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Background and Hypothesis: Corollary discharge mechanism suppresses the conscious auditory sensory perception of self-generated speech and attenuates electrophysiological markers such as the auditory N1 Event-Related Potential (ERP) during Electroencephalographic (EEG) recordings. This phenomenon contributes to self-identification and seems to be altered in people with schizophrenia. Therefore, its alteration could be related to the anomalous self-experiences (ASEs) frequently found in these patients., Study Design: To analyze corollary discharge dysfunction as a possible substrate of ASEs, we recorded EEG ERP from 43 participants with schizophrenia and 43 healthy controls and scored ASEs with the 'Inventory of Psychotic-Like Anomalous Self-Experiences' (IPASE). Positive and negative symptoms were also scored with the 'Positive and Negative Syndrome Scale for Schizophrenia' (PANSS) and with the 'Brief Negative Symptom Scale' (BNSS) respectively. The N1 components were elicited by two task conditions: (1) concurrent listening to self-pronounced vowels (talk condition) and (2) subsequent non-concurrent listening to the same previously self-uttered vowels (listen condition)., Study Results: The amplitude of the N1 component elicited by the talk condition was lower compared to the listen condition in people with schizophrenia and healthy controls. However, the difference in N1 amplitude between both conditions was significantly higher in controls than in schizophrenia patients. The values of these differences in patients correlated significantly and negatively with the IPASE, PANSS, and BNSS scores., Conclusions: These results corroborate previous data relating auditory N1 ERP amplitude with altered corollary discharge mechanisms in schizophrenia and support corollary discharge dysfunction as a possible underpinning of ASEs in this illness., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The objective of this study was to understand the psychosocial and pharmacological approaches linked to better treatment adherence and outcomes (psychiatric hospitalizations, clinical severity, and suicide attempts) among patients with schizophrenia receiving the standard treatment in mental health units (MHUs) compared with patients in a community-based, case-managed program (CMP). An observational, prospective (10 y) study was conducted involving patients with severe schizophrenia (N=688). The treatment adherence of patients in the CMP was higher than among those in the MHUs (12.2% vs. 84.3% abandoning treatment; P<0.0001). Hospital admissions and suicide attempts were significantly lower among those treated in the CMP than among those receiving standard care in the MHUs (P<0.001). Scores on the clinical severity scale decreased significantly more in the group in the CMP than in the group in the MHUs (P<0.005). Treatment with long-acting injectable antipsychotic medication was closely linked with higher treatment retention (P<0.001) and fewer hospital admissions and suicide attempts compared with treatment with oral antipsychotics in both patient groups, with the effect greater in the group in the CMP (P<0.001). We highlight how patients with severe schizophrenia treated in a CMP with integrated treatment showed a higher retention rate, fewer psychiatric hospital admissions and suicide attempts, and less clinical severity compared with those receiving standard treatment in MHUs. Treatment with long-acting antipsychotics was also clearly related to these outcomes. A combination of intensive case-managed integrated treatment and treatment with long-acting antipsychotic medication facilitated the achievement of clinical and rehabilitation goals in patients with schizophrenia with severe symptoms and impairment compared with standard care and treatment with oral antipsychotics., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The objective here is to compare the effectiveness of long-acting injectable antipsychotics (LAI-APs) and oral ones (OAPs) in patients with severe (Global Clinical Impression-Severity ≥ 5) schizophrenia (N = 688). A 5-year follow-up study has been conducted in patients undergoing standard treatment in mental health units (MHUs) or on a severe mental illness program (SMIP). A total of 8.7% of the patients on the SMIP discontinued treatment, whereas 43.6% did so in MHUs (p < 0.0001). In both cases, treatment retention was significantly higher in patients on LAI-APs (p < 0.001). Also, hospital admissions were in both cases fewer among those on LAI-APs (p < 0.001). There was a significant link between suicide attempts and OAP treatment (p < 0.01). Given the relationship between the use of LAI-APs versus oral treatments in achieving higher adherence and less relapses and suicide attempts, the use of second-generation antipsychotics LAIs should be considered more suitable for people with severe schizophrenia., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Diagnosis of schizophrenia lacks reliable medical diagnostic tests and robust biomarkers applied to clinical practice. Schizophrenic patients undergoing treatment with antipsychotics suffer reduced life expectancy due to metabolic disarrangements that co-exist with their mental illness and predispose them to develop metabolic syndrome, which is also exacerbated by medication. Metabolomics is an emerging and potent technology able to accelerate this biomedical research., Aim: This review focus on a detailed vision of the molecular mechanisms involved both in schizophrenia and antipsychotic-induced metabolic syndrome, based on innovative metabolites that consistently change in nascent metabolic syndrome, drug-naïve, first episode psychosis and/or schizophrenic patients compared to healthy subjects. Main Lines: Supported by metabolomic approaches, although not exclusively, noteworthy variations are reported mainly through serum samples of patients and controls in several scenes: 1) alterations in fatty acids, inflammatory response indicators, amino acids and biogenic amines, biometals, and gut microbiota metabolites (schizophrenia); 2) alterations in metabolites involved in carbohydrate and gut microbiota metabolism, inflammation and oxidative stress (metabolic syndrome), some of them shared with schizophrenia; 3) alterations of cytokines secreted by adipose tissue, phosphatidylcholines, acylcarnitines, Sirtuin 1, orexin-A, and changes in microbiota composition (antipsychotic-induced metabolic syndrome)., Conclusion: Novel insights into the pathogenesis of schizophrenia and metabolic side-effects associated with its antipsychotic treatment represent an urgent request for scientists and clinicians. Leptin, carnitines, adiponectin, insulin, or interleukin-6 represent some examples of candidate biomarkers. Cutting-edge technologies like metabolomics have the power to strengthen research for achieving preventive, diagnostic, and therapeutical solutions for schizophrenia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The evaluation of long-term effectiveness and tolerability of aripiprazole once-monthly (AOM) is yet scarce, and severely ill patients have not been specifically studied., Objective: The aim of the study was to explore the long-term adherence, effectiveness and tolerability of AOM in the treatment of patients with severe (Clinical Global Impression-Severity, CGI-S ≥ 5) schizophrenia, and whether high-dose therapy may benefit patients inadequately controlled on standard doses., Methods: Six-year mirror-image study, with a 36-month prospective follow-up, was conducted on patients with severe schizophrenia who underwent treatment with AOM (n = 60). The assessment included the CGI-S, the WHO Disability Assessment Schedule (WHO- DAS), the Medication Adherence Report Scale (MARS), the laboratory tests, the assessment of weight and adverse effects reported. Reasons for treatment discontinuation, hospital admissions and psychiatric medications in the previous three years and during the follow-up were recorded., Results: The average dose was found to be 780 (120) mg/28 days. Tolerability was good, with fewer side effects or biological parameters alterations reported. There were three discharges due to adverse effects, two due to lack of effectiveness and one treatment abandoning. Weight and prolactin levels were decreased. CGI-S and WHO-DAS were decreased (p < 0.001), and MARS increased (p < 0.001). There were less treatment abandoning, hospital admissions (p < 0.0001) and concomitant medication (p < 0.01) observed than during the previous 36 months., Conclusion: Treatment adherence and tolerability of AOM were found to be remarkable, even in those patients on high doses. AOM showed effectiveness in patients with severe schizophrenia, who recorded less hospitalizations and clinical severity and disability, although a considerable percentage of them required higher doses than labeled., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

