Glutathione Deficiency during Early Postnatal Development Causes Schizophrenia-Like Symptoms and a Reduction in BDNF Levels in the Cortex and Hippocampus of Adult Sprague–Dawley Rats

Growing body of evidence points to dysregulation of redox status in the brain as an important factor in the pathogenesis of schizophrenia. The aim of our study was to evaluate the effects of l-buthionine-(S,R)-sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, and 1-[2-Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12909), a dopamine reuptake inhibitor, given alone or in combination, to Sprague–Dawley pups during early postnatal development (p5–p16), on the time course of the onset of schizophrenia-like behaviors, and on the expression of brain-derived neurotrophic factor (BDNF) mRNA and its protein in the prefrontal cortex (PFC) and hippocampus (HIP) during adulthood. BSO administered alone decreased the levels of BDNF mRNA and its protein both in the PFC and HIP. Treatment with the combination of BSO + GBR 12909 also decreased BDNF mRNA and its protein in the PFC, but in the HIP, only the level of BDNF protein was decreased. Schizophrenia-like behaviors in rats were assessed at three time points of adolescence (p30, p42–p44, p60–p62) and in early adulthood (p90–p92) using the social interaction test, novel object recognition test, and open field test. Social and cognitive deficits first appeared in the middle adolescence stage and continued to occur into adulthood, both in rats treated with BSO alone or with the BSO + GBR 12909 combination. Behavior corresponding to positive symptoms in humans occurred in the middle adolescence period, only in rats treated with BSO + GBR 12909. Only in the latter group, amphetamine exacerbated the existing positive symptoms in adulthood. Our data show that rats receiving the BSO + GBR 12909 combination in the early postnatal life reproduced virtually all symptoms observed in patients with schizophrenia and, therefore, can be considered a valuable neurodevelopmental model of this disease.     

Visual hallucinations in schizophrenia: Confusion between imagination and perception.

Objective: An association between hallucinations and reality-monitoring deficit has been repeatedly observed in patients with schizophrenia. Most data concern auditory/verbal hallucinations. The aim of this study was to investigate the association between visual hallucinations and a specific type of reality-monitoring deficit, namely confusion between imagined and perceived pictures. Method: Forty-one patients with schizophrenia and 43 healthy control participants completed a reality-monitoring task. Thirty-two items were presented either as written words or as pictures. After the presentation phase, participants had to recognize the target words and pictures among distractors, and then remember their mode of presentation. Results: All groups of participants recognized the pictures better than the words, except the patients with visual hallucinations, who presented the opposite pattern. The participants with visual hallucinations made more misattributions to pictures than did the others, and higher ratings of visual hallucinations were correlated with increased tendency to remember words as pictures. No association with auditory hallucinations was revealed. Conclusions: Our data suggest that visual hallucinations are associated with confusion between visual mental images and perception. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Methodology for identifying specific psychological deficits: Introduction to the Special Section.

A long-standing problem in psychopathology research is establishing that patterns of differences between groups reflects differences of underlying constructs and not artifacts of research design, measurement, or analysis. This introduction provides a context for 4 articles that consider several controversial issues regarding this problem and presents a précis. Although these articles focus on schizophrenia, it is noted how the issues are of more general relevance to psychopathology researchers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Deanna M. Barch: Award for Distinguished Scientific Early Career Contributions to Psychology.

Announces Deanna M. Barch as a recipient of the Award for Distinguished Scientific Early Career Contributions to Psychology for 2002. A biographical statement is included, along with major works and contributions for the field. Barch received this award for research on the relationship between clinical, cognitive, and neurobiological disturbances in schizophrenia. Using behavioral methods, functional neuroimaging, and computational modeling, her work has taken ideas from basic research on the function of prefrontal cortex and used these to dissect the specific contribution that prefrontal deficits make to cognitive abnormalities in attention, memory, and language in schizophrenia and their expression as clinical symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Patterns of recovery of autonomic dysfunctions and neurocognitive deficits in schizophrenics after acute psychotic episodes.

In this study, the authors aimed to identify patterns of autonomic dysfunction and neurocognitive deficit recovery. The authors performed laboratory assessments on 66 patients with schizophrenia immediately after an acute psychotic episode and 6, 12, and 18 months later. Shortly after the psychotic episode, the patients displayed cardiovascular hyperarousal at rest, cardiovascular and electrodermal hyporeactivity during 2 Continuous Performance Tasks (CPTs) and deficits in 2 behavioral CPT measures (i.e., reaction time and omission error rate) compared with 29 normal controls. In the subsequent postpsychotic course, changes indicative of a process of recovery occurred in all measurement areas, although with regard to autonomic hyporeactivity amelioration was limited to a subgroup of schizophrenics with complete and persistent symptomatic remission. Neurocognitive improvement in CPTs did not appear to depend on unimpaired autonomic reactivity mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Heme Oxygenase-1 Transducer Model of Degenerative and Developmental Brain Disorders

Heme oxygenase-1 (HO-1) is a 32 kDa protein which catalyzes the breakdown of heme to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains numerous consensus sequences that render the gene exquisitely sensitive to induction by diverse pro-oxidant and inflammatory stimuli. In “stressed” astroglia, HO-1 hyperactivity promotes mitochondrial iron sequestration and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure documented in Alzheimer disease, Parkinson disease and certain neurodevelopmental conditions. Glial HO-1 expression may also impact neuroplasticity and cell survival by modulating brain sterol metabolism and the proteasomal degradation of neurotoxic proteins. The glial HO-1 response may represent a pivotal transducer of noxious environmental and endogenous stressors into patterns of neural damage and repair characteristic of many human degenerative and developmental CNS disorders.     

Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia

Phosphoinositides (PIs) play important roles in the structure and function of the brain. Associations between PIs and the pathophysiology of schizophrenia have been studied. However, the significance of the PI metabolic pathway in the pathology of schizophrenia is unknown. We examined the expression of PI signaling-associated proteins in the postmortem brain of schizophrenia patients. Protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA, also known as PIK4A), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), protein kinase B (Akt), and glycogen synthase kinase 3β (GSK3β) were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays of the prefrontal cortex (PFC) of postmortem samples from 23 schizophrenia patients and 47 normal controls. We also examined the association between PIK4CA expression and its genetic variants in the same brain samples. PIK4CA expression was lower, whereas Akt expression was higher, in the PFC of schizophrenia patients than in that of controls; PIP5K1C, PTEN, and GSK3β expression was not different. No single-nucleotide polymorphism significantly affected protein expression. We identified molecules involved in the pathology of schizophrenia via this lipid metabolic pathway. These results suggest that PIK4CA is involved in the mechanism underlying the pathogenesis of schizophrenia and is a potential novel therapeutic target.     

Role of Melatonin in Schizophrenia

Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia’s biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research into melatonin regarding schizophrenia has followed two different approaches. The first approach is related to the use of melatonin as a biological marker. The second approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized.     

Philip S. Holzman.

The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in 4 areas of psychology. The 1997 recipient of the Gold Medal Award for Life Achievement in the Application of Psychology is Philip S. Holzman. This article discusses Holzman's life and contribution to psychology especially in schizophrenia and psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Second-order facial information processing in schizophrenia.

This study investigated the processing of second-order relational face information in schizophrenia. Twenty-eight schizophrenic patients and 28 controls were asked to say whether the space between the eyes was the same in 2 side-by-side faces. The 2 faces were derived from the same original face, but the spacing between the eyes was either the same or differed by various distances. The results showed that schizophrenic patients needed a space that was twice as great as controls to see a difference. The authors conclude that schizophrenic patients have a deficit in processing second-order relational face information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)