Philip A. Berger

Auditory event-related potentials in schizophrenia and depression.

Event-related potentials in two auditory target detection paradigms and two auditory paradigms without overt tasks were studied in 22 schizophrenic, 21 depressed, and 28 matched control subjects meeting Research Diagnostic Criteria. In the target detection paradigms, schizophrenics showed a pattern of reduced N120 amplitude and shorter P200 latency to frequently occurring tones, and reduced P300 and Slow Wave amplitude to infrequent target and nontarget tones. This pattern is consistent with impaired selective attention for stimuli. For depressed patients these variables were generally intermediate between those of schizophrenics and controls. In the other paradigms N120 latency was greater for schizophrenics, and P200 amplitude was less for depressed patients.

P3 reduction in auditory evoked potentials of schizophrenics

Fifteen schizophrenics and 15 age-matched controls performed a reaction time (RT) task. A Bernoulli sequence of 85 dB SPL, 50 msec, 800 c/sec (P = 0.85) and 1200 c/sec (P = 0.15) tones was presented with an interstimulus interval of 1 sec. Subjects were instructed to press a button quickly upon hearing the 1200 c/sec tone. If a subject failed to respond within 650 msec, a 50 msec white noise burst occurred. In averages synchronized with target tones and computed without respect to RT, P3 was maximal at PZ with a mean latency of 330 msec for both schizophrenics and controls. P3 amplitude at PZ, however, averaged 6 muV in schizophrenics and 14 muV in controls (P < 0.001). Both mean RT and mean within-subject variance were greater in schizophrenices than controls. Other kinds of averages were computed to investigate the possibility that the amplitude differences were associated with different RTs or with differences in P3 latency variability in underlying trails. Averages of trials associated with short RTs (100--286 msec) had larger P3s than averages associated with long RTs (287--600 msec) (P < 0.01). Within each RT range, however, schizophrenic P3s were smaller than control P3s. Neither response-synchronized averaging nor adaptive filtering eliminated P3 amplitude differences between groups, indicating that P3 latency variability cannot account for these differences. We hypothesize that the smaller P3s in schizophrenics represent a deficit in reactivity to unexpected stimuli that is compatible with normal RT performance.

Choline in tardive dyskinesia and Huntington's disease.

Abstract Eight men, 4 with tardive dyskinesia and 4 with Huntingtons disease, were treated with oral doses of choline chloride up to 20 g daily for three to eight weeks. Prior to treatment, 7 of the 8 patients were tested with a graded dose of 3 mg of physostigmine salicylate, a cholinesterase inhibitor. Six of these 7 patients had a favorable acute response to physostigmine. The same six patients had a favorable response to chronic treatment with choline chloride. Relapses following a switch from active treatment to placebo were delayed, but this could not be explained on the basis of the rate of choline disappearance from plasma. Re-treatment with choline chloride reversed relapse in most instances. Choline chloride may ameliorate these movement disorders by increasing central cholinergic activity, but other mechanisms are possible. Its practical importance as a treatment needs further elucidation.

Brain acetylcholine and neuropsychiatric disease

Brain Acetylcholine and Psychiatric Disorders.- Psychological Effects of Cholinomimetic Agents.- Pharmacological Investigations of Cholinergic Mechanisms in Schizophrenia and Manic Psychosis.- Affective Changes with Deanol.- Lithium and Acetylcholine Interactions.- Cerebrospinal Fluid Acetylcholinesterase in Psychosis and Movement Disorders.- Brain Cholinergic Enzymes in Schizophrenia.- Red Cell Choline and Affective Disease.- Brain Acetylcholine and Movement Disorders.- Treatment of Huntingtons Disease and Tardive Dyskinesia with Choline Chloride.- Choline Administration to Patients with Huntingtons Disease or Tardive Dyskinesia.- Deanol Trials in Tardive Dyskinesia.- Oral Physostigmine and Inherited Ataxias.- Alterations in Muscarinic Cholinergic Receptor Binding in Huntingtons Disease.- Brain Acetylcholine and Cognitive Function.- Cholinergic Excitability and Memory: Animal Studies and their Clinical Implications.- Brain Acetylcholine and Disorders of Memory.- Carbohydrates and Acetylcholine Synthesis: Implications for Cognitive Disorders.- Cognitive Effects of Physostigmine and Choline Chloride in Normal Subjects.- The Treatment of Memory Deficits in the Aged with Choline Chloride.- The Electrophysiology of Cholinergic Agents.- Brain Acetylcholine and Animal Electrophysiology.- Acetylcholine: Possible Involvement in Sleep and Analgesia.- Electrophysiological Effects of Physostigmine in Humans.- Electrophysiological Effects of Choline Chloride in Elderly Subjects.- Interactions of Brain Acetylcholine and Other Neurotransmitters.- The Role of Cholinergic and Dopaminergic Interactions in Diseases of the Central Nervous System.- Interactions Between Acetylcholine and Dopamine in the Basal Ganglia.- Evidence for the Existence of Two Striatal Dopamine Receptors.- Physostigmine Related Changes in Cerebrospinal Fluid Neurotransmitter Metabolites in Man.- Acetylcholine and Anterior Pituitary Hormone Secretion.- Biochemical and Pharmacological Aspects of Cholinergic Treatment Strategies.- Dietary Control of Central Cholinergic Activity.- The Neurochemical Basis of Acetylcholine Precursor Loading as a Therapeutic Strategy.- Choline Availability - Choline High Affinity Transport and the Regulation of Acetylcholine Synthesis.- Pharmacokinetic Studies with Choline Chloride: A Preliminary Report.- Choline Chloride: Effect on Hypeidopamineigic States in Animals.- Author Index.