To date, only a few studies compared some long-acting injectables (LAIs) antipsychotics showing similar symptom improvement, relapse rates and adherence to treatment. We evaluated the use of LAIs antipsychotics [aripiprazole-1-month (A1M); paliperidone-1-month and 3-month (PP1M and PP3M) and biweekly (2w)-LAIs] and their corresponding oral formulations through (1) the number of hospital re-admissions, (2) the number of documented suicidal behaviour/attempts and (3) the use of concomitant benzodiazepines, oral antipsychotics and biperiden. A total of 277 patients, ≥18 years old, were included if were treated with the corresponding oral or LAI antipsychotic during at least 12 months and were previously diagnosed with schizophrenia. Our results showed that LAIs associated significantly lower suicidal behaviour, reduced the number of hospital admissions, lower diazepam and haloperidol equivalents and mean daily dose of biperiden intake versus oral antipsychotics. Furthermore, significant differences were found between LAIs. Specifically, PP3M was associated to lower hospital admissions versus A1M; PP1M and PP3M lower doses of diazepam equivalents versus 2w-LAIs and finally, PP1M lower antipsychotic intake versus 2w-LAIs. In conclusion, LAIs improved clinical outcomes by reducing the need for concomitant treatments and hospital admissions over oral antipsychotics. PP1M and PP3M showed better outcomes versus A1M and biweekly LAIs.

