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PubMed2002

Is there a common mechanism of serotonin dysregulation in anorexia nervosa and obsessive compulsive disorder?

Numerous studies have documented increased rates of comorbidity in patients with anorexia nervosa (AN) or obsessive compulsive disorder (OCD). The interaction of many possible factors influences this comorbidity, but one possible explanation involves the neurotransmitter serotonin, which is widely distributed in the brain and has been implicated in a number of psychological behaviours. Although low serotonin levels have been found in patients with impulsive and aggressive behaviour, high levels have been correlated with obsessive and compulsive behaviour. In an attempt to further our understanding of this relationship, a large number of studies have measured serotonin levels throughout different stages of illness in both AN and OCD; furthermore, serotonin challenge studies and drug treatment trials have provided further support for this theory. This paper discusses the evidence supporting the view that the obsessive behaviour characteristic of AN and OCD may be partially due to a dysregulation in the serotonergic system.

Anorexia Nervosa↗
PubMed2006

Obsessive-compulsive disorder and personality disorder: evidence from the British National Survey of Psychiatric Morbidity 2000.

BACKGROUND: Previous studies indicate that most individuals with obsessive-compulsive disorder (OCD) have comorbid personality disorders (PDs), particularly from the anxious cluster. However, the nature and strength of this association remains unclear, as the majority of previous studies have relied heavily on clinical populations. We analysed the prevalence of screen positive personality disorder in a representative sample of adults with OCD living in private households in the UK. METHODS: A secondary analysis of data from the 2000 British National Survey of Psychiatric Morbidity. The prevalence of PD, as determined by the SCID-II questionnaire, was compared in participants with OCD, with other neuroses and non-neurotic controls. Within the OCD group we also analysed possible differences relating to sex and subtypes of the disorder. RESULTS: The prevalence of any screen positive PD in the OCD group (N=108) was 74%, significantly greater than in both control groups. The most common screen positive categories were paranoid, obsessive-compulsive, avoidant, schizoid and schizotypal. Compared to participants with other neuroses, OCD cases were more likely to screen positively for paranoid, avoidant, schizotypal, dependent and narcissistic PDs. Men with OCD were more likely to screen positively for PDs in general, cluster A PDs, antisocial, obsessive-compulsive and narcissistic categories. The presence of comorbid neuroses in people with OCD had no significant effect on the prevalence of PD. CONCLUSIONS: Personality pathology is highly prevalent among people with OCD who are living in the community and should be routinely assessed, as it may affect help-seeking behaviour and response to treatment.

Adolescent↗
PubMed2000

Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder.

RATIONALE: Non-selective serotonin (5-HT) receptor agonists like meta-chlorophenylpiperazine and MK-212 have been used to explore the role of 5-HT in obsessive compulsive disorder (OCD). The results of these studies and the findings of autoradiography and neuroimaging studies, pointed to a possible role of the 5-HT1B/1D receptor in the pathophysiology of OCD. Recently the selective 5-HT1B/1D receptor agonist sumatriptan was used to further explore the role of the 5-HT1B/1D receptor in OCD. Equivocal results with respect to the increase of obsessive compulsive symptoms in patients with OCD were reported. In one study a significant increase in plasma growth hormone (GH) concentration was observed, although sumatriptan does not pass the blood-brain barrier. OBJECTIVES: In order to further explore the role of the 5-HT1B/1D receptor in the pathophysiology of OCD, we performed this study, following the same design as Ho Pian et al. (Psychopharmacology 140:365-370). METHODS: In the present study we performed a randomized, double-blind, placebo-controlled, cross-over design with zolmitriptan (5 mg per os), a selective 5-HT1B/1D receptor agonist with better brain penetrating properties than sumatriptan. RESULTS: We could not detect any changes in obsessive compulsive symptoms, mood, or anxiety levels, although we found a (nonsignificant) increase in plasma GH levels. CONCLUSIONS: Based upon these findings, no evidence was found for a specific role of the 5-HT1B/1D receptor in OCD. It should be noted, however, that challenge studies in OCD are difficult to perform. Perhaps in the future better challenge paradigms will make it possible to further explore the role of specific receptor types in OCD.

