Familial associations with EEG variants in manic-depressive disease.

Electroencephalographic (EEG) studies of 60 patients with bipolar manic-depressive disease disclosed an incidence of small sharp spikes plus a few other variations in 47% of the sample. In women these EEG features were significantly associated with a history of mental illness in the patient's mother or the maternal side of the family and an absence of mental disorder in the fathers. The reverse was true of women probands without these EEG characteristics. In the men small sharp spikes did not relate to parental psychopathology but half of the sisters of men with these EEG characteristics were found to be mentally ill. On the basis of these observations and previous work, we hypothesize that the small sharp spike EEG pattern might be an inherited characteristic related in some way to the familal transmission of manic-depressive disease.

Carbamazepine compared with lithium in the treatment of mania.

Fifty-two hospitalized manic patients were randomized to treatment with either carbamazepine or lithium carbonate after a 2-week drug withdrawal period. All of the probands were tertiary referrals with a high proportion of failures of previous lithium and other treatment. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for 8 weeks, and responders were followed up for up to 2 years. One third of patients responded favorably. Double-blind assessments revealed no statistically reliable differences between the two treatment groups. Patients receiving carbamazepine were somewhat more manageable than patients treated with lithium early in the study, whereas lithium-treated patients remained longer in the follow-up phase. However, numbers of long-term survivors were too small to be conclusive. This study adds to the growing body of evidence that acutely manic patients respond as well to carbamazepine as to lithium. However, monotherapy with either drug is not sufficient for the majority of manic patients who are referred for tertiary care.

Electroconvulsive treatment compared with lithium in the management of manic states.

Thirty-four hospitalized manic patients were randomized to treatment with either lithium carbonate or an average series of nine bilateral electroconvulsive treatments (ECTs), followed by maintenance with lithium carbonate. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for eight weeks, and patients were followed up monthly for up to two years. Ratings by nonblind and blind observers indicated that the patients who underwent ECT improved more during the first eight weeks than did patients who were treated with lithium carbonate. This was especially true of patients with mixed symptoms of mania and depression and/or extreme manic behavior. Clinical ratings after eight weeks showed no significant differences between the lithium carbonate- and ECT-treated patients. Likewise, the two groups had comparable rates of relapse, recurrence, and rehospitalization during the follow-up period.

Mechanisms of action of ECT: schizophrenia and schizoaffective disorder.

A variety of neurophysiological mechanisms have been suggested to explain the therapeutic action of electroconvulsive therapy (ECT). Processes of kindling, resolution of hemispheric dysfunctions, anticonvulsant effects, and diencephalic stimulation all have been proposed to account for the beneficial effects of ECT. To investigate these, we analyzed clinical, neuropsychological, and electroencephalographic (EEG) data from 110 ECT-treated patients with schizophrenia and schizoaffective disorders, comparing responders with nonresponders. Fifty-four percent of all the patients were rated as very much or much improved. Mechanisms of kindling or anticonvulsant effects were not supported by the data. Dominant hemispheric dysfunctions in schizophrenics were suggested by the neuropsychological test data. There was tenuous support for the sensitization theory and both the neuropsychological and EEG data contradicted the dominant accentuation theory. Taken together with our previous report on ECT-treated patients with affective disorders, we propose that ECT might act by restoration of equilibrium between the hemispheres.

Manic symptoms: an indication for bilateral ECT.

