Frederick W. Malloy

Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder.

The safety and tolerability of clozapine combined with lithium were investigated because of potential additive risks as well as frequent usage in clinical practice. Ten hospitalized schizophrenic and 10 schizoaffective patients receiving clozapine maintenance therapy with partial therapeutic response were studied in a randomized controlled trial. CGI and PANSS outcome ratings were employed and a cognitive battery was administered at baseline and after 4 weeks of lithium and placebo administration. Barnes and UKU side effect ratings and laboratory safety data were obtained. Combined lithium-clozapine treatment was well tolerated except for reversible neurotoxic reactions in two schizophrenic patients. Safety measures showed no significant variations, even during lithium toxicity. Total WBC and absolute granulocyte counts increased with lithium and declined with placebo. Schizoaffective patients improved with lithium on CGI and PANSS total and negative symptom scales and the cognitive measures, whereas schizophrenic patients did not. Lithium added to clozapine in treatment regimens for hospitalized, treatment-resistant, schizoaffective patients appears to afford potential benefit without harmful effects; for schizophrenic patients, however, it did not afford improvement but posed a risk of lithium toxicity.

Increased temporal variability of auditory event-related potentials in schizophrenia and Schizotypal Personality Disorder

Previous studies suggest that deficits in neural synchronization and temporal integration are characteristic of schizophrenia. These phenomena have been rarely studied in SPD, which shares phenomenological and genetic similarities with schizophrenia. Event-related potentials (ERPs) were obtained using an auditory oddball task from 21 patients with schizophrenia, 19 subjects with SPD and 19 healthy control subjects. Inter-trial coherence (ITC) and event-related spectral perturbation (ERSP) were measured across trials to target tones using time-frequency analysis. ITC measures phase locking or consistency, while ERSP measures changes in power relative to baseline activity. P300 latency and amplitude were also measured from the averaged ERP to target tones. In the time-frequency analysis, subjects with SPD showed intact power but a deficit in the ITC in delta and theta frequencies compared to control subjects. Patients with schizophrenia showed deficits for both ERSP and ITC in the delta and theta frequencies. While patients with schizophrenia showed reduced P300 amplitude and delayed latency for averaged ERPs, subjects with SPD did not differ from either group. Synchronization or timing abnormalities may represent a biomarker for schizophrenia spectrum disorders, and contribute to aberrant perceptual and cognitive integration.

Topographic EEG studies of mania

QEEG findings from 39 hospitalized manic patients were accomplished after a drug free period and following pharmacotherapy with lithium or carbamazepine alone or lithium combined with carbamazepine, haloperidol or risperidone. A subsample of 10 drug-free manic patients was compared with normal controls, which revealed lower qEEG amplitudes in the left anterior and midtemporal regions in the patients. Comparisons of drug therapies showed increased delta amplitudes and total power with lithium compared with carbamazepine. Increased fast frequencies were observed in the lithium and carbamazepine plus lithium groups compared with carbamazepine alone. Comparisons of the three drug combination groups revealed increased alpha and beta 1 amplitudes, most with risperidone and least with carbamazepine. Anterior delta and beta 2 amplitudes and interhemispheric coherence were increased directly proportional to plasma lithium levels. Nonresponders to treatment were identified at baseline by increased generalized theta amplitudes. After treatment, the nonresponders had higher amplitudes in the left temporal areas. Numerous qEEG associations with individual ratings of manic symptoms were found, more at baseline than after treatment. In general levels of psychopathology were negatively correlated with qEEG amplitudes. The qEEG findings appear to implicate dominant temporal lobe dysfunctions in mania.

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.

Quantitative electroencephalographic frequencies and relative neuroleptic receptor affinities in schizophrenia

Information is now available about the receptor binding properties of standard and atypical antipsychotic drugs (Kerwin 1994; Lieberman 1993; Pickar 1995). As yet there has been minimal attention to neurophysiological attributes that may correspond to receptor affinities, although Czobor and Volavka (1993) have hypothesized that changes in power spectral density and symmetry may be related to serotonergic and dopaminergic mechanisms. Sloan et al (1992) have shown that the central effects of anticholinergic drugs are reflected in increased electroencephalographic (EEG) slowing and reduced coherence. An opportunity to examine such relationships was afforded by our practice of collecting quantitative EEG data before and during chronic administration of neuroleptics in chronic schizophrenic patients.