1Nord J Psychiatry 2004 -1 58: 421-7
PMID16195085
TitleThe influence of the patients' ethnicity, socio-demographic conditions and strain on psychiatric diagnoses given at an outpatient clinic.
AbstractAlthough psychiatric diagnoses are influenced by cultural and social conditions, with large global variations, the ICD and DSM systems are applied worldwide. The aims of this study were to describe the distribution of different ethnic patient groups in psychiatric outpatient services and the influence of ethnicity, demographic conditions and social strain on psychiatric diagnoses. An entire year's cohort of psychiatric outpatients (n = 839) in an outpatient register was divided into nine groups, according to country of birth. The proportion of each group in the outpatient population was compared with its corresponding proportion in the catchment area. In order to examine the relationship between socio-demographic variables and strain on the one hand, and DSM-III-R diagnoses on the other, stepwise logistic regression analyses were carried out. Swedes were the only group under-represented as outpatients (P < 0.001). Africans RAN a higher risk (OR = 5.55, 95% CI = 2.56-12.04) than other ethnic groups of receiving a diagnosis of psychotic disorder--except schizophrenia--and Greek patients were more likely to receive a diagnosis of somatoform disorder (OR = 8.81, 95% CI = 4.41-17.59). Swedes were twice as likely to receive a diagnosis of personality disorder (OR = 2.16, 95% CI = 1.55-3.15). schizophrenia was related to male gender (OR = 1.75, 95% CI = 1.04-2.94) and affective disorders to age >40 years (OR = 1.71, 95% CI = 1.22-2.40). Ethnicity has a strong impact on how diagnoses are given in cross-cultural settings. We could not confirm earlier findings of under-representation of ethnic minorities in outpatient services.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
2J Clin Psychiatry 2007 May 68: 705-10
PMID17503979
TitleA randomized, double-blind, placebo-controlled trial of modafinil for negative symptoms in schizophrenia.
AbstractNegative symptoms are core features of schizophrenia that are functionally debilitating, associated with poor outcomes, and resistant to existing pharmacotherapies. We performed a RANdomized, double-blind, placebo-controlled study of modafinil, a medication approved for the treatment of excessive daytime sleepiness, to explore its efficacy as an adjunctive therapy for negative symptoms in schizophrenia.
Twenty subjects with DSM-IV schizophrenia or schizoaffective disorder were RANdomly assigned to double-blind treatment with modafinil or placebo for 8 weeks. The study RAN from March 2002 through March 2006. Outcome measures included the Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI) scale, Quality of Life Interview, neurocognitive assessments (California Verbal Learning Test, Degraded Performance-Continuous Performance Test, Trail-Making Test B), and somatic measures (sleep, weight, side effects).
Modafinil treatment was associated with a greater rate (CGI-Improvement [CGI-I] score < or = 3, 7/10 vs. 1/10) and degree (mean CGI-I score, 3.2 vs. 4.1) of global improvement at study endpoint compared with placebo. However, modafinil did not significantly improve global negative symptoms as measured by the total SANS or SANS individual global items. Modafinil did not significantly worsen psycho-pathology (according to the BPRS), compared with placebo, and was well tolerated.
Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
3J Clin Psychiatry 2007 Mar 68: 368-79
PMID17388705
TitleA randomized controlled trial of olanzapine versus haloperidol in the treatment of primary negative symptoms and neurocognitive deficits in schizophrenia.
AbstractPrimary negative symptoms are intrinsic to the pathology of schizophrenia and are associated with significant deficits in motivation, verbal and nonverbal communication, affect, and cognitive and social functioning. Overall, atypical antipsychotic medications have been found to be more efficacious than conventional antipsychotics in the treatment of negative symptoms, based on studies with acute patients. Results have been confounded by concomitant improvements in positive, depressive, and extrapyramidal symptoms. This 12-week, double-blind, controlled study aimed to examine the effects of the atypical antipsychotic olanzapine versus haloperidol on persistent, primary negative symptoms and neurocognitive functions in stable schizophrenic patients with the deficit syndrome and low levels of concomitant positive, depressive, and extrapyramidal symptoms.
