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Biomedical subjects

Stuart Watson

Publications and source records attributed to Stuart Watson.

At least 19 recordsLinked to original sources
PubMed2007

Plasma cortisol-dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar disorder.

Hypercortisolaemia is a feature of many severe psychiatric illnesses and has been suggested to be both a causal and exacerbating factor of clinical symptoms and neurocognitive impairment. The adrenal steroid dehydroepiandrosterone (DHEA) has antiglucocorticoid properties that may have regulatory effects on glucocorticoid action in the brain. However, there is a paucity of data on these steroids and their ratio in schizophrenia and bipolar disorder. We therefore sought to assess cortisol and DHEA levels and the cortisol-DHEA ratio in patients with schizophrenia (n=20) and bipolar disorder (n=20), on stable medication for a minimum of 6 weeks, and healthy age- and sex-matched control subjects (n=20). Steroid levels were measured from plasma samples collected at 30 min intervals from 1:00 p.m. to 4:00 p.m. Cortisol levels were found to be significantly elevated in both patient groups compared with controls. DHEA levels were elevated in schizophrenic patients compared with bipolar patients and controls, but there was no evidence of a difference in the cortisol-DHEA ratio of the groups. These data suggest that afternoon hypercortisolaemia is evident in symptomatic bipolar and schizophrenic patients compared to controls. However, an elevation in DHEA levels may represent a specific endocrine marker in schizophrenia.

Adult↗
PubMed2006

Laser-machined fibers as Fabry-Perot pressure sensors.

Cavities have been laser ablated in the ends of single-mode optical fibers and sealed by aluminized polycarbonate diaphragms to produce Fabry-Perot pressure sensors. Both conventional fibers and novel, multicore fibers were used, demonstrating the possibility of producing compact arrays of sensors and multiple sensors on an individual fiber 125 microm in diameter. This high spatial resolution can be combined with high temporal resolution by simultaneously interrogating the sensors by using separate laser sources at three wavelengths. Shock tube tests showed a sensor response time of 3 micros to a step increase in pressure.

Journal Article↗
PubMed2006

The dex/CRH test--is it better than the DST?

The dexamethasone suppression test (DST), frequently abnormal in mood disorder patients, is considered to measure glucocorticoid receptor-mediated negative feedback. We examined the hypothesis that the, apparently more sensitive, dexamethasone/corticotrophin-releasing-hormone (dex/CRH) test unveils subtle hypothalamic-pituitary-adrenal axis disturbance not detected by the DST in 82 patients with mood disorders and 28 controls. There was a close correlation between the cortisol responses on the two tests (r(s)=0.73, p<0.0005). However, ROC analysis revealed that the dex/CRH test had better diagnostic performance than the DST (p=0.031). The sensitivity of delta cortisol (from the dex/CRH) was 61.9% and the specificity 71.4%. The sensitivity of 1500 h cortisol (the DST) was 66.6% and the specificity was 47.6%. This suggests that the two tests measure common pathology but that the dex/CRH test has better diagnostic utility.

Adult↗
PubMed2006

Topiramate for acute affective episodes in bipolar disorder.

BACKGROUND: Bipolar disorder is a common recurrent illness with high levels of chronicity. Treatment resistance persists despite the use of established medications, such as lithium and valproate. New medications are required for the treatment of refractory cases. Retrospective and open-label trials have suggested that the anticonvulsant topiramate may be efficacious in bipolar disorder. There is a need to clarify the evidence available in the form of randomised controlled trials for its use in bipolar disorder. OBJECTIVES: To review the evidence for the efficacy and acceptability of topiramate in the treatment of acute mood episodes in bipolar disorder. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) group search strategy was used. The following databases were searched:The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), September 2003;The Cochrane Controlled Clinical Trials Register (CCCTR), September 2003;EMBASE (1980 to December 2003);MEDLINE (1966 to December 2003);LILACS;PsycLIT;Psyndex.Reference lists of relevant papers and major textbooks of mood disorder. Handsearches (specialist journals and conference proceedings). Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials which compared topiramate with placebo or with active agents in the treatment of any acute mood episodes in bipolar disorder. Participants were patients with bipolar disorder and were males and females of all ages. DATA COLLECTION AND ANALYSIS: Data extraction and methodological quality assessment were performed independently by two reviewers. For analysis, relative risk was used for binary efficacy outcomes and the weighted mean difference or standardised mean difference was used for continuously distributed outcomes. MAIN RESULTS: One randomised controlled trial met the inclusion criteria for the review, a comparison between topiramate and bupropion sustained release (SR) in the adjunctive treatment of depressed patients with bipolar disorder. However, the trial had several limitations in methodology and in the description of data. Its data regarding efficacy required clarification before it could be analysed according to the protocol of this systematic review. From the limited data available, topiramate had efficacy similar to bupropion SR in the adjunctive treatment of bipolar depression. Both groups of subjects suffered a high drop-out rate. There was no significant difference between the topiramate and the bupropion treated groups in those dropping out for any reason (relative risk 1.60, 95% confidence interval 0.65 to 3.96). There was no significant difference in those withdrawing from the study due to adverse effects (relative risk 1.50, 95% confidence interval 0.51 to 4.43). Although the data on weight loss were not analysed formally, weight loss was marked in the topiramate treated group. Several unpublished trials have been identified and data from these trials may be included in future reviews. AUTHORS' CONCLUSIONS: There is insufficient evidence on which to base any recommendations regarding the use of topiramate in any phase of bipolar illness, either in monotherapy or as an adjunctive treatment.

