Experiments on perception in schizophrenia (author's transl)]

Acute and chronic schizophrenic subjects were tested with 6 simple experimental tasks of visual stimulus selection. The 2 control groups were a group of non-psychiatric subjects and one of patients with other psychiatric diagnoses. The 6 experimental tasks represented three different types of attention: 1) differentiation between "figure" and "background", 2) concentration; 3) visual integration (Gestalt completion). The main result was that the acute group with paranoidal psychosis and hallucinations made significantly more mistakes in figure-background differentiation (grouping of patterns). But there was no difference between this group and the other patients in the concentration tasks. Both schizophrenic groups performed more poorly in the Gestalt completion task. The results are discussed in light of the information theory (breakdown of a hypothetical filter mechanism) and Sokolow's psychophysiological model of stimulus selection. The hypothesis is put forward that in the acute schizophrenic group a disturbance in an arousal-modulation system is responsible for attenuation of irrelevant input.     

Schizophrenia with obsessive-compulsive disorder and obsessive-compulsive disorder with poor insight: a neuropsychological comparison

Schizophrenia patients with obsessive-compulsive disorder (OCD) may be a subgroup of schizophrenia, and OCD patients with poor insight may show psychotic-like symptoms. The aim of this work is to compare the neuropsychological performance of those patients with schizophrenic patients who do not have OCD symptoms and with OCD patients who have good insight. The sample consisted of 89 patients (16 OCD-schizophrenic patients, 30 non-OCD schizophrenic patients, 30 OCD patients with good insight, 13 OCD patients with poor insight). Neuropsychological evaluation included executive functions, verbal and visual memory and attention tasks. While schizophrenic patients with OCD did not differ from the non-OCD schizophrenia and OCD with poor insight groups on long-term visual and verbal memory performance, they showed poorer performance than the OCD group on long-term visual and verbal memory tests. Considering executive function, the OCD group with poor insight performed significantly worse than their counterparts with good insight, and the latter group performed better than the schizophrenia patients. The results of this study suggest that the neuropsychological performance of schizophrenia patients with OCD did not differ from that of non-OCD schizophrenic patients, and that OCD patients with poor insight were more likely to share similar cognitive characteristics with the schizophrenia groups. Our results also provide neuropsychological support for the hypothesis that OCD and schizophrenia may be a spectrum disorders.     

Deficit in suppression of interference in visual information processing by schizophrenic subjects

Although many studies have indicated information processing deficits in schizophrenic patients, the precise nature and underlying causes of these deficits remain largely uncertain. One prominent hypothesis is that these patients show insufficient attentional inhibition. This deficit to inhibition has been linked to certain cognitive disorders in schizophrenic patients, including attention deficits, as well as to some clinical symptoms, especially those involving delusional thought, hallucinations,and poor contact with reality. The hypothesis of deficient attentional inhibition, although attractive in some ways, is difficult to work with, because it is not easy to directly measure "attentional inhibition". Several studies involving normal subjects have linked attentional inhibition with performance on a task demanding the suppression of distracting information: the presumption is that efficient attentional inhibition will permit rapid responses because the distracting information will be quickly suppressed, allowing undistracted processing of the target information. The present study measures schizophrenic patients' performance on a task demanding suppression of rapidly-presented visual information. An important methodological feature of this study is that performance is measured in terms of "percent correct responses" rather than the reaction time measures typically used in tasks demanding distractor suppression, such as Stroop-like selective attention tasks. Since reaction times are not considered, the results cannot be interpreted in terms of deficient response organization and execution. Schizophrenic (18) and normal (18) subjects underwent trials in which a visual target was the second of two stimuli presented in rapid succession. Interference produced by a non-target significantly impaired perception of the target for schizophrenic patients. This effect persisted longer in the schizophrenic subjects possibly because of deficient attentional inhibition.     