Thirty-five patients with DSM-IV-TR schizophrenia and predominant negative symptoms were RANdomly assigned in a 12-week double-blind study to either olanzapine (15-20 mg/day) or haloperidol (15-20 mg/day). Patients taking haloperidol received additional blinded benztropine. Inclusion criteria were Positive and Negative Syndrome Scale (PANSS) negative score of >or=20, PANSS positive score < 20, and fulfilling the criteria for the Schedule for the Deficit Syndrome. The PANSS, Clinical Global Impressions, Hamilton Rating Scale for Depression (HAM-D), Simpson-Angus Scale, and Abnormal Involuntary Movement Scale were assessed at regular subsequent intervals. A neuropsychological battery examining declarative verbal learning memory, attention and processing speed, executive functioning, and simple motor functioning domains of cognition was assessed at baseline and endpoint. The study RAN from September 1998 through May 2005.

There was a statistically significant difference for PANSS negative symptoms (F = 5.44, df = 1,15; p The results of this study suggest that olanzapine treatment was associated with significant improvement in primary negative symptoms, overall symptomatic improvement as measured by the PANSS total score, and improvement in some areas of neurocognition as compared with haloperidol/benztropine mesylate treatment.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
4J Clin Psychiatry 2007 Mar 68: 368-79
PMID17388705
TitleA randomized controlled trial of olanzapine versus haloperidol in the treatment of primary negative symptoms and neurocognitive deficits in schizophrenia.
AbstractPrimary negative symptoms are intrinsic to the pathology of schizophrenia and are associated with significant deficits in motivation, verbal and nonverbal communication, affect, and cognitive and social functioning. Overall, atypical antipsychotic medications have been found to be more efficacious than conventional antipsychotics in the treatment of negative symptoms, based on studies with acute patients. Results have been confounded by concomitant improvements in positive, depressive, and extrapyramidal symptoms. This 12-week, double-blind, controlled study aimed to examine the effects of the atypical antipsychotic olanzapine versus haloperidol on persistent, primary negative symptoms and neurocognitive functions in stable schizophrenic patients with the deficit syndrome and low levels of concomitant positive, depressive, and extrapyramidal symptoms.
Thirty-five patients with DSM-IV-TR schizophrenia and predominant negative symptoms were RANdomly assigned in a 12-week double-blind study to either olanzapine (15-20 mg/day) or haloperidol (15-20 mg/day). Patients taking haloperidol received additional blinded benztropine. Inclusion criteria were Positive and Negative Syndrome Scale (PANSS) negative score of >or=20, PANSS positive score < 20, and fulfilling the criteria for the Schedule for the Deficit Syndrome. The PANSS, Clinical Global Impressions, Hamilton Rating Scale for Depression (HAM-D), Simpson-Angus Scale, and Abnormal Involuntary Movement Scale were assessed at regular subsequent intervals. A neuropsychological battery examining declarative verbal learning memory, attention and processing speed, executive functioning, and simple motor functioning domains of cognition was assessed at baseline and endpoint. The study RAN from September 1998 through May 2005.

There was a statistically significant difference for PANSS negative symptoms (F = 5.44, df = 1,15; p The results of this study suggest that olanzapine treatment was associated with significant improvement in primary negative symptoms, overall symptomatic improvement as measured by the PANSS total score, and improvement in some areas of neurocognition as compared with haloperidol/benztropine mesylate treatment.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
5Arch. Gen. Psychiatry 2008 Jun 65: 634-40
PMID18519821
TitlePrevention of negative symptom psychopathologies in first-episode schizophrenia: two-year effects of reducing the duration of untreated psychosis.
AbstractThe duration of untreated psychosis (DUP)-the time from onset of psychotic symptoms to the start of adequate treatment--is consistently correlated with better course and outcome, but the mechanisms are poorly understood.
To report the effects of reducing DUP on 2-year course and outcome.
A total of 281 patients with a DSM-IV diagnosis of nonorganic, nonaffective psychosis coming to their first treatment during 4 consecutive years were recruited, of which 231 participated in the 2-year follow-up. A comprehensive early detection (ED) system, based on public information campaigns and low-threshold-psychosis-detecting teams, was introduced in 1 health care area (ED area), but not in a comparable area (no-ED area). Both areas RAN equivalent 2-year treatment programs.
