Value and effectiveness of consumer advocacy groups: a survey of the anxiety disorders support group in South Africa.
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Adult↗
Biomedical subjects
D J Stein
Publications and source records attributed to D J Stein.
The selective serotonin reuptake inhibitor paroxetine is effective in more generalized and in less generalized social anxiety disorder.
RATIONALE: The DSM-IV includes the specifier "generalized" to refer to social anxiety disorder (social phobia) patients if the fears include "most social situations". The focus on interventions such as the selective serotonin reuptake inhibitors (SSRIs) for generalized social anxiety disorder arguably runs the risk that inadequate treatment will be provided to patients with the non-generalized or discrete subtypes. There are, however, few data to address whether more generalized and less generalized subgroups of social anxiety disorder differ in response to medication. OBJECTIVE: To compare response of more generalized and less generalized social anxiety disorder to pharmacotherapy. METHODS: Data from three randomized placebo-controlled double-blind multicenter trials of the SSRI paroxetine in social anxiety disorder were pooled. Response on the Clinical Global Impression Global Improvement item was analyzed using logistic regression, and change in total Liebowitz Social Anxiety Score was analyzed using analysis of variance, with both models incorporating treatment (paroxetine vs placebo), subgroup (more generalized vs less generalized), demographic, and clinical variables. RESULTS: The prevalence of more generalized social anxiety disorder was higher in females than in males. However, there was no significant difference in terms of age or clinical characteristics (duration of condition, baseline pulse, mean arterial blood pressure). At treatment endpoint there were significant treatment effects (for paroxetine vs placebo), but no significant subgroup effects (for more generalized vs less generalized). CONCLUSIONS: Although the current database is limited insofar as few patients with discrete social anxiety disorder would have been included, it is helpful in addressing the value of medication for patients lying on the spectrum from generalized to non-generalized and discrete social anxiety disorder. Paroxetine was effective in both more generalized and in less generalized social anxiety disorder.
Adult↗
The psychobiology of obsessive-compulsive disorder: how important is the role of disgust?
Psychobiologic models of obsessive-compulsive disorder (OCD) have focused on cortico-striatal-thalamic-cortical (CTSC) circuits, noting normal function in cognitive and motoric procedural strategies. Such models have relied on the classification of OCD as an anxiety disorder, seldom exploring other relevant emotions. Based on the hypothesis that a central emotion in OCD is disgust, the authors review the literature on its psychobiology and its relevance to current models of OCD. There are important parallels between the psychobiology of OCD and that of disgust. Obsessive- compulsive disorder may be conceptualized in terms of a false contamination alarm in which disgust plays a crucial organizing or embodying role, not only at a basic brain level, but also in terms of the psychosocial aspects of the disorder. Just as psychobiologic models of panic disorder and post- traumatic stress disorder have been strengthened by the inclusion of preclinical work on amygdala-mediated fear conditioning, so findings on disgust and its mediating CSTC circuits may generate useful hypotheses for OCD research.
Affect↗
Chronic inositol increases striatal D(2) receptors but does not modify dexamphetamine-induced motor behavior. Relevance to obsessive-compulsive disorder.
A large body of evidence suggests that the neuropathology of obsessive-compulsive disorder (OCD) lies in the complex neurotransmitter network of the cortico-striatal-thalamo-cortical (CSTC) circuit, where dopamine (DA), serotonin (5HT), glutamate (Glu), and gamma-amino butyric acid (GABA) dysfunction have been implicated in the disorder. Chronic inositol has been found to be effective in specific disorders that respond to selective serotonin reuptake inhibitors (SSRIs), including OCD, panic, and depression. This selective mechanism of action is obscure. Since nigro-striatal DA tracts are subject to 5HT(2) heteroreceptor regulation, one possible mechanism of inositol in OCD may involve its effects on inositol-dependent receptors, especially the 5HT(2) receptor, and a resulting effect on DA pathways in the striatum. In order to investigate this possible interaction, we exposed guinea pigs to oral inositol (1.2 g/kg) for 12 weeks. Subsequently, effects on locomotor behavior (LB) and stereotype behavior (SB), together with possible changes to striatal 5HT(2) and D(2) receptor function, were determined. In addition, the effects of chronic inositol on dexamphetamine (DEX)-induced motor behavior were evaluated. Acute DEX (3 mg/kg, ip) induced a significant increase in both SB and LB, while chronic inositol alone did not modify LA or SB. The behavioral response to DEX was also not modified by chronic inositol pretreatment. However, chronic inositol induced a significant increase in striatal D(2) receptor density (B(max)) with a slight, albeit insignificant, increase in 5HT(2) receptor density. This suggests that D(2) receptor upregulation may play an important role in the behavioral effects of inositol although the role of the 5HT(2) receptor in this response is questionable.