Premorbid abnormalities in mania,schizomania, acute schizophrenia and chronic schizophrenia

The aim of this study was to examine the hypothesis that differences in outcome among affective and non-affective psychoses are associated with differences in the degree of developmental deviance. We conducted a retrospective survey of first contact cases treated over a 20-year period in a psychiatric hospital serving a catchment area in South London. All patients with non-depressive functional psychoses residing in the catchment area who received their first psychiatric treatment between 1965 and 1984 were included in the study. Cases were classified according to the relative chronicity of their illness into four non-overlapping groups: mania, schizomania, acute schizophrenia and chronic schizophrenia. There was a linear trend in the association between illness chronicity and proxy measures of developmental deviance, such as premorbid unemployment, single status and poor academic achievement. Compared to individuals with mania, schizophrenic patients had a 3–6 times increased risk of premorbid abnormality. For patients with schizomania and acute schizophrenia, the risk was 1.5–3 times greater than for manic subjects. We conclude that the prevalence of premorbid abnormalities is highest among chronic schizophrenia, but similar disturbances also occur, to a lesser degree, in less disabling affective and non-affective psychotic disorders.MRC Social Psychiatry Unit, Institute of Psychiatry     

Reduced implicit and explicit sequence learning in first-episode schizophrenia

A high prevalence of deficits in explicit learning has been reported for schizophrenic patients, but it is less clear whether these patients are impaired in implicit learning. Deficits in implicit learning indicative of a fronto-striatal dysfunction have been reported using a serial reaction-time task (SRT), but the impact of typical neuroleptic medication and chronicity remains controversial. The present study compared 37 patients with first-episode schizophrenia treated with atypical neuroleptics and 37 healthy matched control participants on two sequence learning tasks: a modified SRT for implicit sequence learning and a serial generation task (SGT) for explicit sequence learning. The two tasks were designed to be procedurally equivalent, in order to provide better comparability between implicit and explicit performance. Although unaffected in global cognitive functioning, schizophrenic patients were significantly impaired in implicit and explicit sequence learning. Deficient sequence learning in schizophrenic patients was neither related to psychopathology nor to chlorpromazine equivalent daily dosage. As performance was impaired even though patients were exclusively treated with atypical neuroleptics, the present findings concur with converging evidence of a sequence learning deficit inherent in schizophrenia. This deficit would be consistent with a fronto-striatal dysfunction and might constitute a crucial factor for the acquisition of new information.     

Perceptional and executive deficits of chronic schizophrenic patients in attentional and intentional tasks

The present study investigated whether schizophrenic patients could develop appropriate visual orientation and motor set under precuing conditions which contrasted attentional (input selective) and intentional (output selective) information. The aim was to evaluate perceptual performance in processing visuospatial information, and executive performance in response preparation. Stimuli and/or elicited responses were controlled for selective hemispheric engagement. Age, sex and handedness matched groups of 33 chronic schizophrenic patients and 33 normal subjects were tested on choice reaction time (RT) tasks in which warning signals were manipulated regarding either where a target stimulus would occur (selective attention) or which hand to use for responding (response preparation). All subjects benefited from precued information regarding subsequent responses. However, schizophrenic patients were not able to use intentional cues as effectively as control subjects did. Interhemispheric asymmetry of spatial attention was found in patients with schizophrenia, with slowing of responses to uncued targets presented in the right visual field. There was also a decreased advantage of within-hemisphere stimulus-response conditions in the schizophrenic group. Our results support the notion that a dysfunction involving parietal and premotor areas has potential importance in the schizophrenic illness. We replicated findings which indicate that deficits of information processing in schizophrenia may affect left hemispheric mechanisms to a larger extent. The results also point toward a possible abnormal connectivity between frontal and parietal circuits in schizophrenia.     

Verbal as well as spatial working memory predicts visuospatial processing in male schizophrenia patients

BACKGROUND: Visuospatial processing (VSP) is impaired in schizophrenia. Recent studies showed significant associations between the Judgment of Line Orientation (JLO) test, a common test of VSP and Verbal (VWM) as well as Spatial (SWM) working memory. VWM and SWM show different associations with various genes so subgroups of patients with similar VSP but different WM impairment profiles may vary in genetic associations. In this study we investigated the relationship among VSP, VWM and SWM. METHODS: Sixty seven men with schizophrenia and 51 healthy men completed computerized JLO and tests of VWM (digit span), and SWM (Dot test). Tests of attention (CPT) and psychomotor processing speed (Finger Tap) were also included. RESULTS: Patients' performance was impaired on all tests. Multivariate regression with JLO as the outcome variable and VWM, SWM, attention, psychomotor processing speed and interactions between group and these variables, as predictors showed significant contribution of VWM and SWM. The model explained 34.4% of the variance (R(2)=0.344). Conclusion: VSP, as measured by JLO, receives independent contributions from VWM and SWM. Patient subgroups matched for VSP may differ in the relative contributions and impairments of VWM and SWM. Such heterogeneity may limit the usefulness of VSP in genetic studies. The possibility that WM may be more useful than VSP in this regard deserves further study.     

Subjective cognitive dysfunction in first-episode and chronic schizophrenic patients

Previous studies indicate that first-episode and chronic schizophrenic patients do not differ regarding neuropsychological performance as assessed with standard cognitive tasks. For the present study, it was investigated whether first-episode and chronic schizophrenics report similar subjective cognitive deficits. The Frankfurt Complaint Questionnaire (FCQ), a scale devised for assessing subjective cognitive disturbances in schizophrenia, was administered to 20 first-episode and 36 chronic schizophrenic patients, as well as 20 healthy controls. The schizophrenic subsamples did not differ on any of the FCQ subscales or on a "lie scale," measuring illness denial. Psychopathological ratings were comparable for both groups. As expected, healthy subjects reported significantly less cognitive and perceptual problems than schizophrenic patients. In marked contrast to a Kraepelinian view of schizophrenia, the present data confirm previous studies conducted with objective neuropsychological tests that schizophrenia is a neurodevelopmental rather than a neurodegenerative disorder.     

Lateralized attentional deficits in drug-free and medicated schizophrenic patients

Performance on a cued reaction time (RT) task, theoretically linked to posterior and anterior neuroanatomical systems in the brain (Posner, M. I. et al., Science, 1988, 210, 1627–1631; Archives of General Psychiatry, 1988, 15, 811–821), was used to assess sensory orienting and maintenance of attention. In schizophrenic patients, Posner et al. found a lateralized abnormality in RT (longer RTs to uncued targets in the right visual field than in the left visual field), as did Maruff et al. (Neuropsychologia, 1995, 33, 1205–1223), but Strauss et al. (Journal of Psychiatric Research, 1991, 37, 139–146), among others, did not replicate this effect. However, the subjects in these studies differed in the percentage of schizophrenic patients taking neuroleptic medication at the time of testing and in the chronicity of the illness. In the present study, we used two groups of schizophrenic subjects to control for the use of neuroleptic medication. The lateralized abnormality in RT was observed in the drug-free group of schizophrenic subjects, but not in the group of drug-treated schizophrenic subjects.     

Regional neural dysfunctions in chronic schizophrenia studied with positron emission tomography

OBJECTIVE: Whether chronicity of illness produces progressive neural abnormality is an important question in current schizophrenia research. Positron emission tomography (PET) offers an opportunity to visualize and measure blood flow in vivo to address this issue. The authors previously compared healthy volunteers with neuroleptic-naive patients experiencing their first episode of schizophrenia and reported that abnormalities in blood flow, including lower flow in prefrontal regions and higher flow in the thalamus and cerebellum, are present at the early stage of schizophrenic illness. The goal of the present study was to measure blood flow with PET in patients with chronic schizophrenia. METHOD: PET was used to examine regional cerebral blood flow (rCBF) in 30 patients with chronic schizophrenia and 30 normal comparison subjects. To determine if the patterns of flow abnormality in the patients with chronic schizophrenia were similar to those of patients experiencing their first episode of schizophrenia, the same cognitive condition was examined as in the earlier study. The patients with chronic schizophrenia in the current study had been neuroleptic-free for at least 3 weeks. RESULTS: As in the authors' previous study, the chronically ill patients showed lower flow in prefrontal areas and higher flow in thalamic and cerebellar regions than normal comparison subjects, suggesting that a similar neural dysfunction occurs in both first-episode and chronic schizophrenia. CONCLUSIONS: rCBF abnormalities in patients with chronic schizophrenia are not due to chronicity of illness or the effects of medication. These results provide evidence that the primary neural abnormalities in schizophrenia may occur in cortical, cerebellar, and thalamic regions and that the dysfunction in these regions may explain the "loosening of associations" that Bleuler considered to be the fundamental cognitive phenotype of schizophrenia. These abnormalities can be reconceptualized as "cognitive dysmetria."     

Neuropsychologic functioning among the nonpsychotic relatives of schizophrenic patients: the effect of genetic loading.

BACKGROUND: We previously reported that the nonpsychotic relatives of schizophrenic patients exhibited disturbances in executive functioning, verbal and visual memory, auditory attention, mental control, and verbal ability. In a 4-year follow-up, we showed that the discriminating power of most of these tests was stable over time. METHODS: In this report we compare 41 nonpsychotic persons who have only one schizophrenic first-degree relative (simplex families) with 36 nonpsychotic persons who have two schizophrenic first-degree relatives (multiplex families). Our goal was to test a hypothesis that neuropsychologic deficits would be worse among the latter. RESULTS: Relatives from multiplex families differed significantly from controls on estimated intelligence, immediate and delayed logical memories, and immediate visual reproductions. In contrast, in comparisons with controls, relatives from simplex families only differed on immediate logical memories. Comparisons between relatives from multiplex and simplex families showed that the former group had significantly worse scores for estimated intelligence, immediate and delayed logical memories, and immediate visual reproductions. We also found group x gender interactions: the worse performance of the multiplex group was seen for females. CONCLUSIONS: These results are consistent with the idea that neuropsychologic deficits in relatives of schizophrenic patients reflect their degree of genetic predisposition to schizophrenia. They also suggest hypotheses about gender differences in the familial transmission of the disorder.     

Forward and backward visual masking in unaffected siblings of schizophrenic patients.

BACKGROUND: Visual masking tasks assess the earliest stages of visual processing. This study examined visual masking performance for forward and backward masking tasks in siblings of schizophrenic patients and healthy comparison subjects. METHODS: A staircase method was used to ensure that unmasked target identification was equivalent across subjects to eliminate differences due to discrimination of simple perceptual inputs. Four computerized visual masking tasks were administered to 43 siblings of patients and 42 normal comparison subjects. The tasks included: 1) locating a target; 2) identifying a target with a high-energy mask; 3) identifying a target with a low-energy mask; and 4) a paracontrast/metacontrast procedure with nonoverlapping target and mask. RESULTS: Across masking conditions, there was a significant group by forward/backward interaction, meaning that siblings showed a larger difference from control subjects in backward versus forward masking. This group difference was more pronounced in the location condition. CONCLUSIONS: These results support the theory that visual masking procedures may be indicators of vulnerability to schizophrenia. The pattern of findings in this report (larger group differences on backward versus forward masking and on the location condition) suggests that the activity of transient visual channels may be particularly linked to vulnerability.     

Characteristic distribution of alpha 2 wave in electroencephalograms of schizophrenic patients during discriminative tasks: support for the hypofrontality hypothesis of schizophrenia.

In a preliminary study, we noticed that alpha 2 activity in the frontal regions was suppressed less in schizophrenic patients than in other patients during the discriminative tasks. This was confirmed with 37 schizophrenic and 16 nonschizophrenic patients under the treatment of neuroleptics, 15 nonmedicated schizophrenic patients and 32 normal controls. The EEGs in eye-closed resting and during the auditory and visual discriminative tasks were recorded. Alpha 2 power values of the frontal, central, parietal, occipital and temporal regions in every subject group were processed by cluster analysis. During the discriminative tasks, the frontal regions were the most isolated cluster in schizophrenic patients and, in the normal and medicated nonschizophrenic groups, the frontal regions were incorporated in a different cluster. The same result was obtained by different statistical analyses of F-alpha 2 power ratio. The relative abundance of alpha 2 power value shifts from the occipital to the frontal regions during the discriminative tasks in schizophrenic patients. The weakened suppression of alpha 2 waves in the frontal regions by the discriminative tasks in schizophrenic patients supports the hypofrontal hypothesis of schizophrenia.     

Psychopathology and wisconsin card sorting test performance in young unmedicated schizophrenic patients

The relationship between psychopathology and Wisconsin Card Sorting Test (WCST) performance was evaluated in 25 unmedicated young acute schizophrenic female patients (14 neuroleptic-naive and 11 neuroleptic-free) and 15 female controls. The schizophrenic patients (especially the neuroleptic-free) performed more poorly than controls in the WCST. In addition, WCST impairment correlated with both negative and positive symptoms. The results suggest that the neuropsychological dysfunction in schizophrenia is present at the onset of the illness, and is neither secondary to previous neuroleptic treatment nor to chronicity of the illness.     

Disruption of neural systems of visual attention in schizophrenia

BACKGROUND: Patients with schizophrenia show attention deficits. The frontal P2a and posterior N2b event-related potential components are early indices of activity in neural systems supporting attention and they are reduced in schizophrenia in auditory tasks. However, the auditory P300 is reduced as well. Thus, the P2a and N2b reductions may simply reflect a general event-related potential amplitude reduction. The visual P300, however, is often spared in schizophrenia. If neural systems supporting attention are specifically disrupted in schizophrenia, the attention-sensitive P2a and N2b should be differentially reduced in patients, compared with the P300, in a visual attention task. METHODS: We analyzed 64-channel event-related potentials from 14 schizophrenic patients and 14 control subjects in a visual object-spatial attention task. We examined the amplitude of the P2a, N2b, and P300 components in the target minus standard difference wave to see if there was a differential reduction of the P2a and N2b compared with the P300. RESULTS: Both the P2a and N2b waveforms were reduced in the patient group (81% [control mean, 1.99 microV; patient mean, 0.38 microV] and 95% [control mean, 0.55 microV; patient mean, 0.03 microV], respectively) while the P300 was not reduced. Measured at the peak of the frontal P2a, the N2b was larger dorsally in the spatial task and larger ventrally in the object task in the control group. CONCLUSIONS: The spatial distribution of the P2a and N2b was consistent with activity in the prefrontal cortex and modality-specific posterior cortex, respectively. The differential reduction of the P2a and N2b waveforms supports the hypothesis of specific disruption in neural systems of visual attention in schizophrenia.     

Neurocognitive Pattern Analysis Reveals Classificatory Hierarchy of Attention Deficits in Schizophrenia

Attention deficits, among other cognitive deficits, are frequently observed in schizophrenia. Although valid and reliable neurocognitive tasks have been established to assess attention deficits in schizophrenia, the hierarchical value of those tests as diagnostic discriminants on a single-subject level remains unclear. Thus, much research is devoted to attention deficits that are unlikely to be translated into clinical practice. On the other hand, a clear hierarchy of attention deficits in schizophrenia could considerably aid diagnostic decisions and may prove beneficial for longitudinal monitoring of therapeutic advances. To propose a diagnostic hierarchy of attention deficits in schizophrenia, we investigated several facets of attention in 86 schizophrenia patients and 86 healthy controls using a set of established attention tests. We applied state-of-the-art machine learning algorithms to determine attentive test variables that enable an automated differentiation between schizophrenia patients and healthy controls. After feature preranking, hypothesis building, and hypothesis validation, the polynomial support vector machine classifier achieved a classification accuracy of 90.70% ± 2.9% using psychomotor speed and 3 different attention parameters derived from sustained and divided attention tasks. Our study proposes, to the best of our knowledge, the first hierarchy of attention deficits in schizophrenia by identifying the most discriminative attention parameters among a variety of attention deficits found in schizophrenia patients. Our results offer a starting point for hierarchy building of schizophrenia-associated attention deficits and contribute to translating these concepts into diagnostic and therapeutic practice on a single-subject level.Key words: focused attention, sustained attention, selective attention, alternating attention, divided attention, machine learning     

Neurocognitive performance in first-episode and chronic schizophrenic patients

Previous research on neuropsychological disturbances in first-episode and chronic schizophrenic patients has provided mixed results which can be partially attributed to methodological inconsistencies. For the present study, 70 schizophrenic patients (40 with chronic and 30 with first-episode schizophrenia) were compared to 30 healthy controls on a large battery of neuropsychological tests. Special attention was paid to potential confounds such as differences in psychopathology, age and educational level between the schizophrenic sub-samples. Healthy controls performed better than both first-episode and chronic patients in almost all cognitive domains (P < 0.01), while the patient samples did not differ in any of the tasks. Results were confirmed in a second series of analyses in which patient subgroups were equated for sociodemographic background variables. The present results confirm recent data collected in longitudinal studies, thus, lending further support for a neurodevelopmental model of schizophrenia. It is suggested that neuropsychological disturbances occur early in schizophrenia and do not worsen in the course beyond age-related decrement. Possible reasons why previous research has produced contradictory findings are discussed. Received: 26 July 2001 / Accepted: 4 December 2001     

Chemistry, physiology and neuropsychology of schizophrenia: towards an earlier diagnosis of schizophrenia I

