A general introduction is given and followed by a review of recent literature under the following subheadings: electrodermal activity, cardiovascular activity, smooth pursuit eye movement, electroencephalogram, and evoked potentials. An attempt is made to assess the clinical significance of the findings reported in each area and to indicate directions for future investigation. The feasibility of defining homogeneous subgroups in schizophrenia using psychophysiological parameters is also considered. The review concludes with the recommendation that peripheral psychophysiological studies entailing (1) comprehensive recording of brain electrical activity and (2) behavioral experimentation on variables thought to be influenced by schizophrenia (e.g., sustained attentional ability) are promising directions for future research. Relationships between behavioral and psychophysiological variables determined by such studies (and possibly subgroupings) may then become the basis for neurophysiological-neurochemical investigations of specific abnormalities underlying such relationships and subgroups.

Recent Studies of Psychophysiology in Schizophrenia

Quantitative EEG in schizophrenia and in response to acute and chronic clozapine treatment.

Despite the widespread use of caffeine as a central nervous stimulant, the central pharmacodynamic properties of the drug have not yet been conclusively evaluated in humans. The present study was unde

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Effects of Caffeine on Topographic Quantitative EEG

1 Antidepressant drugs produce significant changes in human brain function as reflected in the quantitatively analysed EEG. Two main types of pharmaco-EEG profiles may be differentiated: a thymeretic (desipramine-like) profile characterised mainly by an alpha increase suggesting activating properties and a thymoleptic (imipramine- or amitriptyline-like) profile showing a concomitant increase of slow and fast activities and a decrease in alpha activity indicating also sedative qualities. A small number of compounds exhibit still different profiles. 2 Aside from determining the type of EEG changes, the pharmaco-EEG method seems to be of value in determining time and dose efficacy relations at the target organ, the human brain. Moreover, the relationships between pharmacodynamics and pharmacokinetics may be determined. 3 Fluvoxamine, a selective 5-hydroxytryptamine (5-HT) re-uptake inhibitor from the new class of 2-aminoethyloximethers of aralkylketones, produced a typical thymoleptic pharmaco-EEG profile after oral doses of 75 mg in a double-blind placebo-controlled study involving 10 healthy volunteers. Fluvoxamine (75 mg) induced less augmentation of slow activity than 75 mg imipramine, indicating less sedative properties of fluvoxamine than imipramine. 4 After 75 mg fluvoxamine psychometric tests demonstrated a tendency towards an improvement in attention, concentration, psychomotor activity, after-effect and mood and a significant increase in critical flicker fusion frequency as compared with placebo. Comparison with the reference drug, 75 mg imipramine, revealed a significant superiority of fluvoxamine regarding concentration, psychomotor activity, tapping, reaction time, mood and affectivity. 5 Side-effects (mostly tiredness) were seen in five out of 10 subjects after 75 mg fluvoxamine and in eight out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.

Pharmaco-EEG profiles of antidepressants. Pharmacodynamic studies with fluvoxamine.

The effect of a single dose of alcohol on the electroencephalograms (EEGs) of healthy male carriers of extreme variants of the EEG was examined. The EEG variants included: low voltage, borderline alpha, diffuse beta, and monotonous alpha EEG. The EEGs were analyzed on a small processor by means of a program for interval-amplitude analysis. The synchronizing effect of alcohol (increase of alpha activity and decrease of variance of frequency) was most pronounced in the borderline alpha EEG. As the interindividual variability of the resting EEG is known to be genetically determined, it can be concluded that the differential effects of ethanol on the EEG have a genetic basis.

Effect of alcohol on genetically determined variants of the normal electroencephalogram.

An objective rule for the classification of psychotropic substances has been developed. Classification is based on data from five basic studies simultaneously designed and performed and involving 75 healthy volunteers who ingested 20 different psychotropic drugs and 5 placebos in single oral dosages. Each volunteer took one psychostimulant, one antidepressant, one neuroleptic, one minor tranquilizer and one placebo in a double-blind Latin square cross-over design. The variables were 6 frequency bands, based on power spectrum estimates and determined by factor analysis, plus total power in the 1.5-30.0 Hz range. An objective classification rule was established by multi-group (5 groups) linear discriminant analysis. Reclassification of the substances by the new rule yielded correct results for 17 out of 20 psychotropic drugs and 4 out of 5 placebos. Of placebos from various studies not used for the establishment of the classification rule, 7/9 were classified correctly. The validity of the rule for other classes of substances will have to be verified in independent studies.

Development of a classification rule for four clinical therapeutic psychotropic drug classes with EEG power-spectrum variables of human volunteers

The acute efficacy of single oral dosages of 20 psychotropic drugs, 5 neuroleptics, 5 anxiolytics, 5 antidepressants and 5 psychostimulants plus 5 placebos has been tested in 5 basic studies simultaneously designed and performed and involving 75 healthy male volunteers. Each study was done in a Latin square double-blind design with 15 subjects, each receiving one placebo and one compound of each of the four clinical therapeutic psychotropic drug classes. Three 5-minute EEG recordings (pre, 1 hr. and 3 hr. post drug intake) are taken to represent the drug effects. The differences in drug efficacy were tested by multivariate analysis of variance using 3 × 7 power spectrum estimates selected from these 3 EEG recordings. 14 of the 20 substances could be distinguished from placebo at a 5%, 16 at a 10% level. In order to demonstrate the results visually, examples of the mean relative power estimates as well as the standard q-score profiles of the 7 variables at three times are given. All 7 variables selected contribute to the differences between the drugs. However, some variables seem to be more specific for a defined drug class than others:υ = 5.5 – 8.5 Hz for the neuroleptics, β1F = 12.0 – 18.0 Hz for the anxiolytics, α1F = 8.5 – 10.5 Hz for the psychostimulants and a combination of δF = 1.5 – 3.5 Hz, lF and α1F for the antidepressants.

T.M. Itil

Papers

Development of a classification rule for four clinical therapeutic psychotropic drug classes with EEG power-spectrum variables of human volunteers

Acute Efficacy of 20 Psychotropic Drugs on Human EEG Power Spectrum Variables Shown by Multivariate and Univariate Statistics