The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques

Late onset schizophrenia: A review [Geç başlangiçli şizofreni: Bir gözden geçirme]

A consensus was reached by International Late Onset Schizophrenia Group that cases in which onset occurs between 40 and 60 be called late onset schizophrenia and that cases in which onset occurs after age 60 should be called very late onset schizophrenia like psychosis. Inconsistencies in diagnostic systems and nomenclature, coupled with a tendency among most schizophrenia researchers to ascribe late onset psychoses to organic factors, have led to such cases occupying an ambiquous position in relation to schizophrenia. In terms of epidemiology, symptom profile and identified pathophysiologies, the diagnoses of late onset schizophrenia have face validity and clinical utility. General adoption of these categories will foster systematic investigation of such patients. Both developmental and degenerative processes that affect specific brain circuitry have been implicated and intensive study of late onset patients may ultimately shed light on etiology. The purpose of this nomenclature is to clarify the position of these patients and to stimulate more research

Importance of depressive symptoms in schizophrenia and theirs pharmacotherapies [Şizofrenide depresif belirtilerin önemi ve psikofarmakolojik sagaltimi]

The importance of depression in schizophrenia is much more emphasized in DSM-IV than DSM-III-R. Although in recent studies the three dimensional model (psychotic, disorganized, negative) is promoted in explaining symptoms of schizophrenia, there are some researchers who propose depression to be a distinct dimension in schizophrenia. The depressive symptoms in schizophrenia are frequent and commonly serious, and negatively influence the prognosis and recovery of the patient. The patients with comorbid diagnosis of schizophrenia an depression present a distinct mortality and morbidity profile including high recurrence and suicide risk. There are a few studies in the literature concerning the treatment of depressive symptoms in spite of their high frequency, prognostic significance and influence on psychosocial outcomes in schizophrenia. In this review, the importance of depressive symptoms in schizophrenia, the role and efficacy of antidepressants in the treatment of depressive symptoms and the effect of atypical antipsychotics with serotonin-dopamine antagonistic activity currently used in Turkey (clozapine, risperidone, olanzapine, quetiapine and ziprasidone) on depressive symptoms in schizophrenia are comprehensively discussed

The effect of galantamine added to clozapine on cognition of five patients with schizophrenia

WOS: 000230220600009PubMed ID: 15965314Although clozapine may be beneficial for the treatment of cognitive dysfunction in schizophrenia, it may also impair some cognitive skills as a result of its anticholinergic activity. In this case series, the impact of galantamine administration on 5 patients with schizophrenia who had been treated with clozapine are reported. Neuropsychological assessment was administered before and after 8 weeks of 16 mg/d galantamine treatment. In this case series, galantamine was well tolerated by all of the patients. Three of the patients were much improved in sustained attention tasks. Most of the patients were also improved in psychomotor speed and selective attention tasks. Two patients with low pretreatment memory scores seemed to also be improved. Our results suggest that the possible role of galantamine as a cognitive enhancer in schizophrenia should be investigated in controlled trials

Empathic abilities in people with schizophrenia

PubMed ID: 18514324Although the existence of empathy deficits in schizophrenia is generally accepted, very few studies have directly investigated the issue. The nature of empathy deficits in healthy subjects and psychiatric patients is an understudied subject. The performances of the 30 outpatients with schizophrenia on a psychometric measure, the Empathy Quotient (EQ), were compared with those of 30 control subjects matched for age, duration of education and gender. The relatives or spouses of the patients also filled out the EQ. A neuropsychological battery, including emotion recognition, emotional reasoning and theory of mind tasks, was also administered. Schizophrenia patients had severe empathy dysfunction based on their relative EQ ratings. There was a serious discrepancy between the self and relative/spouse assessments of the empathic skills of schizophrenia patients. Consistent with the previous findings schizophrenia patients were impaired in nearly all cognitive tasks. The empathy deficits of schizophrenia patients were associated with their impairments in other social cognitive tasks. Studies focusing on dysfunctional brain networks underlying empathy deficits and studies using more experimental measures of empathy should be helpful to unravel the true nature of the empathic failure in patients with schizophrenia. © 2007 Elsevier Ireland Ltd. All rights reserved.John D. and Catherine T. MacArthur FoundationDevelopment of the MacBrain Face Stimulus Set was overseen by Nim Tottenham and supported by the John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development. Please contact Nim Tottenham at [email protected] for more information concerning the stimulus set. -

The effects of atypical antipsychotics on obsessive compulsive symptoms in schizophrenic patients: A comparative-naturalistic study with typical antipsychotics [Atipik antipsikotik i·lâçlarin şizofrenlerde obsesif kompulsif belirtiler üzerindeki etkisi: Tipik antipsikotiklerle karşilaştirmali bir dogal i·zlem çaliş masi]