Adult↗
PubMed1998

Sumatriptan (5-HT1D receptor agonist) does not exacerbate symptoms in obsessive compulsive disorder.

The non-selective serotonin (5-HT) receptor agonist meta-chlorophenylpiperazine (mCPP) has been reported to elicit symptoms in patients with obsessive compulsive disorder (OCD). MK-212, another non-selective 5-HT receptor agonist, does not seem to induce obsessive compulsive symptoms in OCD patients. The major pharmacological difference between mCPP and MK-212 is their affinity for the 5-HT(ID) receptor. The aim of this study was to explore the role of the 5-HT(ID) receptor in the pathophysiology of OCD, by using a challenge paradigm with the selective 5-HT(ID) receptor agonist sumatriptan (Imigran). A randomized, double-blind, placebo-controlled crossover challenge with sumatriptan (100 mg PO) was performed in 15 OCD patients. Neither the obsessive compulsive symptoms nor mood or anxiety symptoms changed significantly following sumatriptan administration as compared to placebo. Sumatriptan did induce a significant increase in plasma growth hormone (GH) levels. In the present study, no indication were found for the role of the 5-HT(ID) receptor in the pathophysiology of OCD. It should be noted, however, that sumatriptan does not readily pass the blood-brain barrier. Selective 5-HT(ID) receptors with better brain penetrating properties may shed more light on the role of this 5-HT receptor subtype in OCD.

Adolescent↗
PubMed1998

Delayed obsessive-compulsive disorder symptom exacerbation after a single dose of a serotonin antagonist in fluoxetine-treated but not untreated patients.

Enhanced serotonergic transmission may underlie therapeutic effects of serotonin reuptake inhibitors in obsessive-compulsive disorder. However, such treatment may decrease serotonin receptor responsivity. We investigated whether the serotonin antagonist metergoline would exacerbate or further improve systems in fluoxetine-responsive patients. Pilot results suggested open metergoline produced delayed symptom worsening in fluoxetine-treated patients. Fourteen patients continuing fluoxetine received metergoline and placebo (double-blind, randomized). Symptom ratings continued for 1 week afterwards. Ten unmedicated patients underwent the same procedures. Symptoms improved 4 h after both metergoline and placebo. The day after metergoline but not placebo, fluoxetine-treated patients had significantly increased anxiety, obsessions and compulsions, abating over several days. Depression was unchanged. Metergoline had no similar delayed effects in unmedicated patients. Metergoline levels were higher in fluoxetine-treated patients. These results, consistent with less conclusive earlier findings, suggest that prolonged changes in brain serotonin function underlie symptom re-emergence following administration of metergoline to fluoxetine-treated patients with obsessive-compulsive disorder.

Adult↗
PubMed1999

The effect of m-CPP on tics and obsessive-compulsive phenomena in Gilles de la Tourette syndrome.

RATIONALE: Family genetic and phenomenological studies support an interrelationship between Gilles de la Tourette syndrome (GTS) and obsessive-compulsive disorder (OCD). Some authors consider GTS as part of a serotonergically mediated cluster of OCD spectrum disorders. OBJECTIVE: To study serotonergic mechanisms in GTS, the effect of the relatively selective 5-HT2c agonist meta-chlorophenylpiperazine (m-CPP) was assessed. METHODS: We studied the behavioural effects of m-CPP on tics, obsessions, compulsions and impulsions of GTS. Twelve medication-free GTS patients (ten men, two women) were included in a single dose 0.5 mg/kg oral m-CPP challenge study with a double-blinded placebo-controlled cross-over design. Global symptom scores, target symptom scores as well as biochemical measures were followed up to 24 h after baseline. RESULTS: While m-CPP caused a significant rise in plasma cortisol and prolactin levels, no significant effects were found on the tics, obsessions and compulsions. Impulsions showed a trend to ameliorate. CONCLUSIONS: This study does not support a predominant role for 5-HT on the tics in GTS. The trend of impulsions to ameliorate after m-CPP can be interpreted as circumstantial support for impulsivity-related 5-HT hypofunctionality in GTS. However, the large variability of m-CPP plasma concentrations found in this study casts doubts upon the reliability of m-CPP as a probe for challenge studies.

