Search PubMed⌕ Search

Biomedical subjects

D J Stein

Publications and source records attributed to D J Stein.

At least 19 recordsLinked to original sources
PubMed2002

Quetiapine augmentation of serotonin reuptake inhibitors in obsessive-compulsive disorder.

The augmentation of serotonin reuptake inhibitors (SRIs) with atypical antipsychotics for the management of treatment-resistant obsessive-compulsive disorder (OCD) is gaining increasing acceptance. Quetiapine is a novel antipsychotic which is well tolerated, and which may therefore be particularly useful in this context. Charts of all patients treated in our OCD clinic with the combination of an SRI and quetiapine were reviewed. Demographic details and clinical symptoms on the Yale-Brown Obsessive-Compulsive Scale and the Clinical Global Impressions Scale (CGI) were tabulated before and after augmentation. Eight OCD patients who had proven resistance to treatment with SRIs had received quetiapine augmentation. Four of these eight patients were responders (CGI of 1 or 2) within 4 weeks. In the treatment-responders, the medication was well tolerated. Although limited by the retrospective design and lack of controls, these data are consistent with the growing literature suggesting that approximately one-half of OCD patients resistant to treatment with SRIs may respond to augmentation with an atypical antipsychotic. Quetiapine, a relatively well tolerated agent, deserves further controlled study in this context.

Adolescent↗
PubMed2002

Moclobemide is effective and well tolerated in the long-term pharmacotherapy of social anxiety disorder with or without comorbid anxiety disorder.

Social phobia (social anxiety disorder) is a highly prevalent and chronic disorder that is associated with significant comorbidity and disability. Despite recent advances in the pharmacotherapy of the disorder, there is a paucity of randomized controlled trials on patients with comorbid disorders and on maintenance treatment. A randomized placebo-controlled, double-blind multi-site trial of moclobemide, a reversible inhibitor of monoamine oxidase A, was undertaken with 390 subjects. After an initial 12 weeks, there was the option of continuing for an additional 6 months of treatment. The primary efficacy parameter chosen was responder status as defined by the Clinical Global Impression scale change item. From week 4 onwards, there was a significantly higher response rate on moclobemide than on placebo. Superiority of medication over placebo was similar in patients with comorbid anxiety disorders (33% of subjects) and without, as well as in patients with different subtypes of social anxiety disorder; indeed, treatment with moclobemide rather than placebo was the strongest predictor of response. Adverse events were similar across treatment groups, and were typically mild and transient. In the extension phase, response rates remained higher in the moclobemide group, and ratings of tolerability were equally high in both groups. Thus, in a large sample of social anxiety disorder patients with and without comorbid anxiety disorders, moclobemide was both effective and well-tolerated in the short as well as long-term. These data confirm and extend previous findings on the value of moclobemide in the treatment of social anxiety disorder, and strengthen the range of therapeutic options for managing this important disorder.

Adolescent↗
PubMed2002

Attitudes towards and beliefs about schizophrenia in Xhosa families with affected probands.

OBJECTIVE: The development of effective psychoeducational programs for the management of schizophrenia requires an understanding of attitudes towards and beliefs about the disorder in families of affected probands. In order to establish the need for adaptation of Western psychoeducational programs, these variables were investigated in Xhosa speaking families in South Africa. DESIGN: Xhosa speaking family members of patients with DSM-IV schizophrenia were recruited on a voluntary basis, and interviewed with a structured belief and attitudes questionnaire adapted from previous studies in the West. SETTING: The study population was drawn from both urban and rural Xhosa communities in South Africa. SUBJECTS: 100 Xhosa speaking family members participated in the study. RESULTS: Family members most often recommended treatment with psychotropic medications (88%) and traditional healers (32%), and least often recommended psychotherapy (4%) and meditation (1%). Of the respondents who recommended traditional healing methods, 92% also recommended simultaneous use of allopathic treatment. CONCLUSION: Attitudes towards and beliefs about schizophrenia in family members of patients with schizophrenia may differ substantially from those described in previous work in the West. An understanding of local attitudes and beliefs is crucial for the successful development of local psychoeducational programs.

Adult↗
PubMed2001

A comparative study of clinical features between pure checkers and pure washers categorized using a lifetime symptom rating method.

The current study assessed lifetime obsessive-compulsive disorder (OCD) symptoms in 156 Japanese patients with OCD in order to investigate clinical differences between pure lifetime checkers and pure lifetime washers. Fifty subjects (32%), who had no lifetime history of washing or checking compulsions, or who had a principal symptom other than washing or checking compulsions, were initially excluded. The remaining 106 subjects were divided into three groups: 43 pure lifetime washers (W), 33 pure lifetime checkers (C) and 30 subjects who had experienced both checking and washing compulsions over their lifetime (WC). No differences in clinical characteristics were observed between the W and C groups, suggesting that the lifetime washer-checker distinction may not be useful in subtyping OCD. However, subjects in the WC group differed from other subjects in a number of respects including poorer level of insight, more severe psychopathology and global dysfunction. Thus, they can be generally distinguished by more pervasive and severe psychopathological features, and may constitute a valid subgroup of OCD. Further work from a multidimensional perspective is required to verify the clinical significance of a typology based on lifetime symptoms.

Adolescent↗
PubMed2001

The factor structure for positive and negative symptoms in South African Xhosa patients with schizophrenia.

Most studies investigating the symptom dimensions of schizophrenia utilising the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) favour a three factor model. This study sought to investigate the factor structure of both the global and individual items of the SANS and SAPS in a large sample of South African Xhosa patients with schizophrenia. A total of 422 subjects participated. Both principal components and factor analytical procedures were applied. For the global items, a two-factor solution representing positive and negative symptoms accounted for 59.9% of the variance. Alternatively, the three-dimensional model of negative, psychotic and disorganisation factors was supported by a five-factor solution if the more heterogeneous items of attention and alogia were ignored. Analysis of the individual items yielded a five-factor solution with the negative symptoms splitting into diminished expression and disordered relating, and the positive symptoms separating into factors for psychosis, thought disorder and bizarre behaviour. Our findings are very similar to those from other parts of the world, providing evidence that the factor structure for the symptoms of schizophrenia is relatively resistant to cultural influences. This is particularly true for negative symptoms.

Adult↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