at a dose of 25 mg/day and titrated up to 200 mg/day. Patients were followed up for 6 months. After 12 weeks, all the patients were classified as "much improved" on the Clinical Global Impression-Improvement scale and showed a Yale-Brown Obsessive-Compulsive Scale score reduction > or =35%. After 6 months of follow-up, all the patients maintained the same level of improvement. Although quetiapine augmentation to SSRIs has shown mixed results in published controlled trials in the acute treatment (12 weeks) of patients with treatment-resistant OCD, this case series indicates that patients who benefit from this pharmacologic regimen in the acute phase tend to maintain such an improvement. Larger follow-up studies are warranted to confirm our findings.

Arnold PD, Rosenberg DR, Mundo E, Tharmalingam S, Kennedy JL, Richter MA. · Child Psychiatry Program, Neurogenetics Section, 1st Floor, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8. · Psychopharmacology (Berl). · Pubmed #15083261 No free full text.

Abstract: RATIONALE: Recent investigation suggests that a reversible glutamatergically mediated thalamocortical-striatal dysfunction may serve as a reliable pathophysiological and treatment response marker for obsessive-compulsive disorder (OCD). We postulated that N-methyl- d-aspartate (NMDA) receptors were involved in OCD, and specifically that polymorphisms in the 3' untranslated region of GRIN2B (glutamate receptor, ionotropic, N-methyl- d-aspartate 2B) were associated with OCD in affected families. OBJECTIVES: The objective of this investigation was to test the association between GRIN2B variants and transmission of the OCD trait using a family-based design. METHODS: Using the Family Based Association Test (FBAT), we tested for association with OCD diagnosis in 130 families, and also performed a haplotype analysis. FBAT was additionally used in a subset of 98 families to test for association with the quantitative phenotype of lifetime OCD symptom severity. RESULTS. Under a non-additive model of inheritance, the 5072T/G variant was significantly associated with OCD even after correcting for the number of models tested ( P=0.014). In addition, there was a significant positive association with OCD diagnosis ( P=0.002) for the 5072G-5988T haplotype under the recessive model. CONCLUSIONS: Although preliminary and requiring replication in larger samples, these results provide evidence that GRIN2B may be associated with susceptibility to OCD. Coupled with basic neuroscience and clinical neuroimaging findings in patients with OCD, our results provide new and converging support for the role of altered glutamatergic neurotransmission in the pathogenesis of OCD.

Altamura AC, Bassetti R, Santini A, Frisoni GB, Mundo E. · Department of Psychiatry and Clinical Sciences Luigi Sacco, University of Milan, Via G.B. Grassi 74, Milan 20157, Italy. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #14751432 No free full text.

Abstract: In this study, the authors investigated if CNS degenerative abnormalities could correlate with depressive symptoms in elderly patients, if the presence of mild/moderate cognitive impairment could be related to the response to treatment and the role of peculiar clinical features in influencing the response to treatment. Fifty-three patients (60-75 years) diagnosed as affected by late onset (after 60 years) Major Depressive Episodes according to DSM-IV criteria were studied. Brain vascular and degenerative markers were assessed by computed tomography (CT) through measurements of a lateralized version of the bifrontal index and a rating scale addressing subcortical disease. The presence of mild/moderate cognitive impairment [(24-28 total score at the Mini-Mental State Examination (MMSE)], and of specific symptoms were assessed at baseline and evaluated with respect to the antidepressant response. Patients with CT abnormalities showed higher baseline scores on Hamilton Rating Scale for Depression (HAM-D) items "late insomnia" (t=-2.674, P=.002), "somatic symptoms" (t=-3.355 P=.002), and Brief Psychiatric Rating Scale (BPRS) item "emotional withdrawal" (t=-3.355, P=.002). No significant correlation was found between the vascular index and baseline clinical symptoms, while the HAM-D "depressed mood" item was negatively correlated to the right frontal index (R=-0.692, P=.006). Patients with CT abnormalities showed a lower reduction of HAM-D total scores than patients with normal CT (time effect: F=29.277, P<.0001; group effect: F=5.154, P<.03), while a significant reduction of symptoms in time (time effect: F=33.33, P<.0001) but no differences between groups were found on Hamilton Rating Scale for Anxiety (HAM-A). Both patients with and without mild cognitive impairment improved on the HAM-D (time effect: F=19.668, P<.0001), BPRS (time effect: F=18.345, P<.0001), and HAM-A (time effect: F=17.959, P<.0001) total scores. Patients with emotional withdrawal showed lower improvement on BPRS total scores (time effect: F=26.946, P<.0001; group effect: F=5.121, P<.03). The results from this study showed that patients with baseline emotional withdrawal and CT abnormalities have poorer outcome. Further investigations on larger samples are needed to confirm these findings.

