Serum melatonin levels in schizophrenic and schizoaffective hospitalized patients

Conflicting results on changes of the diurnal melatonin rhythms of patients with affective disorders have been reported in the literature. The heterogeneous data may derive from the great discrepancy in the diagnostic criteria of different authors. A study of 12 schizoaffective and chronic schizophrenic psychotic patients found a constant pattern of an obliterated nocturnal melatonin rise only in the latter group. The presence or absence of the nocturnal melatonin rise was determined in drug-free hospitalized patients and remained unchanged despite 2 months of drug treatment including large doses of neuroleptics. This finding, when confirmed in a larger number of patients, could possibly serve as a marker for the type of mental disorder, drug to be applied and response expected.     

Lithium combined with neuroleptics in chronic schizophrenic and schizoaffective patients

In a placebo-controlled double-blind crossover study lithium carbonate was added to the neuroleptic treatment of 11 chronic schizophrenic and 7 schizoaffective inpatients. Nurses' ratings of behavior indicated significant improvement in 8 patients in agitation or manic behavior, 5 patients in psychosis, and 5 patients in depression. A greater initial severity of symptoms, presence of affective symptoms and episodic course characterized the favorable response group. No neurotoxicity was encountered in this study.     

Urinary phenylacetic acid excretion in depressive patients

Phenylacetic acid (PAA), a metabolite of phenylethylamine, has been found in the urine of depressed patients at lower levels than in control subjects. It has been suggested that the determination of PAA in urine could be used as a biological marker of the depressive condition. In this study the levels of PAA in urine were investigated by gas-liquid chromatography in 39 patients diagnosed as having major depression according to DSM-III criteria, and in 32 healthy subjects. The values found in the patients were markedly lower than in controls. No relationship was found between the decrease of PAA excretion and weight loss. Using a discriminant equation, a value of 69% was obtained for both sensitivity and specificity. The results suggest that the determination of urine PAA could be a biological parameter comparable to the dexamethasone suppression test.     

Plasma levels of phenylacetic acid, m- and p-hydroxyphenylacetic acid, and platelet monoamine oxidase activity in schizophrenic and other patients

Blood from chronic schizophrenic patients in two hospitals (A and B) and from institutional and noninstitutional controls was analyzed for platelet monoamine oxidase (MAO) activity toward three different substrates (tryptamine, phenylethylamine, and p-tyramine) and for plasma levels of conjugated and unconjugated phenylacetic acid (PAA) and m- and p-hydroxyphenylacetic acids (mHPA and pHPA). Compared to the controls, schizophrenic patients were found to have significantly reduced MAO activity. Although significant differences were found between unconjugated PAA (reduced) in Hospital B, conjugated pHPA (increased) in Hospital A, and conjugated PAA (increased) in Hospitals A and B and noninstitutional controls, the most consistent significant finding was a reduced unconjugated mHPA in both groups of schizophrenic patients compared with both control groups.     

Fine motor performance before and after treatment in schizophrenic and schizoaffective patients

Twenty-three hospitalized patients with schizophrenia or schizoaffective disorder were tested for fine motor performance by the Crawford Small Parts Dexterity Test (CSP) and a measure of finger tapping (FT) after a 1-week medication-free period. In an attempt to evaluate potential impairment of fine motor performance, these patients were retested after 1 month's treatment with antipsychotic medication. Thirty-eight control subjects were tested and retested after 1 month by the same procedures. On medication, patients showed no decrement of performance on either test. A small practice effect was observed in both patients and control subjects between initial and second testing. Unmedicated patients had significantly lower CSP and FT scores than control subjects. On repeated testing, medicated patients also had significantly lower scores than control subjects. In the patient group, CSP and FT scores during medication were not related to dosage of medication, use of antiparkinsonian agents, or ratings of motor side effects. CSP and FT scores were significantly and inversely correlated with Brief Psychiatric Rating Scale (BPRS) subscale ratings of withdrawal- retardation (R-subscale). FT performance was positively correlated with the schizophrenia (S-subscale) of the BPRS. Global improvement, as measured by change in BPRS total score, was significantly related to improvement in CSP scores. Impairment in fine motor performance after 1 month's treatment with antipsychotic agents could not be documented. The impairment in fine motor performance in drug-free patients may be in part related to deficits of attention and cooperation. However, other deficits in motor performance have been reported in schizophrenic patients. Failure to identify fine motor impairment produced by psychotropic drugs may be related to competing effects of improved attention and motor impairment of extrapyramidal effects.     