Background: Regarding the treatment of patients with resistant schizophrenia, different options exit, although they are supported by limited evidence. In this study, antipsychotic polypharmacy, comprising 1200 mg of amisulpride and 600 mg of quetiapine, was used. Clinical change evaluation was performed using neurocognitive evaluations., Study Question: The use of amisulpride and quetiapine will imply a clinical improvement in patients affected by schizophrenia, which will be specially reflected in a cognitive improvement., Study Design: Naturalistic and prospective study. Twenty-six patients were applied and assessed by a battery of neurocognitive evaluations since the pretreatment baseline until 6-month treatment. The patients had no biological response to medication, high social maladjustment, and a long clinical history of the disease. Kane and Brenner criteria for treatment-resistant schizophrenia were applied to choose the subjects., Measures and Outcomes: The cognitive improvement will imply a significant betterment, from the pretreatment baseline until 6-month treatment, in the following cognitive tests: Stroop Test, WAIS Coding Subtest, and Comprehensive Trail Making Test (CTMT). An improvement in the Calgary Depression Scale, Simpson-Angus Scale, and Visual Analogue Scale (EVA) will also be observed. This scales were been used during the baseline, 3 months after, and then, 6 months., Results: Subjects, after 6-month treatment with amisulpride and quetiapine, did show statistically significant differences in the assessed areas: WAIS Coding Subtest (P < 0.001), CTMT A and B (CTMT A P < 0.034; CTMT B P < 0.000), and Stroop Tests: Word (P < 0.001), Word-Color (P < 0.007), and Interference (P < 0.039). Furthermore, they showed a statistically significant difference in the Calgary Depression Scale (P < 0.002), Simpson-Angus Scale (P < 0.019), and EVA (P < 0.001)., Conclusions: The results of this report show a cognitive and clinical improvement in refractory patients after the administration of amisulpride and quetiapine.

We have carried out a bibliometric study about the international scientific publications on clozapine. We have used the EMBASE and MEDLINE databases, and we applied bibliometric indicators of production, as Price's Law on the increase of scientific literature. We also calculated the participation index (PI) of the different countries. The bibliometric data have also been correlated with some social and health data from the 12 most productive countries in biomedicine and health sciences. In addition, 5607 original documents dealing with clozapine, published between 1970 and 2013, were downloaded. Our results state non-fulfilment of Price's Law, with scientific production on clozapine showing linear growth (r=0.8691, vs. r=0.8478 after exponential adjustment). Seven of the 12 journals with the highest numbers of publications on clozapine have an Impact Factor>2. Among the countries generating clozapine research, the most prominent is the USA (PI=24.32), followed by the UK (PI=6.27) and Germany (PI=5.40). The differences among countries on clozapine research are significantly related to economic variables linked to research. The scientific interest in clozapine remains remarkable, although after the application of bibliometric indicators of production, a saturation point is evident in the growth of scientific literature on this topic.