Carter TD, Mundo E, Parikh SV, Kennedy JL. · Neurogenetics Section, R-31, Centre for Addiction and Mental Health, Dept. of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, Canada M5T 1R8. · J Psychiatr Res. · Pubmed #12765852 No free full text.

Abstract: The primary aim of our study was to investigate the effect of the age at onset (AAO) of Bipolar Disorder (BP) on the clinical course of the illness. We studied 320 subjects with a diagnosis of BP I or BP II who had been previously recruited for a genetic research protocol. All subjects gave their informed consent to participate in the study. Each subject was interviewed using the SCID I. The main clinical variables were compared between subjects with early (</=18 years) and later (>/=18 years) age at onset of BP (chi square tests and t-tests for independent samples). In addition, a logistic regression analysis was applied to the variables that were significantly related to earlier onset of BP in the exploratory analyses. We found a significantly earlier AAO in subjects with anxiety disorders (t=2.44, P=0.015) and rapid cycling course (t=3.16, P=0.002). When we compared a number of clinical characteristics between early and later onset of BP, subjects with early AAO had more frequent suicidal ideation/attempts (chi(2)=12.12, P=0.002), Axis I comorbidity (chi(2)=8.12, P=0.004), substance use disorders (chi(2)=5.45, P=0.019) and rapid cycling course (chi(2)=9.87, P=0.002). The Odds Ratios associated with these variables were: 1.407 (suicide ideation), 1.646 (Axis I comorbidity), 1.468 (substance abuse), and 2.082 (rapid cycling course). Overall, these results suggest a role of early AAO as a significant predictor of poor outcome in BP and, if replicated, they may have important clinical implications.

Mundo E, Richter MA, Zai G, Sam F, McBride J, Macciardi F, Kennedy JL. · Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada. · Mol Psychiatry. · Pubmed #12192628 links to  free full text

Abstract: Obsessive-Compulsive Disorder (OCD) is a psychiatric condition with strong evidence for a genetic component and for the involvement of genes of the serotonin system. In a recent family-based association study we reported an association between the G allele of the G861C polymorphism of the 5HT1Dbeta receptor gene and OCD. The aim of the present study was to further investigate for the presence of linkage disequilibrium between each of two polymorphisms of the 5HT1Dbeta receptor gene and OCD in a larger sample of OCD families. In a total of 121 families the G861C and the T371G polymorphisms of the 5HT1Dbeta receptor gene were genotyped using standard protocols. The genotyping data were analyzed with a new extension of the Transmission Disequilibrium Test (FBAT). The phenotypes considered in the analyses were the diagnosis of OCD and two quantitative phenotypes related to the diagnosis and clinically relevant, ie, the age at onset and the severity of OCD symptoms. We confirmed the previously found preferential transmission of the G861 allele to the affected subjects (z = 2.262, P = 0.02). No significant association was found between the polymorphism and the quantitative phenotypes considered. These results represent a confirmation of our previous published study and thus, could have important implications for the role of the 5HT1Dbeta receptor gene in the pathogenesis and treatment of OCD. Further genetic investigations on this marker considering additional polymorphisms and other quantitative phenotypes related to OCD are warranted.

Pirola R, Mundo E, Bellodi L, Bareggi SR. · Department of Pharmacology, University of Milan, Via Vanvitelli 32, I-20129, Milan, Italy. · J Chromatogr B Analyt Technol Biomed Life Sci. · Pubmed #12007764 No free full text.