Animals↗
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.
Adult↗
Cross-cultural aspects of social anxiety disorder.
Cross-cultural perspectives have much to teach about psychopathology in general and about SAD in particular. The authors accept that the construct of SAD (like that of other anxiety disorders) cannot simply be interpreted as a category fallacy. Universal psychobiological mechanisms are likely important in determining the onset of SAD; empiric, epidemiologic, and neurobiological data provide some support for this argument, and clinical data confirm that patients can experience onset of anxiety disorders in the absence of exposure to cultural narratives about their symptoms. Nevertheless, culture may exert important influences on the experience and expression of anxiety disorders. In the clinic, the authors believe that it is often useful to ask patients about their view of disorders such as SAD and about their opinion of the etiology and optimal treatment of their symptoms. Subsequent negotiation can take place between the clinician's model of the disorder and that of the patient. A shared view of the etiology and treatment is likely to result in the patient feeling more understood and in greater compliance with prescribed treatment. There is an important clinical lesson in the observation that Western scales of anxiety are not always cross-culturally valid. It is also important to recognize that anxiety disorders are not simply the result of culturally influenced interpretations of an underlying disease but rather that anxiety disorders are also disorders of the interpretive process. From the perspective of research, cross-cultural differences in social anxiety disorder suggest a number of interesting leads for further work. Neurobiological and psychopharmacologic investigation of overlap and differences between Western SAD and Eastern TKS may provide helpful new insights. The possible existence of a group of Western SAD patients with poor insight, for example, deserves further scrutiny and research. Women and people with lower socioeconomic status are at greater risk for developing SAD; the mechanisms underlying these associations require further study. Future investigation of the contribution of sociocultural mechanisms to the course of SAD may provide an important avenue toward understanding this complex disorder.
Americas↗
Taijin kyofusho: a form of social anxiety disorder that responds to serotonin reuptake inhibitors?
Taijin kyofusho (TKS) has been categorized as a "culture-bound" illness that is unique to the East, although an alternative view holds that some TKS patients are best conceptualized as having a form of social anxiety disorder (SAD). However, pharmacotherapeutic interventions for TKS have not yet been rigorously investigated. A review was undertaken of 48 TKS patients initially treated with serotonin reuptake inhibitors (SRIs) in an outpatient setting of a Japanese hospital. Psychiatric diagnoses were determined according to DSM-IV, and a set of TKS diagnostic criteria based on a modification of DSM-IV SAD criteria. In addition, response to SRIs (clomipramine and fluvoxamine) was evaluated retrospectively using the Clinical Global Impressions (CGI) scale. All 48 patients met SAD-based TKS diagnostic criteria. In the pretreatment assessment, DSM-IV Axis I diagnoses included SAD (38%), major depressive episode (27%), and delusional disorder somatic type (15%). Sixteen (48%) of 33 patients treated with clomipramine or fluvoxamine for at least 6 months were categorized as responders (CGI = 1 or 2). Compared to responders, non-responders were significantly less likely to have pretreatment major depression, and significantly more likely to have comorbid cluster A personality disorders and to have received augmentation with antipsychotic drugs. Although TKS may be a heterogeneous condition with various comorbidities, patients invariably fulfilled diagnostic criteria for TKS based on SAD criteria. SRIs may be effective for a substantial number of TKS patients. Prospective controlled trials are necessary to confirm these findings and to delineate the pharmacotherapeutic profile of TKS.
Adolescent↗
The role of genes and family in trauma exposure and posttraumatic stress disorder.
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Animals↗
Executive function in traumatic brain injury and obsessive-compulsive disorder: an overlap?
Thirteen individuals with traumatic brain injury, 13 individuals with obsessive-compulsive disorder (OCD) and 10 normal controls were compared on neuropsychological measures of executive function. Individuals with a traumatic brain injury performed significantly poorer than the other two groups on a test measuring visuo-spatial strategy. Although the traumatic brain injury group made more errors on a test of maze learning and the OCD group less than the control group, this did not reach statistical significance. No support for an overlap in executive dysfunction in traumatic brain injury and OCD was found. It may be that the 'error prevention system' in the brain was influenced in a contrasting way by executive dysfunction in these disorders. This difference may reveal itself clinically in impulsivity/perseveration and slowness, respectively. Further studies were needed to test this hypothesis.
Adolescent↗
Muscle dysmorphia: a South African sample.
