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Background Serine racemase (SRR) is a brain-enriched enzyme that converts l -serine to d -serine, which acts as an endogenous ligand of N-methyl d -aspartate (NMDA) receptors. Dysfunction of SRR may reduce the function of NMDA receptors and susceptibility to schizophrenia. Methods We genotyped three single-nucleotide polymorphisms (SNPs) of the 5′ region of the SRR gene in 525 patients with schizophrenia and 524 healthy controls. Effects of SNPs on the promoter activity and on serum levels of total and d -serine were examined. Results We found a significant excess of the IVS1a+465C allele of the SRR gene in schizophrenia, especially in the paranoid subtype (p = .0028). A reporter assay showed that the IVS1a+465C allele had 60% lower promoter activity than did the IVS1a+465G allele. Conclusions The IVS1a+465C allele of the SRR gene, which reduces expression of the gene, is a risk factor for schizophrenia, especially the paranoid subtype.

Objective: This study aimed to investigate the outcome of an 18-month randomized controlled trial (RCT) on subjective burden and psychopathology of patients suffering from schizophrenia. Method: An RCT was used to compare hallucination-focused integrative treatment (HIT) and routine treatment (RT) in schizophrenia patients who persistently hear voices. We performed an intent-to-treat analysis on each of the 63 patients who were assessed at baseline, 9, and 18 months. On each of the 3 occasions, the differential effects of the treatment conditions were tested repeatedly. Sex, age, education, and illness (hallucination) duration were used as covariates. Results: Patients in the experimental group retained improvements over time. Improvements in hallucinations, distress, and negative content of voices remained significant at the 5% level. Conclusion: HIT seems to be an effective treatment strategy with long-lasting effects for treatment-refractory voice-hearing patients.

The purpose of the present study was to investigate basal ganglia (BG) and medial temporal lobe (MTL) dependent learning in patients with schizophrenia. Acquired equivalence is a phenomenon in which prior training to treat two stimuli as equivalent (if two stimuli are associated with the same response) increases generalization between them. The learning of stimulus-response pairs is related to the BG, whereas the MTL system participates in stimulus generalization. Forty-three patients with DSM-IV schizophrenia and 28 matched healthy controls participated in the study. Volunteers received the acquired equivalence associative learning task (FISHES) during which associations between faces and pet fishes are learned. Results revealed that patients with schizophrenia showed a selective deficit on stimulus generalization, whereas stimulus-response learning was unaffected. The number of errors during stimulus-response learning correlated with the daily chlorpromazine-equivalent dose of antipsychotics. In conclusion, patients with schizophrenia showed deficits during MTL-dependent learning, but not during BG-dependent learning. High-dose first generation antipsychotics may disrupt BG-dependent learning by blocking dopaminergic neurotransmission in the nigro-striatal system.

Objective A substantial number of patients treated with clozapine shows insufficient response. The author presents the results of adding aripiprazole in patients resistant to clozapine. Method Three cases of individuals with psychotic symptoms despite clozapine use and with significant side effects that were treated via this combination are presented. Response was evaluated by clinical assessment. Results Good clinical results were obtained in all three patients, with improvement of psychotic symptoms and of some of the side effects of clozapine. Conclusion The findings from this case series suggest that adjunctive therapy with aripiprazole can be of benefit for treating clozapine resistant schizophrenic patients.

Cognitive deficits are increasingly considered as essential in schizophrenic disorders. Positive symptoms and cognitive deficits have been found to be independent, whereas negative symptoms show only weak correlations to cognitive impairment. However, the relationship to a third symptom dimension, disorganization, is yet unclear. In a sample of n = 151 schizophrenia inpatients (DSM-IV/SCID) we assessed cognitive impairment using a comprehensive neuropsychological test battery and symptoms of schizophrenia applying the Positive and Negative Syndrome Scale (PANSS). Factor analyses resulted in three neuropsychological (attention, memory, abstraction) and five symptom factor scores (negative, impulsiveness, positive, disorganization, depression). The disorganization factor did not correlate significantly with any of the neuropsychological factor scores. Even after controlling for different demographic and clinical variables partial correlation coefficients did not reach a significant level. Thus, we could not confirm the previously reported associations between disorganization and measures of cognitive impairment. Despite a considerable conceptual overlap between interview based symptom ratings and classic neuropsychological tests the empirical association is limited. Our results suggest that disorganization and cognitive impairment represent different symptom dimensions.