It is known that patients with schizophrenia show a deficiency in the prepulse inhibition reflex (PPI). These patients display abnormalities in autonomic nervous system and hypothalamic-pituitary-adrenal function and may have an altered sensitivity to stress. To date, no studies have been carried out to determine the effect of acute stress on the PPI. We investigated whether there was a differential response in reactivity to acute stress caused by the socially evaluated cold-pressor test (SECPT) in a sample of 58 chronic male patients with schizophrenia and 28 healthy control subjects. PPI, salivary cortisol and heart rate (HR) were measured. The patients were evaluated in two sessions (with and without the SECPT) 72 h apart and basal measurements were carried out and 30 min post-startle probe. We found an increase in salivary cortisol levels and the HR with SECPT condition in both groups and a significantly lower PPI% in patients with schizophrenia. The most relevant findings of this study are that the impairment of the PPI is increased by stress. Stress-induced increase in cortisol in both groups, mainly in healthy control group which allows us to hypothesize that at least such deterioration may be due to the hypercortisolemia caused by the SECPT., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The association of antipsychotics is a widespread therapeutic resource in clinical practice. The purpose of the present work was to evaluate the efficacy and safety of amisulpride augmentation in patients responding at least partially to olanzapine., Methods: In this observational 3-months open-label investigation, we evaluated the effectiveness of the addition of amisulpride to 49 subjects, after having scored at least 25 on the brief psychiatric rating scale (BPRS) following olanzapine monotherapy for 6 weeks. Patients were assessed at baseline, 1 and 3 months using the BPRS, the clinical global impression severity of illness (CGI-S) scale and the Udvalg for Kliniske Undersogelser side effect rating scale (UKU)., Results: In subjects who were at least partially responsive to monotherapy with olanzapine, coadjuvant treatment with amisulpride achieved a statistically significant improvement in mental status over a 3 month period as measured by the BPRS, CGI and UKU scales. The response rate (>20% reduction in BPRS score) was 75.51%., Conclusions: Amisulpride augmentation, in a group of patients partially or non-responsive to olanzapine, may lead to an improvement in schizophrenic symptoms. However, these results are subject to several limitations making it difficult to derive firm clinical recommendations, and underscoring the need for future research into the value of these therapeutic alternatives in poor responders., (© Georg Thieme Verlag KG Stuttgart · New York.)

Psychopharmacology of schizophrenia has remained static for many years because the mechanisms explored have been basically monoaminergics, primarily focused toward the modification of dopaminergic function and, later on, serotonergic. In fact, most of the antipsychotics introduced in clinical practice in the last years have been antagonists or selective agonists of these receptors (D(2)/5-HT(2)). The exploration of other receptor pathways, and in particular those additionally involved in the action of the paradigmatic "atypical" antipsychotic clozapine (ie, cholinergic and noradrenergic), has not been very significant. Besides, research in the antipsychotics field has developed also by exploring pathways that are beyond the spectrum of clozapine. Among the most promising mechanisms are those based on the glutamatergic hypothesis of schizophrenia (agonists at the glycine-binding modulatory site of the N-methyl-D-aspartate receptor, glycine transporter inhibitors, modulators of the AMPA [α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid] receptor and selective agonists of the metabotropic receptor Glu(2)). Other less classic pathways are also under study and have led to some agents that are found in very early stages of development such as those acting on sigma receptors, cholecystokinin antagonists, neurotensin agonists, neurokinin receptor antagonists, GABAergic (+-aminobutyric acid [GABA]) enhancers, and cannabinoid(gamma-aminobutiric) receptor modulators.

