Symptoms In Chronic Schizophrenia Research Articles

Antipsychotic Augmentation with Venlafaxine for Treatment of Negative Symptoms in Chronic Schizophrenia - A Case Series

Negative symptoms represent a core feature in schizophrenia and the deficit syndrome in chronic schizophrenic patients is closely related to their poor outcome and global failure in community adaptation. Atypical antipsychotics have been widely used in the treatment of negative symptoms in schizophrenia, and tend to produce a better response when used in association with antidepressants. We describe a case series of patients with a clinical diagnosis of residual type of schizophrenia, who have undergone an augmentative treatment of antipsychotic medication with venlafaxine. Both primary and secondary negative symptoms, as well as the overall functioning in these patients were substantially improved following this treatment. This is the first clinical study describing the combination of venlafaxine with both conventional antipsychotics and novel antipsychotics, such as risperidone, to treat successfully both secondary and primary negative symptoms in schizophrenia. We also discuss possible modes of action of the joint use of this particular antidepressant with antipsychotic medication.

L-lysine as an adjunct to risperidone in patients with chronic schizophrenia: A double-blind, placebo-controlled, randomized trial

Increasing evidence suggest that the nitric oxide signaling system of the brain may contribute to the pathophysiology of schizophrenia, making this system a target for development of novel therapeutics. The objective of this study was to investigate the efficacy and safety of l-lysine as an adjunctive to risperidone in the treatment of patients with chronic schizophrenia during an 8-week trial. Seventy-two chronic schizophrenia inpatients with a Positive and Negative Syndrome Scale (PANSS) total score of ≥60 participated in a randomized, double-blind, placebo-controlled trial in the active phase of their disease and underwent 8 weeks of treatment with either l-lysine (6 g/day) or placebo as an adjunctive to risperidone. Patients were evaluated using PANSS and its subscales at baseline and weeks 2, 4, 6 and 8. The primary outcome measure was to evaluate the efficacy of l-lysine in improving schizophrenia symptoms. Repeated measures analysis demonstrated significant effect for time × treatment interaction on the PANSS total (P < 0.001), negative (P < 0.001) and general psychopathology (P < 0.001) subscale scores but not the PANSS positive subscale scores (P = 0.61). The frequency of adverse events (AEs) did not differ significantly between the two treatment groups and no serious AE was observed. The present study demonstrated that l-lysine can be a tolerable and efficacious adjunctive therapy for improving negative and general psychopathology symptoms in chronic schizophrenia. However, the safety and efficacy of higher doses of l-lysine and longer treatment periods still remain unknown. Trial registrationIranian registry of clinical trials (www.irct.ir): IRCT201202201556N33.

CBT Addresses Most-Debilitating Symptoms in Chronic Schizophrenia

CBT Addresses Most-Debilitating Symptoms in Chronic Schizophrenia

1382 – High prevalence of low testosterone levels in male patients with schizophrenia

Introduction Recent neuroendocrinological studies have suggested that gonadal sex hormones play a significant role in the pathophysiology of schizophrenia. Low testosterone levels are also associated with negative symptoms in chronic schizophrenia. Patients receiving treatment for schizophrenia or schizoaffective disorder also show high rates of sexual dysfunction. Studies suggest that testosterone augmentation may play a potential therapeutic role in these patients. Objectives To study a cohort of schizophrenia patients for the presence of hypotestosteronemia. Aims To establish that low testosterone hormone levels occur at a lower age in schizophrenia population. Methods We reviewed the total testosterone levels of all male schizophrenic patients seen in our office over a period of one year for a routine yearly physical. The blood was tested by LabCorp using the liquid chromatography/tandem mass spectrometry (L/MS-MS). Normal values using this sensitive method are between 348.0–1197 ng/dL. Results There were a total of 61 male schizophrenia patients who had their testosterone levels tested during this period. Their ages ranged from 22 to 48 years. 23 (38%) out of the 61 men had serum testosterone less than 348 ng/dl, while 38 (62%) had testosterone levels between 348 ng/dl and 1197 ng/dl. None had testosterone levels above normal. Conclusions A significant number of our male patients with schizophrenia had hypotestosteronemia. Since gonadal sex hormones play a significant role in the patho-physiology of schizophrenia, testosterone levels should be routinely measured in the male patients. The role of testosterone supplementation in these patients needs to be further explored.

