Evaluating prolactin response to dopamine agonists in schizophrenia. Methodological problems.

Serum prolactin (PRL) level was assessed after challenges with apomorphine hydrochloride, saline, dopamine hydrochloride, or levodopa-carbidopa (Sinemet) in 19 control and 38 chronic schizophrenic subjects. Baseline PRL level varied inversely with age. High correlations existed between baseline PRL level and any subsequent absolute measure of PRL after administration of a dopamine agonist or placebo. Percent decrease was not a function of baseline concentrations and was therefore the only independent measure of drug response. Baseline PRL level was generally lower during exacerbation than remission in patients studied during two states of illness. Percent PRL level decrease after apomorphine administration was significantly greater in normal subjects than in schizophrenics. Correction of apomorphine responses for corresponding placebo (saline) values abolished differences between groups. Prolactin responses after dopamine or levodopa-carbidopa did not differ; however, placebo correction was not possible.

Age and the dexamethasone suppression test in depression.

The authors examined the effects of age on plasma cortisol concentrations of 81 depressed men after dexamethasone administration. Dexamethasone nonsuppression was significantly more frequent in patients older than age 55 than those younger. Similarly, older patients had significantly higher postdexamethasone cortisol concentrations than younger patients at all time points sampled. These differences could not be attributed to severity or to the prevalence of psychosis in older and younger depressed patients.

Acetylcholinesterase activity in CSF in schizophrenia, depression, Alzheimer's disease and normals.

Acetylcholinesterase (AChE) activity and protein were measured in the CSF of patients with Alzheimer's disease, depression, schizophrenia with and without tardive dyskinesia, and control subjects. AChE activity was assayed by a radioenzymatic method involving the direct extraction of hydrolyzed 3H-acetate into a toluene-based scintillation fluid followed by liquid scintillation spectrometry. AChE activity was proportional to the amount of CSF protein. Greater than 90% of AChE activity in CSF could be inhibited by 10(-3) M eserine. In addition, activity remained stable despite repeated freeze-thawing in an acetone-dry ice bath. Age was found to be positively correlated with CSF protein and AChE activity expressed per volume CSF, but not with AChE measured per milligram protein. No differences between diagnostic groups were found on either measure of AChE when the extraneous factors of age and CSF protein concentrations were controlled, nor were any differences found between groups for CSF protein when age was controlled.

Neuroendocrine and neurochemical measurements in depression.

The authors performed dexamethasone suppression tests (DST), TRH infusions, 72-hour urine collections, and lumbar punctures on a group of male depressed patients. Approximately 60% of the patients were DST positive and 33% had a blunted TSH response. Two biologic variables, the 8 a.m. postdexamethasone cortisol and the postprobenecid CSF 5-hydroxyindoleacetic acid (5-HIAA), accounted for over half of the variance in the behavioral measure, the Hamilton score. Plasma cortisol elevation was associated with high 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion; TSH blunting was associated with low urinary MHPG excretion. Comprehensive biologic measures showed certain significant interrelationships and correlations with the severity of depression.

Statistical power in biological psychiatry.

The use of statistical power and power analysis in both the design and evaluation of experiments in biological psychiatry is described. The possible consequences of low power investigations are discussed, and guidelines are provided to facilitate the application of power analysis. Power curves are provided for sample sizes ranging from 10 to 100 for the Student's t test, and for testing the significance of an obtained Pearson correlation coefficient at both the 0.01 and 0.05 alpha levels. Additionally, difference scales are provided for plasma cortisol and for several neurotransmitter metabolites that are frequently measured in cerebrospinal fluid (CSF). Power evaluation of selected CSF studies measuring neurotransmitter metabolites in depressives and controls suggests the majority had less than a 50% chance of detecting a medium size difference before the experiment was actually performed.