First-episode patients from the ED area had a significantly lower DUP, better clinical status, and milder negative symptoms at the start of treatment. There were no differences in treatment received for the first 2 years between the groups. The difference in negative symptoms was maintained at the 1-year follow-up. There was a statistically significant difference in the Positive and Negative Syndrome Scale negative component, cognitive component, and depressive component in favor of the ED group at the 2-year follow-up. Multiple linear regression analyses gave no indication that these differences were due to confounders.
Reducing the DUP has effects on the course of symptoms and functioning, including negative symptoms, suggesting secondary prevention of the negative psychopathologies in first-episode schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
6Eur J Public Health 2010 Oct 20: 511-6
PMID20371499
TitleGender, hospitalization and mental disorders among homeless people compared with the general population in Stockholm.
AbstractThe aim was to study the prevalence of mental disorders among homeless men and women admitted for inpatient treatment in hospitals.
Hospital care utilization of homeless people, 1364 men and 340 women, was compared with a control group consisting of 3750 men and 1250 women from the general population, 1996-2002.
Homeless women RAN a higher risk for mental disorders than women in the population [risk ratio (RR) 20.88]; their risk was also higher than the risk for homeless men (RR 1.20). Younger homeless women had the highest risk (RR 2.17). Alcohol use disorders were equally common among homeless men and women, but women had more drug use disorders (RR 1.32). Women had higher risk of schizophrenia (RR 2.79), and personality disorders (RR 2.73). When adjustment was made for substance use disorders, no increased risk for mental disorder was found in the homeless group.
The elevated risk for mental disorders among the homeless was mainly related to substance use problems. Younger homeless women had the highest risk of mental disorder.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
7Neuroimage 2010 Oct 52: 1505-13
PMID20406692
TitleQuantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C]OMAR.
AbstractSeveral studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we present our first human studies in both healthy control patients and patients with schizophrenia using the novel PET tracer, [(11)C]OMAR (JHU75528), we have shown its utility as a tracer for imaging human CB1 receptors and to investigate normal aging and the differences in the cannabinoid system of healthy controls versus patients with schizophrenia. A total of ten healthy controls and nine patients with schizophrenia were included and studied with high specific activity [(11)C]OMAR. The CB1 binding (expressed as the distribution volume; V(T)) was highest in the globus pallidus and the cortex in both controls and patients with schizophrenia. Controls showed a correlation with the known distribution of CB1 and decline of [(11)C]OMAR binding with age, most significantly in the globus pallidus. Overall, we observed elevated mean binding in patients with schizophrenia across all regions studied, and this increase was statistically significant in the pons (p<0.05), by the Students t-test. When we RAN a regression of the control subjects V(T) values with age and then compared the patient data to 95% prediction limits of the linear regression, three patients fell completely outside for the globus pallidus, and in all other regions there were at least 1-3 patients outside of the prediction intervals. There was no statistically significant correlations between PET measures and the individual Brief Psychiatry Rating Score (BPRS) subscores (r=0.49), but there was a significant correlation between V(T) and the ratio of the BPRS psychosis to withdrawal score in the frontal lobe (r=0.60), and middle and posterior cingulate regions (r=0.71 and r=0.79 respectively). In conclusion, we found that [(11)C] OMAR can image human CB1 receptors in normal aging and schizophrenia. In addition, our initial data in subjects with schizophrenia seem to suggest an association of elevated binding specific brain regions and symptoms of the disease.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
8Neuropsychologia 2011 Feb 49: 435-43
PMID21167849
TitleVisuo-perceptual organization and working memory in patients with schizophrenia.