Adult↗
PubMed2006

The clinical impact of mood disorder comorbidity on obsessive-compulsive disorder.

The present study examines the effect of concomitant major depressive or bipolar disorder on clinical symptoms of patients with obsessive-compulsive disorder (OCD). Forty-nine patients classified as OCD without a mood disorder, 26 classified as OCD with bipolar disorder (OCD-BD) and 42 classified as OCD with major depressive disorder (OCD-MDD) according to DSM-IV diagnostic criteria were included in the study. The groups were compared with respect to demographic variables and scores obtained on various scales. The OCD-BD group had more symmetry/exactness obsessions and ordering/arranging compulsions, and a more episodic course of illness and had better insight compared to the other two groups. Levels of anxiety, depression, disability and obsessive-compulsive symptom severity were significantly higher in the OCDMDD group. The rate of social phobia was higher in OCD-BD patients, whereas the rates of generalized anxiety disorder and simple phobias were higher in OCDMDD group. These findings suggest that comorbidity of major depressive disorder may increase the severity of OCD symptoms. On the other hand, bipolar disorder comorbidity may constitute a subgroup which is characterized by a higher rate of episodic course and better insight.

Adult↗
PubMed2005

Epidemiology and phenomenology of obsessive-compulsive disorder in non-referred young adolescents: a Polish perspective.

OBJECTIVE: The aim of this study was to investigate the frequency and phenomenology of obsessive-compulsive disorder (OCD) and subclinical OCD in a non-referred population of young Polish adolescents. METHOD: A two stage ascertainment procedure (school screening and diagnostic evaluation) was used to identify affected individuals. In the first stage, 3,100 pupils were asked to complete the Polish version of the 20-item Leyton Obsessional Inventory-Child Version (LOI-CV). In the diagnostic stage, the presence of obsessions and compulsions was assessed with the author's structured interview questionnaire based on DSM-IV and ICD-10 diagnostic criteria for OCD; the Polish version of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) was used to rate the symptom severity. RESULTS: A frequency of 0.38 % was found for OCD and 2.7 % for subclinical OCD. There was no significant difference in the phenomenology, demographic characteristic or socio-familial variables comparing the diagnosed OCD and subclinical OCD subjects. CONCLUSIONS: The identified OCD cases had characteristics similar to those of previously described clinical and non-referred samples.

Adolescent↗
PubMed2001

Long-term outcome and prognosis of obsessive-compulsive disorder with onset in childhood or adolescence.

The aim of the catch-up follow-up study is to describe the long-term outcome of obsessive-compulsive disorder (OCD) with onset in childhood and adolescence. The psychiatric morbidity in adulthood including personality disorders was assessed and predictors in childhood for the course of obsessive-compulsive symptoms were examined. The total study group consisted of the entire patient population treated for OCD at our departments for child and adolescent psychiatry between 1980 and 1991. We reassessed 55 patients personally by way of structured interviews. The mean age of onset of OCD was 12.5 years and the mean follow-up time was 11.2 years. At the follow-up investigation 71% of the patients met the criteria for some form of psychiatric disorder, while 36% were still suffering from OCD. Of the patients with a present diagnosis of OCD 70% had at least one further clinical disorder (especially anxiety and affective disorders). The most frequent personality disorders diagnosed were obsessive-compulsive (25.5%), avoidant (21.8%), and paranoid (12.7%) personality disorders. In-patient treatment, terminating treatment against advice and tics in childhood or adolescence significantly correlated with more severe OC symptoms in adulthood.

Adolescent↗
PubMed1991

A standardized behavioral group treatment program for obsessive-compulsive disorder: preliminary outcomes.

This paper provides outcome data about the efficacy of a behavioral group therapy program for obsessive-compulsive disorder (OCD). Thirty-six patients completed a 7-week outpatient treatment program which provides: (1) education about OCD and its treatment, (2) instruction in a cognitive and behavioral approach to the self-treatment of OCD and (3) guided behavioral treatment. Significant improvement in obsession, compulsion, and depression scores were observed at completion of the group and at 3 month follow-up. Significant improvement in obsessions and compulsions was observed for both patients taking anti-obsessional medications and those who did not.

