Robert H. Gerner

Biological and behavioral effects of one night's sleep deprivation in depressed patients and normals

Abstract Twenty-five patients with major depressive illness and 20 normal volunteers were sleep deprived for one night in order to assess mood, physiology, and biochemistry. Fifteen patients showed mild to moderate improvement in depression, normally lasting one day, while volunteers tended to experience slight increases in dysphoria following sleep deprivation (SD). Prior to SD depressed patient responders had lower baseline levels of HVA in CSF than non-responders. Following SD responders tended to have decreases in CSF calcium and MHPG and increases in serum cortisol compared to nonresponders. Nonresponders also showed a flattened diurnal temperature rhythm following SD. Alterations in central neurotransmitters, circadian rhythms, and stress activation are discussed as possible mediators of the selective mood improvement in depressed patients compared to normal volunteer controls.

Altered neuropeptide concentrations in cerebrospinal fluid of psychiatric patients

Immunoreactive somatostatin, bombesin, and cholecystokinin were measured in cerebrospinal fluid of normal subjects and patients with anorexia nervosa, depression, mania, and schizophrenia. Somatostatin-like immunoreactivity was decreased in anorexic and depressed patients. Bombesin-like immunoreactivity tended to be decreased in schizophrenics. Cholecystokinin-like immunoreactivity did not differ between groups. These data suggest a possible function for neuropeptides in regulation of human behavior.

CSF β-endorphin-immunoreactivity in normal, schiziphrenic, depressed, manic and anorexic subjects

beta-Endorphin immunoreactivity was measured in cerebrospinal fluid of 75 medication-free subjects: normal, depressed, schizophrenic, and anorexic. No significant differences in beta-endorphin immunoreactivity were found. Affinity extraction chromatography revealed beta-lipotropin and beta-endorphin, but no apparent precursors.

Assessment of naltrexone in the treatment of schizophrenia

Naltrexone, a long acting opiate antagonist, and placebo were administered to eight schizophrenics in doses of 200 mg per day for 1 week in a double-blind, crossover design. No improvement was noted, and no side effects resembling the opiate withdrawal syndrome with naltrexone were found. Naltrexone does not appear to alter schizophrenic symptomatology.

Selection of control populations for clinical cerebrospinal fluid GABA investigations based on comparison with normal volunteers

Abstract Altered cerebrospinal fluid (CSF) GABA levels have been implicated in various neurologic and psychiatric disorders, therefore, the establishment of the normal range of human CSF GABA is essential. The GABA content in 111 samples of lumbar CSF from 87 drug-free normal individuals obtained from three medical centers was measured by ion-exhange/fluorometric assay. The overall mean value (± SD) was 214 ± 74 pmol / ml ; however, significant variations in lumbar CSF GABA concentrations with respect to age, sex, and aliquot were documented among homogeneous subgroups of the overall population. CSF GABA levels were negatively correlated with age among females ( p

Bombesin-like immunoreactivity in human cerebrospinal fluid.

Abstract Bombesin-like immunoreactivity (BLI) was detected in the cerebrospinal fluid of healthy human volunteers. The mean concentration+-S.E. for 29 subjects was34.4 +- 1.8fmol/ml. Chromatography of human spinal fluid BLI on Sephadex G50 revealed a single peak which coeluted with bombesin nonapeptide.

Present status of drug therapy of depression in late life

The increasing proportion of elderly to the general population and the relatively high prevalence rate of depression in this age group justifies concern for specific clinical indications for antidepressant selection. Of the numerous agents that possess antidepressant activity, some have a more narrow therapeutic window for the old (lithium), while others may be more efficacious for the old than traditional tricyclics (stimulants and monoamine oxidase inhibitors). Stimulants and monoamine oxidase inhibitors require close monitoring to obviate complications, and this limits their use in this population. Prescription of the more common reuptake inhibitors in this age group can be based on consideration of efficacy and especially predictable incidence of side effects. Efficacy of all the reuptake inhibitors is essentially equivalent over 4 weeks, if the patient can tolerate treatment. Antidepressants with many side effects are, thus, less efficacious if we consider only whether the patient will be better 4 weeks after we start treatment since drop outs must be considered treatment failures for that particular treatment. Side effects are more clearly different among the antidepressants with demonstrably fewer cardiac effects (i.e. ECG changes, orthostatic hypotension) for buproprion, mianserin, nomifensine, and trazodone in the geriatric group compared to older agents such as amitriptyline and imipramine. Further, anticholinergic effects in the periphery (dry mouth, constipation, blurred vision, and urinary hesitancy) and centrally (confusion, sedation, decreased memory recall) are substantially less with several of the newer antidepressants: buproprion, maprotiline, nomifensine and trazodone.

CLINICAL PHARMACOLOGY OF β‐ENDORPHIN IN DEPRESSION AND SCHIZOPHRENIA*

The history of clinical studies with 8-endorphin (8-EP) differs in sequence from that of most drugs. Clinical trials of drugs usually begin with studies on the metabolism, biological activity and toxicity in normal volunteers (FDA phase I ) , then proceed to efficacy studies in diseased subjects (phase 11). This has not been the sequence with 8-ep in part because of uncertainty in identifying the appropriate diseased population. This paper reviews the results of our work on the clinical pharmacology of 8-EP in depression and schizophrenia. We have focused not only on the efficacy of 8-EP in these disease states, but also on other aspects of its clinical pharmacology, for example dosage form, pharmacokinetics, pharmacodynamics, and physiological effects. Because of the unusual history of clinical trials with &EP, these variables have never been studied in normal subjects. We believe they should not be neglected, because knowledge of the clinical pharmacology of a drug is important in designing valid efficacy studies.

Dose-Dependent Valproic Acid Thrombocytopenia in Bipolar Disorder

The increased use of anticonvulsants in the treatment of bipolar disorders necessitates a greater appreciation of potential complications from these agents. The authors present a bipolar disorder patient with dose-dependent valproic acid thrombocytopenia and suggest treatment strategies.

Geriatric Depression and Treatment with Trazodone

With the growing number of Americans over the age of 65 years, the high incidence of geriatric depression has become a major concern in the United States. Age-related circumstances--increased incidence of illness, bereavement, financial difficulties, and institutionalization--may contribute to an increased rate of depression in this age group. The signs and symptoms of depression in elderly patients are similar to those seen in younger individuals; therefore, standard Diagnostic and Statistic Manual III (DSM-III) criteria are reliable for making a diagnosis. However, symptoms such as insomnia, obsessional thought, and hypochondriasis may be relatively increased in the elderly patient; and the diagnosis of geriatric depression can be complicated by signs and symptoms of depression that may overlap with those of dementia. In the geriatric group, the mainstay of pharmacotherapy has been the reuptake antidepressant agents. Choice of antidepressant therapy is largely based on the side-effect profile. Thus, the fewer and less severe side effects associated with trazodone make it a suitable drug choice in these patients. Trazodone has been shown to demonstrate comparable efficacy to the other reuptake and monoamine oxidase inhibitors, but has the advantages of a low cardiovascular-risk profile, extremely low suicide toxicity, absence of anticholinergic side effects, and minimal effects on cognition.