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Biomedical subjects

Peter Gallagher

Publications and source records attributed to Peter Gallagher.

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

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

Racial disparities in access after regulatory surveillance of benzodiazepines.

BACKGROUND: We examined the effects of a prescription-monitoring program on benzodiazepine access among Medicaid enrollees living in neighborhoods of different racial composition. METHODS: We used interrupted time series and logistic regression to analyze data from noninstitutionalized persons aged 18 years or older (N = 124 867) enrolled continuously in New York Medicaid 12 months before and 24 months and 7 years after initiation of the program. We used census data to identify the racial composition of the neighborhoods. Outcome measures were nonproblematic use (short term, within dosing guidelines), potentially problematic use (>120 days' use or more than twice the recommended dose), and pharmacy hopping (filling prescriptions for the same benzodiazepine in different pharmacies within 7 days). RESULTS: There was a sudden, sustained reduction in benzodiazepine use in all the neighborhoods after the program's introduction. Despite the lowest rates of baseline use, enrollees in predominantly (> or = 75%) black neighborhoods experienced the highest rates of discontinuation after introduction of the program. This difference remained 7 years after policy initiation. Compared with white participants, black participants were more likely to discontinue nonproblematic (odds ratio, 1.78; 95% confidence interval, 1.47-2.17) and potentially problematic (odds ratio, 1.77; 95% confidence interval, 1.45-2.17) benzodiazepine use, after adjusting for sex, eligibility status, neighborhood poverty, and baseline use. The program almost completely eliminated pharmacy hopping in all racial groups, although less among white participants (82.6%) vs black participants (88.7%). CONCLUSIONS: A systematic benzodiazepine prescription-monitoring program reduced inappropriate prescribing, with a stronger effect in predominantly black neighborhoods despite lower baseline use. The policy may have resulted in an unintended decrease in nonproblematic use that disproportionately affects black populations.

Adult↗
PubMed2006

Effects of rapid tryptophan depletion on salivary cortisol in older people recovered from depression, and the healthy elderly.

Reduced serotonin (5-HT) function and abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are thought to play a role in the aetiology of major depression. We sought to examine this issue in the elderly by assessing the effects of lowering brain 5-HT on salivary and plasma cortisol in elderly patients who had recovered from at least one episode of major depression and in a healthy, age matched comparison group. A double-blind, cross-over design involving administration of two nutritionally balanced amino acid mixtures (with or without tryptophan) was used. Salivary cortisol was measured at intervals before and after the drink. There was no effect of acute tryptophan depletion (ATD) on salivary cortisol (ATD by time; F=0.97, df=7,210, p=0.454) but a significant interaction between group and time (F=3.91, df=7,210, p=0.010). Healthy subjects showed a marked increase in cortisol levels 2-3 hours into the procedure regardless of drink composition while recovered depressed subjects did not. In elderly patients who had recovered from depression there was no evidence of greater vulnerability of hypothalamic 5-HT pathways to 5-HT depletion. However, they demonstrated reduced reactivity of the HPA axis compared to healthy subjects.

Aged↗
PubMed2006

A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder.

BACKGROUND: A number of studies have reported evidence of cognitive deficits in euthymic bipolar patients. Qualitative reviews of the literature have indicated impairments in executive functions and declarative memory are most consistently reported. However, not all primary studies conducted to date have had sufficient power to detect statistically significant differences and there have been few attempts to quantify the magnitude of impairments. This review aims to combine data from available studies to identify the profile of neuropsychological deficits in euthymic bipolar patients and quantify their magnitude. METHOD: Systematic literature review and meta-analysis. RESULTS: Large effect sizes (d>or=0.8) were noted for aspects of executive function (category fluency, mental manipulation) and verbal learning. Medium effect sizes (0.5<or=d<0.8) were found for aspects of immediate and delayed verbal memory, abstraction and set-shifting, sustained attention, response inhibition, and psychomotor speed. Small effect sizes (0.2<or=d<0.5) were reported for verbal fluency by letter, immediate memory, and sustained attention. LIMITATIONS: Sufficient data were not available to investigate all domains. For example analyses did not include measures of visuospatial function. CONCLUSION: Euthymic bipolar patients demonstrate relatively marked impairment in aspects of executive function and verbal memory. It is not yet clear whether these are two discrete areas of impairment or are related to one another. Future investigations should clarify the functional significance of deficits and indicate whether patients will benefit from ameliorative interventions.

Affect↗
PubMed2006

The adult psychiatrist's dilemma: psychostimulant use in attention deficit/hyperactivity disorder.

Children who have taken psychostimulants long term for attention deficit/hyperactivity disorder (ADHD) are now presenting at adult psychiatry clinics at an age at which bipolar disorder and schizophrenia may first appear and at which pregnancy is a possibility. Doctors who may have little experience in the management of ADHD or use of psychostimulants are faced with decisions on whether to continue or withdraw medication. A literature search conducted to clarify these issues revealed that, although psychostimulants are generally efficacious in ADHD, the risks of withdrawal reactions and of possible long-term effects such as drug addiction, psychosis and depression, or effects in pregnancy, have not been adequately investigated. In particular, there is little information on the effects of withdrawal and no firm guidelines on methods of psychostimulant discontinuation. There is a need for further research to clarify the pharmacological issues involved in the drug treatment of ADHD and for overlapping arrangements between child and adult psychiatry clinics in the management of ADHD.

Adult↗
PubMed2006

Assessing cortisol and dehydroepiandrosterone (DHEA) in saliva: effects of collection method.