Changes in glucose metabolism were studied in the brains of schizophrenic patients treated with neuroleptics, using [ 18 F]fluoro-deoxy-glucose positron emission tomography (FDG-PET). Fourteen male and eight female patients in their thirties and forties were studied in a resting state. Data from FDG-PET were processed with an anatomic standardization method, three-dimensional stereotactic surface projections (3D-SSP), which provided relative glucose metabolic values that mitigated the contamination of brain atrophy. Z -score maps indicating metabolic differences between the patient and control groups were also acquired. Metabolic values in 19 regions were evaluated in the right and left hemispheres. Patients showed decreased values in the frontal cortex, primary sensory regions and anterior cingulate cortex, more in the rostral affective subdivision than the dorsal cognitive subdivision in both hemispheres, and increased metabolic values in left and right basal ganglia, left temporal and right medial parietal regions. Values were more decreased in both anterior cingulate regions, and more increased in the right thalamus in male than female patients, suggesting gender-related dysfunction in the anterior cingulate and thalamus in schizophrenia. FDG-PET demonstrated that schizophrenia may be a disorder with a dysfunction of fronto–striatal–thalamic circuitry including the cingulate cortex.

Previous studies on schizophrenia have suggested that context-processing disturbances were one of the core cognitive deficits present in schizophrenia. Schizophrenic patients have a failure either of inhibition strategy and maintenance of visuospatial information (25) in condition of contextual interference. In the present study, we explored the performances of untreated schizophrenic patients with 2 tasks exploring detection and long term retention of complex visual features and field dependence-independence tasks were selected. These abilities involve temporary maintenance of visuospatial information and executive functioning of visual working memory system. Several studies have shown that cognitive deficit may depend on schizophrenic symptomatology. However results remain controversial in determining the specific influence of negative and positive symptomatologies as well as clinical disorganization. Our goal was to explore the processing of spatial context and its relation to disorganized syndrome. This study was approved by the local ethic committee.Thirty-six schizophrenic patients were included according to DSM IV criteria (19 neuroleptic naïve, 17 unmedicated patients during more than 3 months). Thirty-six healthy controls were matched to patients for age, gender and level of education. Absence of axis 1 pathology was attested for controls with SCID-NP. Current symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) (14). Clinical disorganisation was evaluated with the disorganisation score established upon a factorial analysis of PANSS by Lepine and Lançon. Items selected to distinguish the disorganised group were abstraction, disorganization, orientation, and attention.Two tasks of embedded figures were administered individually to patients and controls. The Faverge task (Research of Figures-RF) (10) evaluates the ability to recognize the target from spatial complex geometrical figures. The Group Embedded Figure Task (GEFT - Oltman) assesses the detection and maintenance of visual target and its recognition within a complex figure. Performance between patients and controls were compared with the Student T test. The comparison of two clinical subgroups of disorganized and low disorganized patients and control group was performed with an ANOVA. Tuckey test was used for pairwise comparisons.We defined two subgroups of patients, disorganized patients (subscore 12, n=17) and low disorganized patients (subscore12, n=19). Theses 2 subgroups were similar for age and level of education. Concerning the two tasks, there was no significant difference between schizophrenic patients and normal controls. The comparison between subgroups of disorganized and low disorganized patients, for RF task, showed a decrease of correct answers with disorganized patients (p0.05). For GEFT task, disorganized patients had a decrease of correct answers p0.01) and more errors (p0.01) and omissions (p0.05). The low disorganized patients exhibited for the two tests comparable performance to controls. The disorganized patients had a decrease of right answers (p0.05) and more errors (p0.05) than controls for GEFT task and no significant difference for RF. However, with IQ (evaluated with an abstract reasoning test) introduced as covariate, only correct answers for GEFT task remain significant (p0.05).The weak performance of disorganized schizophrenic patients for two tasks RF and GEFT showed that treatment of visuospatial information was impaired in the first perceptive phase of selection and in the organization of information (RF), especially with the maintenance of visual information in memory (GEFT). By contrast, low disorganized patients demonstrated a correct analytic treatment of elementary processing and visuospatial working memory.The severity of disorganization influences the visuospatial context processing and visuospatial working memory. These results show the heterogeneity of cognitive functioning regarding to schizophrenic symptomatologies. This difficulty could be related to a problem of central executive functioning in the visuospatial component of working memory, possibly mediated by the dysfunction of dorsolateral prefrontal cortex.

