| 1 | J Psychother Pract Res 2000 -1 9: 149-56 |
|---|---|
| PMID | 10896740 |
| Title | Development of an integrated cognitive-behavioral and social skills training intervention for older patients with schizophrenia. |
| Abstract | There is considerable evidence that psychosocial treatments benefit younger adults with schizophrenia. However, no studies have been undertaken of such interventions for older patients with schizophrenia. This report describes the development of a novel integrated treatment combining cognitive-behavioral therapy (CBT) and social skills training (SST). This intervention is designed to address the needs of older patients with schizophrenia by challenging beliefs common in this population that interfere with treatment and by providing repetitive practice of behaviors to improve retention and skill development. The authors provide two case reports and pilot data suggesting benefits of this approach. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Psychiatry Clin. Neurosci. 2003 Jun 57: 295-302 |
| PMID | 12753570 |
| Title | Efficacy of open-system social skills training in inpatients with mood, neurotic and eating disorders. |
| Abstract | Open-system social skills training (SST) was performed in an open psychiatric ward of the hospital of Yokohama City University. Between June 1998 and March 2000, 223 patients were being treated for various mental disorders and 136 of these patients voluntarily participated in the open-system SST at least once. The SST participants' ages were 37.2 +/- 16.9 years and the admission period was 102.6 +/- 61.4 days, while non-participants' ages were 49.8 +/- 18.8 years and the admission period was 71.8 +/- 55.6 days. The correlation between participation time and the admission period showed a ratio of approximately 0.5. As for diagnoses, schizophrenia, eating disorder and personality disorder patients tended to participate in SST, while organic mental disorder patients tended to be non-participants. After October 1998 there were 26 patients continuing to attend SST who participated in the evaluation study that compared social skills estimation before SST with that after SST by self-evaluation and by the staff using a social skills questionnaire. After SST sessions, the average staff evaluation score was 43.9% in schizophrenia, 64.4% in mood disorder, 64.9% in neurotic disorder and 55.3% in eating disorders, while they were 29.1%, 33.8%, 44.4% and 34.5% before the sessions, respectively. After the SST sessions, mood disorder patients showed a 25-30% increase of both self-estimation and staff estimation in all subcategories of social skills. These findings suggest that SST was effective for all patients motivated to improve their social skills despite diagnoses and that the SST program had different effects in each diagnosis group. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Psychiatr. Clin. North Am. 2003 Mar 26: 191-211 |
| PMID | 12683266 |
| Title | Maximizing the synergy between pharmacotherapy and psychosocial therapies for schizophrenia. |
| Abstract | Although the traditional antipsychotic medications were a major advancement in schizophrenia therapeutics and made possible the era of deinstitutionalization, just maintaining a patient out of the hospital no longer can be viewed as the final goal of treatment. Most patients are able to maintain outpatient status despite persistent psychotic symptoms, pervasive negative symptoms and poor social competence. It is hoped that the availability of the atypical antipsychotic drugs will improve significantly compliance, treatment of symptoms, and possibly relapse rates and overall outcome. It should be the norm and not the exception for patients to be treated with these new medications as early as possible in their illness. The clinician should not be complacent and quick to accept persistent psychosis, and patients with various forms of treatment resistance should be tried early in the course of illness with clozapine (or other medications as they become available if they show superiority for treatment-resistant patients). Pharmacologic interventions aimed at deficit symptoms may become available in the future. Psychosocial interventions have a place in the modern therapeutic armamentarium. Relatively simple sustained family interventions and more comprehensive ACT programs are effective for relapse prevention and reduction of the "revolving door syndrome," whereas patients with psychosis nonresponsive to medication may benefit from new modalities of CBT. For patients with persistent negative symptoms and limited social competence, SST is indicated where available, and even in places where staff may be limited and social skills and other programs difficult to implement, family psychoeducational interventions can be carried out to good effect. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Psychiatr Rehabil J 2004 -1 27: 375-91 |
| PMID | 15222149 |
| Title | Skills training for people with severe mental illness. |