Data supporting the glutamate hypothesis of schizophrenia are presented. The glutamate hypothesis is linked to the dopamine hypothesis by the fact that dopamine synapses inhibit the release of glutamate in the striate and mesolimbic system. The glutamate hypothesis of schizophrenia may open a way to find better drugs for treatment. The concept of schizophrenia I is described. It consists of "negative symptoms" such as disconcentration or reduction of energy. Schizophrenia I precedes and follows schizophrenia II with "positive symptoms," e.g. hallucinations and delusions. Schizophrenia I so far cannot be diagnosed as schizophrenia unless schizophrenia II appears. Chemical, physiological or neuropsychological methods for the diagnosis of schizophrenia I would render an earlier treatment of schizophrenia possible and thus make social and occupational rehabilitation more efficient. An objective diagnosis of schizophrenia I may also elucidate the mode of genetic transmission of schizophrenia. Several neuropsychological methods distinguish schizophrenic patients as a group from normals. Some of them are based on a specific disturbance of long term concentration. The EEG also distinguishes schizophrenics from normals when analyzed during voluntary movement. For schizophrenics it takes more effort to initiate a voluntary movement, and there are several features of the EEG correlated to this. Moreover, the longer motor reaction time of schizophrenics is paralleled by a longer duration of the Bereitschaftspotential in schizophrenia. Furthermore, there is a difference in the theta rhythm between schizophrenic patients and normals in a task which requires concentration. Some of the children of schizophrenic parents show a disturbance of concentration in both reaction time tasks and the d 2 test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Origine et renouveau du concept de démence dans la schizophrénie

An increasing amount of current literature on schizophrenia is devoted to the role dementia may play in its course. This renewed interest had the way paved by the very history of the dementia concept. Before Kraepelin coined the term of "dementia praecox" as the hallmark of a common terminal state for hebephrenia, catatonia and paranoid psychosis, dementia acquired, as soon as the end of the 18th-century its cognitive meaning. In France, Pinel yet spoke of an "abolition of thinking", but in the same time considered dementia as one of the four forms of mental alienation, alongside with mania, melancolia and idiotism. During the 19-th century dementia was defined as an acquired deficit of intelligence supported by a brain disease, but which could be due to a mental illness. Owing to progress in neuropathology, several diseases such as Alzheimer or Pick illnesses were identified as causes of dementia, so that the concept was annexed by neurologists and received less interest from psychiatrists, during the last century. That seemed to change, twenty years ago, when clinical discussions emerged around the issues raised by depressive (pseudo) dementia. In psychiatry, the broader conceptualization of schizophrenia introduced by Bleuler in 1911 has not been widely adopted, many authors having been continuing sharing the Kraepelinian view that, at least one form of the disease, was a chronic progressive illness leading to severe impairments in cognitive and social functioning. Historical variations in diagnostic criteria used for schizophrenia had an impact on the way psychiatrists assessed outcome of the disease, leading some of them to consider schizophrenia as a nosological category without natural boundaries and propose to abandon the concept. However the use of narrow criteria is currently prevailing. Advances in neurocognitive testing and changes in theoretical models allowed, at the end of the last century, to document that schizophrenia was characterized by a broadly based cognitive impairment. Deficits were found in various domains: global and selective verbal memory, non-verbal memory, bilateral and unilateral motor performance, visual and auditory attention, general intelligence, spatial ability, executive function, language and interhemispheric tactile-transfer test performance. The hypothesis according to which the vast majority of these cognitive deficits had a neurodevelopmental origin was recently challenged by findings from longitudinal neurocognitive and neuroimaging studies. Some studies, for example, show that if first episode patients have smaller left hippocampal volumes as compared with controls, there is also an association of smaller right hippocampal volumes with increased illness duration in chronic schizophrenia. Others have shown that neuropsychological evaluations before treatment permitted differentiation of primary deficits from changes secondary to medication or chronicity. Clinicians reported that in some cases of chronic schizophrenic patients, dementia could be a complication of the disease, sharing common neuropsychological features with frontotemporal dementia. The effect of age was discussed too, as seeming to play sometimes a part. Even if the cause of the degenerative process that appears to occur in the brains of some schizophrenic patients remains largely unknown, advances in neuropathological models of degeneration in the brain as well as in mechanisms and factors underlying its process, gave rise to hypotheses liable to explain how degenerative dementia could occur in schizophrenia. Excess products of membrane degeneration which was evidenced by magnetic resonance spectroscopy suggests increased apoptosis in some schizophrenic patients. Deficits in neurotrophic factors, free radical oxidation, excess glutamate activity have been implicated as well as abnormalities in dopamine and cortisol metabolism. Growing evidence that some newer antipsychotics seem capable to interfere with these processes, slowing down their progression and even stopping it, has contributed to the renewal of the concept, opening new avenues to preventive strategies in the treatment of schizophrenia.