We present a case of blindness and Anton’s syndrome in a psychiatric patient with late diagnosis of a giant frontal meningioma. The criteria for advanced diagnostic imaging in the psychiatric population are discussed. We conclude that MR or CT scan is indicated in psychiatric in-patients who fail to improve with standard psychiatric treatment. This strategy should be submitted to a cost-benefit analysis.

We describe the cases of 2 sisters with adult metachromatic leukodystrophy (MLD). Whereas one sister presented with disorganized schizophrenia-like symptoms as the initial manifestation of MLD, the other remained symptom free except for a 4-week period of postpartum depression. In both patients, there was some residual activity of leukocyte arylsulfatase A (1.7% and 5.5% of normal), and a marked increase in urinary sulfatides was present, as measured by tandem mass spectrometry. An arylsulfatase A pseudodeficiency was therefore excluded. The most common mutations of the adult phenotype, Ile-179-Ser and Pro-426-Leu, were not found. In the literature, only 1 case of adult MLD manifesting as disorganized schizophrenia-like symptoms has been described, whereas postpartum depression has been so far unknown as a presenting symptom of MLD.

We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over a 10-week period after initiation of clozapine treatment. In contrast to increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no significant change in SGL was detected. Inverse correlations between delta SGL and delta SLL did not reach statistical significance. Linear mixed model analysis could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL. Our results do not support a causal involvement of ghrelin in clozapine-related weight gain.

This article focuses on the schizophrenic disorganization syndrome, which was initially described by Bleuler (who used the term "dissociation") as lying at the heart of schizophrenia. While adopting a neo-Bleulerian approach, we describe schizophrenic disorganization using a pathogenetic hypothesis and a three-part structure. First, we discuss previous approaches to characterizing and defining schizophrenic disorganization, providing arguments in favor of a complementary approach to describing schizophrenic disorganization that relies on a pathogenetic analysis of the disorganization syndrome, and especially thought and language disorders. Second, we present two possible cognitive pathophysiological mechanisms that may explain schizophrenic disorganization: (1) a deficit in the integration of contextual information, based on the results of semantic priming studies; and (2) a theory of mind deficit, based on the results of studies of the attribution of mental states to others. We propose a cognitive model of schizophrenic dysfunctioning on the basis of these two anomalies. Third, we summarize our published findings to examine the implications of these two cognitive pathophysiological mechanisms for schizophrenic disorganization. On the basis of the same two anomalies, we then propose and illustrate a neo-Bleulerian approach to the assessment of communication disorders that is critical to the improvement of schizophrenic disorganization's clinical description.

Previous research on schizophrenia has reported conflicting findings regarding the association between Stroop performance and the disorganization syndrome, as well as performance on verbal fluency tests and the psychomotor poverty syndrome. In the present work, we consider whether these inconsistencies may be increased due to variations in test format and failures to report the appropriate test parameters. In 36 schizophrenic inpatients, we administered list and single-trial versions of the Stroop test, and report the correlation with the disorganization syndrome for both errors and speed. For verbal fluency, we separated the total score into measures of switching and clustering, and observed the relationship with psychomotor poverty. For both versions of the Stroop test, accuracy, but not speed, was correlated with disorganization. For verbal fluency, decreased cluster production relative to total words generated was associated with psychomotor poverty, but the number of switches between clusters was not. It is suggested that assessing and reporting a full range of test parameters can reduce between-study inconsistencies. Cognitive interpretations for the present set of results are discussed.

This study examined the prolactin (PRL), adrenocorticotropin (ACTH) and cortisol responses to the direct DA receptor agonist apomorphine (APO) and the selective 5HT-releasing agent d-fenfluramine (d-FEN) in 20 untreated inpatients with DSM-IV schizophrenia and without a history of suicide attempt, compared to 23 hospitalized healthy controls. We hypothesized that different patterns of responsiveness of the DA and 5-HT systems might be associated with specific schizophrenic symptom clusters. A positive correlation was observed between pituitary-adrenal response to APO and d-FEN tests (i.e. deltaACTH and deltacortisol) in the overall population and in schizophrenic patients. Pituitary-adrenal response to APO was lower in patients than in normal controls. Moreover, lower pituitary-adrenal response to APO and d-FEN was associated with increased severity of BPRS thought disturbance score. Lower pituitary-adrenal responses to APO (and to a lesser degree to d-FEN) differentiated paranoid from disorganized schizophrenic patients. Neither PRL suppression to APO, nor PRL stimulation to d-FEN were altered in schizophrenic patients. Our results suggest that decreased hypothalamic DA receptor activity (possibly secondary to increased presynaptic DA release) together with relatively decreased 5-HT tone characterize paranoid SCH, while normal hypothalamic DA receptor activity together with relatively increased 5-HT tone characterize the disorganized SCH subtype.