Abstract: Clomipramine (CMI) is a typical tricyclic antidepressant with a wide clinical spectrum, being used in major depressive, panic and obsessive-compulsive disorders. The relationship between clinical response and plasma levels of clomipramine and its N-desmethylated (N-desmethylclomipramine, DMCMI) and hydroxy-metabolites remains unclear. In particular, limited information is available on the correlation with clinical response in patients with obsessive-compulsive disorder (OCD). This study describes a new sensitive method to simultaneously determine CMI and its major N-desmethylated and hydroxy-metabolites present in human plasma by HPLC with a UV detector. After a solid-phase extraction from plasma (Isolute C2 columns) the separation of the compounds was performed on a Lichrospher CN column (250 x 4 mm, 5 microm with a 2-cm pre-column) by an eluent consisting of 10 mM K(2)HPO(4)-acetonitrile-methanol (35:25:40 v/v/v) at a flow of 1.5 ml/min. UV detector was set at 214 nm. The lower limit of quantification for all the analytes was at least 5 ng/ml. The coefficients of variation ranged between 2.0 and 4.9% with recovery rates between 97.0 and 100.3%. Linear regression analyses showed correlation coefficients between 0.98 and 0.99. This method is simple, fast and reliable with good specificity and sensitivity. Solid phase extraction is efficient and rapid, allowing the extraction of several plasma samples on the same day and may therefore be usefully and realistically applied in the clinical context. We thus investigated the relevance of plasma levels of CMI and its metabolites as a predictor of clinical outcome in a group of 15 patients with OCD.

Altamura C, Paluello MM, Mundo E, Medda S, Mannu P. · Psychiatry, University of Milan, Italy. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #11697569 No free full text.

Abstract: BACKGROUND: The aim of the study was to define the main demographic and clinical characteristics of Body Dysmorphic Disorder (BDD) and subclinical BDD (sBDD) in a sample derived by a screening survey done on a population of individuals referring to aesthetical medicine centers. METHOD: 487 subjects referring to hospital centers for aesthetical medicine were administered the SCID-I and the Yale-Brown Obsessive-Compulsive Scale adapted for BDD (BDD-YBOCS). The sample was thus sub-divided in three sub-samples: 1) BDD, 2) sub-clinical BDD, and 3) controls. The main demographic and clinical variables were considered and compared between the BDD and the sBDD samples. RESULTS: As previously reported, the prevalence of BDD and sBDD was 6.3% and 18.4%, respectively. The most frequent comorbid diagnosis in both BDD and sBDD patients and their relatives was Obsessive-Compulsive Disorder (OCD). A higher severity of symptoms was found in male BDD patients, while no gender-related differences were found in the sBDD group. Suicidal ideation was found in 12.1% of the sBDD and in 49.7% of the BDD patients. CONCLUSIONS: These results support the hypothesis of BDD and sBDD belonging to the OCD spectrum, and appear to advise long-term follow-up studies on the course and the prognosis of sBDD.

Mundo E, Richter MA, Sam F, Macciardi F, Kennedy JL. · Neurogenetics Section, University of Toronto, Ontario, Canada. · Am J Psychiatry. · Pubmed #10873927 links to  free full text

Abstract: OBJECTIVE: Obsessive-compulsive disorder (OCD) is a psychiatric condition for which strong evidence of a genetic component and serotonergic system involvement exists. Recent studies have shown that sumatriptan, a selective ligand of the serotonin (5-HT)(1Dbeta) autoreceptor, modifies OCD symptoms. The aim of this study was to investigate the presence of linkage disequilibrium between the 5-HT(1Dbeta) receptor gene, which has a variant caused by a silent G to C substitution at nucleotide 861 of the coding region, and OCD. METHOD: DNA was collected from 67 probands who met DSM-IV criteria for OCD and from their living parents or siblings. Transmission Disequilibrium Test/sib-Transmission Disequilibrium Test analyses were then conducted with the DNA data. RESULTS: Thirty-two families were informative for the analysis, which showed a preferential transmission of the G allele to the affected subjects. CONCLUSIONS: If the results are confirmed, there may be important implications for the 5-HT(1Dbeta) receptor gene in the pathogenesis and treatment of OCD.

Mundo E, Pirola R, Bellodi L, Smeraldi E, Bareggi SR. · No affiliation provided · J Clin Psychopharmacol. · Pubmed #12006911 No free full text.

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