Markovian analysis of phasic measures of REM sleep in normal, depressed, and schizophrenic subjects.

Rapid eye movement (REM) phasic activity refers to brief events that occur in periods of REM sleep, such as individual eye movements (EMs). REM density (RD) is the best-known measure of such activity, although reports of RD differences among normal, depressed, and schizophrenic subjects have been equivocal. RD is a measure with a large variability, and its physiological substrate is not known. We sought a more consistent measure which might also suggest the underlying physiology. Using the time intervals between individual EMs, we calculated empirical probability distributions which showed that EMs fell into two subgroups or states: "burst" and "isolated." Then, a novel Markov chain model of sequential transition between the states was calculated for nine normal, eight schizophrenic, and seven depressed male veterans. A significantly higher probability of remaining in the burst state was observed in both patient groups. The actual number of EMs in the isolated state was nearly identical in the three groups. Possible pontine neurochemical explanations involving cholinergic and serotonergic mechanisms are discussed.     

Prolactin responses to neuroleptics in normal and schizophrenic subjects.

The prolactin response to neuroleptics can serve as an index of dopamine blockade in humans. Plasma prolactin increments to single doses of chlorpromazine, and prolactin decrements to single doses of levodopa, were similar in normal and schizophrenic subjects. Antischizophrenic drugs of all chemical classes stimulated prolactin release,while chemically related drugs and other psychotropic agents ineffective in schizophrenia did not. The prolactin response to neuroleptic therapy occurred in all patients, and tolerance did not develop. Within subjects, prolactin responses were graded according to neuroleptic dose, but the upper limit of sensitivity of the response curve was achieved at doses below the therapeutic range. Relative prolactin-stimulating potency in humans of chlorpromazine, thioridazine, trifluoperazine, butaperazine, and haloperidol correlated well with their relative clinical potencies.     

Judging emotions of normal and schizophrenic subjects.

Thirty-two nursing students were shown silent films in which 10 normal and 10 schizophrenic women described a happy, sad, and an angry personal experience. Accuracy in judging the content of films of normal subjects was associated with social detachment and mechanical interests, whereas accuracy in judging the emotions of the schizophrenic subjects was associated with social involvement and nursing interests. Further, the students nurses' ability to relate to patients, as judged by their nursing supervisors, was associated with their ability to accurately identify the nonverbal emotional communications of the schizophrenic patients but not of the normal persons.     

Autonomic responses of paranoid, nonparanoid schizophrenic, and normal subjects to affective visual stimulation.

This investigation utilized a procedure designed to determine patterns of cognitive appraisal, and autonomic reactivity which characterize groups of normals, and paranoid and nonparanoid schizophrenics. Results indicated that both groups of schizophrenics evidenced electrodermal habituation and increased finger pulse constriction. Normals indicated that stress stimuli became less disturbing over trials and displayed both electrodermal and digital vasomotor habituation. Electrodermal habituation curves for paranoids and normals were similar, with nonparanoids evidencing slower habituation. Paranoids tended to under-rate or deny their emotional reactions.     

Characterisation of messenger RNA extracted post-mortem from the brains of schizophrenic, depressed and control subjects.

Messenger RNA, obtained from post-mortem brain of 10 schizophrenics, five depressed patients and 10 control subjects, was characterised with respect to a number of parameters. It was found that post-mortem delay was not the major factor in determining RNA yield, size (as determined by cDNA synthesis) and biological activity. Biological activity, as determined by in vitro translation in a reticulocyte-lysate system, could be observed using messenger RNA from periods of 0 to 84 hours post-mortem. Two-dimensional gel analysis of the newly-synthesised radiolabelled products obtained from this material revealed several hundred individual species but no consistent degradation of any particular species with post-mortem delay. It is suggested, therefore, that premortem changes are as important as post-mortem changes in determining RNA yield, size and biological activity. Although no consistent difference could be found between patients and controls using any of these parameters, this study confirms that, by isolating messenger RNA from post-mortem human brain, valuable information can be gained on gene expression in psychiatric disorders.     

Skin conductance orienting response in unmedicated RDC schizophrenic, schizoaffective, depressed, and control subjects.

In an evaluation of the skin conductance orienting response (SCOR) as a marker for schizophrenia, skin conductance (SC) activity was studied in 36 Research Diagnostic Criteria (RDC) schizophrenic (SCZ), 17 schizoaffective--mainly schizophrenic (SA), 24 depressed (DEP), and 25 psychiatrically well control (CONT) subjects. All subjects were unmedicated. Data are presented from four paradigms: a series of 1 s 70 dB tones in a no-task habituation paradigm; a similar series of 103 dB tones; a series of tones with a button-press (reaction time) task; and a loud white noise stimulus (without task). The proportion of SCOR nonresponse to the first 70 dB tone was 39% for SCZ, 82% for SA, 46% for DEP, and 36% for CONT subjects; the response rate for SA subjects was significantly lower than for all other groups. The CONT group was less responsive than in most previous studies. SCZ subjects did not show increased responsivity to more intense and to task-relevant stimuli, although SA subjects did show such increases. DEP subjects showed some evidence of autonomic hyperarousal (higher tonic SC level, trend toward more spontaneous SC responses). The overall pattern of results does not support SCOR to neutral, moderate-intensity tones as a specific marker for schizophrenia, although there was some evidence for a generalized decrease in autonomic responsivity to stimuli.     

Computer analyses of auditory evoked cortical potentials in schizophrenic subjects.

Averaged cortical evoked potentials from single clicks were recorded from 51 patients and controls. The patient group consisted of 40 subjects with a diagnosis of 'nuclear' schizophrenia, and 11 subjects with diagnoses including mania, anxiety neurosis and personality disorder. Changes in auditory evoked cortical responses (AECR's) were most marked in clinically stable, dysphoric, chronic schizophrenics. These subjects showed reproducible, low amplitude, 'untidy' responses in which the amplitude of the primary peak was lower than the amplitude of later peaks. Chronic schizophrenics who were rated as being depressed, showed a more 'normal' AECR. AECR changes during the memorising of nonsense syllables demonstrated a functional separation between early and later peaks of the AECR. It was postulated that the AECR changes in schizophrenia and during memorising result from pathological patterns of cortical desynchronisation produced by altered mid-brain activity different from that of anxious arousal, and that the clinical 'steady-state' of chronic schizophrenia is reflected in the 'steady-state' desynchronisation changes in the AECR.     

Dimensions of self-rated mood in depressed, manic, and normal subjects

Self-rated scales allow the comparison of subjective mood across the spectrum of manic, depressive, and euthymic states. This study examined the self-reported mood of manic, depressed, and normal subjects using a 23-item research instrument based on the Carroll-Klein model of bipolar disorder. The Multiple Visual Analog Scale (MVAS) measures the following dimensions: consummatory reward (seven items), incentive reward (two items), psychomotor speed (seven items), and central pain (seven items). The MVAS was completed by 31 manic inpatients, 43 depressed inpatients, and 29 normal volunteer subjects. Total scores, average item scores, and total dimension scores were obtained. Subjects also completed a global mood VAS and the Carroll Depression Scale (CDS). Groups were compared by analysis of variance (ANOVA) and post hoc Bonferroni-Dunn methods. In a separate post hoc analysis, the group of manic patients was divided at the median CDS score into "pure" and "dysphoric" manic subgroups. We found excellent congruence of average 23-item total MVAS scores with global VAS and CDS scores. Dimension scores on the MVAS conformed to the predictions of the Carroll-Klein model. Depressed patients differed significantly from both manic and normal subjects on each dimension. MVAS dimension scores of normal subjects did not differ significantly from those of manic patients. On the dimension of central pain, normal subjects had significantly less inhibited scores than the "pure" subgroup of manics. The results confirmed that the dimensions of the Carroll-Klein model are bipolar and orthogonal. By the MVAS technique, the self-reported mood of normal subjects is similar to the self-reported mood of manic patients on all dimensions of the Carroll-Klein model of bipolar disorder. The positive scores of both groups are clearly distinguished from the negative scores of depressed patients. Average MVAS scores of normal subjects approximated the conventional zero score only on the dimension of central pain. Normal subjects exhibit megalothymic (hyperthymia) on most dimensions of subjective mood. The negative MVAS scores of depressed patients are even more deviant from normal than the conventional scoring system would suggest.     

Successful separation of depressed, normal, and insomniac subjects by EEG sleep data.

Data from all-night EEG sleep studies were used to distinguish normal subjects, primary depressed patients, and primary insomniac patients. In part 1, we compared 41 normal subjects, 56 depressed patients, and 18 insomniacs. In a univariate comparison with normal subjects, depressed patients showed less total sleep, longer sleep latency, more early morning awake time, more intermittent awake time, less delta sleep, less sleep efficiency, and shorter rapid eye movement (REM) latencies; compared with insomniacs, depressed patients showed greater early morning awake time, shorter REM latency, greater REM index, and greater REM density. Using multivariate discriminant analysis, 82% of the sample were correctly classified by diagnosis: 100% of the normal subjects, 72% of the depressed patients, and 77% of the insomniacs. Eight variables contributed to the multivariate separation of depressed individuals from insomniacs and normals: total sleep time, total recording period, sleep efficiency, sleep latency, early morning awake time, awake time, REM time and REM%. When the discriminant functions were applied to a second group of 18 primary depressed patients, 82% were correctly classified as depressed. These results suggest that primary depressed patients and primary insomniac patients may show relatively characteristic patterns of sleep abnormality.     

The N2 component of the event-related potential in schizophrenic patients

Event-related potentials (ERPs) to easy and difficult infrequent visual target stimuli were recorded in unmedicated schizophrenic patients and age-matched controls. N2 difference wave forms were computed by subtracting the ERP to a frequent non-target stimulus from the ERP to each target. The N2 component was identified in these difference wave forms. All subjects showed longer latency N2 and P3 peaks to the difficult target than to the easy target. Schizophrenic patients had longer latency N2 peaks than controls to both targets. Schizophrenic patients also showed reduced P3 amplitudes to both targets compared to controls. The prolonged N2 latency in schizophrenics accounts for a substantial portion of the delayed reaction time commonly observed in this group. N2 latency prolongation appears to be yet another evoked potential abnormality in schizophrenic patients.     

Interpeak components of event-related potentials--comparison between normal and schizophrenic groups]

Event-related potentials (ERPs) during a two-tone discrimination task were recorded in 85 normal subjects and 110 schizophrenic subjects. We divided ERPs into 4 interpeak components. We named them A, A', B and B'. A is the component from the stimulus point to n100 peak. A' is the one from n100 peak to p200 peak. B is the one from p200 peak to n200 peak. B' is the one from n200 peak to p300 peak. Their latency was named Al, A'l, Bl, and B'l respectively. Their amplitude was also named Aa, A'a, Ba and B'a respectively. Bl and A'l of the schizophrenic group were both significantly longer than those of the normal group. B'a of the schizophrenic group was significantly smaller than that of the normal group. Interrelations between interpeak components of the normal group were examined statistically. Regarding latency, a significant negative correlation was seen between Al and A'l, and also between Bl and B'l. Regarding amplitude, a significant positive one was seen between Aa and A'a, and also between Ba and B'a. Interrelations between Al and A'l, Bl and B'l, Aa and A'a, and Ba and B'a of the schizophrenic group were the same as those of the normal group. These negative correlations in latency suggest that n100 peaks and n200 peaks have 'jitter'. A combination of interpeak components is supposed to reflect a higher function of the brain. There was a significant negative correlation between (A + A')l and (B + B')l in the normal group, but there was not a significant one between them in the schizophrenic group. The schizophrenic group is supposed to have a certain abnormality in a higher function of the brain. Our result suggests that we may possibly be able to associate an abnormal focus around p200 peak with some symptoms and signs of schizophrenia.     

Thyroid stimulating hormone response after thyrotropin releasing hormone in depressed, schizophrenic and normal women.

(1) Thyroid stimulating hormone (TSH) response after injection of thyrotropin releasing hormone (TRH) was studied in 23 depressed, 9 schizophrenic and 40 normal women. (2) In no group was TSH response correlated with age. (3) In the depressed patients, no relationship was found between TSH response and (i) severity of illness, (ii) clinical subtypes (unipolar/bipolar) and (iii) clinical remission. (4) There were no statistically significant differences in TSH baseline values between the groups. (5) Neither of the two patient groups showed reliable differences from controls regarding TSH response. However, depressed patients tended to show lower values than controls, while schizophrenic patients tended to show higher values than normal controls. (6) Significant differences were found between depressed and schizophrenic patients in regard to TSH response. In three depressed patients a TSH response below 5 μU/ml was found. This deficient TSH response occurred in unipolar depressed patients and was not seen in bipolar depressed patients, schizophrenic patients or normal controls. (7) These data provide evidence for a fault in hypothalamic pituitary regulation in some depressed patients but not in schizophrenic patients.     

Variability of TRH test responses in depressed and normal elderly subjects.

Thyrotropin releasing hormone (TRH) tests were conducted in 33 elderly patients with Major Depressive Disorder and 99 normal elderly volunteers. A wide range of thyrotropin-stimulating hormone (TSH) responses to TRH injection was revealed. A gender effect was found such that men had significantly diminished TSH responses to TRH relative to women (p = 0.008). However, there were no significant differences noted between depressed patients and normal elderly subjects of either gender. It appears that the wide range of TSH responses to TRH found in normal elderly men and women blurs any measurable differentiation between depressed patients and normal subjects and thereby limits the usefulness of the TRH test in the study of depressive disorder in elderly patients.     

Rapid dynamic CT scanning to distinguish schizophrenic from normal subjects

Rapid dynamic computerized axial tomography (CT) density-time curves were used to detect abnormal brain regions in groups of controls and DSM-III diagnosed schizophrenics. Density-time curves were designated as plateau curves if, following a bolus injection of contrast material, they exhibited a plateau from the peak value rather than a decrease. Five of the 10 schizophrenics versus none of the 11 controls were found to possess two or more plateau curves. The physiological basis for the plateau curves is not known, but an increase in blood-brain-barrier permeability could be involved.