Affective Disorders, Psychotic↗
PubMed2006

Association between childhood trauma and dissociation among patients with borderline personality disorder.

OBJECTIVE: To examine the relationship between childhood trauma and dissociative experience in adulthood in patients with borderline personality disorder. METHOD: Dissociative experiences scale scores and subscale scores for the Childhood Trauma Questionnaire were correlated in 139 patients. Patients were dichotomized into high or low dissociators using the Median Dissociative Experiences Scale score as the cut-off. RESULTS: Childhood Trauma Questionnaire Subscale scores for emotional and physical abuse and emotional neglect but not sexual abuse correlated significantly with Dissociative Experiences Scale scores. High dissociators reported significantly greater levels of emotional abuse, physical abuse, emotional neglect and physical neglect but not sexual abuse than low dissociators. CONCLUSION: Patients with borderline personality disorder therefore demonstrated levels of dissociation that increased with levels of childhood trauma, supporting the hypothesis that traumatic childhood experiences engender dissociative symptoms later in life. Emotional abuse and neglect may be at least as important as physical and sexual abuse in the development of dissociative symptoms.

Adolescent↗
PubMed2006

Neuropsychological impairment in bipolar disorder: the relationship with glucocorticoid receptor function.

OBJECTIVE: Basal levels of glucocorticoids, such as cortisol, are generally unaltered in bipolar disorder. However, neuroendocrine tests of glucocorticoid receptor (GR) function such as the dexamethasone suppression test (DST) are frequently abnormal. Neuropsychological impairment is well documented in healthy volunteers after administration of glucocorticoids and in patients with bipolar affective disorder. This suggests a potential link between neuropsychological and hypothalamic-pituitary-adrenal axis function. We examined the hypothesis that neuropsychological impairment in bipolar disorder is associated with abnormal GR function. METHODS: Seventeen euthymic bipolar patients and 16 controls completed tests of verbal declarative and working memory (WM) tests and the DST. The correlation between neuroendocrine and neuropsychological function was examined. RESULTS: Bipolar patients made significantly more errors of omission and commission on the WM paradigm and demonstrated impaired verbal recognition memory. Patients' post-dexamethasone cortisol correlated with WM commission errors (r(s) = 0.64, p = 0.0006). No such relationship was evident in controls. CONCLUSION: Deficits in declarative memory and WM are evident in patients with bipolar disorder. The deficit in retrieval accuracy from WM appears to be correlated with abnormal GR function.

Adolescent↗
PubMed2006

Increased libido associated with quetiapine.

We report sexual symptoms in a 44 year old man with schizophrenia who was receiving treatment with the atypical antipsychotic quetiapine. The symptoms consisted of an increased drive to masturbate and spontaneous ejaculations at night time. We discuss the potential neuro-chemical mechanisms for this and argue that quetiapine's unique pharmacological profile may have contributed to the development of his symptoms.

Adult↗
PubMed2005

Post-dexamethasone arginine vasopressin levels in patients with severe mood disorders.