A patient with refractory chronic schizophrenia having severe polydipsia and hyponatremia was treated with clozapine. There followed a dramatic improvement in the polydipsia and correction of the hyponatremia. This improvement has been sustained throughout a 6-month follow-up.

Background: Several studies have suggested a theory of mind (ToM) deficit in schizophrenic disorders. However, the role of interfering variables such as IQ, attention, memory, and severity of the disorder has remained ambiguous. Methods: A theory of mind picture story comprising a sequencing task, a first and a second order false belief test, and a tactical deception test was given to a group of 23 patients with chronic disorganized schizophrenia and to 12 healthy control persons. In addition, a nonsocial picture story had to be sequenced. Severity of the psychopathology was measured by using the brief psychiatric rating scale (BPRS), IQ was estimated using the ‘Mehrfachwahlwortschatztest’ (MWT, multiple choice verbal comprehension test). Results: The schizophrenic group was impaired relative to controls on the theory of mind task, but not on the sequencing task of the nonsocial picture story. However, when controlled for IQ, no such difference was found. These findings were neither related to severity, duration, nor age at onset of the disorder. Conclusions: Theory of mind deficits in schizophrenia may be related to domain general impairments, e.g., intelligence and working memory load, rather than reflecting a ‘genuine’ compromised mental state attribution similar to autistic spectrum disorders. Schizophrenic patients may, however, rather be impaired in how and when to apply strategic social reasoning. Further studies to investigate the nature of social deficiency in schizophrenia are warranted.

Paraphilias or disorders of sexual behavior have markedly increased in prevalence during the last decade. Until now no published neuropathological studies on paraphilia have appeared in the medical literature. A computerized search was done on all available medical and autopsy records of a large urban hospital (St. Elizabeths Hospital, Washington, DC) for any mention of deviant sexual behavior. Cases were then reviewed for presence of a history consistent with DSM-IV diagnoses of paraphilia. Two such cases were identified. Neuropathological examination in both cases revealed simple cell atrophy of pyramidal cells confined to different hippocampal subfields. Reactive astrocytosis was present in the outer strata of the affected regions. The pathological changes in the hippocampus resemble those reported after persistent stress or long-term chronic glucocorticoid administration. The accompanying astrocytosis indicates a reactive, ongoing process. The findings suggest new therapeutic interventions in the treatment of paraphilia.

The time elapsed between the first onset of symptoms and the onset of first hospitalisation was analysed in 355 participants diagnosed with paranoid, simple, hebephrenic and catatonic schizophrenia and shizoaffective disorder. The real onset of the disease was assessed from interviews with reliable relatives and by reviewing medical records in general practices and out-patient psychiatric services. In 184 patients a family history of schizophrenia was identified. A positive family history was found to significantly increase the interval preceding first hospitalisation in all analysed types, except in catatonic schizophrenia. Possible reasons causing this prolongation are discussed, as well as repercussions of the results to studies using age of first hospitalisation as the leading indicator.

International audience; The aim of the study was to examine the action of low-dose amisulpride (100 mg/d), an atypical antipsychotic from the benzamide class with a high affinity for the D2 and D3 dopamine receptors, given for 4 weeks in 19 schizophrenic patients with the deficit syndrome, in terms of clinical response, modifications in their cognitive performance and changes in brain perfusion values. A secondary objective was to distinguish between primary and secondary deficit, according to Carpenter's definition. Both efficacy and a relatively low rate of side effects of low-dose amisulpride in the deficit forms of schizophrenia were found as expected from earlier placebo-controlled studies. Our study found significant changes in the cerebral blood flow, before and after treatment, more marked in the frontal area and particularly in the dorso-lateral frontal area. A significant improvement of cognitive function was found after treatment, without a link to any particular changes in a loco-regional perfusion value. Finally, a distinction between primary and secondary deficit showed a higher percentage of clinical improvement in the patients with a secondary deficit. The psychometric and cerebral perfusion changes were no different in the two groups.