AbstractWe explore the mechanisms sub-tending the re-organization and memorization of visual information by studying how these mechanisms fail in patients with schizophrenia. Several studies have suggested that patients have difficulties in organizing information in perception and memory. We explore to what extent prompting patients to group items influences memory performance. We distinguish automatic grouping from top-down grouping processes, which are especially involved in re-organizing information. The main task was to memorize pairs of figures. Following manipulation of proximity, pairs of figures were part of the same perceptual group (within-group pair, formed on the basis of automatic grouping) or belonged to different groups (between-group pairs, re-grouped through top-down processes). Prior to the memory task, subjects RAN a perception task prompting them to prioritize either within-group or between-group pairs. Unlike patients, controls globally benefited from grouping by proximity in the memory task. In addition, the results showed that prioritizing between-group pairs had a deleterious effect in patients, but with a large decrement in memory performance in the case of within-group rather than between-group figures. This occurred despite preserved focalization on within-group figures, as shown by eye-movement recordings. The suggestion is that when patients are prompted to re-group separate items, they can do so, but the benefit derived from automatic grouping is then not only lost but also reversed. This suggests re-organizing visual information not only involves re-grouping separate items but also integrating these new groups in a unified representation, which is impaired in patients with schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
9J Clin Psychiatry 2012 Sep 73: e1168-74
PMID23059159
TitleBl-1020, a new ?-aminobutyric acid-enhanced antipsychotic: results of 6-week, randomized, double-blind, controlled, efficacy and safety study.
AbstractBL-1020 is a ?-aminobutyric acid (GABA)-enhanced antipsychotic that combines dopamine antagonism with GABA agonist activity. On the basis of animal models, we tested the hypotheses that BL-1020 would be effective in ameliorating both psychotic symptoms and cognitive impairments, with a favorable safety profile in acutely ill schizophrenia patients.
363 hospital-based psychiatric patients in India, Romania, and United States aged 18 to 65 years and meeting criteria for DSM-IV-TR diagnosis of chronic schizophrenia were RANdomized double-blind to receive BL-1020 10 mg/d, BL-1020 20-30 mg/d, placebo, or risperidone (2-8 mg/d) for 6 weeks. The main outcome measures were the positive and negative syndrome scale (PANSS), brief assessment of cognition in schizophrenia, readiness for discharge questionnaire, clinical global impressions scale (CGI) , and extrapyramidal symptom rating scale. The study RAN from July 2008 to June 2009.
BL-1020 20-30 mg was significantly better than placebo on PANSS (P = .02) and CGI (P < .001) measurements, with no significant differences noted between BL-1020 20-30 mg and risperidone. There were no significant differences in the maximum change on extrapyramidal symptom rating scale between risperidone and BL-1020 20-30 mg, and both were significantly worse (P < .001) than placebo. BL-1020 20-30 mg was associated with significantly greater improvements on cognitive functioning as measured by the brief assessment of cognition in schizophrenia composite score when compared to placebo (effect size = 0.50, P = .009), risperidone (effect size = 0.43, P = .019), and BL-1020 10 mg (effect size = 0.42, P = .013) after 6 weeks.
BL-1020 appears to be an effective antipsychotic with possible procognitive effects that will need to be further tested for short- and long-term effects. A further RANdomized controlled trial using the U.S. Food and Drug Administration-recommended Measurement and Treatment Research to Improve Cognition in schizophrenia cognitive battery is ongoing.
ClinicalTrials.gov identifier: NCT00567710.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
10Health Technol Assess 2012 -1 16: iii-iv, 1-76
PMID22364962
TitleGroup art therapy as an adjunctive treatment for people with schizophrenia: a randomised controlled trial (MATISSE).
AbstractTo examine the clinical effectiveness and cost-effectiveness of referral to group art therapy plus standard care, compared with referral to an activity group plus standard care and standard care alone, among people with schizophrenia.
A three-arm, parallel group, single-blind, pragmatic, RANdomised controlled trial. Participants were RANdomised via an independent and remote telephone RANdomisation service using permuted blocks, stratified by study centre.
Study participants were recruited from secondary care mental health and social services in four UK centres.
Potential participants were aged 18 years or over, had a clinical diagnosis of schizophrenia, confirmed by an examination of case notes, and provided written informed consent. We excluded those who were unable to speak sufficient English to complete the baseline assessment, those with severe cognitive impairment and those already receiving arts therapy.