| Abstract | There is a growing empirical literature on psychosocial rehabilitation strategies for schizophrenia and other severe mental illnesses. Three of the best-supported and most promising approaches were reviewed: social skills training (SST), cognitive behavior therapy (CBT), and cognitive remediation (CR). Of the three, SST has the strongest empirical support and can be considered an evidence-based treatment. However, it is appropriate as a targeted treatment for social impairment, not as a broad based treatment for schizophrenia. CBT has only recently been applied to patients with psychotic disorders and the preliminary results are promising for reducing distress associated with residual psychotic symptoms. All but a handful of trials have been carried out in the context of the public health system in the UK with specially selected patients. Consequently, it is not yet clear if it would be effective in public health systems in the US, with highly impaired patients, or for patients with comorbid substance abuse. There is an extensive literature documenting that a variety of training techniques can improve performance on neuropsychological tests, and there is a growing literature of more clinically relevant CR trials that have produced small to medium effect sizes. No studies have yet demonstrated a clinically significant effect on community functioning. This is a promising area for further research, but CR, like CBT, does not have a sufficient evidentiary base for widespread dissemination to the public mental health system at this time. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Int J Psychiatr Nurs Res 2006 Sep 12: 1364-77 |
| PMID | 17016899 |
| Title | The efficacy of family intervention in adolescent mental health. |
| Abstract | The term 'family therapy' is used to encompass a range of approaches that share a common view about the importance of family involvement in psychiatric disorders. This paper reviews the effectiveness of family interventions in adolescent mental health with a special emphasis on single session therapy. Research evidence shows that the family intervention in psychiatric disorders such as schizophrenia, depression, attention deficit hyperactive disorder, anxiety and anorexia not only provides better outcomes, but also increases client satisfaction with services. Among the family therapy approaches, single session therapy (SST) seems to be a flexible and very effective model for adolescent mental disorders, which seem to offer an efficient means of providing rapid access to services whilst removing some of the difficulties associated with other forms of family therapy approaches. A new service development model is also discussed by drawing together a number of ideas encountered in practice settings. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Hum. Mol. Genet. 2006 Jun 15: 1949-62 |
| PMID | 16687443 |
| Title | Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: relevance to neuronal network perturbation. |
| Abstract | The limited number of genome-wide transcriptome analyses using the postmortem brains of bipolar disorder sufferers has not produced a clear consensus on the molecular pathways affected by the disorder. To expand the knowledge in this area, we examined the expression levels of more than 12 000 genes in Brodmann's Area (BA), 46 (dorsolateral prefrontal cortex) from bipolar I disorder and control samples using Affymetrix GeneChips. This analysis detected 108 differentially expressed genes in bipolar brains. Validation studies using quantitative RT-PCR on the two original diagnostic cohorts plus tissue from schizophrenic subjects, confirmed the differential expressions of eight genes (RAP1GA1, SST, HLA-DRA, KATNB1, PURA, NDUFV2, STAR and PAFAH1B3) in a bipolar-specific manner and one gene (CCL3) which was downregulated in both bipolar and schizophrenic brains. Of these, protein levels of RAP1GA1 (RAP1 GTPase activating protein 1) showed a trend of increase in BA46 from bipolar brains, in keeping with mRNA transcript levels. Transmission disequilibrium analysis of the nine genes using 43 single nucleotide polymorphisms (SNPs) in 229 National Institute of Mental Health bipolar trios exposed nominal SNP association and modest empirical haplotypic association (P=0.033) between SST (somatostatin) and disease. Finally, gene network analysis using the currently obtained expression data highlighted cellular growth and nervous system development pathways as potential targets in the molecular pathophysiology of bipolar disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | J Rehabil Res Dev 2007 -1 44: 827-35 |
| PMID | 18075940 |
| Title | Is learning potential associated with social skills in schizophrenia? |
| Abstract | Cognitive deficits are a primary factor in the social and functional impairments characteristic of schizophrenia and an important predictor of treatment success in psychosocial rehabilitation. This study examined the association between abstract reasoning and social functioning by assessing whether learning potential on the Wisconsin Card Sorting Test (WCST) relates to changes in social competence following social skills training (SST). Fifty-six veterans with schizophrenia or schizoaffective disorder completed a series of assessments followed by eight SST sessions. To evaluate learning potential, we assessed participants with the WCST and Category Test (CT), taught them a training protocol for the WCST, and retested on both measures. Participants learned the WCST, generalized this learning to improve their performance on the CT, and retained these gains for several weeks. Participants showed small improvements on the Maryland Assessment of Social Competence (MASC), but WCST learning potential and CT generalization were unrelated to improvement on the MASC. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | J. Neurosci. 2007 Oct 27: 11254-62 |
| PMID | 17942719 |
| Title | Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. |
