Ronald D. Franks

Sensory Physiology and Catecholamines in Schizophrenia and Mania

Hypersensitivity to sensory stimulation is a prominent characteristic of both schizophrenia and mania. Neurophysiological recordings suggest a common deficit in a central neuronal sensory gating mechanism which regulates sensitivity to repeated auditory stimuli. Dopamine and norepinephrine are hypothesized to have major roles in these illnesses, but their role in aberrant sensory processing has not yet been proved. Presumptive evidence for effects of catecholamines on sensory processing comes from psychophysiological studies of normal subjects challenged with stimulants who show decreased sensory gating, and studies of psychotic patients treated with neuroleptics who show improved function. Studies of similar phenomena in animals show comparable effects of catecholamines on sensory processing, both behaviorally and at the single neuron level. In this study, gating of auditory evoked potentials (EPs) during treatment of both illnesses was compared with plasma dopamine and norepinephrine metabolites. Comparisons of medicated and unmedicated states showed that schizophrenic patients have a fixed deficit in sensory gating, which is a familial trait, unchanged by medication. During acute illness, they have an additional transient hypersensitivity to stimuli, manifested as smaller EPs, which seems to be mediated by dopamine. Manic patients have only the deficit in sensory gating, which is transient and seems to be mediated by norepinephrine. Thus, similar neurophysiological deficits in the two psychoses are associated with different biochemical abnormalities, which may explain similarities in acute symptoms and differences in other aspects of the illnesses, such as their response to treatment.

Neurophysiological assessment of sensory gating in psychiatric inpatients: Comparison between schizophrenia and other diagnoses

Gating of auditory sensory responsiveness was examined in 75 psychiatric inpatients using a conditioning-testing paradigm with the P50 wave of the auditory evoked response, in which pairs of stimuli are presented to the subject. In previous studies, most schizophrenics did not decrement the second response to the extent seen in normals. Acutely ill patients, who were representative of patients admitted to a public university teaching service and a proprietary hospital, were used to examine the extent to which diminished sensory gating is found in diagnoses other than schizophrenia. About half of these patients showed diminished sensory gating that correlated with measures of severity of illness. The data, taken together with that from other studies using this paradigm, suggest that diminished sensory gating, like several other psychophysiological abnormalities, is a trait deficit in schizophrenia, but a state deficit in many other mental illnesses.

Calcium antagonists in mania: A double-blind study of verapamil

Five of seven acutely manic patients improved significantly when taking verapamil but not placebo in a double-blind crossover study. This finding adds support to two other formal studies of verapamil, several case reports of verapamil in manic patients, and one small study of nifedipine suggesting that some calcium antagonists may have antimanic properties. Indirect evidence links this antimanic action to correction of a disturbance of intracellular calcium dynamics in affective disorders. However, the effectiveness of calcium antagonist drugs could also be related to some property other than interference with the action of calcium within brain neurons.

Comparison of self-reports and clinicians' ratings of unipolar major depression.

Recent literature has unfavorably compared self-report measures of depression to clinician-administered measures such as the Hamilton Rating Scale. In the present study, the Beck Depression Inventory and the MMPI D scale were compared to the Hamilton Rating Scale to assess the effectiveness of each measure in discriminating unipolar depressed psychiatric inpatients (n = 26) from inpatients without a major affective disorder (n = 11). Scores on the Beck scale and the MMPI Depression scale but not the Hamilton Rating Scale were significantly related to the diagnosis of unipolar major depression.

MMPI Results Associated with Abnormal Responses to the DST and TRH Tests

In the present study, it was predicted that psychiatric inpatients who obtained abnormal responses on the Dexamethasone Suppression Test (DST) and the Thyrotropin Releasing Hormone Stimulation Test (TRH) would obtain higher elevations on the MMPI scales associated with depressive symptomatology than inpatients with normal DST and TRH responses. Patients with abnormal DST responses obtained significantly lower scores on the F, Psychopathic Deviate, and Paranoia scales, suggesting that they present themselves on the MMPI as less socially maladjusted, and less alienated from societal values than their depressed inpatient peers who obtained normal DST results. No differences were obtained between abnormal and normal responders on either the DST or TRH with respect to the MMPI scales that are typically associated with depression.

Hypocalciuric effect of lithium: a confirmatory study.

Abstract This study confirms previous observations that short-term lithium therapy decreases urinary calcium excretion. Hypocalciuria begins within a few days of administering lithium carbonate (but not sodium carbonate) in low doses (300–600 mg/day) to normal volunteers. It is not due to an alteration in gastrointestinal absorption of calcium. Rather, it may be caused by increased renal calcium conservation secondary to increased parathyroid hormone secretion. Its exact clinical significance remains to be elucidated.