Group art therapy was delivered by registered art therapists according to nationally agreed standards. Groups had up to eight members, lasted for 90 minutes and RAN for 12 months. Members were given access to a RANge of art materials and encouraged to use these to express themselves freely. Activity groups were designed to control for the non-specific effects of group art therapy. Group facilitators offered various activities and encouraged participants to collectively select those they wanted to pursue. Standard care involved follow-up from secondary care mental health services and the option of referral to other services, except arts therapies, as required.
Our co-primary outcomes were global functioning (measured using the Global Assessment of Functioning Scale - GAF) and mental health symptoms (measured using the Positive and Negative Syndrome Scale - PANSS) at 24 months. The main secondary outcomes were level of group attendance, social functioning, well-being, health-related quality of life, service utilisation and other costs measured 12 and 24 months after RANdomisation.
Four hundred and seventeen people were recruited, of whom 355 (85%) were followed up at 2 years. Eighty-six (61%) of those RANdomised to art therapy and 73 (52%) of those RANdomised to activity groups attended at least one group. No differences in primary outcomes were found between the three study arms. The adjusted mean difference between art therapy and standard care at 24 months was -0.9 [95% confidence interval (CI) -3.8 to 2.1] on the GAF Scale and 0.7 (95% CI -3.1 to 4.6) on the PANSS Scale. Differences in secondary outcomes were not found, except that those referred to an activity group had fewer positive symptoms of schizophrenia at 24 months than those RANdomised to art therapy. Secondary analysis indicated that attendance at art therapy groups was not associated with improvements in global functioning or mental health. Although the total cost of the art therapy group was lower than the cost of the two comparison groups, referral to group art therapy did not appear to provide a cost-effective use of resources.
Referring people with established schizophrenia to group art therapy as delivered in this RANdomised trial does not appear to improve global functioning or mental health of patients or provide a more cost-effective use of resources than standard care alone.
Current Controlled Trials ISRCTN 46150447.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 8. See the HTA programme website for further project information.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
11Psychol Psychother 2013 Jun 86: 139-45
PMID23674465
TitleCognitive-behavioural therapy for schizophrenia: a critical commentary on the Newton-Howes and Wood meta-analysis.
AbstractNewton-Howes and Wood (published online, this journal, 8 Dec 2011) report the results of their systematic review and meta-analysis of clinical trials of cognitive-behavioural therapy (CBT) for schizophrenia. They RAN a RANdom effects analysis of endpoint data from trials where participants were RANdomly allocated to receive either CBT or a control therapy, which could be inactive (e.g., befriending) or active (e.g., analytic supportive psychotherapy), found no difference between the groups and concluded 'it (CBT) does not outperform supportive therapy in effecting change in phenomenology.' Such a conclusion is premature, if not unwarRANted, for a number of reasons, including basic mistakes, lack of tRANsparency, and failure to consider dose.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
12PLoS ONE 2014 -1 9: e100188
PMID24932798
TitleChronic treatment with mood-stabilizers attenuates abnormal hyperlocomotion of GluA1-subunit deficient mice.
AbstractAbnormal excitatory glutamate neurotRANsmission and plasticity have been implicated in schizophrenia and affective disorders. Gria1-/- mice lacking GluA1 subunit (encoded by Gria1 gene) of AMPA-type glutamate receptor show robust novelty-induced hyperactivity, social deficits and heightened approach features, suggesting that they could be used to test for anti-manic activity of drugs. Here, we tested the efficacy of chronic treatment with established anti-manic drugs on behavioural properties of the Gria1-/- mice. The mice received standard mood stabilizers (lithium and valproate) and novel ones (topiramate and lamotrigine, used more as anticonvulsants) as supplements in rodent chow for at least 4 weeks. All drugs attenuated novelty-induced locomotor hyperactivity of the Gria1-/- mice, especially by promoting the habituation, while none of them attenuated 2-mg/kg amphetamine-induced hyperactivity as compared to control diet. Treatment with lithium and valproate reversed the elevated exploratory activity of Gria1-/- mice. Valproate treatment also reduced struggling behaviour in tail suspension test and restored reciprocally-initiated social contacts of Gria1-/- mice to the level shown by the wild-type Gria1+/+ mice. Gria1-/- mice consumed slightly more sucrose during intermittent sucrose exposure than the wild-types, but RAN similar distances on running wheels. These behaviours were not consistently affected by lithium and valproate in the Gria1-/- mice. The efficacy of various anti-manic drug treatments on novelty-induced hyperactivity suggests that the Gria1-/- mouse line can be utilized in screening for new therapeutics.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
13Eur Neuropsychopharmacol 2014 Apr 24: 575-84
PMID24418213
TitleOpen, randomized trial of the effects of aripiprazole versus risperidone on social cognition in schizophrenia.
