Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research.

The psychological, neuropsychological, and neurometabolic effects of the hallucinogenic agent mescaline were investigated in 12 normal men who were volunteers. Mescaline produced an acute psychotic state 3 1/2-4 hr after drug intake, as measured by the Brief Psychiatric Rating Scale (BPRS) and Paranoid Depression Scale (PDS). The Assessment of Altered States of Consciousness (APZ) questionnaire revealed specific effects of mescaline in the visual system. Neuropsychological effects were studied with a face/nonface decision task with known right-hemisphere advantage, in which mescaline induced a decrease of functioning of the right hemisphere. In functional brain imaging using single photon emission computed tomography (SPECT), mescaline produced a "hyperfrontal" pattern with an emphasis on the right hemisphere, which was correlated with mescaline-induced psychotic psychopathology. Our findings question the validity of the concept of hypofrontality as an explanation for schizophrenic symptomatology. The study of psychoactive substances under controlled laboratory conditions has the methodological advantage of intraindividual control, and hence, minimal variability of data.

One hundred years of schizophrenia: a meta-analysis of the outcome literature.

OBJECTIVE: This study was undertaken to assess the twentieth-century literature on outcome in schizophrenia for historical trends that might be associated with changes in diagnostic and therapeutic practice and to test the hypothesis that both improved biological treatment and changes in diagnostic criteria have influenced outcome. METHOD: Meta-analysis of the international literature on outcome in schizophrenia or dementia praecox from 1895 to 1992 identified 821 studies; 320 of these, with 51,800 subjects in 368 cohorts, met the inclusion criteria for the study. RESULTS: Only 40.2% of patients were considered improved after follow-ups averaging 5.6 years (range = 1-40). Outcome was significantly better when patients were diagnosed according to systems with broad criteria (46.5% were improved) or undefined criteria (41.0% were improved) rather than narrow criteria (27.3% were improved). The proportion of patients who improved increased significantly after mid-century (for 1956-1985 versus 1895-1955, 48.5% versus 35.4%), probably reflecting improved treatment as well as a broadened concept of schizophrenia. However, in the past decade, the average rate of favorable outcome has declined to 36.4%, perhaps reflecting the re-emergence of narrow diagnostic concepts. CONCLUSIONS: Overall, less than half of patients diagnosed with schizophrenia have shown substantial clinical improvement after follow-up averaging nearly 6 years. Despite considerable gains in improvement rates after mid-century, there has been a decline since the 1970s. These historical changes probably reflect improved treatment, shifts in diagnostic criteria, and selection bias related to changes in health care.

Zinc salts for the treatment of olfactory and gustatory symptoms in psychiatric patients: a case series.

BACKGROUND: Zinc salts have been used extensively in medical settings to treat disorders of gustatory and olfactory function. However, zinc supplements have not been tested in psychiatric patients with smell or taste symptoms. METHOD: The authors examined the effects of zinc supplements on five consecutive patients with symptoms of abnormal taste and smell perception in the context of acute psychiatric illness or treatment. RESULTS: All five patients had complete or partial amelioration of these olfactory and gustatory symptoms after treatment with zinc sulfate or zinc gluconate, apparently independent of the improvement in their underlying psychiatric disorder. CONCLUSION: We recommend treating unusual olfactory and gustatory symptoms with zinc salts, independent of the treatment for the underlying psychiatric disorder.

Diagnostic value of CT in patients with Huntington's chorea and their offspring.

Striatal and cortical atrophy are significant features in the pathology of Huntington's chorea (HCh). A correlative study revealed that the CT findings of atrophy in HCh (8 patients) parallel the clinical and neurophysiological findings. In offspring (8 subjects) of HCh patients, however, the CT changes were insignificant although neurophysiological data were already suspicious in four of them. One patient with hereditary non-progressive chorea showed no CT changes at all. Perhaps with a more sensitive CT scanning technique minor morphological alterations may also be detected and used for a pre-clinical diagnosis.

Foveal interocular time thresholds and latency differences in multiple sclerosis.

Nineteen patients with suspected multiple sclerosis (MS) and 28 control subjects were foveally stimulated by a small cross formed by rectangular red-light-emitting diodes. By means of crossed polarizers one eye was exposed only to the horizontal bar of the cross, the other to the vertical. Stimulus onset asynchrony ranged from 0 to +/- 300 ms (the horizontal bar preceding or following the vertical). The task was to indicate whether the horizontal or vertical bar had appeared first. Compared with normal subjects, MS patients exhibited much higher time thresholds (ranging from -150 to +130 ms) and had considerable interocular latency differences (up to 29 ms), indicating unilateral or asymmetrical impairment of the visual pathways. The psychophysical latency differences of the patients were compared to monocular latencies and interocular latency differences of the visually evoked cortical potential (VEP) obtained by foveal stimulation. Under the stimulus conditions chosen in this study, the diagnostic value of the psychophysical measurements was equal to or, for McAlpine's classes I and II of definite and probable MS patients, better than that based on VEP recordings.