Earlier studies that used two symptom dimensions indicate that the caregiver burden for patients with schizophrenia is significantly determined by their negative symptoms. The purpose of this study is to examine the relationship between symptom severity in recent-onset schizophrenia and caregiver burden in a more differentiated way (i.e., five-symptom dimensions). Based on previous research, which shows that patients' personality traits influence the course of schizophrenia, we theorize that personality traits could also influence caregiver burden. So far, this hypothesis has never been studied. Therefore, the second purpose of a-Lis study is to examine whether patients' personality traits would contribute to caregiver burden. The results of this study showed that the disorganization symptom component was the predicting variable of the subscales supervision, tension, urging, distress, and the overall amount of caregiver burden in a linear regression analysis. Personality traits of patients played no substantial role in caregiver burden. These findings suggest that psychoeducational programs should address the severity of disorganization symptoms to reduce caregiver burden in the early phase of schizophrenia.

The concept of hebephrenia according to Kleist and Leonhard describes distinct clinical entities with a chronically progressive course leading to residual syndroms with a clear cut symptom constellation which is stable over time. The main symptom is a specific kind of pathological affectivity resulting in a lack of profound future- orientated tension. In six case-reports we illustrate the characteristical clinical picture of the autistic hebephrenia, one of the four subforms of hebephrenic psychoses according to Leonhard. The characteristical clinical syndrom consists of an affective blunting, autistic withdrawal, unfathomable facial expression, unhappy mood and periods of moodiness with aggressive excitement. The concept of hebephrenia according to Kleist and Leonhard presents a promising heuristic attempt for biological-etiological research. In ICD-10 and DSM-IV the usual concept of hebephrenia is a rather vaguely defined nosological category with a polymorphous non-specific symptomatology.

SummaryThere is widespread evidence that schizophrenic symptomatology is best represented by three syndromes (positive, negative, disorganized). Both the disorganized and negative syndrome have been found to correlate with several neurocognitive dysfunctions. However, previous studies investigated samples predominantly treated with typical neuroleptics, which frequently induce parkinsonian symptoms that are hard to disentangle from primary negative symptoms and may have inflated correlations with neurocognition. A newly developed psychopathological instrument called the Positive and Negative and Disorganized Symptoms Scale (PANADSS) was evaluated in 60 schizophrenic patients. Forty-seven participants treated with atypical neuroleptics performed several neurocognitive tasks.A three-factor solution of schizophrenic symptomatology emerged. Negative symptomatology was associated with diminished creative verbal fluency and digit span backward, whereas disorganization was significantly correlated with impaired Stroop, WCST and Trail-Making Test B performance.Data suggest that disorganization is associated with tasks that demand executive functioning. Previous findings reporting correlations between negative symptomatology and neurocognition may have been confounded by the adverse consequences of typical neuroleptics.

We demonstrated the effect of clonazepam (2 mg/day) on Meige syndrome in two schizophrenic patients under continuous treatment with antipsychotic drugs, and changes in the plasma levels of gamma-aminobutyric acid (GABA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in these cases. The plasma levels of HVA and MHPG during treatment with clonazepam were decreased in the responder, while not changed in the non-responder to clonazepam. A difference between the responder and the non-responder was not found in the plasma GABA levels. These results suggest that hyperactivities of the central dopaminergic and noradrenergic neurones are involved in the pathophysiology of Meige syndrome.

To examine the cannabinoid hypothesis for pathogenesis of schizophrenia, we examined two kinds of polymorphisms of the CNR1 gene, which encodes human CB1 receptor, a subclass of central cannabinoid receptors, in schizophrenics and age-matched controls in the Japanese population. Allelic and genotypic distributions of polymorphism 1359G/A at codon 453 in the coding region and AAT triplet repeats in the 3' flanking region in the Japanese population were quite different from those in Caucasians. Although the polymorphism 1359G/A was not associated with schizophrenia, the triplet repeat polymorphism of the CNR1 gene was significantly associated with schizophrenia, especially the hebephrenic subtype (P = 0.0028). Hebephrenic schizophrenia showed significantly increased rate of the 9 repeat allele (P = 0.032, OR = 2.30, 95% CI (1.91-2.69)), and decreased rate of the 17 repeat allele (P = 0.011, OR = 0.208, 95% CI (0.098-0.439)). The present findings indicated that certain alleles or genotypes of the CNR1 gene may confer a susceptibility of schizophrenia, especially of the hebephrenic type.