It has recently been suggested that muscle dysmorphia, a pathological preoccupation with muscularity, is a subtype of body dysmorphic disorder (BDD). There are, however, few studies of the phenomenology of this putative entity. Twenty-eight amateur competitive body builders in the Western Cape, South Africa, were studied using a structured diagnostic interview that incorporated demographic data, body-building activities and clinical questions focusing on muscle dysmorphia and BDD. There was a high rate of muscle dysmorphia in the sample (53.6%). Those with muscle dysmorphia were significantly more likely to have comorbid BDD based on preoccupations other than muscularity (33%). Use of the proposed diagnostic criteria for muscle dysmorphia indicated that this is a common and relevant entity. Its conceptualization as a subtype of BDD seems valid. The disorder deserves additional attention from both clinicians and researchers.
Adolescent↗
Characterization of a backbone cleavage product of BMS-196854 (Oncostatin M), a recombinant anti-inflammatory cytokine.
PURPOSE: BMS-196843 (Oncostatin M) is a therapeutic recombinant protein in development. Scale-up process changes led to unexpected instability of the bulk drug substance solution during storage. A product with an apparent higher MW than the parent protein was observed by the size-exclusion chromatography (SEC). This study was aimed to fully characterize the product and to identify a solution to stabilize the protein. METHODS: SEC, SDS-PAGE, tryptic mapping, and N-terminal sequencing were performed to characterize the unknown product. The effect of pH, temperature, bulk concentration, and immobilized trypsin inhibitor on the degradation rate was studied to elucidate the mechanism and to identify stabilization strategies. RESULTS: Despite the apparent high MW indicated initially by SEC, the unknown was characterized to be a degradation product resulted from a backbone cleavage between residues Arg145-Gly146. The resulting fragments from the backbone cleavage were, however, still linked through an intramolecular disulfide bond. Thus, the final product had a more open structure with an increased hydrodynamic radius compared to the parent protein, which explains the initial SEC results. The site-specific backbone cleavage was suspected to be catalyzed by trypsin-like protease impurities in the bulk solution. The bulk drug substance solution was subsequently treated with immobilized soybean trypsin inhibitor, and the degradation rate was significantly reduced. Furthermore, increasing the solution pH from 5 to 8 led to an increase in the degradation rate, which was consistent with the expected pH dependency of trypsin activity. In addition, the effect of bulk concentration also supported the involvement of protease impurities rather than a spontaneous peptide bond hydrolysis reaction. CONCLUSION: Trace trypsin-like protease impurities led to an unusual site-specific backbone cleavage of BMS-196854. The proteolytic degradation can be minimized by treating the bulk solution with immobilized soybean trypsin inhibitor and/or controlling the solution pH and storage temperature.
Anti-Inflammatory Agents↗
Identification of polysubstance abuse in the parturient.
Illicit drugs are widely used by inner city patients and their use by pregnant women has increased in recent years. The aim of this study was to determine the prevalence of polysubstance abuse among parturients at our institution who received no prenatal care ('unbooked') and to determine the accuracy of the Ontrak TesTcup an in vitro immunodiagnostic assay. We prospectively analysed urine from 50 'unbooked' parturients and found that 26 (52%) tested positive for cocaine. Of these, six patients (23%) were also positive for morphine. All TesTcup results were confirmed by the hospital laboratory using alternate chemical methods. When comparing TesTcup to the hospital laboratory, there were no false positive or negative results. Given the high frequency of concomitant opioid abuse in cocaine-abusing parturients, anyone suspected of cocaine abuse should be tested for other illicit substances. TesTcup is a clinically accurate test that allows the rapid assessment of several drugs of abuse, which may impact on anaesthetic care.
Cocaine-Related Disorders↗
The effect of intrathecal analgesia on the success of external cephalic version.
UNLABELLED: External cephalic version (ECV), the procedure whereby a fetus in the breech position is converted to vertex, is often performed to avoid an operative delivery. Potential benefits of epidural and spinal anesthesia for this procedure are controversial. Several previous studies have evaluated the use of epidural anesthesia with varying results. We sought to determine whether analgesia produced by subarachnoid sufentanil would safely improve the success of ECV. Patients who received subarachnoid analgesia (n = 20) were compared with those who did not (n = 15) in regard to success of ECV, level of pain during ECV, and satisfaction. ECV was successful in 21 patients (60%), with more frequent success in women who received spinal analgesia as compared with those who did not (80% vs 33%, respectively; P = 0.005). Patients who received spinals also reported smaller pain scores and were more satisfied with ECV. None of the women who received spinal analgesia developed a postdural puncture headache, and the only case of fetal bradycardia occurred in a patient who did not receive spinal analgesia. More profound patient comfort after spinal analgesia may have permitted greater manipulation of the abdomen during ECV, thus improving success rates of ECV without increasing risk. IMPLICATIONS: The success of external cephalic version (ECV) was compared in women who received spinal analgesia and those who did not. Successful ECV occurred more frequently in those women who received spinal analgesia. Because term singleton pregnancies associated with breech position usually require cesarean delivery, an increase in success of ECV may decrease the number of cesarean deliveries performed.