Objective: Antipsychotic monotherapy is considered as the reference standard in the pharmacological treatment of schizophrenia. Nonetheless, there is a large rate of studies showing polypharmacy with antipsychotics as more frequent than would be expected attending experts' recommendations. The objective of this study is to describe polypharmacy with antipsychotic regimen in patients with schizophrenia discharged with amisulpride from the short-term hospitalization unit., Methods: We have analyzed the prescription of psychotropic drugs upon discharge of 52 patients with schizophrenia or schizoaffective disorder who were discharged with amisulpride from January to December 2005. Variables were included to describe the following treatments: antipsychotic (drug and dose), benzodiazepine, and anticholinergic drugs. Sociodemographic and clinical variables were also collected., Results: In the group treated with 2 antipsychotics, the most frequently used common combination was with a classic antipsychotic in depot formulation. Patients (17.5%) were prescribed to another 2 antipsychotics in addition to amisulpride, being the most common combination with a second generation antipsychotic, and a classic or depot antipsychotic., Conclusions: The results of our study show that the use of amisulpride as an adjuvant can be a suitable therapeutic strategy for patients with schizophrenia resistant to treatment and for the rapid control of symptoms in schizophrenic patients with acute episodes. However, its clinical use does not have to be reserved exclusively for patients with resistant schizophrenia to clozapine.

Schizophrenia is a heterogeneous clinical condition that may reflect a variety of biological processes. In particular, treatment-resistant (TR) schizophrenia may have a distinct neurobiological substrate. Within the context of clinical data, a simultaneous study with different imaging techniques could help to elucidate differences in cerebral substrates among schizophrenia patients with different responses to treatment. In the present work we used a set of biological data (basal and longitudinal volumetry, and P300 event-related potential measurements) to compare TR and treatment-responsive chronic schizophrenia patients with healthy controls. The TR patients showed higher baseline clinical scores, a more severe basal profile of brain alterations, as well as a different outcome as regards to volume deficits. These data support the notion that biological substrates vary among groups of different psychotic patients, even when they have the same diagnosis, and that those substrates may be related to the response to treatment.

Objectives: Long-term studies show that 47% to 63% of schizophrenic patients treated with clozapine fail to respond after 12 years of treatment. Such high rates of resistance justify the growing interest in therapeutic strategies based on enhancing the effect of clozapine with other antipsychotics. The combination of clozapine and risperidone in the treatment of partial responders to clozapine has been one of those receiving most interest from research., Methods and Results: The present work reports the case of a 26-year-old man, diagnosed with schizophrenia who, after treatment with clozapine at appropriate doses over 12 weeks without observable response, showed a marked and sustained improvement after the addition of risperidone to the clozapine treatment. We also present a detailed review of publications related to the therapeutic combination of clozapine and risperidone in clozapine-resistant schizophrenia., Conclusions: Despite the contradictory nature of the published data, our results are in support of other work reporting that treatment with a combination of clozapine and risperidone, apart from being well tolerated, may constitute an effective alternative in this type of patient. Nevertheless, there is a need for further, controlled studies, with larger samples, with a view to drawing definitive conclusions and making specific recommendations.

Objective: This study aimed to compare the efficacy of long-acting risperidone and zuclopenthixol in subjects with schizophrenia and substance abuse., Method: A total of 115 subjects with schizophrenia and substance use disorders were enrolled for an open, randomized, controlled, 6-month follow-up study. Fifty-seven subjects were selected for treatment with long-acting injectable risperidone, while another 58 were treated with zuclopenthixol-depot., Results: Long-acting risperidone patients presented fewer positive urine tests (8.67 compared with 10.36, P = 0.005), showed improved scores on the Positive and Negative Syndrome Scale, and showed better compliance with the Substance Abuse Management program. The use of long-acting risperidone and less severe dependence explained the outcome at the end of the follow-up., Conclusions: Long-acting injectable risperidone was more effective than zuclopenthixol-depot in improving substance abuse and schizophrenia symptoms in subjects with dual diagnosis.