Data on 14 males with autism and 14 with schizophrenia were collected to examine symptom overlap. The Structured Clinical Interview (SCID), the schedule for positive symptoms (SAPS) and the schedule for negative symptoms (SANS) of schizophrenia, the Childhood Autism Rating Scale (CARS), and the DSM-III-R were administered. On the SCID, none of the men with paranoid schizophrenia met criteria for autism while 7 of those with autism met criteria for schizophrenia, disorganized type, showing negative symptoms. In addition, 5 showed positive symptoms on the SAPS and 6 negative symptoms on the SANS. As the difference in measured nonverbal intelligence was not significant, the effects could not be attributed to it. Although the findings continue to support the differentiation of autism and schizophrenia, they are also consistent with a comorbidity of the two disorders, mainly in those diagnosed with autism.

We assessed hemisphere function in right-handed male chronic, disorganized type schizophrenic patients (N = 60, age range 18–45 years) using the Quality Extinction Test (QET), in comparison to 20 right-handed male healthy controls in the same age range. The QET analysis discriminated between the disorganized schizophrenic patients and the controls. QET results indicated that chronic schizophrenic patients were less sensitive to tactile stimuli in both hands as compared to controls. Furthermore, the sensitivity to tactile stimuli of the left hand was less than that of the right hand in the schizophrenic patients. In contrast, in the normal controls the sensitivity was similar in both hands. These results indicate possible right hemisphere dysfunction together with disturbance in interhemispheric transmission through the corpus callosum in chronic, disorganized type schizophrenic patients.

Mr B is a 32-year-old patient with a disorganized type of schizophrenia and his treatment, started when he was 20, has always been difficult and his social integration has become progressively worse. In 1998, treatment with olanzapine was started when he suffered acute decompensation on top of his disorganized condition which had an adverse effect on his symptoms. In a short space of time, a very satisfactory improvement was seen, not only in his symptoms but also in his social integration. This improvement has been sustained throughout two and a half years of follow-up. The perspectives offered by the new antipsychotic drugs in the management of acute episodes of schizophrenia are discussed in the light of recent data from the literature and lead to a reconsideration of our therapeutic practices.

There is growing evidence for a relationship between the duration of untreated psychosis (DUP) and the prognosis. However, determinants of the DUP have been minimally explored, as is the detailed initial temporal unfolding of untreated psychosis. In this study, in-depth interviews with 19 first-episode DSM-IV schizophrenia patients and their relatives revealed detailed phenomenology of the initial prodrome and untreated psychosis. The findings suggest that a later prodrome onset (mean age in this sample, 20.5 years), a prodrome shorter than 2 years, acute initial psychosis development, the initial presence of grandiosity and/or disorganization, and a mild level of withdrawal all may reduce treatment delay. This set of characteristics might therefore represent built-in components of psychotic illnesses related to a shortened DUP, irrespective of early intervention efforts. In other words, the DUP could partly reflect these built-in aspects of psychosis. The rate of initial (untreated) psychosis development could contribute to broaden the prevailing mode of onset concept (presently defined as the duration of the initial prodrome) to comprise both the duration and content of the initial prodrome, as well as untreated psychosis, tentatively designated as the mode of initial psychosis development.

Schizophrenic patients were rated on three syndromal dimensions derived from positive and negative symptom ratings. Scores on each dimension were compared to performance on neuropsychological tests before and after coaching instructions. Patients evidenced significant improvement in performance on all measures readministered immediately after instruction. Disorganization symptoms were correlated with lower levels of performance on all pre-coaching, trial 1 tests. Disorganization symptoms were also associated with lower levels of trial 2 post-coaching performance, independent of pre-coaching scores. These results suggest that, within a population of schizophrenic patients, symptoms of disorganization are associated with relatively greater impairments in performance on neuropsychological tests and with impaired ability to improve test performance following coaching instructions. The three symptom dimensions show promise for reducing heterogeneity within samples of schizophrenic patients.

We report a patient with metachromatic leukodystrophy (MLD) with a first manifestation of homicide. On admission the patient showed a hebephrenia-like syndrome with inappropriate affect, thought disorder and behavioral changes. Magnetic resonance tomography (MRT) findings suggested a diagnosis of MLD, which was confirmed by a decreased activity of leucocyte arylsulfatase A and an excessive urinary sulfatide excretion.