Adult↗
An open trial of citalopram in adolescents with post-traumatic stress disorder.
In this preliminary, 12-week open-label study, eight adolescents with moderate to severe post-traumatic stress disorder (PTSD) were treated with citalopram (the most selective of the selective serotonin reuptake inhibitors) in a fixed daily dose of 20 mg, and rated at 2-week intervals. The Clinician-Administered PTSD Scale (Child and Adolescent Version) was the primary measure used to assess treatment outcome. Core PTSD symptoms (re-experiencing, avoidance, and hyperarousal symptoms) showed statistically significant improvement at week 12 on the Clinician-Administered PTSD Scale (Child and Adolescent Version) (CAPS-CA), with a 38% reduction in total CAPS scores between baseline and endpoint. Citalopram failed to effect improvement on self-reported depressive symptoms. All seven adolescent completers were rated as much improved or very much improved on Clinical Global Impression Improvement scores. Citalopram was well-tolerated overall with reported adverse experiences being relatively benign. However, larger, controlled trials are needed to consolidate these preliminary results.
Adolescent↗
Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder.
Serotonin reuptake inhibitors appear to be uniquely effective treatments for obsessive-compulsive disorder (OCD). This double-blind, placebo-controlled study was the first trial to assess the efficacy of the most selective of the serotonin reuptake inhibitors, citalopram, in OCD. A total of 401 patients were randomized to receive citalopram 20, 40 or 60 mg/day or placebo for 12 weeks. All three doses of citalopram were significantly more effective than placebo measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) change score (P < 0.01). The highest response rate, defined as 25% improvement in Y-BOCS entry score, was observed in the 60 mg group (65%). This compared with 52% and 57.4% in the 40 mg and 20 mg groups. Response rate on placebo was 36.6% (P < 0.05 for all three doses of citalopram compared to placebo). There was no significant difference between the individual doses of citalopram. An advantage was seen for citalopram on the Sheehan Disability Scale compared with placebo (P < 0.05 on all three citalopram groups versus placebo for both the work situation and the family life and home responsibilities and P < 0.05 on citalopram 60 mg and 20 mg versus placebo for the social life and home activities). Citalopram was well tolerated; only 4 to 6 patients in each dose group discontinued the study prematurely due to adverse events.
Activities of Daily Living↗
Predictors of response to pharmacotherapy with citalopram in obsessive-compulsive disorder.
Although serotonin reuptake inhibitors (SRIs) are the medications of choice in the treatment of obsessive-compulsive disorder (OCD), only 50-60% of patients respond to a single trial of any of these agents. Improved knowledge of the predictors of response to treatment may have important clinical implications. Data from a large randomized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response. Demographic (age, sex), clinical (OCD severity and duration, depression severity, prior treatment) and trial variables (citalopram dose, treatment duration) were included. Subjects with longer duration of OCD, more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial. In contrast, subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders. Despite greater awareness of OCD in recent years, there is evidence that the disorder continues to be underdiagnosed and undertreated. The data here emphasize the crucial importance of early diagnosis and treatment of OCD, and of pharmacotherapy with appropriate dose and duration.
Adolescent↗
Obsessive-compulsive disorder and a novel polymorphism adjacent to the oestrogen response element (ERE 6) upstream from the COMT gene.
Family and twin studies have consistently provided evidence for involvement of genetic mechanisms in obsessive-compulsive disorder (OCD). This has given rise to association studies involving several candidate genes in an endeavour to identify susceptibility factors. One of the more promising candidate genes appears to be the catecol-O-methyltransferase (COMT) gene. Recent association studies in North American and Afrikaner populations have reported a likely association between a functional polymorphism of COMT (linked with COMT enzyme activity levels) and OCD. COMT expression has been demonstrated to be regulated by oestrogen through the oestrogen-response elements (EREs) in the promoter region of the gene. In the light of this association, the authors tested for an association between a novel polymorphism (C --> T transition) adjacent to ERE 6 in the promoter area of COMT and OCD in 48 Afrikaners and 48 ethnically matched controls. The C --> T transition was not significantly associated with OCD (P = 0.93) or gender (P = 0.67). These findings, although limited by a small sample size, suggest that the novel polymorphism adjacent to ERE 6 in the promoter area of COMT does not play a major role in the genetic predisposition to OCD.
Catechol O-Methyltransferase↗
Hypersexual disorder and preoccupation with internet pornography.
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Adult↗