Huntington's chorea-- measurements of somatostatin, substance P and cyclic nucleotides in the cerebrospinal fluid.

Somatostatin, substance P, cyclic AMP and cyclic GMP were determined in the cerebrospinal fluid of patients with Huntington's disease, in first generation relatives of choreic patients and in neurological control patients. Substance P levels were not significantly altered, but somatostatin levels were markedly decreased both in affected patients and symptom-free offspring. Cyclic AMP was decreased only in patients with advanced stages of the disease while cyclic GMP was normal. Evidence is discussed which may support a role of somatostatin deficiency in the pathophysiology of chorea.

Huntington's disease: alterations of visual and somatosensory cortical evoked potentials in patients and offspring.

In 13 patients suffering form Huntington's chorea (H.Ch.), VEPs and SEPs were investigated in comparison to 9 clinically inconspicuous offspring and normal adults. 1. The mean amplitude of VEP was reduced in choreatic patients and in four out of nine offspring. 2. Latencies of P100 in VEP were normal in all subjects. 3. The late components were reduced in amplitude and rather irregular in shape. 4. The latencies of SEPs were slightly prolonged, less marked in the early peaks and more pronounced in the later ones. 5. The late components after 70 to 100 msec were often attenuated or even absent. 6. The mean amplitude of the first two peaks was reduced. 7. Interhemispheric asymmetries were pronounced in three out of nine offspring.

Visual evoked potentials by central foveal and checkerboard reversal stimulation in multiple sclerosis.

In 200 patients with suspected MS, the diagnostic value of VEP elicited by checkerboard reversal and central foveal stimulation was compared. No significant difference was evident, but both methods overlap. The more stable checkerboard reversal stimulation should be preferred as a diagnostic method. Only in suspected MS with normal checkerboard responses, additional foveal responses may give supplementary information. Normal VEPs cannot exclude a prior retrobulbar neuritis.

Schizophrenia--an emotional hypersensitivity of the right cerebral hemisphere.

While modern neuropsychological and electrophysiological studies claim a functional disturbance of the left hemisphere (LH) in schizophrenia, historical clinical and anatomical work rather points to the right hemisphere (RH) as the main site of psychosis. In the light of an interhemispheric functional balance of inhibition and release, LH-dysfunction in schizophrenia could be interpreted as a consequence of an overactive and inhibiting RH. Since the RH is especially activated by emotional stimuli, and exaggerated distractability and sensitivity to emotional stimuli are hallmarks of schizophrenia, we compared the emotional irritability of the RH and LH in 35 acute schizophrenics and 22 matched controls. Using tachistoscopic half-field presentation we found in acute schizophrenics a selective impairment of RH-function with simultaneous improvement of LH-performance induced by emotional distractors. We therefore suggest that a right hemispheric dysfunction and hypersensitivity to emotional material plays an essential catalytic role in acute schizophrenia.

[SPECT studies with 99mTc-HMPAO in Huntington's chorea patients]. / SPECT-Untersuchungen mit 99mTc-HMPAO bei Patienten mit Huntingtonscher Chorea.

Huntington's chorea is an autosomal dominant inherited disease with a chronic course and atrophy of the corpus striatum. PET examination shows reduced glucose metabolism in the caudate nucleus. We examined seven patients with Huntington's chorea by SPECT, using 99mTc-HMPAO. All patients had cortical defects of varying severity. In addition, five patients showed increased uptake in the region of the caudate nucleus. The specific tracer uptake due to the metabolic processes in the region of the caudate nucleus in Huntington's chorea is discussed.

Neurological comorbidity in treatment-resistant dual diagnosis patients.

This paper discusses the possible role of neurological dysfunction in the frequent treatment-resistance of dual diagnosis patients. Through case vignettes, the complex treatment process of three dual diagnosis patients is presented. Each case demonstrates how in addition to both psychiatric and substance abuse problems, the patients also experienced neurological difficulties that made treatment even more complicated. The authors suggest that treatment providers should carefully screen for neurological disorders among this patient population. Attending to such comorbid difficulties in addition to patients' psychiatric and substance abuse problems may sometimes play a pivotal role in enabling patients to attain abstinence. The authors also speculate concerning the role of neurological dysfunction in the etiology of the dual diagnosis syndrome in at least a subgroup of dual diagnosis patients.

A neuropsychological perspective on dual diagnosis.