As a follow-up to pilot observations that six manic patients who failed to respond to unilateral electroconvulsive therapy (ECT) recovered rapidly when switched to bilateral treatment, a retrospective study was conducted. Twenty-five patients who responded after switchover from unilateral to bilateral ECT, 25 age- and sex-matched controls, and 25 concurrent controls who responded to right unilateral ECT alone were evaluated. Demographic variables and DSM-III diagnosis did not discriminate between the groups, nor were they different in terms of electroencephalographic (EEG) findings, neuropsychological test results, numbers of ECT, and duration of seizure discharges. Standard assessments of psychopathology performed by independent psychiatrists showed no differences in ratings of psychosis or depressive phenomena. However, scales assessing manic symptoms showed highly significant differences with many more features of unrestrained behavior, elevated mood, hurried speech, and other typical features of mania in the patients who were switched from unilateral to bilateral ECT. Although there were no differences in prescribed drugs, the use of prn medications for sleep was greater in the experimental-switched patients than in controls. Patients who responded to unilateral ECT alone exhibited virtually no manic features, whereas those who demonstrated these characteristics failed to respond to unilateral ECT but benefited when switched to bilateral treatment.

Follow-up of stereotaxic amygdalotomy for seizure and behavior disorders.

Stereotaxic amygdalotomy for the control of unmanageable behavior and/or intractable seizures is a controversial treatment approach with unknown risk-to-benefit ratios. Information about this subject was obtained from a retrospective follow-up study of 58 patients who received this form of treatment 1 to 11 years earlier (average 6 years). Assessments of the patients were made by invesgators external to the surgical treatment system, using structured psychiatric interviews, neuropsychological tests, and EEGs. In addition, global assessments were made, comparing pre- versus postoperative status. The objective data revealed no indication of worsening or damage with similar pre- and postoperative test scores and EEG features. Computer-scored interviews revealed considerable psychopathology in the ambulatory patients. Overall judgments of behavior, seizures, and functional levels indicated that more than a third of the group was probably improved, although the relationship of outcome to the surgery was indeterminate.

Changes in neuropsychological test performance after electroconvulsive therapy.

A group of 231 psychiatric patients were evaluated (with the Wechsler Adult Intelligence Scale and the Halstead-Reitan Neuropsychological Test Battery) before and after electroconvulsive therapy. Improvement during the course of therapy was shown in 96% of the measures and significant improvement (p less than 0.05) occurred in 37.5% of the measures, indicating generally improved functioning. The performance of these patients on the pre-ECT testing was generally in the range characteristic of patients with documented brain damage, but the score improved during the course of treatment to the borderline normal level.

Electroencephalographic findings in relation to diagnostic constructs in psychiatry.

A group of 759 patients with final DSM-I and -II diagnoses of schizophrenia was identified among a cohort of 1494 adults who were hospitalized between 1965 and 1972. Admission EEG recordings were done in each patient during waking, activation procedures, drowsiness, and sleep. All cases were reclassified according to the Feighner et al. criteria, and relationships between the EEG, reassigned diagnosis, and outcome were examined. One-third of the schizophrenics were rediagnosed as having affective, organic, or other disorders. EEG abnormalities predicted diagnostic change and relatively favorable prognosis. Mean alpha frequencies were slower in schizophrenics than in patients with other DSM I-II disorders, and less in patients with Feighner et al. diagnoses of schizophrenia than in some rediagnosed categories. In 1980-82, matched samples from the original cohort with affective, schizophrenic, and mixed Feighner et al. diagnoses were followed and evaluated blindly with the SADS-L. RDC follow-up diagnoses were significantly correlated with the index EEG findings in terms of higher alpha average frequencies proportional to the amount of affective psychopathology. A subgroup of high functioning individuals within the RDC schizophrenic category was identified with affective symptomatology early in the course of illness, normal EEGs, and high alpha average frequencies. Patients with a consistent diagnosis of schizophrenia according to the three nosologic systems were shown to function better in some areas if the index EEG was abnormal. Discriminant function analysis established that DSM-I and -II categories possessed the greatest long-term predictive accuracy which was enhanced by the EEG diagnosis and alpha average to a level of more than 50%. The Feighner et al. and RDC diagnostic systems were not as relevant for prediction of long-term follow-up status.

Electroconvulsive therapy for mania.