Rating scales in research: The case of negative symptoms

Two measures of negative schizophrenic symptoms, the Scale for the Assessment of Negative Symptoms and the withdrawal-retardation subscale of the Brief Psychiatric Rating Scale, are found to be redundant when used together. Studies incorporating redundant measures have numerous disadvantages. Using multiple scales increases the cost and effort for the investigator, places a greater burden on research subjects, and compromises the interpretability of findings by increasing the probability of both Type I and Type II errors. A strategy for evaluating the use of multiple rating scales is suggested, and the theoretical basis of this strategy is discussed.

CSF dopamine levels correlate with extraversion in depressed patients

Cerebrospinal fluid (CSF) dopamine levels were studied in 16 male patients who also were tested for self-reported extraversion using the Eysenck Personality Inventory. Log CSF dopamine was significantly correlated with extraversion as predicted by recent theoretical work integrating mesolimbic dopamine function and active responding to external incentives as psychobiological traits. CSF dopamine levels were uncorrelated with the total score on the Hamilton Rating Scale for Depression, self-reported neuroticism, and age. The results are discussed in relation to other biological models of extraversion such as the construct of sensation-seeking behavior.

Speech and voice parameters of depression: a pilot study.

This pilot study tests one model for interdisciplinary research between speech science and psychiatry. Strengths and weaknesses of the model are noted. Thirteen depressed subjects were evaluated before and after treatment with antidepressant medication. Subjects were rated on scales for severity of depression and speech deviations. Scores on a depressed voice scale, comprising seven of the speech dimensions found to be most consistently altered in depression, showed significant improvement after treatment for depression. The constellation of speech signs found in depression suggested a hypokinetic disturbance of the extrapyramidal system. Several directions for further inquiry into this potential relationship are suggested.

Brain serotonin and pituitary-adrenal function

Publisher Summary This chapter describes the serotonin (5-HT) and pituitary-adrenal function. The effects of altering 5-HT synthesis on the diurnal rhythm of plasma corticosterone and on the pituitary adrenal response to stress were studied in rats and man. The hypothesis is proposed that 5-HT mediates the corticosteroid negative feedback mechanism that regulates corticotrophin (ACTH) secretion and that the primary site of this feedback is extra hypothalamic. In contrast, pretreatment with I-tryptophan, 5-HTP alone or 5-HTP and MK 486 reduced slightly the stress response in intact rats and 5-HTP with MK 486 reduced 24 h urinary 17-hydroxycorticosteroids (17-OHCS) excretion in humans. On the other hand corticosterone administration or stress increased the activity of tryptophan hydroxylase in the midbrain and the conversion of tryptophan to 5-HT. In addition, there appears to be a correlation between the daily rhythm of 5-HT content in the limbic system and that of circulating corticosterone. It is reported that treatment with parachlorophenylalanine (PCPA) abolished the diurnal variation of plasma corticosterone at an intermediate level in the rat, affect the metabolism or action of 5-HT abolished the daily rise in plasma 17-OHCS in the cat but did not block the response to stress.

Single case study. Possible organophosphate-induced parkinsonism

A case of possible organophosphate-induced parkinsonism is presented. The patient was a crop duster with numerous episodes of acute organophosphate intoxication and chronic organophosphate exposure. The etiology of parkinsonism is discussed in terms of a balance hypothesis between cholinergic and dopaminergic neurotransmission in the striatum. A possible relationship between chronic organophosphate exposure and alterations in central cholinergic or dopaminergic activity is suggested. The course of this patient raises the possibility that agricultural workers may be at risk for the late development of parkinsonism.

Platelet alpha2-adrenergic receptor sensitivity in major depressive disorder

Abstract We have investigated the functioning of α 2 -adrenergic receptors in patients with major depressive disorder by measuring the specific binding of 3 H-yohimbine, an α 2 -adrenergic receptor antagonist, to platelet membranes. B max and K d values for platelet 3 H-yohimbine binding were normal in unmedicated patients with major depressive disorder, and did not correlate with scores on the Hamilton rating scale for depression. Platelet α 2 -adrenergic antagonist sites were also unchanged in number or affinity in depressed patients after long-term treatment with a variety of antidepressant medications.