Psychometric analysis in support of shortening the Scale for the Assessment of Negative Symptoms

Despite recent emphasis on the measurement and treatment of negative symptoms, studies of the Scale for the Assessment of Negative Symptoms (SANS) identify different symptom clusters, offer mixed support for its psychometric properties and suggest that it is shortened. The current study objective is to examine the psychometric properties of the SANS and the feasibility of a short research version of the SANS. Data were re-analyzed from three clinical trials that compared placebo and amisulpride to 60 days. Participants had chronic schizophrenia and predominantly negative symptoms (n=487). Baseline data were examined with exploratory factor analysis and Item Response Theory (IRT) to identify a short SANS. The short and original SANS were compared: with confirmatory factor analysis at endpoint; and on symptom response with mixed modeling to compare. Results showed that at baseline the SANS consisted of three factors labeled Affective-flattening, Asociality and Alogia-inattentiveness. IRT suggested a short SANS with 11 items and 3 response options. Comparisons of the original and short SANS showed: the short version was a better fit to the data based on confirmatory factor analysis at endpoint; similar significant (p<.001) correlations between the baseline and subsequent scores; similar reliability; and similar significance (p<.05) on response based on mixed modeling. It is concluded that a short SANS is feasible to assess predominantly negative symptoms in chronic schizophrenia in research settings.

Triiodothyronine may be possibly associated with better cognitive function and less extrapyramidal symptoms in chronic schizophrenia

Many chronic inpatients with schizophrenia demonstrate enduring psychiatric symptoms and various side effects of antipsychotic drugs. Several biological markers such as prolactin, thyroid hormones and brain-derived neurotrophic factor (BDNF) are reportedly associated with psychiatric symptoms and/or antipsychotic side effects in patients with schizophrenia but to date findings are inconsistent. The objective of the present study was to comprehensively investigate the association of psychiatric and extrapyramidal symptoms with hormones and BDNF in chronic schizophrenia. In this study, 93 chronic inpatients with schizophrenia were comprehensively investigated in order to examine the association of psychiatric and extrapyramidal symptoms with prolactin, thyroid hormones (free triiodothyronine (T₃), free thyroxine (T₄), thyroid stimulating hormone), cortisol and BDNF. Symptoms were assessed via the Positive and Negative Syndrome Scale (PANSS), Mini-Mental State Examination (MMSE), and drug-induced extrapyramidal symptoms scale (DIEPSS). Multiple regression analyses revealed that antipsychotic dose was the only variable that predicted significant variance in PANSS positive subscale scores, that BDNF and free T₃ predicted significant variance in MMSE scores, and that prolactin and free T₃ predicted significant variance in DIEPSS scores. These findings suggest that BDNF, free T₃, and prolactin may be associated with cognitive function and/or extrapyramidal symptoms in patients with chronic schizophrenia. Notably, free T₃ may be possibly associated with better cognitive function and less extrapyramidal symptoms, although our cross-sectional study could not reveal a causal relationship.

Application of Token Economy in the Management of Chronic Schizophrenia: A Case Report

A case of chronic schizophrenia with “inability to walk” in the absence of a neurological basis is presented. Patient responded to antipsychotic medications in terms of improvement in the symptoms of schizophrenia but “inability to walk” persisted necessitating the introduction of graded tokens / incentives to the treatment regimen. The patient regained the use of his leg and sustained improvements in mental state at discharge. Voluntary ambulation was sustained for three months after discharge before patient was lost to follow-up. Token economy may be very useful in rehabilitation of chronic psychotic illness as this case illustrates. This treatment approach may be essential in a developing country like Nigeria where socio-economic deprivations may modify the presentation of chronic schizophrenia symptoms. Key Words : chronic schizophrenia, inability to walk, token economy.