Adult↗
PubMed1993

Can the Yale-Brown Obsessive Compulsive Scale be used to assess trichotillomania? A preliminary report.

Given recent conceptualizations of trichotillomania (TM) as a variant of obsessive compulsive disorder (OCD), clinician-rated measures of obsessive compulsive symptoms have been adapted for use in the assessment of TM. Although the reliability and validity of these instruments have been well-documented in patients with OCD, psychometric properties have not been examined systematically in patients with TM. Here, we evaluate the reliability and validity of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in a sample of 11 patients with a primary diagnosis of TM. Data addressed the utility of the Y-BOCS for evaluating symptoms of TM, and provided information regarding the proposed overlap between OCD and TM. Initial analyses suggested that interrater reliability, internal consistency, and test-retest reliability for the total score were adequate. However, the range of scores was somewhat restricted, and suggested in particular that interference in daily functioning from TM symptoms is quite low. Both internal consistency and test-retest reliability for the Target Behaviors subscale were inadequate, suggesting that this combined score is inappropriate for use with TM patients. Concurrent validity data using the total score were mixed, although the Y-BOCS did appear to be sensitive to change in TM symptoms over treatment. Implications for the use of the Y-BOCS with TM patients and hypothesized phenomenological differences between TM and OCD are discussed.

Adult↗
PubMed1993

Exposure with response prevention and serotonergic antidepressants in the treatment of obsessive compulsive disorder: a review and implications for interdisciplinary treatment.

A comprehensive review of controlled investigations examining the effectiveness of exposure with response prevention (ERP) and clomipramine (CMI), as well as other serotonergic anti-depressants, in the treatment of Obsessive Compulsive Disorder (OCD) was conducted. Overall, findings suggested that ERP is more effective than CMI, particularly in alleviating rituals, but CMI may be more effective in reducing obsessive compulsive behavior among individuals with concomitant severe depression, obsessions only, and overvalued ideation. In addition, the literature favors ERP in terms of side-effects and risks, dropout, and maintenance, while one advantage of drug therapy is that less time and effort are required by the therapist and patient. Directions for interdisciplinary treatment are discussed.

Antidepressive Agents↗
PubMed1994

Obsessive intrusive thoughts in nonclinical subjects. Part II. Cognitive appraisal, emotional response and thought control strategies.

This second part of the study reports on the appraisal and thought control responses of 270 students to their most upsetting intrusive thought. Multiple regression analysis revealed that belief that one could act on the intrusive thought and perceived uncontrollability of the thought were the two most important predictors of the frequency, or persistence of the distressing intrusion. Intrusions rated as very difficult to control were also associated with increased belief that one could act on the intrusion, avoidance of situations that may trigger the intrusion, reduced success with one's most typical thought control strategy and higher thought frequency. Based on the Padua Inventory Total score, high and low obsessional Ss were selected. Highly obsessional individuals reported more unwanted obsessive intrusive thoughts and rated their thoughts as significantly more frequent and believable than low obsessive individuals. The type of thought control strategy typically used was not a factor in thought frequency and controllability, nor did it differentiate between high and low obsessional groups. The results are discussed in terms of Salkovskis' cognitive model of obsessions and intrusive thoughts.

Anxiety↗
PubMed1995

Perfectionism, responsibility and obsessive-compulsive symptoms.

Although both perfectionism and responsibility have been associated with OCD at a theoretical level, responsibility has been the focus of a number of recent articles. This study was conducted in order to empirically test the relative importance of perfectionism and responsibility in Obsessive-Compulsive symptoms. Perfectionism and two measures of responsibility showed moderate correlations with Obsessive-Compulsive symptoms. A hierarchical regression analysis revealed that although responsibility accounted for more variance, perfectionism was still a significant predictor of Obsessive-Compulsive symptoms, once responsibility had been partialled out. These results suggest that although responsibility is related to OC symptoms, perfectionism is also independently associated. While responsibility has received much attention lately from OCD theorists and clinicians, perfectionism may also play a significant if underestimated role in some OC patients. The results are discussed in terms of their implications for current cognitive models and treatment procedures that give responsibility a central role in OCD. A new definition of perfectionism is also proposed.