The purpose of this study was to investigate whether patients experiencing both a major psychiatric disorder and a concurrent substance abuse problem (dual diagnosis) manifest greater neuropsychological dysfunctions than patients experiencing a major psychiatric disorder alone. Differences in diagnostic variability and fluidity between dual diagnosis and non-dual diagnosis patients and the occurrence of polysubstance abuse among the dual diagnosis patients were also investigated. The hypotheses were tested by retrospectively reviewing the psychiatric records of 50 dual diagnosis patients and comparing them to 36 chronically hospitalized non-dual diagnosis psychiatric patients. Results revealed that dual diagnosis patients manifested significantly greater neuropsychological impairments than non-dual diagnosis patients and that dual diagnosis patients showed a greater range of diagnoses and diagnostic fluidity than non-dual diagnosis patients. Results also revealed that over one-half of the dual diagnosis patients abused a variety of different substances. An etiological role of neuropsychological dysfunction in the development of the dual diagnosis syndrome in at least a subgroup of dual diagnosis patients is suggested. More specifically, it is suggested that the neuropsychological dysfunctional pattern that is described may represent an organic substrate of a nonspecific vulnerability to developing both (atypical) psychoses and (poly) substance abuse.

Processing and recognition of facial affect in schizophrenia.

A deficit in the recognition of facial affect has been well documented in people with schizophrenia. Our 1995 research with normal subjects showed that hemispheric bias for processing facial affect is related to accuracy of recognition of facial affect. We tested whether this relationship holds in a sample of 25 people with schizophrenia who completed tasks of identification of facial affect and chimeric facial affect. Subjects with a left visual-field bias were significantly more accurate in identifying one facial emotion (sad) than were other subjects. Individual differences in hemispheric advantage for processing affect appears to be an important variable related to functional brain capacity within different populations.

[Differential diagnosis of acute life threatening catatonia and malignant neuroleptic syndrome--a case report]. / Zur Differentialdiagnose der akut lebensbedrohlichen Katatonie und des malignen Neuroleptikasyndroms--ein kasuistischer Beitrag.

This study reports the development of a severe life threatening catatonia in a 19 years old woman. Initially she displayed paranoia and hallucinations, which were complicated under neuroleptic treatment by extended rigor, temperature and autism. ECT led to a certain improvement of all symptoms, but complete recovery was only reached after neuroleptic drug withdrawal. The course of this case shows that the differential-diagnosis between genuine "pernicious" catatonia and the neuroleptica malignant syndrome is very difficult clinically. Therefore, before the application of ECT, an observation period without any neuroleptic drugs is recommended in similar cases with rigor, stupor and raised temperature, to avoid additional risks by narcosis and ECT itself. Diagnostic and therapeutic outlines are given.

[Hemispheric laterality and early childhood autism. A case study of the etiologic and nosologic problem of the autistic syndrome in childhood]. / Hemisphärenlateralität und frühkindlicher Autismus. Eine kasuistische Studie zum ätiologischen und nosologischen Problem des autistischen Syndroms im Kindesalter.

Most studies on childhood autism emphasize a left hemispheric disturbance. In the presented case a primary right (and only secondary left) hemispheric dysfunction seems to be obvious. This seems to be true also for other reports in the literature. Supported by the hypermasculine aspect of our patient a pathological intrauterine testosterone level is suggested to be responsible for the observed altered cerebral asymmetry and consecutive hemispheric dysfunction. The advantage of such neuropsychologic findings and hypothesis should stimulate further studies on autism and other psychiatric disturbances.

"Whole brain" politics and brain laterality research.

The paper discusses a recent international conference in Munich (FRG) on brain-laterality research. An open letter on the goals of the conference is considered. In this letter, the "automatic" moral and intellectual decay of "left brain" modern society was predicted, and a clarion call for the reinsertion of "whole brain" values into our over-mechanized culture was sounded. Discussion of the conference itself focuses on the political and social risks involved in selling irrationalist ideologies - even well-meaning ones - in the name of science. The paper calls for a more responsible attitude among modern brain-laterality researchers who would participate in scientific conferences that blur the distinction between description and social prescription.

Qualitative H-reflex testing in huntington's disease.

The occurrence of H-reflexes over both the anterior tibial muscle and the thenar muscle on both sides was investigated in 15 patients suffering from Huntington's disease, 8 clinically inconspicuous offspring, and 30 healthy normal controls. The following results were obtained: 1. An obvious H-reflex over the anterior tibial muscle was found in 12 of 15 patients; there was no H-reflex in only 3 patients. 2. After stimulation on the median nerve there was an H-reflex in 12 of 13 patients investigated. 3. In 5 of 8 clinically inconspicuous offspring there was an H-reflex after peroneal [4] or median [5] nerve stimulation. In 30 normal controls, 1 displayed a weak H-reflex over the anterior tibial muscle, 9 showed a weak H-reflex after median nerve stimulation. 5. The possibility is discussed that an abnormal H-reflex might be an early sign of central reflex disinhibition in otherwise asymptomatic offspring.