AbstractTo date, only few studies have examined the impact of medication on social cognition and none have examined the effects of aripiprazole in this respect. The goal of this 8-week, RANdomized, multicenter, open-label study was to examine the effects of aripiprazole and risperidone on social cognition and neurocognition in individuals with schizophrenia. Eighty schizophrenia patients (DSM-IV-TR) aged 16-50 years were administered multiple computerized measures of social cognition and neurocognition including reaction times at baseline and the end of week 8. Social functioning was mapped with the Social Functioning scale and Quality of Life scale. The study RAN from June 2005 to March 2011. Scores on social cognitive and neurocognitive tests improved with both treatments, as did reaction time. There were few differences between the two antipsychotics on (social) cognitive test-scores. The aripiprazole group performed better (more correct items) on symbol substitution (P=.003). Aripiprazole was also superior to risperidone on reaction time for emotional working memory and working memory (P=.006 and P=.023, respectively). Improvements on these tests were correlated with social functioning. In conclusion, aripiprazole and risperidone showed a similar impact on social cognitive test-scores. However, aripiprazole treatment produced a greater effect on patients' processing speed compared to risperidone, with these improvements being associated with concurrent improvements in social functioning. Further research on the long-term effects of aripiprazole on cognition is warRANted.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
14Neuroscience 2015 Dec 310: 723-30
PMID26475744
TitleThe CCDC55 couples cannabinoid receptor CNR1 to a putative DISC1 schizophrenia pathway.
AbstractOur previous study suggested that the coiled coil domain-containing 55 gene (CCDC55), also named as NSRP1 (nuclear speckle splicing regulatory protein 1 (NSRP1)), was encompassed in a haplotype block spanning over the serotonin tRANsporter (5-HTT) gene in patients with schizophrenia (SCZ). However, the neurobiological function of CCDC55 gene remains unknown. This study aims to uncover the potential role of CCDC55 in SCZ-associated molecular pathways.
Using molecular cloning, sequencing and immune blotting to identify basic properties, yeast two-hybrid screening and glutathione S-tRANsferase (GST) pull-down assay to test protein-protein interaction, and confocal laser scanning microscopy (CSLM) to show intracellular interaction of proteins.
(i) CCDC55 is expressed as a nuclear protein in human neuronal cells; (ii) Protein-protein interaction analyses showed CCDC55 physically interacted with RAN binding protein 9 (RANBP9) and disrupted in schizophrenia 1 (DISC1); (iii) CCDC55 and RANBP9 co-localized in the nucleus of human neuronal cells; (iv) CCDC55 also interacted with the cannabinoid receptor 1 (CNR1), and with the brain cannabinoid receptor-interacting protein 1a (CNRIP1a); (v) CNR1 activation in differentiated human neuronal cells resulted in an altered RANBP9 localization.
CCDC55 may be involved in a functional bridging between the CNR1 activation and the DISC1/RANBP9-associated pathways.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
15Cereb. Cortex 2015 Oct 25: 3977-93
PMID25452572
TitleRanbp1, Deleted in DiGeorge/22q11.2 Deletion Syndrome, is a Microcephaly Gene That Selectively Disrupts Layer 2/3 Cortical Projection Neuron Generation.