Effect of phased reward behavior therapy on rehabilitation of patients with chronic schizophrenia

Objective To discuss the effect of phased reward behavior therapy on rehabilitation of patients with chronic schizophrenia.Methods 60 patients were randomly divided into treatment group (30 cases) and control group (30 cases) according to admission time.The treatment group received reward behavior therapy on the basis of drug treatment and traditional nursing care,while the control group received conventional work entertainment treatment activities.Brief Psychiatric Rating Scale (BPRS),Scale for Schizophrenia Positive Symptoms (SAPS),Negative Symptoms Scale (SANS) and the efficacy of inpatient rehabilitation of mental patients rating scale (IPROS)were used to evaluate the deficiency level of social function,degree of remission and rehabilitation of the patients before and 6 months after the treatment.Results The total average score of BPRS and IPROS of the treatment group were lower than the control group and the differences were significant [(8.81 ±6.41) vs (11.10±8.5),(19.15 ±14.11 ) vs (31.14 ± 16.10 ) ;t =3.18,7.61 ;P ＜ 0.01 ].SAPS and SANS scores of the treatment group were lower than the control group,the differences were significant [ (7.31 ± 1.51) vs ( 10.16 ± 2.10),( 12.32 ± 2.16) vs ( 15.65 ±1.48) ;t =3.62,3.12;P＜0.01].Conclusions Reward behavior therapy could help reduce some of the symptoms of chronic schizophrenia,improve self-care ability,prevent deterioration and regain mental function. Key words: Chronic schizophrenia; Rehabilitation; Phased behavior therapy

Meta-Analysis of the Efficacy of Adjunctive NMDA Receptor Modulators in Chronic Schizophrenia

Based on the glutamatergic NMDA receptor hypofunction theory of schizophrenia, NMDA receptor modulators (NMDARMs) may have therapeutic potential in the treatment of schizophrenia. This meta-analysis aimed to evaluate the potential of modulators of the NMDA receptor as adjunctive therapy for schizophrenia, using the results from published trials. A primary electronic search for controlled clinical trials using NMDARMs in schizophrenia was conducted on the PubMed, Cochrane Library, EMBASE, CINAHL® and PsycINFO databases. A secondary manual search of references from primary publications was also performed. Inclusion criteria were the application of an established method of diagnosis, randomized case assignment, comparison of NMDARM add-on therapy with placebo, and double-blind assessment of symptoms in chronic schizophrenia using standardized rating scales. Results were based on a total sample size of 1253 cases from 29 trials that fulfilled the specified criteria. Scores on rating scales or on their relevant subscales were obtained for all selected studies from published results for the minimum dataset to compute the difference between post- and pre-trial scores and their pooled standard deviation for NMDARM add-on therapy and placebo groups for negative, positive and total symptoms. A negative standardized mean difference (SMD) indicates therapeutic benefit in favour of NMDARM add-on therapy and all SMD results mentioned here are statistically significant. The overall effect size for NMDARMs as a group was small for negative (SMD -0.27) and medium for total (SMD -0.40) symptoms of chronic schizophrenia. Subgroup analysis revealed medium effect sizes for D-serine and N-acetyl-cysteine (NAC) for negative (SMD -0.53 and -0.45, respectively) and total (SMD -0.40 and -0.64, respectively) symptoms, and for glycine (SMD -0.66) and sarcosine (SMD -0.41) for total symptoms. As adjuvants to non-clozapine antipsychotics, additional therapeutic benefits were observed for NMDARM as a group (SMD -0.14) and glycine (SMD -0.54) for positive symptoms; D-serine (SMD -0.54), NAC (SMD -0.45) and sarcosine (SMD -0.39) for negative symptoms; and NMDARM as a group (SMD -0.38), D-serine (SMD -0.40), glycine (SMD -1.12), NAC (SMD -0.64) and sarcosine (SMD -0.53) for total symptoms. When added to clozapine, none of the drugs demonstrated therapeutic potential, while addition of glycine (SMD +0.56) worsened positive symptoms. Taking into consideration the number of trials and sample size in subgroup analyses, D-serine, NAC and sarcosine as adjuncts to non-clozapine antipsychotics have therapeutic benefit in the treatment of negative and total symptoms of chronic schizophrenia. While glycine improves positive and total symptoms as an adjuvant to non-clozapine antipsychotics, it worsens them when added to clozapine.

