Functional brain imaging and pharmacotherapy in social phobia: single photon emission computed tomography before and after treatment with the selective serotonin reuptake inhibitor citalopram.

1. Despite increased understanding of the prevalence and pharmacotherapy of social phobia (or social anxiety disorder), the neurobiology of the disorder is little understood. 2. Little data exists on the effect of pharmacotherapeutic intervention on regional cerebral blood flow (rCBF) in this disorder. Patients (n=15) who met DSM-IV diagnostic criteria for social phobia were subjected to single photon emission computed tomography (SPECT) with technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) before and after an eight-week trial of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) citalopram. 3. Pharmacotherapy led to significantly reduced activity in the anterior and lateral part of the left temporal cortex; the anterior, lateral and posterior part of the left mid frontal cortex; and the left cingulum. 4. Despite the small sample size, medication non-responders (n=6) had higher activity at baseline in the anterior and lateral part of the left temporal cortex and the lateral part of the left mid frontal regions compared with responders (n=9). These data from this exploratory study are consistent with work suggesting that the anxiety disorders share certain mediating neurocircuitry, although activity in other brain regions may differ. 5. Further research is necessary to determine the neurobiological underpinnings of social phobia.

Single photon emission computed tomography of the brain with Tc-99m HMPAO during sumatriptan challenge in obsessive-compulsive disorder: investigating the functional role of the serotonin auto-receptor.

1. Symptoms of obsessive-compulsive disorder (OCD) may be acutely exacerbated by administration of certain serotonin agonists Exacerbation of OCD symptoms by sumatriptan, a 5HT1D agonist (Zohar, 1993), is consistent with pre-clinical data suggesting that the serotonin auto-receptor plays an important role in this disorder (El Mansari et al, 1995). 2. In order to investigate the functional role of the serotonin auto-receptor in OCD, the authors undertook single photon emission computed tomography in OCD patients after administration of sumatriptan and placebo. The authors hypothesized that, as in the case of m-chlorophenylpiperazine (mCPP) challenge (Hollander et al, 1995), exacerbation of OCD symptoms would be accompanied by increased cortical metabolism and thus blood flow, and more specifically by increased activity in the orbitofrontal-striatal circuit. They also expected, that as in the case of mCPP challenge (Hollander et al, 1993), exacerbation of OCD symptoms would be associated with a relatively poor response to subsequent treatment with serotonin specific reuptake inhibitors. 3. Sumatriptan (100 mg orally) and placebo were administered on separate days to 14 patients who met DSM-IV diagnostic criteria for OCD, using a randomized double-blind design. After 90 minutes, patients were injected with Tc-99m HMPAO and underwent single photon emission computed tomography (SPECT) of the brain. Activity in regions of interest was calculated, and compared using repeated measures analysis of variance. Patients were subsequently treated with a serotonin specific reuptake inhibitor (SSRI). 4. Behavioral response to sumatriptan was heterogenous, with 4 patients showing acute exacerbation, and 4 patients demonstrating a decrease in symptoms. On sumatriptan challenge, there was a significant association between symptom exacerbation and decreased activity in frontal areas. There was an association between decreased activity in an inferior frontal area with worse response to treatment, and also patients with symptom exacerbation after sumatriptan had poorer response to SSRI treatment. 5. Heterogeneity of behavioral response to sumatriptan in OCD is consistent with previous studies demonstrating conflicting and heterogenous behavioral responses to serotonergic challenges (Hollander et al, 1992), and with underlying heterogeneity in the neurobiology of this disorder. 6. It may be hypothesized that increased frontal activity in some patients with OCD is itself a compensatory mechanism. In patients with such compensatory hyperactivity, administration of a serotonin auto-receptor agonist results in decreased frontal activity and exacerbation of OCD symptoms. These patients may also be less likely to respond to treatment with a SSRI. 7. Further work combining pharmacological challenge paradigms and functional imaging techniques in OCD may be helpful in elucidating the neurobiology of this complex disorder.

Association between a catechol-o-methyltransferase polymorphism and obsessive-compulsive disorder in the Afrikaner population.

BACKGROUND: It has been proposed that the catechol-o-methyl transferase gene (COMT) may play a role in the pathogenesis of obsessive-compulsive disorder (OCD). Whereas studies in a North American population showed that the low activity (L) allele of a functional polymorphism in COMT was associated with OCD in male patients, this result was not supported by studies in a Japanese population. The present association study assessed the risk for OCD conferred by this COMT polymorphism in a geographically different patient group, namely, the relatively genetically homogeneous Afrikaner population of South Africa. METHODS: Fifty-four unrelated OCD patients and fifty-four sex-matched controls were recruited from the same Afrikaner community. Patients and controls were phenotyped (DSM-IV) and genotyped for a NlaIII polymorphism with H (high activity) or L (low activity) alleles in the COMT gene. RESULTS: The H/L genotype was significantly more common than expected in the OCD patient group (P = 0.0017). LIMITATIONS: Replication studies with related individuals may be useful in discovering factors underpinning the H/L genotype abundance in the Afrikaner population. CONCLUSIONS: These results emphasise the need for further studies in genetically homogeneous populations to help define the complex etiology of this disease.