Schizophrenia, a psychiatric disease that is highly prevalent among the general population, has polymorphic clinical manifestations at onset and during its evolution. The most frequent manifestations are an abrupt onset with positive symptoms, perception and thought disorders, which were included by Kurt Schneider in the first range symptoms. However, on other occasions the onset is insidious and the so-called negative symptoms are present, resulting in clinical manifestations that are similar to the state of absence and a less favorable patient prognosis. Since the last century when Kraepelin defined early dementia, various authors have tried to explain the nature of this disease, resulting in Bleauler's definition of the fundamental symptoms. A clinical case of hebephrenic schizophrenia is presented in which disorders in thought, affect and volition predominated. We discuss the psychopathological views of less well-known, but not for that reason less important, authors, such as Guirod and Dice, and the similarities and differences between their views and current classifications.

In a woman aged 35 who for the last 5 years had been suffering from conduct disorders, especially kleptomania, compulsive cleaning behaviour and affective neglect of her children, psychodiagnostic examination initially suggested a delusional disorder. In view of the gradual aggravation of bizarre behaviour, the diagnosis 'schizophrenic psychosis of the hebephrenic type' was made; supplementary examination revealed no abnormalities. Finally, in view of the ununderstood and progressive behavioural changes, the diagnosis was reconsidered; on the basis of clinical findings, SPECT examination and results of repeated CT of the brain, the diagnosis of 'frontotemporal dementia, type Pick' was made.

Background The nosologic structure of psychotic illness, still influenced as much by historical as empirical perspectives, remains controversial. Methods Latent class analysis was applied to detailed symptomatic and outcome assessments of probands (n=343) with broadly defined schizophrenia and affective illness ascertained from a population-based psychiatric registry in Roscommon County, Ireland. First-degree relatives (n=942) were assessed by personal interview and/or review of hospital record. Results Six classes were found, all of which bore substantial resemblance to current or historical nosologic constructs. In order of decreasing frequency, they were (1) classic schizophrenia, (2) major depression, (3) schizophreniform disorder, (4) bipolar-schizomania, (5) schizodepression, and (6) hebephrenia. These classes differed on many historical and clinical variables not used in the latent class analysis. Compared with relatives of controls, significantly increased rates of major depression were seen in relatives of depressed and schizodepressed probands. Significantly increased rates of bipolar illness were restricted to relatives of bipolar-schizomanic probands. The risks for schizophrenia and schizophrenia spectrum disorders were significantly increased in relatives of all proband classes except major depression. This increase was moderate for bipolar-schizomanic probands, substantial for schizophrenic, schizophreniform, and schizodepressed probands, and marked for hebephrenic probands. Conclusions These results suggest a relatively complex typology of psychotic syndromes consistent neither with a unitary model nor with a Kraepelinian dichotomy. The familial vulnerability to psychosis extends across several syndromes, being most pronounced in those with schizophrenialike symptoms. The familial vulnerability to depressive and manic affective illness is somewhat more specific.

Malignant catatonia, associated with different somatic and psychiatric disorders, is a rare, life-threatening syndrome. Immediate recognition and adequate treatment are essential and may be life-saving. We describe a case of malignant catatonia and discuss the clinical implications. Additionally, we review the recent literature regarding epidemiology, nosology, current pathophysiological concepts, differential diagnosis, and treatment recommendations.

A case of late onset metachromatic leukodystrophy with a clinical picture of paranoid hallucinatory psychosis and severe dyskinesia is described. The problem of diagnostic recognition is discussed. In the case, diagnostic procedures were initiated after atypical clinical course, and established on the basis of MRI and specific biochemical tests.

Huntington's disease (HD) may cause considerable diagnostic problems because of the highly variable clinical features, especially at the beginning of the illness. We report the case of a 21-year-old woman with definite HD whose main symptoms were psychopathological changes that were misinterpreted as schizophrenia for 7 years. One reason for this misdiagnosis was the unusual, very early onset and the remarkable earlier age of onset of HD compared with that of other affected relatives. The phenomenon of earlier onset within one affected family is well documented in the literature in cases with the paternally transmitted mutated gene. Diagnostic landmarks were consideration of the initially mild disturbances of movement and the once again repeated detailed examination of the family history.