Differential effects of childhood abuse and neglect: Mediation by posttraumatic distress in neurotic disorder and negative symptoms in schizophrenia?

Dissociation, though understood as a response to trauma, lacks a proven etiology. The assumption of a dose–response relationship between trauma, dissociation and Schneiderian symptoms led to the proposal of a dissociative subtype of schizophrenia characterized by severe child maltreatment, dissociation and psychosis. Child maltreatment and dissociation are common features of neurotic disorders as well, and the link between trauma, dissociation, and hallucinations is not specific for schizophrenia. This study compares childhood abuse and neglect, posttraumatic distress and adult dissociation in patients with psychotic vs. non-psychotic disorder. Thirty-five participants with non-psychotic disorder and twenty-five with schizophrenia were analyzed using the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery–Åsberg Depression Rating Scale (MADRS), the Posttraumatic Stress Diagnostic Scale PDS (PDS), the Childhood Trauma Questionnaire (CTO) and the Arbeitsgemeinschaft Methodik und Dokumentation in der Psychiatrie (AMDP)-module on dissociation. Trauma and clinical syndromes were compared by means of T-testing and logistic regression between 1) the diagnoses and 2) groups with and without post-traumatic stress disorder (PTSD), marked dissociation and psychotic symptoms. While non-psychotic disorder was related to abuse, schizophrenia showed an association with neglect. Childhood trauma predicted posttraumatic symptomatology and negative symptoms. Childhood abuse and neglect may effectuate different outcomes in neurotic and psychotic disorder. The underlying mechanisms, including dissociation, dovetail with cognitive, emotional and behavioural changes involved in depression, posttraumatic distress and chronic schizophrenia symptoms rather than being directly linked to trauma.

Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis

Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue. To analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia. Systematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms. There were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (-0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin. Antidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.

Cognitive‐behaviour therapy for medication‐resistant positive symptoms in early psychosis: a case series

Cognitive-behaviour therapy (CBT) for psychosis reduces the severity of medication-resistant positive symptoms in chronic schizophrenia, but its efficacy for early psychosis outpatients with a similar profile has not been established. This paper describes an uncontrolled evaluation of CBT, added to medication and comprehensive care in an early psychosis program, in a group of stable outpatients. The sample was drawn from 24 consecutive referrals. Fourteen were eligible, i.e. had positive symptom(s) and had been on the same medication regime for 3 months. Patients received an average of 16 individual sessions with a senior psychologist. Symptom severity was assessed both by an independent rater, and by patient self-report. Eleven of 14 patients completed treatment. Both clinician and self-report post-treatment ratings of positive symptoms were significantly reduced following CBT. For positive symptom totals, effect sizes ranged from d = 1.0 to 1.3. Clinically significant changes were apparent in at least eight of 11 patients. While case-series studies have significant limitations, the large effect sizes described here suggest that CBT shows promise for effectiveness with early psychosis patients. A randomized trial is needed to establish both the effect size over and above a control condition, and the durability of gains of CBT for medication-resistant symptoms in early psychosis.

Antipsychotic Augmentation with Venlafaxine for Treatment of Negative Symptoms in Chronic Schizophrenia - A Case Series

Negative symptoms represent a core feature in schizophrenia and the deficit syndrome in chronic schizophrenic patients is closely related to their poor outcome and global failure in community adaptation. Atypical antipsychotics have been widely used in the treatment of negative symptoms in schizophrenia, and tend to produce a better response when used in association with antidepressants. We describe a case series of patients with a clinical diagnosis of residual type of schizophrenia, who have undergone an augmentative treatment of antipsychotic medication with venlafaxine. Both primary and secondary negative symptoms, as well as the overall functioning in these patients were substantially improved following this treatment. This is the first clinical study describing the combination of venlafaxine with both conventional antipsychotics and novel antipsychotics, such as risperidone, to treat successfully both secondary and primary negative symptoms in schizophrenia. We also discuss possible modes of action of the joint use of this particular antidepressant with antipsychotic medication.