Narrative themes in responses to trauma in a religious community.

OBJECTIVE: The development of a meaningful narrative of trauma experiences is an important factor in recovery, and religious beliefs may constitute an important meaning system for trauma survivors. The study examined the narrative themes which emerged from interviews with survivors of the massacre of a church congregation in South Africa (N = 19). DESIGN: A descriptive, retrospective study. SETTING: Community based study. SUBJECTS: A volunteer sample of 19 participants. OUTCOME MEASURES: An open ended interview and the Structured Clinical Interview for DSM-IV (SCID). RESULTS: Thematic analysis revealed that religious beliefs and practices were frequently utilised to construct a meaningful retrospective narrative of the massacre. The implications of the findings for future research with trauma survivors are discussed. CONCLUSIONS: Religion may provide a framework by which survivors of trauma construct a meaningful account of their experience, and may be a useful focus for intervention with trauma survivors.

Comparison of obsessive-compulsive disorder patients with and without comorbid putative obsessive-compulsive spectrum disorders using a structured clinical interview.

Increasing attention has been paid to the possibility that a range of disorders, the putative obsessive-compulsive spectrum disorders (OCSDs), may share overlapping phenomenological and neurobiological features with obsessive-compulsive disorder (OCD). The development of a structured clinician-administered interview for the putative OCSDs (SCID-OCSD) is described. This instrument was used to investigate differences between OCD patients with a comorbid putative OCSD and OCD patients without a comorbid putative OCSD. A sample of 85 adult patients (38 men and 47 women) presenting for treatment of OCD was interviewed with the SCID-OCSD. OCD patients without comorbid putative OCSDs (n = 36) were compared to patients with comorbid OCSDs (n = 49) in terms of demographic features, clinical characteristics, and associated comorbidity with other non-OCSD DSM-IV axis I disorders. Of the OCD patients, 57.6% currently met criteria for at least one putative OCSD and 67.1% had a lifetime history of at least one comorbid OCSD. The OCSDs with the highest prevalence rates were compulsive self-injury (22.4%), compulsive buying (10.6%), and intermittent explosive disorder (10.6%). There was a significantly larger proportion of women in the group with comorbid OCSDs. Although the two groups did not differ in terms of severity of OCD symptoms, the group with comorbid OCSDs had significantly more obsessions and compulsions. The two groups did not differ significantly in terms of associated psychopathology other than OCSDs. We conclude that the SCID-OCSD provides clinicians and researchers with an instrument for the diagnosis of putative OCSDs. Our findings suggest that putative OCSDs have a relatively high prevalence rate in OCD patients. In addition, OCD patients with comorbid OCSDs differ with regard to certain demographic and clinical features. Further research, particularly genetic and neuroimmunological work, may ultimately be useful in validating the obsessive-compulsive spectrum.

Characteristics and phenomenology of hair-pulling: an exploration of subtypes.

This study was designed to detail the demographic and phenomenological features of adult chronic hair-pullers. Key possible subtypes were identified a priori. On the basis of the phenomenological data, differences between the following possible subtypes were investigated: hair-pullers with and without DSM-IV trichotillomania (TTM), oral habits, automatic versus focused hair-pulling, positive versus negative affective cues prior to hair-pulling, comorbid self-injurious habits, obsessive-compulsive disorder (OCD), and tics. Forty-seven participants were drawn from an outpatient population of chronic adult hair-pullers. A structured interview that focused on hair-pulling and associated behaviors was administered to participants. Six of the participants (12.8%) were male, and 41 (87.7%) were female. A large number of hair-pullers (63.8%) had comorbid self-injurious habits. A greater proportion of male hair-pullers had comorbid tics when compared with females. Certain subgroups of chronic hair-pullers (e.g., hairpullers with or without automatic/focused hair-pulling, comorbid self-injurious habits, and oral habits) were found to differ on a number of phenomenological and hair-pulling characteristics. However, differences between other possible subgroups (e.g., hair-pullers with or without DSM-IV TTM, comorbid OCD, and negative versus positive affective cues) may reflect greater severity in hair-pulling symptomatology rather than distinct subtypes of chronic hair-pulling. The findings of the present study also indicated that chronic hair-pulling (even in cases where DSM-IV criteria for TTM were not met) has a significant impact on quality of life. The present study provided limited support for the existence of possible subtypes of chronic hair-pulling. Recommendations are made for further investigations into such subtypes.