An increasing number of studies are utilizing saliva sampling as a method of assessing adrenal steroid secretion. Saliva samples have certain advantages over plasma, being non-invasive and easily collected. However, some methods of collection may compromise the accuracy of the assay, particularly those which employ aids to stimulate saliva production. We sought to compare the accuracy of cortisol and dehydroepiandrosterone (DHEA) measurement by examining the association between plasma levels, saliva and saliva collected using a citric acid-treated salivette device. Twenty six healthy male volunteers were recruited for the study. To increase the range of steroid levels in the samples collected, half the subjects were pre-treated with hydrocortisone (20mg, twice a day for 7 days) and half with placebo. Saliva samples were then collected from each subject using both a 'passive drool' method and a citric acid-treated salivette. A plasma sample was also collected. Cortisol and DHEA levels were measured by radioimmunoassay. For cortisol levels, both methods of saliva collection correlated highly with plasma levels and with each other (r 0.85; R(2) 0.72 for all). For DHEA levels, only saliva samples collected using the unstimulated collection method correlated with plasma levels. DHEA collected using the salivette device did not correlate significantly with either plasma or the unstimulated saliva (r 0.2;R(2) 0.04). It is crucial that future studies are aware of these issues and are cognizant of the effects of the method of collection when examining steroid levels in saliva.

Adolescent↗
PubMed2006

Neuropsychological dysfunction, soft neurological signs and social disability in euthymic patients with bipolar disorder.

BACKGROUND: Neurocognitive deficits exist in euthymic patients with bipolar disorder, but relationships between symptoms, psychosocial and neurological factors remain uncertain. AIMS: To measure neurocognitive function in bipolar disorder and explore links to sub-syndromal mood symptoms, soft neurological signs and psychosocial impairment. METHOD: Attention, memory and executive function were tested in 37 euthymic patients with bipolar disorder and 37 controls. Psychosocial functioning, soft neurological signs and residual mood symptoms were assessed. RESULTS: Performances on tests reflecting executive function and verbal memory (but not attention) were significantly poorer in the bipolar disorder group. Sub-syndromal mood symptoms produced small cognitive effects, predominantly on verbal memory. Soft neurological signs, especially frontal signs, were marked; some patients showed marked social disability which correlated strongly with soft neurological signs but weakly with executive dysfunction, which was linked to illness episodes. CONCLUSIONS: Cognitive dysfunction, social dysfunction and soft signs occur in euthymic patients with bipolar disorder and may represent trait deficits.

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

Effects of acute tryptophan depletion on mood and cognitive functioning in older recovered depressed subjects.

OBJECTIVE: Previous studies show that acute tryptophan depletion (ATD), by administration of an amino acid drink lacking tryptophan, can produce clinically significant depressive symptoms in subjects who have recovered from major depression. This is more likely in female patients who have had suicidal ideation, recurrent depression, and treatment with specific serotonin reuptake inhibitors. These risk factors are frequent in older recovered depressed people. The authors investigated the effects of ATD on mood and cognitive functioning in this group. METHODS: Sixteen recovered depressed (RD) subjects and 17 healthy-comparison subjects, over 60 years old, participated in a double-blind, placebo-controlled, crossover study involving administration of a tryptophan-depleting and a placebo drink. Mood ratings scales were administered at baseline and at 4 and 7 hours post-drink on each test day. A battery of neuropsychological tests, including the modified Mini-Mental State Examination (MMSE) was administered between 4 and 6 hours post-drink. RESULTS: Depletion of plasma free tryptophan was 71% at 4 and 7 hours after the active drink. There was no evidence of mood change at any time in either group. On the MMSE, however, the ATD/RD group showed a significant decrease compared with placebo. CONCLUSIONS: There was no evidence of mood disturbance during ATD in any subject. This may imply less sensitivity to acute disturbance of the 5HT system than in younger recovered patients.

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↗
PubMed2004

Corticosteroid-serotonin interactions in depression: a review of the human evidence.

RATIONALE: It has been suggested that corticosteroid-serotonin interactions are central to the pathophysiology of depression. These interactions have been investigated in healthy and depressed humans, primarily using neuroendocrine techniques. OBJECTIVES: To review the evidence regarding the nature of these interactions in healthy and depressed humans. METHODS: Electronic searches were performed for relevant papers, employing MEDLINE and Web of Science. To focus the review, we selected only those articles involving (i) assessment of serotonergic function following experimental manipulation of the HPA axis in healthy volunteers; and (ii) assessment of both serotonergic and HPA axis function in clinically depressed subjects. RESULTS: Pre-treatment with hydrocortisone, both acutely and sub-acutely attenuates the GH response to GHRH in healthy subjects. This complicates the interpretation of 5-HT neuroendocrine studies employing GH output as a measure. In depression there is evidence that reduced availability of l-tryptophan impairs HPA axis feedback. There is also evidence that depressed and healthy subjects may adapt differently both to low tryptophan and hypercortisolaemic challenges. There is no consistent evidence of a simple relationship between HPA axis function and 5-HT function in depression. CONCLUSIONS: The putative reduction in central 5-HT function has not been shown to be a direct consequence of hypercortisolaemia. Rather, the 5-HT system and HPA axis have complex inter-relationships. Challenges to either system, such as stress or reduced dietary tryptophan, may perturb the other and subjects vulnerable to depression may fail to adapt to such challenges.

Adrenal Cortex Hormones↗