Adult↗
PubMed1985

Gilles de la Tourette syndrome and the neurological basis of obsessions and compulsions.

Gilles de la Tourette syndrome (GTS) is a chronic neurological disorder manifested by involuntary motor tics and vocalizations. Many GTS patients also suffer from obsessions and compulsions. The clinical similarities between GTS and obsessive-compulsive disorder (OCD), their occurrence among members of the same families, and the fact that both can be observed as symptoms of known basal ganglia disturbances suggest that GTS and OCD share common neurological mechanisms. It is hypothesized that the tics and vocalizations of GTS are aberrant manifestations of simple motor programs that are spontaneously generated by the basal ganglia and that obsessions and compulsions represent more complex motor plans initiated by similar anomalous activities.

Basal Ganglia↗
PubMed1990

Clomipramine in obsessive-compulsive disorder.

The effects of clomipramine hydrochloride (CMI) versus placebo upon DSM-III-defined obsessive-compulsive disorder (OCD) were assessed in a 10-week double-blind multicenter trial and in a corresponding 1-year double-blind extension study. The NIMH global O-C scale, a 15-point ordinal severity scale, incorporating categorical features specific to OCD, was used to evaluate the severity of obsessive compulsive symptoms over the course of treatment, and a physician's rating of global therapeutic effect was used to assess overall change from baseline. In the core study, patients receiving placebo demonstrated minor and nonsystematic changes, whereas patients who received CMI had clinically and statistically significant reductions in the global severity of their disorder. Findings from the extension study were consistent with continuing efficacy for CMI, whereas corresponding data for patients receiving long-term placebo were difficult to interpret. Based upon shifts in categorical severity, symptoms for over half those patients who received CMI were rendered subclinical or within a range of normal functioning. In contast, less than 5% of patients receiving placebo had their symptoms reduced to a subclinical level. Generally, both treatments were well tolerated. Previous studies have indicated therapeutic potential for CMI in obsessive compulsive disorder. These findings confirm and extend previous observations.

Adolescent↗
PubMed1991

Childhood obsessive-compulsive disorder and cingulate epilepsy.

There are no reports of an association between obsessive-compulsive disorder and cingulate epilepsy in childhood. We report the behavioral, cognitive, and EEG findings in a young girl with medically resistant seizures and severe obsessive-compulsive symptomatology. Her scalp EEG and neuropsychological test scores suggested right frontal lobe dysfunction. The intractability of her seizures and progressive intellectual and psychosocial deterioration prompted evaluation for excisional surgery. Intracranial EEG recording demonstrated a focal seizure origin in the right anterior cingulate gyrus. Cingulotomy resulted in freedom from seizures and significant improvement in her obsessive-compulsive symptoms.

Brain Mapping↗
PubMed1993

Platelet serotonin-2 receptors in obsessive-compulsive disorder.

To examine the role of serotonin-2 (5-HT2) receptors in obsessive-compulsive disorder (OCD), we studied 5-HT2 receptors in platelets obtained from patients with OCD (n = 20) during a drug free baseline period, as well as in normal control subjects (n = 25). The maximum number of binding sites (Bmax) and the apparent dissociation constant (Kd) of 5-HT2 receptors were determined by receptor binding techniques using 125I-lysergic acid diethylamide (LSD) as radioligand. We observed that the mean Bmax of 125I-LSD binding in platelets of patients with OCD was not significantly different when compared with normal control subjects. There was also no significant difference in Kd values between patients with OCD and normal control subjects. To examine whether the baseline 5-HT2 receptors are related to the severity of illness, we determined the relationships of the baseline Bmax and Kd with baseline scores of the Hamilton Depression Rating Scale (HDRS), the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the National Institute of Mental Health (NIMH) Obsessive-Compulsive scale (GOCS). We found no significant correlation between baseline Bmax and Kd with the baseline HDRS, Y-BOCS, or NIMH-GOCS scores. Our results do not indicate abnormal 5-HT2 receptors in platelets of patients with OCD.

Adult↗