We examined the relationships between symptom dimensions derived from factor analytic studies of schizophrenic symptoms and sustained attention deficits. Four factors, negative, delusion/hallucination, disorganization, and excitement, were yielded from factor analysis on 14 items of the Positive and Negative Syndrome Scale (PANSS) among 60 Chinese inpatients with acute schizophrenia. The negative dimension was associated with lower sensitivity index (d′) while the excitement dimension was associated with higher d′ on the Continuous Performance Test (CPT) after sex, age and education were adjusted for in multiple linear regressions. The positive dimension affected only response criterion (1nβ) and was not associated with the d′ on the CPT. In contrast, the summed scores of PANSS Positive and Negative scales did not have significant correlations with d′ on the CPT. Thus, the discriminant validity of these symptom dimensions of schizophrenia is supported by their correlations with CPT performance indices.

Factor analysis was performed on OPCRIT checklist psychotic symptoms rated on 102 patients with DSM-III-R schizophrenia. An initial three-factor solution produced positive, negative, and disorganisation factors. However, application of the scree test suggested five substantive factors, with the positive factor dividing into three factors characterised, respectively, by paranoid symptoms, first rank delusions and first rank hallucinations.

The diagnosis of schizophrenia is made on the basis of a diverse set of characteristic signs and symptoms. These include disturbances in perception and inference, abnormalities in communication, behaviour and motor activity, and deficits in emotional expressivity, hedonic capacity and drive. No single symptom or set of symptoms is pathognomonic, and the question of which symptoms are indeed at the ‘core’ of schizophrenia has been an issue of much debate, opinion and study since the disorder was first described a century ago. In this review, the symptoms emphasized in current diagnostic criteria for schizophrenia are described and the relative importance of these symptoms in the evolution of the schizophrenia construct is discussed.

Clozapine is an antipsychotic drug that has a very low incidence of extrapyramidal side effects. Only few dyskinetic and dystonic motoric alterations are described. This brief review describes three patients who developed chorea-like symptoms during a Clozapine therapy. The possible causal mechanisms of these side effect are suggested.

Subgroups of patients with schizophrenia were examined in relation to repetition and seman- tic priming under conditions in which the prime stimulus was to be either attended to or ignored (unattended). Attended conditions normally would produce positive priming; and unattended condi- tions, negative priming (i.e., a delayed reaction resulting from inhibition of target information previously presented as a to-be- ignored stimulus). Cluster anal- ysis of participants' ratings on the Schedule for the Assessment of Positive Symptoms and the Schedule for the Assessment of Negative Symptoms revealed three subgroups that aligned broadly previous research citing with disorganization, reality dis- tortion, and psychomotor poverty syndromes, and a fourth episodic subgroup. The Disorganization, Reality Distortion, and Episodic subgroups were associated with reduced, indeed reversed, nega- tive priming in unattended prim- ing conditions, whereas the Psy- chomotor Poverty subgroup ex- hibited the usual negative priming effect. Participants in the former three subgroups also exhibited reversed positive prim- ing for the repetition condition, while the Psychomotor Poverty group displayed the expected positive priming effect These re- sults indicate that weakening of inhibitory processes may underlie both the reality distortion and disorganization dimensions of positive schizophrenic symp- tomatology, including the latent presence of these symptoms. In contrast, negative symptoms con- tributing to the psychomotor poverty dimension of schizophre- nia are not linked to reduced in- hibition. The association of posi- tive symptom subgroups with reversed positive priming sug- gested that, for these partici- pants, stimuli and task dif- ferences have an impact on the preattentive activation of infor- mation underlying such priming. It is proposed that a "reduced inhibition" model of schizo- phrenic symptomatology may need to be extended to account for influences on preattentive processing. Schizophrenia Bulletin, 22(1): 139-151, 1996.

Recent factor-analytic studies have derived several trisyndromic models for schizophrenia, all based on the positive, negative, and disorganization syndromes. The goal of this study was to examine cognitive disorders in these three schizophrenic syndromes. The study group was composed of 40 schizophrenic patients consecutively admitted to the hospital due to a recrudescence of their symptomatology. They were selected on the basis of a semistructured interview, diagnosed with DSM-III-R criteria, and evaluated with scales for positive and negative symptoms. Their cognitive disorders were assessed with a battery of neuropsychological tests. The schizophrenic syndromes were weakly associated with cognitive performance through direct correlations and after correction for confounding variables. The disorganization and negative syndromes were more strongly associated with cognitive disturbances than was the positive syndrome, and both were associated with disturbances of visual-motor processes. Moreover, the disorganization syndrome was associated with disturbances in language and verbal memory and in time-controlled performance.