Analysis of association between the catechol- O-methyltransferase ( COMT) gene and negative symptoms in chronic schizophrenia

Negative symptoms commonly seen in chronic schizophrenia are related to prefrontal hypodopaminergia. Dysfunction of the catechol- O-methyltransferase ( COMT) gene has long been thought to confer susceptibility to schizophrenia because of its catalytic activity for dopamine degradation. The present study is an attempt to perform a quantitative trait test for genetic association between the COMT gene and negative symptoms in a Chinese population. A total of 290 unrelated individuals with schizophrenia patients were recruited and their symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED programme to examine the correlation between the scored negative symptoms and the coding single nucleotide polymorphisms (SNPs) present in the COMT gene. The rs4633-rs4680 haplotype showed significant association with the overall score of negative symptoms, and four individual negative symptoms, including blunted affect, emotional withdrawal, poor rapport and passive/apathetic social withdrawal. SNP rs4680 (Val/Met) showed significant association with blunted affect. The present finding suggests that the COMT gene may a etiologically contribute to the severity of negative symptoms in schizophrenia, but its precise mechanism needs further investigating.

An fMRI Study of Functional Abnormalities in the Verbal Working Memory System and the Relationship to Clinical Symptoms in Chronic Schizophrenia

There has been evidence for functional abnormalities of the verbal working memory system in schizophrenia. Verbal working memory crucially involves the interplay between the anterior and posterior language systems, and previous studies have shown converging evidence for abnormalities in the posterior language system in schizophrenia. In this functional magnetic resonance imaging study, we measured cortical activity in chronic schizophrenic patients and matched healthy controls during auditory and visual verbal working memory tasks. We employed 1) regional analyses specifically targeting the posterior language system and 2) analyses of functional connectivity between anterior and posterior language regions. We performed these analyses separately for each memory stage and modality. In the regional analyses, the left sylvian-parietal-temporal (Spt) area consistently showed reduced activation during encoding and retrieval stages in schizophrenia. Magnitudes of activation in the left posterior superior temporal sulcus were correlated with the severity of delusions at every memory stage. Functional connectivity analyses revealed reduced connectivity between the left Spt and the anterior insula during the encoding of auditory words. In addition, the connectivity strength was correlated with the severity of auditory hallucinations. These findings identify abnormal components in the verbal working memory system and illustrate their possible overlap with the mechanisms of core schizophrenic symptoms.

Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study

Despite the availability of atypical antipsychotics, the treatment of negative symptoms in schizophrenia remains a challenge. This study was designed to confirm the positive effect observed in our pilot study with paroxetine as augmentation to antipsychotics in the treatment of negative symptoms in chronic schizophrenia. Twenty-nine patients with chronic schizophrenia, as defined by DSM-IV, who scored at least 20 points on the negative subscale of the Positive and Negative Syndrome Scale (PANSS) were randomized for treatment with 30 mg paroxetine or placebo in a double-blind, placebo-controlled study for 12 weeks. Ratings included the PANSS, the Hamilton Rating Scale for Depression (HAM-D) and scales for extrapyramidal side-effects. An intention-to-treat analysis was based on the 25 patients who were available for at least one follow-up assessment. The last observation carried forward principle was applied. The mean score of the negative subscale of the PANSS decreased in both groups. Using an analysis of covariance, there was a significant treatment effect with paroxetine compared to placebo with respect to negative symptoms (-4.53; 95% confidence interval -9.054 to -0.015). The mean HAM-D scores remained almost constant. The study suggests the efficacy of paroxetine with respect to the treatment of negative symptoms in chronic schizophrenia.