Objective: To investigate the effect of atypical antipsychotics on obsessive compulsive symptoms in schizophrenic patients. Method: A total of 63 patients of whom 38 received atypical and 25 typical antipsychotics were enrolled to the study. The obsessive-compulsive symptoms were assessed by Yale-Brown Obsessive Compulsive Symptoms Scale (Y-BOCS) at baseline and at the end of second month that was blind to which group the patient belongs. Schizophrenic symptoms were assessed by Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). Findings: 55 patients completed the study. 31 of them were on atypical antipsychotic treatment and 24 of them were on typical antipsychotic treatment. Negative symptoms were significantly higher among atypical antipsychotic group at baseline of treatment. At the end of second month there was no significant difference in the severity of obsessive-compulsive symptoms between two groups. Discussion and Conclusion: No significant difference was found between atypical and typical antipsychotic drugs in their effects on obsessive compulsive symptoms in schizophrenia

Association between cerebral blood-flow measured by single photon emission computed tomography (Spect) and neurological soft signs in schizophrenia [Şizofrenide silik nörolojik belirtiler ile tek foton emisyon bilgisayarli{dotless} tomografi (Spect) ile ölçülen beyin kan aki{dotless}mi{dotless} anasi{dotless}ndaki i·lişki]

Objective: Neurological soft signs (NSS) are minor neurological abnormalities in sensory and motor performances identified by clinical examination that are not readily localizable to a specific brain region. NSS have been described to be abundant in schizophrenic patients. Studying anatomical correlates of NSS can provide a better understanding of the mechanism of NSS and the pathophysiology of schizophrenia. The main aim of this study was to explore the relationship between NSS and regional cerebral blood flow (rCBF) measured by Single Photon Emission Computed Tomography (SPECT). Methods: Forty four patients with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria, were studied by SPECT and performed "Neurological Evaluation Scale" (NES) test to calculate NSS. Clinical characteristics investigated in this study were: duration of illness (months), duration of hospitalization (months), current antipsychotic dose (chlorpromazine equivalents in mg), negative and positive symptoms of schizophrenia, level of functioning, level of intelligence, verbal performance on intelligence test, way of onset of the illness (insidious vs. acute), response to treatment, family history of schizophrenia and family history of psychiatric illness. Negative and positive symptoms were evaluated with The Scale for the Assessment of Negative (SANS) and The Scale for the Assessment of Positive Symptoms (SAPS). Level of functioning was evaluated with The Global Assessment of Functioning Scale (GAF). The level of intelligence was evaluated by two clinical psychologists who were blind to the clinical attributes, using Wechsler Adult Intelligence Scale-Revised (WAIS-R). Findings: Cerebellum and whole brain normalized right frontal and right basal ganglia rCBF's are found to be associated with sensory integration subscale, while left temporal rCBF is found to be associated with motor sequencing subscale of NES, although this association is lost when a strict statistical significance level is applied by Bonferroni corrections for multiple comparisons. Discussion and Conclusion: The discrepancy between NSS and cognitive impairments and SPECT reveals a partial overlap between two different functional areas: one corresponding to the sensory integrative system and the other to a more generalized cognitive system, including the motor system

Premenstrual symptoms and premenstrual exacerbation in patients with schizophrenia [Şi·zofreni·k bozukluklu hastalarda premenstrüel beli·rti·ler ve premenstrüel alevlenme]

Objective: Schizophrenia is a severe psychiatric disorder. Much attention has been paid to the relationship between psychiatric disorders and the menstrual cycle. Premenstrual syndrome is a medical condition which is related to various pstciatric disorders. The aim of this study was to investigate premenstrual symptoms (PMS) and premenstrual exacerbation (PME) in patients with schizophrenia. Material and metheods: We completed this study with outpatiens who were diagnosed as schizophrenia according to DSM-IV and followed in psychosis unit, Deparment of Psychiatry, Ege Medical School. Thirty women (aged between 18 an 45) with regular menstruations are included in the study. Premenstrual syndrome was assessed with a symptom checklist based on International Classification of Diseases (10th revision; ICD-10) criteria. Premenstrual exacerbation was defined clinically as premenstrual worsening of schizophrenic symptoms. Results: All the patiens had at least one PMS symptom. The avarage number of PMS symptoms in patients was 3.4±1.2; the prevalance of PMS with considerable clinical importance was %50; and the prevalance of PME was %26. The most frequently reported PMS symptom was'bloating or weight gain'(%80), and the least was 'poor concentration' (%6.7). 'Changes in appetite' were more frequent in patients with PME (p<0.05). There was no difference in patients with and without PMS orPME by means of age, marital status, employment, education, duration of illness, antipsychotic dosage, use of antidepressants or mood stabilizers. Conclusion: The results of this study suggest that PMS and PME are considerably common in female patients with schizophrenia; and that PMS and PME are comparatively different clinical entities. Premenstrual changes in appetite should carefully be monitored. Antidepressants and mood stabilizers do not seem to be helpful in treating PMS in patients with shizophrenia