Biomedical subjects
Publications and source records attributed to D R Rubinow.
An oral contraceptive was used successfully to treat recurrent premenstrual depressions and a subsequent major depressive episode in a 20-year-old woman. The relationship between premenstrual and major depressions is explored and the overlapping CNS effects of gonadal steroids and classical antidepressants are discussed.
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Somatostatin is a hypothalamic tetradecapeptide with many actions. We investigated a potential role for somatostatinergic neuron dysfunction in affective disorder by measuring somatostatin in the CSF of 47 patients with affective illness and of 39 normal volunteers. Medication-free depressed patients showed significantly lower levels of CSF somatostatin than normal volunteers (P less than .001) or patients during the improved state (P less than .01). A significant inverse correlation was observed between somatostatin and the duration of sleep on the night of the lumbar puncture. We also observed significant correlations between somatostatin and 5-hydroxyindoleacetic acid and norepinephrine in the CSF. Also noted were the significance of depression-related decreases in CSF somatostatin in relation to information about central somatostatin secretion, reported abnormalities of somatostatin activity, and potential interactions between alterations in somatostatin activity and the pathophysiology of depression.
Red blood cell Na+, K+-, Mg2+-, and Ca2+-adenosine triphosphatase (ATPase) activities were studied longitudinally in eight patients with affective disorders and 12 healthy volunteers. The patients had a higher mean Ca2+-ATPase activity than the volunteers, and the fluctuations in all three ATPase activities were greater in the patients than in the volunteers. Even though the mean Ca2+-ATPase activity was higher during manias and euthymic periods than during depressions, mood and ATPase activities did not correlate with each other in all patients. Lithium carbonate treatment did not alter the ATPase activities, and the quantity of vanadium present in the membranes could not account for the variations in the enzyme activities observed. We suggest that either the RBCs of manic-depressive patients are very sensitive to fluctuations of a lipophilic ATPase activity--regulating factor present in plasma or the patients have at times high levels of such a factor. In some patients, the level of this hypothesized regulator may fluctuate in synchrony with mood changes.
The rapid growth of the neurosciences in the past decade has served to blur the differences and enhance the similarities between research in medicine and in psychiatry. As the number of relevant biological variables and the questions asked in relation to them has expanded, so has the number of medical disorders of interest to the clinical researcher in psychiatry. In addition to these new areas of common interest, consultation-liaison psychiatry and clinical psychiatric research share a common conceptual foundation based upon model development and testing. It is proposed, therefore, that research at the interface between medicine and psychiatry represents a new frontier for both consultation-liaison psychiatry and clinical psychiatric research. Goals and strategies for research at the interface are discussed with specific reference to current research efforts at the National Institutes of Health.
Preliminary data showing a correlation between urinary free cortisol levels and ventricular-brain ratio in 10 affectively ill patients are presented. The literature on hypercortisolism and computed tomography (CT scan) abnormalities is reviewed. The authors suggest that the increased cortisol production in some psychiatric patients might be capable of altering the gross structure of the brain and that such alterations might be reversible.
Personal and family histories of suicidality were gathered in 45 patients who met Research Diagnostic Criteria for major affective disorder (n = 32, bipolar; n = 13, unipolar) and compared to CSF values of 5HIAA obtained by two different assays (n = 20, fluorometric; n = 25, high performance liquid chromatography). In separate analyses of the two assay groups, patients who had made a suicide attempt were not significantly different from those who had not in terms of 5HIAA value or family history of suicidality. Furthermore, in suicide attempters, 5HIAA was unrelated to the severity of the attempt.
Carbamazepine has a unique spectrum of clinical efficacy in paroxysmal pain syndromes and epilepsy, as well as in affective illness. Evidence of its therapeutic effects in lithium-resistant manic-depressive illness and schizoaffective illness is reviewed. The biochemical effects of carbamazepine as they might be related to either its anticonvulsant or psychotropic properties are presented and discussed. Carbamazepine alters classical neurotransmitter and second messenger systems, as well as a variety of neuropeptides which could relate to mechanisms of action or side effects. Comparison and contrast of the biological effects of carbamazepine with classical treatment agents, such as lithium carbonate, tricyclic antidepressants, and neuroleptics may help elucidate mechanisms underlying the pathophysiology of the mood disorders.
Carbamazepine, a drug used to treat manic-depressive illness, has been reported to possess antidiuretic properties, but its effects on arginine vasopressin (AVP) secretion are controversial. Consequently, we examined plasma AVP secretion during hypertonic (5%) saline infusion in seven manic-depressive patients while on placebo and after 3-5 weeks of carbamazepine treatment. We also measured carbamazepine's effects on basal levels of the hormone in cerebrospinal fluid. Carbamazepine significantly reduced the sensitivity of the plasma AVP response to osmotic stimulation without affecting the osmotic threshold for AVP secretion. Moreover, carbamazepine did not affect baseline weight, plasma osmolality, plasma sodium, urine output, plasma AVP, or cerebrospinal fluid AVP. Although the functional significance of these findings remain to be fully determined, the fact that carbamazepine significantly reduced AVP secretion without inducing diuresis supports previous suggestions that carbamazepine enhances renal responsivity to available AVP. In addition, since carbamazepine failed to affect the osmotic threshold, the reported cases of carbamazepine-induced inappropriate AVP secretion and water intoxication must be very uncommon and probably represent idiosyncratic responses.
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This review highlights that essentially all of the recently discovered putative central nervous system (CNS) peptides and other peptide substances are measurable in human cerebrospinal fluid (CSF). Preliminary evidence also suggests that peptides in CSF may have an active regulatory role in relation to CNS function and behavior. Even if this is not the case, CSF peptides may prove to be a useful indirect marker of CNS peptide function and metabolism. Alterations in peptides have been reported in neurological and psychiatric illness, pain symptoms and their treatment, symptoms such as anxiety, and following treatment with CNS active drugs such as carbamazepine. CSF methodologies provide a strategy for the study of the interaction of classical neurotransmitters and peptide substances and their relationship to neural function and behavior in man. Assessment of peptides in CSF may supplement post mortem studies of peptide levels and receptor distribution and help lead to new diagnostic and treatment approaches in neuropsychiatric disorders.
In this paper we have reported the results of studies in psychiatric patient groups using the strategy of measuring opioid activity and beta-endorphin (ir) in CSF. Our findings do not lend support to the notion of excess endorphin activity in schizophrenia, but rather suggest the possibility of a decrease in endogenous opioid activity in some schizophrenic patients. In affectively ill patients our data suggest that there may be a relative change in endogenous opioid system activity across state change in manic-depressive illness. Who also found a relationship between nurses' ratings of anxiety and CSF opioid activity in depressed patients, although it is unknown whether this directly relates to the pathophysiology of this symptom, or is related to stress response. The relationship between CSF opioid activity and HPA axis activity, as reflected by urinary free cortisol excretion, supports the notion of important physiologic relationships between these systems and raises the issue of a role for the endogenous opioid system in the abnormal activation of this system in depression. Finally, the finding of increased CSF opioid activity in anorexia nervosa patients when a minimum weight coupled with data relating endogenous opioids to eating behavior raises interesting questions regarding a possible involvement of the endogenous opioid system involvement in this illness.
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A case of probable exacerbation of an undiagnosed diabetic uropathy by a tricyclic antidepressant in a 67-year-old man with hypothyroidism, diabetes mellitus, and recurrent major depressive disorder is reported. The presumed mode of interaction is discussed and pertinent literature reviewed. It is emphasized that the clinician must be alert to the possibility of psychotropic drugs producing physiologic changes that can interact with or aggravate preexisting disorders.