Felt affect in good- and poor-outcome schizophrenia

Background:Family members and caregivers may misinterpret blunted affect as a true lack of emotion in patients with schizophrenia.Aim:To assess felt affect or experienced emotion among low- and high-functioning schizophrenics.Methods:Two hundred people with schizophrenia were assessed using the Global Assessment of Functioning scale of DSM-IV and the Positive and Negative Affect Schedule (PANAS).Results:The findings reveal that people with good- and poor-outcome schizophrenia show no significant differences in the emotions experienced, implying that felt affect is comparable regardless of the severity of symptoms in chronic schizophrenia. In fact, low-functioning patients scored a mean (SD) of 46.07 (13.13) on the PANAS, in contrast to a slightly lower scored by high-functioning patients (44.33 [12.03]).Conclusion:Although patients may show flat affect, and therefore be mistakenly considered withdrawn and apathetic by the observer, they do, in fact, experience as much, or perhaps even more emotion than their higher-functioning counterparts.

The GABA-glutamate connection in schizophrenia: which is the proximate cause?

Schizophrenia is a chronic, disabling psychiatric disorder that genetic studies have shown to be highly heritable. Although the dopamine hypothesis has dominated the thinking about the cause of schizophrenia for 40 years, post-mortem and genetic studies have provided little support for it. Rather, post-mortem studies point to hypofunction of subsets of GABAergic interneurons in the prefrontal cortex and the hippocampus. Furthermore, clinical pharmacologic, post-mortem and genetic studies have provided compelling evidence of hypofunction of a subpopulation of NMDA receptors in schizophrenia. In support of this inference, agents that directly or indirectly activate the glycine modulatory site on the NMDA receptor (the Glycine B receptor) reduce symptoms in chronic schizophrenia, especially negative symptoms and cognitive impairments. Electrophysiologic and pharmacologic studies suggest that the vulnerable NMDA receptors in schizophrenia may be concentrated on cortico-limbic GABAergic interneurons, thereby linking these two neuropathologic features of the disorder.

Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: A double-blind placebo-controlled study

Despite the availability of atypical antipsychotics, the treatment of negative symptoms in schizophrenia remains a challenge. This study was designed to confirm the positive effect observed in our pilot study with paroxetine as augmentation to antipsychotics in the treatment of negative symptoms in chronic schizophrenia. Twenty-nine patients with chronic schizophrenia, as defined by DSM-IV, who scored at least 20 points on the negative subscale of the Positive and Negative Syndrome Scale (PANSS) were randomized for treatment with 30 mg paroxetine or placebo in a double-blind, placebo-controlled study for 12 weeks. Ratings included the PANSS, the Hamilton Rating Scale for Depression (HAM-D) and scales for extrapyramidal side-effects. An intention-to-treat analysis was based on the 25 patients who were available for at least one follow-up assessment. The last observation carried forward principle was applied. The mean score of the negative subscale of the PANSS decreased in both groups. Using an analysis of covariance, there was a significant treatment effect with paroxetine compared to placebo with respect to negative symptoms (-4.53; 95% confidence interval -9.054 to -0.015). The mean HAM-D scores remained almost constant. The study suggests the efficacy of paroxetine with respect to the treatment of negative symptoms in chronic schizophrenia.

An MRI study of temporal lobe abnormalities and negative symptoms in chronic schizophrenia

Previous magnetic resonance imaging (MRI) studies have reported various subtle brain abnormalities in schizophrenic patients, including temporal lobe abnormalities, which are of particular interest given the role of this brain region in auditory and language processing, and the characteristic deficits in these processes in schizophrenia . Subjects in this study were 16 male patients diagnosed with chronic schizophrenia and 15 healthy male comparison subjects. These patients were characterized by negative symptoms. High spatial resolution coronal MRI 1.5-mm-thick slices were used to measure the gray matter volume of the superior temporal gyrus, anterior and posterior amygdala/hippocampal complex, and parahippocampal gyrus. Patients, relative to normal comparison subjects, evinced a reduction of gray matter volume in bilateral superior temporal gyri and anterior amygdala/hippocampal complex. The reduction in gray matter of the superior temporal gyrus in patients with schizophrenia is consistent with previous findings, and is noteworthy in that it was found in this group of patients with predominantly negative symptoms. The reduction in the anterior amygdala/hippocampal complex was an additional temporal lobe finding. These results underscore the role of temporal lobe structures in the pathophysiology of schizophrenia.