AbstractRANbp1, a RAN GTPase-binding protein implicated in nuclear/cytoplasmic trafficking, is included within the DiGeorge/22q11.2 Deletion Syndrome (22q11.2 DS) critical region associated with behavioral impairments including autism and schizophrenia. RANbp1 is highly expressed in the developing forebrain ventricular/subventricular zone but has no known obligate function during brain development. We assessed the role of RANbp1 in a targeted mouse mutant. RANbp1(-/-) mice are not recovered live at birth, and over 60% of RANbp1(-/-) embryos are exencephalic. Non-exencephalic RANbp1(-/-) embryos are microcephalic, and proliferation of cortical progenitors is altered. At E10.5, radial progenitors divide more slowly in the RANpb1(-/-) dorsal pallium. At E14.5, basal, but not apical/radial glial progenitors, are compromised in the cortex. In both E10.5 apical and E14.5 basal progenitors, M phase of the cell cycle appears selectively retarded by loss of RANpb1 function. RANbp1(-/-)-dependent proliferative deficits substantially diminish the frequency of layer 2/3, but not layer 5/6 cortical projection neurons. RANbp1(-/-) cortical phenotypes parallel less severe alterations in LgDel mice that carry a deletion parallel to many (but not all) 22q11.2 DS patients. Thus, RANbp1 emerges as a microcephaly gene within the 22q11.2 deleted region that may contribute to altered cortical precursor proliferation and neurogenesis associated with broader 22q11.2 deletion.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
16Nucl. Med. Biol. 2015 Aug 42: 643-53
PMID25963911
TitleRadiolabeling of [18F]-fluoroethylnormemantine and initial in vivo evaluation of this innovative PET tracer for imaging the PCP sites of NMDA receptors.
AbstractThe N-methyl-D-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory tRANsmission. NMDAr overexcitation is thought to be involved in neurological and neuropsychiatric disorders such as Alzheimer disease and schizophrenia. We synthesized [(18)F]-fluoroethylnormemantine ([(18)F]-FNM), a memantine derivative that binds to phencyclidine (PCP) sites within the NMDA channel pore. These sites are primarily accessible when the channel is in the active and open state.
Radiosynthesis was carried out using the Raytest« SynChrom R&D fluorination module. Affinity of this new compound was determined by competition assay. We RAN a kinetic study in rats and computed a time-activity curve based on a volume-of-interest analysis, using CARIMAS« software. We performed an ex vivo autoradiography, exposing frozen rat brain sections to a phosphorscreen. Adjacent sections were used to detect NMDAr by immunohistochemistry with an anti-NR1 antibody. As a control of the specificity of our compound for NMDAr, we used a rat anesthetized with ketamine. Correlation analysis was performed with ImageJ software between signal of autoradiography and immunostaining.
Fluorination yield was 10.5% (end of synthesis), with a mean activity of 3145 MBq and a specific activity above 355 GBq/?mol. Affinity assessment allowed us to determine [(19)F]-FNM IC50 at 6.1 10(-6)M. [(18)F]-FMN concentration gradually increased in the brain, stabilizing at 40 minutes post injection. The brain-to-blood ratio was 6, and 0.4% of the injected dose was found in the brain. Combined ex vivo autoradiography and immunohistochemical staining demonstrated colocalization of NMDAr and [(18)F]-FNM (r=0.622, p<0.0001). The highest intensity was found in the cortex and cerebellum, and the lowest in white matter. A low and homogeneous signal corresponding to unspecific binding was observed when PCP sites were blocked with ketamine.
[(18)F]-FNM appears to be a promising tracer for imaging NMDAr activity for undertaking preclinical studies in perspective of clinical detection of neurological or neuropsychological disorders.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
17Encephale 2015 Oct 41: 435-43
PMID25238902
Title[Exploring the relationship between internalized stigma, insight and depression for inpatients with schizophrenia].
AbstractRecent studies on insight in people with schizophrenia showed that insight level is linked with treatment compliance. Therefore, many therapies are aimed at increasing the insight level, such as psycho-education. However, insight level is also probably linked with depression level. So, improving insight is at risk of increasing the level of depression. Nevertheless, results on this topic are not consensual in the scientific literature. Presumably, this could be due to the concept of insight itself, although we could hypothesise that some confounding variables are implied in the interaction between insight and depression, such as internalized stigma.
to test the hypothesis that the relationship between insight and depression is mediated by internalized stigma in people with schizophrenia.