High serum homocysteine levels in young male schizophrenic and schizoaffective patients with tardive parkinsonism and/or tardive dyskinesia

BACKGROUND: The pathogenesis of neuroleptic-induced tardive movement disorders (TMD), including tardive parkinsonism and tardive dyskinesia (TD), has not yet been established. An elevated serum level of total homocysteine has been implicated as a risk factor for various neuropathologic states and some movement disorders. The aim of our study was to determine whether there is an association between serum total homocysteine level and the presence of TMD among schizophrenic and schizoaffective patients. METHOD: This study was conducted in Be'er Sheva Mental Health Center from August 2002 to May 2004. Fifty-eight patients with schizophrenia or schizoaffective disorder (DSM-IV) and TMD for at least 1 year (38 men, 20 women; age range, 28-73 years) were compared to a control group of 188 patients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder without TMD (123 men, 65 women; age range, 19-66 years) regarding serum total homocysteine levels. RESULTS: Men with TMD (demonstrating tardive parkinsonism and/or TD) had significantly higher mean serum total homocysteine levels compared to sex- and age group-matched controls. The difference between groups was almost entirely attributable to the homocysteine levels of young male patients (age group, 19-40 years old) with TMD. CONCLUSION: High serum total homocysteine level may constitute a risk factor for certain variants of TMD, especially in young schizophrenic or schizo-affective male patients. Further prospective studies are needed to clarify these findings.     

Serum vitamin B6 in schizophrenic and schizoaffective patients with and without tardive dyskinesia

There are several reports regarding the efficacy of vitamin B6 in the treatment of tardive dyskinesia (TD). Vitamin B6 plays a key role in the synthesis of several neurotransmitters, including serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid, all of which have been proposed to be involved in the development of TD. The purpose of this study was to examine whether there are special markers to distinguish long-term neuroleptic exposure patients who have TD from those patients who do not develop this side effect. In view of the pivotal role of vitamin B6 in the synthesis of all neurotransmitters believed to take part in the pathogenesis of TD, we decided to examine whether basal levels of vitamin B6 might explain the difference between these two groups. Such a finding could provide a predictive marker for vulnerable patients. The active metabolite of vitamin B6 is pyridoxal phosphate (PP). Pyridoxal phosphate blood levels were measured in 15 schizophrenic and schizoaffective patients with TD and compared with 15 patients without evidence of TD (matched by sex, age, smoking, and diagnosis). We found that, although patients in the TD group were exposed to neuroleptic drugs for significantly longer periods of time, there were no differences in serum PP levels between the groups. The reports of the effectiveness of vitamin B6 supplementation in the treatment of TD could therefore be explained by the assumption that central nervous system or intracellular vitamin B6 levels, which are involved in the pathogenesis of TD, are not the same as vitamin B6 peripheral serum levels. There is need for further studies, which will clarify the relationship between vitamin B6 and TD.     

Predicting suicidal risk in schizophrenic and schizoaffective patients in a prospective two-year trial.

BACKGROUND: Enhanced ability to reliably identify risk factors for suicidal behavior permits more focused decisions concerning treatment interventions and support services, with potential reduction in lives lost to suicide. METHODS: This study followed 980 patients at high risk for suicide in a multicenter prospective study for 2 years after randomization to clozapine or olanzapine. A priori predictors related to diagnosis, treatment resistance, and clinical constructs of disease symptoms were evaluated as possible predictors of subsequent suicide-related events. RESULTS: Ten baseline univariate predictors were identified. Historical predictors were diagnosis of schizoaffective disorder, history or current use at baseline of alcohol or substance abuse, cigarette smoking, number of lifetime suicide attempts, and the number of hospitalizations in the previous 36 months to prevent suicide. Predictive clinical features included greater baseline scores on the InterSePT scale for suicidal thinking, the Covi Anxiety Scale, the Calgary Depression Scale (CDS), and severity of Parkinsonism. Subsequent multivariate analysis revealed the number of hospitalizations in the previous 36 months, baseline CDS, severity of Parkinson's, history of substance abuse, and lifetime suicide attempts. Clozapine, in general, was more effective than olanzapine in decreasing the risk of suicidality, regardless of risk factors present. CONCLUSIONS: This is the first prospective analysis of predictors of suicide risk in a large schizophrenic and schizoaffective population judged to be at high risk for suicide. Assessment of these risk factors may aid clinicians in evaluating risk for suicidal behaviors so that appropriate interventions can be made.     

Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients.

A recent report suggested that neurons in the prefrontal, anterior cingulate, and primary motor cortex of the brains of schizophrenic subjects may be less dense than those in the brains of nonschizophrenic subjects. We have determined whether pyramidal neurons and/or interneurons are preferentially reduced in schizophrenic subjects. Twelve control subjects and 18 schizophrenic subjects were studied in a blind, quantitative analysis of the density of pyramidal cells, interneurons, and glial cells in each of the six layers of the anterior cingulate and prefrontal cortex. The results showed that numbers of small neurons (interneurons) were reduced in most layers of the cingulate cortex in schizophrenic subjects compared with nonschizophrenic subjects, with the differences being greatest in layer II. In the prefrontal area, interneuronal density was also lower in layer II and, to a lesser extent, in layer I in schizophrenic subjects compared with control subjects. In most cases, the differences were similar, although more significant, in schizophrenic subjects who had had superimposed mood disturbances than in schizophrenic subjects who had not had such comorbidity. Numbers of pyramidal neurons generally were not different between control and schizophrenic subjects, except in layer V of the prefrontal area, where schizophrenic subjects showed higher densities of these neurons. Glial numbers did not differ between the control and schizophrenic subjects, suggesting that a neurodegenerative process did not cause the reduced interneuronal density observed. Using multiple regression analysis and analysis of covariance, decreases in the density of layer II interneurons could not be adequately explained by the effects of various confounding variables, such as age, postmortem interval, duration of specimen fixation, or administration of neuroleptic agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlations between the MMPI and the Brief Psychiatric Rating Scale in schizophrenic and schizoaffective patients

Though self-report measures and clinician-based ratings are extensively used to document psychopathology, there has been little work examining the relationship between these different types of measurement techniques. The current work examined the relationship between the Minnesota Multiphasic Personality Inventory (MMPI) and the Brief Psychiatric Rating Scale (BPRS) in patients with schizophrenia and schizoaffective disorder. Correlations were calculated in an initial exploratory sample, and a set of relationships was selected for confirmation in a second sample. The BPRS items of hallucinatory behavior and tension significantly correlated with MMPI measures of psychoticism. BPRS measures of hostility correlated with scale 4 (Psychopathic Deviate) of the MMPI. BPRS and MMPI measures of depression also were related. In contrast, BPRS and MMPI measures thought to reflect negative symptoms were uncorrelated. These results offer behavioral validity for the use of the MMPI in schizophrenic samples and suggest that the two measures tap similar as well as separable symptom constructs thought to be common in schizophrenia.     

Red blood cell/plasma lithium ratio in manic-depressive, schizoaffective, and schizophrenic patients

The red blood cell/plasma lithium ratio (LR) has been studied in 14 schizophrenic (paranoid type), 22 schizoaffective, and 86 manic-depressive patients. Mean LR proved to be significantly higher in manic-depressive patients (p less than 0.001) as compared to the other two groups which on the other hand did not differ significantly from each other. There was no significant difference in the LR between female and male patients. Analyzing the LR according to family history and subtype of illness (i.e., bipolar I/bipolar II dichotomization) of 86 manic-depressive patients we found that neither sex nor type of illness had consistent influence on LR, but patients with positive family history of affective illness had a significantly higher LR than patients with negative ones (p less than 0.01).     

Gender differences in affective, schizoaffective, and schizophrenic disorders

This study examines gender differences in the clinical profiles and long-term outcomes of chronic DSM-III Axis I psychotic inpatients from the Chestnut Lodge followup study. Diagnostic groups include schizophrenia, schizoaffective psychosis, and unipolar affective disorder. Sex differences were frequent, especially in schizophrenia. Females with schizophrenia, for example, had superior premorbid social, sexual, and marital adjustments. They presented at index hospitalization with more depression, self-destructive behaviors, and troubled interpersonal relationships. Their long-term outcomes were better than males in terms of social activity, work competence, time symptomatic, substance abuse, and marital and parental status. Baseline gender differences were comparatively sparse for the schizoaffective and unipolar cohorts. Outcome differences were virtually nonexistent among the schizoaffective patients but unipolar females received better ratings than males in work competence and substance abuse. Females had a later onset of illness and males presented with more antisocial behaviors across all three diagnostic groups. Results highlight the importance of analyzing data by gender in studies of the psychotic disorders.     

Stability of diagnoses in affective,schizoaffective and schizophrenic disorders

Summary The present study investigated the syndrome shift during the course of disease in 355 patients with functional psychoses. The mean observation time was 25.2 years. Every episode was diagnosed cross-sectionally as schizophrenic, melancholic, manic, manic-depressive mixed, schizodepressive, schizomanic or schizomanic-depressive mixed. With regard to the whole course, 148 patients fulfilled the diagnostic criteria of schizophrenic, 106 of affective and 101 of schizoaffective disorders. Patients with a schizophrenic initial episode showed the greatest stability: 90% had no other type of episode. The majority of patients who suffered a melancholic initial episode remained unipolar melancholics or developed manic symptomatology, and only a few suffered schizoaffective or schizophrenic episodes. Patients with a manic symptomatology at the beginning had a very unstable and changeable course. The stability of patients with initial schizodepressive episodes lay between that of patients with melancholic initial episodes and that of those with manic initial episodes. The findings demonstrate the relevance of longitudinal considerations in making the final diagnosis.Supported by grants Ma 915-1/1, 915-1/2 and 915-2/1 from the German Research Association (Deutsche Forschungsgemeinschaft)     

Subjective cognitive dysfunction, eye tracking, and slow brain potentials in schizophrenic and schizoaffective patients

The relationships between subjective cognitive dysfunction (so-called basic symptoms) and some psychophysiological measures were examined repeatedly in schizophrenic and schizoaffective patients during an acute psychotic episode, and comparisons were made with psychotic symptom ratings. Psychophysiological variables were: quality of eye tracking, amplitude measures of the contingent negative variation, and reaction time. Ratings of psychotic and basic symptoms were significantly correlated, but only the basic symptom score showed significant associations with eye tracking, contingent negative variation, and reaction time. Although this pattern was confined to the recovery phase of the psychotic episode, the results suggest that the core psychopathological correlates of these psychophysiological measures consist of basic symptoms rather than florid psychotic symptoms.