There appears to be an allostatic shift in the hypothalamic-pituitary-adrenal (HPA) axis of animals exposed to chronic stress, such that vasopressinergic regulation of the HPA axis becomes critical for sustaining corticotroph responsiveness in the presence of high circulating glucocorticoid levels. It has been hypothesised that this is also a feature of patients with mood disorders and is mediated by a shift in hypothalamic drive in favour of arginine vasopressin (AVP) rather than corticotrophin releasing hormone (CRH), by up-regulation of AVP receptors in the pituitary and by a relatively reduced impact of glucocorticoid induced negative feedback on AVP release. We examined the latter, by comparing AVP levels after pretreatment with the glucocorticoid, dexamethasone in 41 bipolar patients (21 of whom were in full remission), 23 patients with chronic major depressive disorder and 21 healthy controls. We found that, as hypothesised, post-dexamethasone AVP levels were significantly elevated in patients with bipolar disorder and chronic depression compared with controls and also that there was no difference between symptomatic and remitted bipolar patients. The data shows that post-dexamethasone AVP levels are a sensitive measure of HPA axis function, that HPA axis dysfunction persists into euthymia in bipolar disorder and that, in contrast to previous reports, patients with chronic depression have a dysfunctional HPA axis.

Adult↗
PubMed2005

Facial expression perception: an objective outcome measure for treatment studies in mood disorders?

Facial expressions are important cues used in social communication. Studies in both patients with mood disorders and healthy volunteers have shown that facial expression perception can vary according to current mood state. Interpretation or perception of facial expressions can also be altered by administration of certain psychopharmacological agents. Novel drug development at present is restricted by the lack of valid and sensitive markers of mood state. This review suggests that measurement of facial expression perception may prove to be a useful experimental tool for assessing efficacy of antidepressant treatments.

Animals↗
PubMed2005

Effects of adjunctive mifepristone (RU-486) administration on neurocognitive function and symptoms in schizophrenia.

BACKGROUND: It has been suggested that hypercortisolemia may cause or exacerbate both neurocognitive impairment and symptoms in schizophrenia. We hypothesized that antiglucocorticoid treatments, particularly glucocorticoid receptor (GR) antagonists, would improve neurocognitive functioning and clinical symptoms in this disorder. METHOD: Twenty patients with schizophrenia were treated with 600 mg/day of the GR-antagonist mifepristone (RU-486) or placebo for 1 week in a double-blind, crossover design. Neurocognitive function was evaluated at baseline and 2 weeks after each treatment. Neuroendocrine profiling was performed at these times and also immediately after each treatment. Symptoms were evaluated weekly. RESULTS: Mifepristone administration resulted in a temporary two- to threefold increase in plasma cortisol levels (p < .0001). No significant effects were observed on any measure of neurocognitive function, including the primary outcome measures of spatial working memory and declarative memory. Minor changes in symptoms occurred in both arms of the study and were indicative of a general improvement over time, irrespective of treatment. CONCLUSIONS: In contrast to our earlier report of positive effects in bipolar disorder, these data suggest that the GR-antagonist mifepristone has no effect on neurocognitive function or symptoms in this group of patients with schizophrenia. Future studies in schizophrenia should examine patients with demonstrable hypothalmic-pituitary-adrenal axis dysfunction.

Adult↗
PubMed2005

Temporal stability of the dex/CRH test in patients with rapid-cycling bipolar I disorder: a pilot study.

OBJECTIVE: To examine the hypothesis that hypothalamic-pituitary-adrenal (HPA) axis function is a trait abnormality in bipolar disorder. METHOD: We examined HPA axis function in a pilot study of five patients with rapid-cycling bipolar disorder in both relapse and remission using the dexamethasone/corticotropin releasing hormone (dex/CRH) test. RESULTS: The cortisol response to the dex/CRH test correlated significantly between the 2 tests (r = 0.997; p < 0.0005). CONCLUSION: The data suggests that the cortisol response to the dex/CRH test is stable over time and independent of mood state.

Adult↗
PubMed2005

Neurocognitive impairment in euthymic patients with bipolar affective disorder.

BACKGROUND: Persistent impairments in neurocognitive function have been described in patients with bipolar disorder whose disease is in remission. However, methodological issues such as the effect of residual mood symptoms and hypercortisolaemia may confound such studies. AIMS: To assess neurocognitive functioning in prospectively verified euthymic patients with bipolar disorder. METHOD: Sixty-three patients with bipolar disorder and a matched control group completed a comprehensive neurocognitive test battery. Euthymia was confirmed in the patient group by prospective clinical ratings over 1 month prior to testing. Saliva samples were collected to profile basal cortisol secretion. RESULTS: Patients were significantly impaired across a broad range of cognitive domains. Across the domains tested, clinically significant impairment was observed in 3% to 42% of patients. Deficits were not causally associated with residual mood symptoms or hypercortisolaemia. CONCLUSIONS: Neurocognitive impairment persists in patients whose bipolar disorder is in remission. This may represent a trait abnormality and be a marker of underlying neurobiological dysfunction.

Adult↗