Abnormalities of the P300 component of the event-related potential are a common finding in schizophrenia. It seems possible that the dysfunction in the dorsolateral prefrontal (DLPF) region that has been reported in schizophrenia contributes to this finding. To explore this possibility, we calculated the relationship between, on the one hand, P300 latency and amplitude and, on the other hand, the degree of DLPF atrophy (as measured by magnetic resonance imaging) and metabolic activity during an attentional task (as measured by positron emission tomography). Seventeen schizophrenia patients with a brief duration of illness and minimal exposition to treatment and 25 healthy controls were studied. Patients exhibited significantly lower metabolic activity in the DLPF region, but they did not show cortical atrophy. P300 amplitude was also significantly reduced in the schizophrenia patients compared with the controls. Right DLPF region metabolic activity correlated significantly with P300 amplitude. This pattern remained after partialling out the influence of activity in the hippocampus, superior temporal gyrus and parietal lobe. It is therefore suggested that the prefrontal cortex could be implicated in the P300 amplitude reduction in schizophrenia.

Background: The historical process of discovery and clinical introduction of chlorpromazine, one of the greatest advances of 20th century medicine and history of psychiatry, is analyzed., Methods: In this review, we have studied the original works of pioneers in the discovery and clinical use of chlorpromazine, as well as the contributions of prestigious researchers (historians, pharmacologists, psychiatrists, etc.) about this topic., Results: The discovery of phenothiazines, the first family of antipsychotic agents has its origin in the development of German dye industry, at the end of the 19th century (Graebe, Liebermann, Bernthsen). Up to 1940 they were employed as antiseptics, antihelminthics and antimalarials (Ehrlich, Schulemann, Gilman). Finally, in the context of research on antihistaminic substances in France after World War II (Bovet, Halpern, Ducrot) the chlorpromazine was synthesized at Rhône-Poulenc Laboratories (Charpentier, Courvoisier, Koetschet) in December 1950. Its introduction in anaesthesiology, in the antishock area (lytic cocktails) and "artificial hibernation" techniques, is reviewed (Laborit), and its further psychiatric clinical introduction in 1952, with initial discrepancies between the Parisian Val-de-Grâce (Laborit, Hamon, Paraire) and Sainte-Anne (Delay, Deniker) hospital groups. The first North-American publications on chlorpromazine took place in 1954 (Lehmann, Winkelman, Bower). The introduction of chlorpromazine in the USA (SKF) was more difficult due to their strong psychoanalytic tradition. The consolidation of the neuroleptic therapy took place in 1955, thanks to a series of scientific events, which confirmed the antipsychotic efficacy of the chlorpromazine., Conclusions: The discovery of the antipsychotic properties of chlorpromazine in the 1950s was a fundamental event for the practice of psychiatry and for the genesis of the so-called "psychopharmacological revolution."

Abnormal activation of semantic networks may be the underlying basis for thought disorder (ThD) in patients with schizophrenia. However, whether this abnormality consists of increased or decreased activation is unclear. Previous behavioral and electrophysiological (N400) data have failed to yield consistent evidence for clarifying this hypothesis. One of the event-related potentials (ERP) components (the recognition potential, RP), presumably reflecting activation of specific semantic networks involved in ThD, has not been used to studies of schizophrenia, and may add additional information to support or refute this hypothesis. In an initial experiment, RP amplitude was reduced in schizophrenic patients, but particularly in those with ThD. In a second experiment, in addition to reduced overall RP amplitude, concrete words were shown to have higher amplitudes than abstract words in both patients and controls, supporting a relative integrity of the lexicon in ThD patients. RP reduction suggests that a fewer number of networks' elements are activated when an incoming word is processed, thus supporting hypoactivation of the semantic networks as the basis for ThD.