Sixty-two patients with schizophrenia (DSM-IV or ICD-10) recruited in mental health services in ╬le de FRANce (75% male), aged 20 to 64 years (m=38.71, ?=0. 43), filled in questionnaires assessing internalized stigma (ISMI), depression (CDSS and BDI) and insight (SAIQ, Q8, IS), after giving their written informed consent. Correlations between insight, depression and different variables were made (Hypothesis 1). Then we RAN multiple regressions and partial correlations to test the internalized stigma mediation (Hypothesis 2).
Insight, internalized stigma and depression are statistically significantly correlated with each scales used (except Q8). Insight is correlated with depressed mood (correlations between IS and CDSS: r=0.27, P=0.04, and BDI, r=0.40, P=0.001). We also found negative correlations between SAIQ and CDSS (r=-0.35, P=0.005) and the BDI (r=-0.4265, P=0.000) which means that good insight is linked with depression. This result validates our hypothesis 1. The statistic tests reveal other complementary results: the association between insight and depression is mediated by the level of internalized stigma: when ISMI is controlled, the correlation between insight and depression decreased moderately with CDSS and with small intensity with SAIQ, but clearly. So, ISMI is probably a mediating variable between IS and BDI-CDSS. In conclusion, internalized stigma could be a mediating variable between insight and depression. This validates our second hypothesis.
Our results suggest that the relationship between insight and depression is mediated by internalized stigma. Patients with good insight who internalize stigma seem to be more depressed than those who don't. This result could have important consequences in clinical practice: improving insight level should be completed by a specific attention to the level and evolution of internalized stigma to avoid increasing depression. Further studies need to be conducted to confirm these results.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
18Cochrane Database Syst Rev 2016 -1 2: CD008919
PMID26848926
TitleAntioxidant treatments for schizophrenia.
AbstractThere is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative stress may be one of the mediators of neuroprogression, grey matter loss and subsequent cognitive and functional impairment. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences. They may act from directly scavenging free radicals to increasing anti-oxidative defences. There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia. The existing literature, however, indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia. As such, there has been interest in developing interventions aimed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction. If antioxidants are to have a place in the treatment of this serious condition, the relevant and up-to-date information should be available to clinicians and investigators.
To evaluate the effect of antioxidants as add-on treatments to standard antipsychotic medication for improving acute psychotic episodes and core symptoms, and preventing relapse in people with schizophrenia.
We searched the CochRANe schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We RAN this search in November 2010, and again on 8 January 2015. We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.
We included reports if they were RANdomised controlled trials (RCTs) involving people with schizophrenia who had been allocated to either a substance with antioxidant potential or to a placebo as an adjunct to standard antipsychotic treatment.
We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
The review includes 22 RCTs of varying quality and sample size studying Ginkgo biloba, N-acetyl cysteine (NAC), allopurinol, dehydroepiandrosterone (DHEA), vitamin C, vitamin E or selegiline. Median follow-up was eight weeks. Only three studies including a minority of the participants reported our a priori selected primary outcome of clinically important response. Short-term data for this outcome (measured as at least 20% improvement in scores on Positive and Negative Syndrome Scale (PANSS)) were similar (3 RCTs, n = 229, RR 0.77, 95% CI 0.53 to 1.12, low quality evidence). Studies usually reported only endpoint psychopathology rating scale scores. Psychotic symptoms were lower in those using an adjunctive antioxidant according to the PANSS ( 7 RCTS, n = 584, MD -6.00, 95% CI -10.35 to -1.65, very low quality evidence) and the Brief Psychiatric Rating Scale (BPRS) (8 RCTS, n = 843, MD -3.20, 95% CI -5.63 to -0.78, low quality evidence). There was no overall short-term difference in leaving the study early (16 RCTs, n = 1584, RR 0.73, 95% CI 0.48 to 1.11, moderate quality evidence), or in general functioning (2 RCTs, n = 52, MD -1.11, 95% CI -8.07 to 5.86, low quality evidence). Adverse events were generally poorly reported. Three studies reported useable data for 'any serious adverse effect', results were equivocal (3 RCTs, n = 234, RR 0.65, 95% CI 0.19 to 2.27, low quality evidence). No evidence was available for relapse, quality of life or service use.
Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics