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Biomedical subjects

P E Stokes

Publications and source records attributed to P E Stokes.

At least 19 recordsLinked to original sources
PubMed1992

Hypothalamic-pituitary-adrenocortical function in mixed and pure mania.

There is little information about hypothalamic-pituitary-adrenocortical (HPA) axis function in mania, particularly in mixed states. We therefore investigated HPA function and its relationship to clinical state in 19 hospitalized manic patients meeting Schedule for Affective Disorders and Schizophrenia - Research Diagnostic Criteria for acute manic episodes, compared patients with and without a mixed presentation, and examined correlations between HPA activity and behavior. Data were available from 13-16 patients. Behavioral and biochemical analyses were conducted during a 15-d placebo period. Patients with mania had elevated cerebrospinal fluid (CSF) and urinary free cortisol excretion compared with healthy subjects, and did not differ from depressed patients in any cortisol measures. Mixed manics had significantly higher morning plasma cortisol, postdexamethasone plasma cortisol and CSF cortisol than pure manics. Five of 7 mixed manics and 3 of 9 pure manics were dexamethasone suppression test (DST) nonsuppressors. Afternoon plasma cortisol and CSF cortisol correlated significantly with depressed mood; urinary free cortisol correlated with anxiety. None of the cortisol measures correlated with mania or agitation scores. These data suggest that increased cortisol secretion is a characteristic of the depressed state in mixed manics, although pure manics may also have increased DST nonsuppression.

Adult↗
PubMed1991

Hypothalamic-pituitary-adrenal axis in psychiatric disorders.

Hypothalamic-pituitary-adrenocortical (HPA) physiology is complex, and dysregulation of this neuroendocrine axis cannot be characterized adequately by isolated or unintegrated measures. Repeated assessments over time, involving multiple measures of axis activity (basal and dynamic tests), have furthered our understanding of the character of the HPA abnormalities reported in various psychiatric disorders. We review the nature and clinical significance of these HPA disturbances in the affective disorders and other psychiatric illnesses.

Humans↗
PubMed1991

The changing horizon in the treatment of depression: scientific/clinical publication overview.

The author provides a critical review of clinical trials that evaluate the efficacy of antidepressants. It is noted that clinical studies often raise more questions even as they address the first questions. Kuhn's study in 1958 is regarded as a benchmark article, although that research was not conducted in the structured manner of current research. A review of prior research is followed by a discussion of the questions raised from the answers generated by the original issues. Evaluation of placebo response, treatment response rates, and the ethical issues surrounding placebo administration are considered. Studies reflecting use of antidepressants in diagnostic categories other than depression are also reviewed, and direction of future research is discussed.

Adolescent↗
PubMed1990

The influence of blood chemistry on T4 and FT4I in major depression.

The pathophysiology underlying thyroid dysfunction in some depressed patients has not yet been determined. In order to clarify possible biochemical influences on thyroid regulation in these patients, we retrospectively examined several thyroid indices in charts from 81 depressed inpatients and 82 psychiatric controls. The depressed group had significantly higher T4 levels and free T4 index (FT4I), as well as lower chloride (CL) levels than controls. Albumin (ALB) also tended to be higher in the depressives. After adjustment for previously reported effects of ALB and CL on thyroid hormone binding in plasma, the initial differences in thyroid indices became non-significant. We suggest from these findings that plasma biochemical factors contribute significantly to the transient changes in thyroid function observed in some acutely depressed patients. Potential explanations for these biochemical alterations are discussed.

Chlorides↗
PubMed1990

Stress, depression, and mania: relationship between perceived role of stressful events and clinical and biochemical characteristics.

We investigated the perceived role of stressful events in episodes of major affective disorder in patients studied in the NIMH Clinical Research Branch Collaborative Program on the Psychobiology of Depression (Biological Studies). Using items from the Schedule for Affective Disorders and Schizophrenia (SADS), episodes were divided into environment-sensitive (high perceived role of stressful events) and autonomous (minimal or no perceived role of stressful events). Patients with environment-sensitive episodes had fewer previous episodes and a longer index episode. The groups did not differ with respect to age, gender, education, socioeconomic group, diagnosis, severity of illness, or eventual response to treatment. Unipolar depressed patients with environment-sensitive episodes had lower CSF 5-HIAA than those with autonomous episodes. Among bipolar depressed patients, those with autonomous episodes had elevated excretion of O-methylated catecholamine metabolites and of epinephrine, while those with environment-sensitive episodes had normal excretion of catecholamines and metabolites. Manic subjects with environment-sensitive episodes had elevated norepinephrine excretion, while this was normal in manics with autonomous episodes. Relationships between environmental sensitivity of affective episodes and neurotransmitter function therefore appear to be related to the type of episode.

Adaptation, Psychological↗
PubMed1988

Cerebrospinal fluid and urinary biogenic amines in depressed patients and healthy controls.

The National Institute of Mental Health-Clinical Research Branch Collaborative Study investigated 132 drug-free, severely depressed patients and 80 healthy controls. Forty-five percent of the depressed patients excreted markedly elevated levels of urinary epinephrine (E) and metanephrine (MET), while only 5% of healthy controls did so. Using gaussian mixture distributions, we identified two subgroups of depressed patients: one excreting normal levels and the other excreting high levels of urinary E, MET, norepinephrine, and normetanephrine. Cerebrospinal fluid homovanillic acid levels were low in a subgroup of depressed patients. When analyzed by subgroup, the elevated E + MET group had markedly lower cerebrospinal fluid homovanillic acid levels than controls, whereas depressed patients with normal catecholamine levels did not. Since it has been postulated that there are two subgroups of depressed patients, those with low 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and normal 5-hydroxyindoleacetic acid (5-HIAA) levels and those with normal MHPG levels and low 5-HIAA levels, several analyses were performed to see if such a group could be identified. Our analysis failed to find evidence of a subgroup of depressives with low MHPG and normal 5-HIAA levels or normal MHPG and low 5-HIAA levels.

Biogenic Amines↗
PubMed1988

Adrenocortical hyperactivity in depression: effects of agitation, delusions, melancholia, and other illness variables.

In an attempt to determine the relative contributions to adrenocortical hyperactivity in depression of agitation, delusions, and melancholic subtype, we measured cortisol levels before and after dexamethasone in 93 unipolar major depressed inpatients. Stepwise multiple regression showed that agitation predicted 22% of the variance in a.m. cortisol level after dexamethasone. Addition of the variables melancholia and delusionality to the regression model accounted for 27% and 34%, respectively, of the variance in the same cortisol variable. Age, illness severity, and weight loss added no further significant predictive value. Age, weight loss, and illness severity did affect cortisol levels when examined separately from the other variables. Rate of nonsuppression on the dexamethasone suppression test (DST) differed between the nonmelancholic major depressive group and any other group with melancholia. These results suggest why some discrepancies may exist between studies of the DST in delusional depression and indicate that agitation merits careful assessment in future studies of DST response.

Adrenal Cortex↗
PubMed1988

Thyroid function in patients maintained on lithium.

To determine the clinical significance of thyroid function abnormalities in patients maintained on lithium, the authors evaluated the relationships of thyroid function tests to clinical response to lithium and side effects from lithium in 20 outpatients meeting DSM-III criteria for major affective disorder. No significant relationships were found between baseline thyroid function tests and clinical response. Thyroxine (T4) and triiodothyronine uptake ratio (T3UR) within the normal range were found to be associated with complaints of lethargy and cognitive impairment. Thirteen subjects were followed prospectively for 6 months with monthly evaluations of affective state, side effects, and occurrence of relapse. Thyroid function tests were repeated at the final visit. Final and mean T3 levels within the normal range were found to be significantly lower in patients who relapsed, and mean T3 level was inversely correlated with affective state as measured by mean scores on the Hamilton Rating Scale for Depression and the Young Mania Rating Scale.

Adult↗
PubMed1988

Insulin-induced hypoglycaemic response and release of growth hormone in depressed patients and healthy controls.

As part of the Collaborative Study of the Psychobiology of Depression, we have examined the pretreatment growth hormone response (delta GH) to insulin (0.1 U/kg) and the magnitude of the hypoglycaemic response in a large number of well-defined depressed patients (N = 132) and healthy controls (N = 80). After applying rigorous exclusion criteria, data were analysed from 93 patients and 66 controls for blood glucose response and from 56 patients and 52 controls for delta GH. Depressed patients, either unipolar or bipolar, showed less of a fall in glucose than controls. A weak association was found between the magnitude of the fall in glucose and the severity of depression. No significant differences were found in values for delta GH between the unipolar or bipolar depressed patients and controls either for males, pre-menopausal or post-menopausal females, or the total female group. These data do not support previous claims of a lowered delta GH response to insulin in depressed patients. However, the resistance to hypoglycaemia seen in the depressed patients is consistent with previous reports.

Adult↗
PubMed1988

Increased extrapyramidal symptoms with addition of lithium to neuroleptics.

To explore whether lithium exacerbates neuroleptic-induced extrapyramidal symptoms (EPS), the authors prospectively rated 10 patients on neuroleptics before and after the addition of lithium. EPS ratings increased steadily after the initiation of lithium and were significantly elevated compared with baseline. Individual items that increased significantly were: gait, shoulder shaking, elbow rigidity, and tremor. These findings indicate that usual therapeutic levels of lithium may significantly worsen neuroleptic-induced EPS. Potential mechanisms for this interaction are discussed.

Adolescent↗
PubMed1988

The hypothalamic-pituitary-adrenocortical axis in major depression.