Reserpine, an alkaloid of the Rauwolfia serpentina plant isolated during the middle of the 20th Century, represented a highly important clinical advance in the treatment of schizophrenia whose pharmacological tools were limited to chlorpromazine that was introduced in the clinical area two years before. Both agents would come into the history as the drugs that made possible the beginning of the psychopharmacological era. In the present article, a revision is made of the complicated process leading to the isolation and synthesis of reserpine, by the Swiss pharmaceutical company Ciba (Schlittler and Müller) and how its pharmacological properties (Bein) were discovered and studied, in the animals laboratory, mainly, the "tranquillizers". The introduction of this antipsychotic in psychiatry, which was initiated in 1954 (half a century ago), and the results obtained in the first clinical studies, as well as the role played by researchers such as Kline, Delay, Noce, Hollister, Altschule, etc. are then described. In addition, and from a historical perspective, the discovery of the adverse effects of this drug, especially those of extrapyramidal nature (dyskinesia and akathisia), are studied, concluding with the reasons that produced its rapid clinical decline, among which the genesis of depressive pictures (phenomenon presently questioned) may be emphasized. Finally, the conclusion reached was that, although the clinical relevance of reserpine was not as evident and long lasting as chlorpromazine, its initial contribution to the treatment of schizophrenic patients was of maximum importance.

The well-known amplitude reduction of the P300 appears to be unaffected by the treatment with classical antipsychotics in schizophrenia, whereas the effects of atypical neuroleptics on this event-related potential are less understood. The study of these changes could help in deciding whether the P300 amplitude reduction in schizophrenia is a trait or state marker of that illness and in better describing the effect of atypical antipsychotics on altered cognitive functions. We present a prospective longitudinal study of P300 amplitude and latency before and after 6 months' treatment with olanzapine in 11 patients with schizophrenia. A healthy control group (n = 30) was also studied. Overall, no significant changes, either in amplitude or in latency as measured at Pz and Fz electrodes, were found when comparing the pre- and postolanzapine conditions, despite the overall improvement in positive and negative symptoms. Nevertheless a direct specific association was observed between a P300 amplitude increase with olanzapine and the improvement in negative symptoms. These data would suggest that P300 amplitude reduction in schizophrenia may be relatively independent from clinical state and treatment, thus constituting a trait marker of schizophrenia. Our data also suggest that, in addition to this, some further changes in P300 amplitude might depend on the clinical state of the patients.

The existence of neurodegeneration is a debated issue in schizophrenia research. The P300 component of event-related electrical potentials (ERP) has been related to the different degree of damage to gray and white matter. This study explores the possible relationship between P300 amplitude and/or latency and the existence of degenerative processes in schizophrenia, by assessing its correlation with volume of sulcal CSF and duration of illness, as transversal indicators of neurodegeneration. Nineteen patients (14 males, 5 females) and 13 controls (6 males, 7 females) were studied with MRI and electrophysiological records (P300). The possible influence of sex and age at the time of the exploration was statistically controlled in both groups. The results show a significant negative correlation between P300 amplitude and prefrontal CSF volume in the patient group. A lower though still significant correlation was also found between P300 amplitude and duration of illness, whereas no correlation was found in the control group. These results support the hypothesis that P300 amplitude may be interpreted as a marker of neurodegeneration in schizophrenia.

Objective: To analyze the character as pathophysiological marker of the P300 component in the evaluation of schizophrenic illness. We therefore review clinical and neuropsychological evidence of studies in which this was used as a tool for evaluation to reach a diagnosis., Development: The P300 component is useful for studying not only cognitive processes but also the physiopathology of complex disorders such as schizophrenia. This component reflects the state of functions of attention control and memory, both necessary for final evaluation of a stimulus. These cognitive functions become altered in schizophrenic illness, as is shown by abnormality in the generation of the P300 component. We review the most relevant results, which permit characterization of the many features of schizophrenia from genetic, symptom, morphology and neuropsychological studies in which the P300 component is particularly relevant. Similarly, we analyze current controversies due to the great heterogeneity of methodology and the nature of the illness itself., Conclusions: Current understanding allows us to establish that the P300 is a biological marker of relevant aspects of schizophrenia such as the genetic risk of suffering a psychotic episode, determine the type and gravity of the symptoms of the disease, as well as the degree of structural deterioration of the patient. The P300 component is sensitive to the effect of different neuroleptic drugs, on both the symptoms and neuropsychological functions of the patient. These findings let us suggest the P300 component as a valid marker for the evaluation of schizophrenia and the neuropsychological processes.