Early literature on the use of electroconvulsive therapy (ECT) for mania is reviewed briefly, followed by an account of retrospective and prospective studies that indicate the usefulness of ECT in the treatment of mania. Case vignettes that involve patients with relatively mild manic illnesses are presented, followed by discussion of technical issues, side effects and complications, drug interactions, monitoring, special populations and circumstances, and regulatory aspects. The article concludes with a brief consideration of possible mechanisms of action.

Influence of sex and handedness on hemispheric functioning.

Forty normal adult volunteers comprising an equal number of right- and left-handed males and females solved simple multiplication problems presented visually to one cerebral hemisphere while various competing stimuli were simultaneously presented to the other hemisphere. The contribution of sex of subject, handedness, hemisphere of presentation and the nature of the competing stimulus in relation to task performance was examined. Each of these variables was significantly associated with correct responses and errors, with few statistically significant interactions. Females and dextrals made more correct responses than males or sinistrals. Type of error depended upon which hemisphere received the problem, with the right hemisphere yielding more errors of commission and the left more errors of omission. Simultaneously presented identical or different arithmetic problems resulted in the most errors compared to the other competing stimuli.

Computerized EEG profiles of haloperidol, chlorpromazine, clozapine and placebo in treatment resistant schizophrenia.

In this paper we have described early applications of computerized EEG techniques in psychopharmacology. Perhaps our most remarkable finding was there were practically no differences between very chronic drug free schizophrenic patients and normals, which contradicts much of the EEG imaging literature. To us, the most likely explanation is that most of the anterior slowing observed in other studies was due to contamination from orbital artifacts, which we took exceptional pains to remove. Lingering effects of neuroleptic medications may also have contributed. Alternatively, EEG deviations in schizophrenia may recede when the illness reaches a very chronic stage, although this hypothesis is less tenable. There were significant differences between placebo and the three neuroleptics in terms of increased amplitudes in the delta and theta frequency bands in the anterior head regions, which is compatible with data from other studies. These changes were most pronounced with clozapine and least prominent with haloperidol, with chlorpromazine occupying an intermediate position. This order happens to parallel their relative antiserotonergic, antihistaminic and anticholinergic properties. The latter may have been partially obscured by the addition of benztropine. In a subgroup of patients who were recorded under each of the treatment conditions, there were more fast frequencies with clozapine than with the other neuroleptics agreeing with Roubicek and Major. This could be a function of clozapine's increased adrenergic activity as reported by Ackenheil. An unexpected finding was that patients who responded to clozapine had higher amplitudes in the alpha spectrum, most pronounced in the left anterior quadrant, than did the nonresponders. These differences between responders and nonresponders obtained whether patients were on placebo, haloperidol or clozapine. Curiously, Buchsbaum et al. found that anxious patients who responded to benzodiazepines also had higher alpha amplitudes in the same brain regions, which differentiated them from nonresponders. These findings clearly warrant future scientific investigation. In this regard, the generalizability of our data is limited by the extremely chronic, treatment-resistant population studied. However, promising directions for further research in EEG and psychopharmacology have been identified.

Electroconvulsive treatment--indications, benefits, and limitations.

Multiple variables were examined in relation to outcome of ECT in a complete population of 261 patients treated over a four-year period. Sixty-three percent were rated as much improved. Response to ECT was not predicted by identifying data, DSM-III Axes I, II and III, Research Diagnostic Categories (RDC) or the majority of the "blind" clinical ratings and neuropsychological and EEG data. ECT response was significantly associated with DSM-III Axis IV and V, history of substance abuse and the Brief Psychiatric Rating Scale (BPRS) withdrawal-retardation factor. Ratings of psychopathology and measures of intelligence improved with ECT, more in the patients who responded favorably than in those who did not. Scores on the neuropsychological test battery were better after ECT but remained within the brain-damaged range. Schizophrenic patients received the greatest number of treatments and showed the least variability in seizure duration. Electrical energy required for seizure induction was highest in depressed patients. Bilateral electrode placement was preferred for the majority of patients.