The clinical utility of the tests of hypothalamic-pituitary-adrenocortical function discussed in this article are still to be ascertained. As with the dexamethasone suppression test, reviewed elsewhere in this issue, the application of other basal and challenge tests have furthered our understanding of the character of observed hypothalamic-pituitary-adrenocortical function in psychiatric patients. Hypothalamic-pituitary-adrenocortical physiology is complex and plastic and cannot be understood in terms of oversimplified explanations or concepts. Repeated measures over time, involving multiple assessments of axis activity, are essential in understanding the modulating effects of prior activity of the system (induced by endogenous regulatory systems or by superimposed environmental stressors) on the current function of the various levels in this closed-loop axis, where all parts influence the function of the remainder. From such an appreciation and understanding of this system can come more simplified assessments of its function, which would allow application to clinical psychiatry.

Adrenocorticotropic Hormone↗
PubMed1988

The hypothalamic-pituitary-adrenocortical axis in major depression.

The clinical utility of the tests of hypothalamic-pituitary-adrenocortical function discussed in this article are still to be ascertained. As with the dexamethasone suppression test, reviewed elsewhere in this issue, the application of other basal and challenge tests have furthered our understanding of the character of observed hypothalamic-pituitary-adrenocortical function in psychiatric patients. Hypothalamic-pituitary-adrenocortical physiology is complex and plastic and cannot be understood in terms of oversimplified explanations or concepts. Repeated measures over time, involving multiple assessments of axis activity, are essential in understanding the modulating effects of prior activity of the system (induced by endogenous regulatory systems or by superimposed environmental stressors) on the current function of the various levels in this closed-loop axis, where all parts influence the function of the remainder. From such an appreciation and understanding of this system can come more simplified assessments of its function, which would allow application to clinical psychiatry.

Adrenocorticotropic Hormone↗
PubMed1987

Weight loss, cortisol levels, and dexamethasone suppression in major depressive disorder.

Appetite and/or weight loss are integral, albeit not necessary, symptoms of depression. We explored the contribution of diminished appetite and/or weight loss ascertained by history to the hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation in 120 patients with primary major depressive disorder. Significant positive relationship for both appetite and weight loss with cortisol levels in plasma and cerebrospinal fluid (CSF) were observed. Plasma cortisol levels were consistently higher in patients who noted both appetite and weight loss as opposed to patients without appetite or weight loss. Depressed patients with weight loss showed higher rates of dexamethasone-nonsuppression. Age and severity of depression influenced but did not eliminate the significance of the findings, suggesting that weight loss accounts in part for the HPA-axis function changes observed in depression.

Adult↗
PubMed1987

Biogenic amine and metabolite levels in depressed patients with high versus normal hypothalamic-pituitary-adrenocortical activity.

The activity of the hypothalamic-pituitary-adrenocortical (HPA) axis is often high in depressive illness. The authors studied 132 depressed patients and 80 healthy control subjects. They report a significant direct association between HPA axis activity and adrenomedullary epinephrine secretion in depressed patients. They also found that depressed patients with high HPA activity tend to have lower CSF levels of 5-hydroxyindoleacetic acid, a serotonin metabolite, and modestly lower levels of 3-methoxy-4-hydroxyphenylglycol, a metabolite of epinephrine and norepinephrine, than patients with normal HPA activity. These findings provide potentially important leads for understanding interactions of biogenic amine systems with HPA axis function.

Biogenic Amines↗
PubMed1986

Aberrant parenting and delayed offspring development in rats exposed to lithium.

Natural lithium (Li) salts, including those used routinely in manic depressive illness, consist of two stable nonradioactive isotopes: lithium-7 (Li-7) (92.6%) and lithium-6 (Li-6) (7.4%). Female rats (3 months old) were treated with either Li-7 chloride or Li-6 chloride or were untreated prior to and during gestation and lactation. Birth weights were lower for Li-treated animals than for normal pups. Maternal behavior of all Li-treated mothers was altered. Li-7 mothers ignored their pups and nursed them infrequently. Li-6 mothers groomed and nursed their pups more often than normal mothers. All pups showed delays in development, especially in the maturation of depth perception. Although Li-6-treated dams were over-protective mothers, their offspring showed longer developmental delays than those of Li-7-treated offspring.

Animals↗
PubMed1986

Path analysis of psychopharmacological data: catecholamine breakdown in man.

This article applies path analysis to the problem of characterizing metabolic alterations in catecholamine systems when only static or single measures of precursor and products are available. In this article, simulated data from kinetic models of norepinephrine metabolism were examined using path analysis. The method of path analysis, which is based on correlations between compartments and not actual flow, correctly identified operative and nonoperative metabolic pathways in simulated models. In addition, actual data from normal subjects as to the 24-hour urinary values for norepinephrine, normetanephrine, vanillylmandelic acid, and 3-methoxy-4-hydroxyphenylglycol were analyzed using path analysis. It was found that metabolic routes that are known to be incomplete did not fit these data, whereas the known metabolic pathways for norepinephrine were correctly identified using path analysis. These results suggest that path analysis may provide a useful tool in identifying normal and abnormal catecholamine metabolic pathways in experimental situations where only single values of precursor and products are available.

Humans↗