| Abstract | Alterations in GABAergic mRNA expression play a key role for prefrontal dysfunction in schizophrenia and other neurodevelopmental disease. Here, we show that histone H3-lysine 4 methylation, a chromatin mark associated with the transcriptional process, progressively increased at GAD1 and other GABAergic gene promoters (GAD2, NPY, SST) in human prefrontal cortex (PFC) from prenatal to peripubertal ages and throughout adulthood. Alterations in schizophrenia included decreased GAD1 expression and H3K4-trimethylation, predominantly in females and in conjunction with a risk haplotype at the 5' end of GAD1. Heterozygosity for a truncated, lacZ knock-in allele of mixed-lineage leukemia 1 (Mll1), a histone methyltransferase expressed in GABAergic and other cortical neurons, resulted in decreased H3K4 methylation at GABAergic gene promoters. In contrast, Gad1 H3K4 (tri)methylation and Mll1 occupancy was increased in cerebral cortex of mice after treatment with the atypical antipsychotic, clozapine. These effects were not mimicked by haloperidol or genetic ablation of dopamine D2 and D3 receptors, suggesting that blockade of D2-like signaling is not sufficient for clozapine-induced histone methylation. Therefore, chromatin remodeling mechanisms at GABAergic gene promoters, including MLL1-mediated histone methylation, operate throughout an extended period of normal human PFC development and play a role in the neurobiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Mol. Psychiatry 2008 Feb 13: 147-61 |
| PMID | 17471287 |
| Title | Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia. |
| Abstract | In subjects with schizophrenia, impairments in working memory are associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction appears to be due, at least in part, to abnormalities in gamma-aminobutyric acid (GABA)-mediated inhibitory circuitry. To test the hypothesis that altered GABA-mediated circuitry in the DLPFC of subjects with schizophrenia reflects expression changes of genes that encode selective presynaptic and postsynaptic components of GABA neurotransmission, we conducted a systematic expression analysis of GABA-related transcripts in the DLPFC of 14 pairs of schizophrenia and age-, sex- and post-mortem interval-matched control subjects using a customized DNA microarray with enhanced sensitivity and specificity. Subjects with schizophrenia exhibited expression deficits in GABA-related transcripts encoding (1) presynaptic regulators of GABA neurotransmission (67 kDa isoform of glutamic acid decarboxylase (GAD(67)) and GABA transporter 1), (2) neuropeptides (somatostatin (SST), neuropeptide Y (NPY) and cholecystokinin (CCK)) and (3) GABA(A) receptor subunits (alpha1, alpha4, beta3, gamma2 and delta). Real-time qPCR and/or in situ hybridization confirmed the deficits for six representative transcripts tested in the same pairs and in an extended cohort, respectively. In contrast, GAD(67), SST and alpha1 subunit mRNA levels, as assessed by in situ hybridization, were not altered in the DLPFC of monkeys chronically exposed to antipsychotic medications. These findings suggest that schizophrenia is associated with alterations in inhibitory inputs from SST/NPY-containing and CCK-containing subpopulations of GABA neurons and in the signaling via certain GABA(A) receptors that mediate synaptic (phasic) or extrasynaptic (tonic) inhibition. In concert with previous findings, these data suggest that working memory dysfunction in schizophrenia is mediated by altered GABA neurotransmission in certain DLPFC microcircuits. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | BMC Psychiatry 2008 -1 8: 87 |
| PMID | 18992145 |
| Title | Putative psychosis genes in the prefrontal cortex: combined analysis of gene expression microarrays. |
| Abstract | Recent studies have shown similarities between schizophrenia and bipolar disorder in phenotypes and in genotypes, and those studies have contributed to an ongoing re-evaluation of the traditional dichotomy between schizophrenia and bipolar disorder. Bipolar disorder with psychotic features may be closely related to schizophrenia and therefore, psychosis may be an alternative phenotype compared to the traditional diagnosis categories. We performed a cross-study analysis of 7 gene expression microarrays that include both psychosis and non-psychosis subjects. These studies include over 400 microarray samples (163 individual subjects) on 3 different Affymetrix microarray platforms. We found that 110 transcripts are differentially regulated (p < 0.001) in psychosis after adjusting for confounding variables with a multiple regression model. Using a quantitative PCR, we validated a set of genes such as up-regulated metallothioneins (MT1E, MT1F, MT1H, MT1K, MT1X, MT2A and MT3) and down-regulated neuropeptides (SST, TAC1 and NPY) in the dorsolateral prefrontal cortex of psychosis patients. This study demonstrates the advantages of cross-study analysis in detecting consensus changes in gene expression across multiple microarray studies. Differential gene expression between individuals with and without psychosis suggests that psychosis may be a useful phenotypic variable to complement the traditional diagnosis categories. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Synapse 2008 Jun 62: 456-65 |
| PMID | 18361442 |
| Title | Dendritic-targeting GABA neurons in monkey prefrontal cortex: comparison of somatostatin- and calretinin-immunoreactive axon terminals. |
| Abstract | Different subclasses of gamma-aminobutyric acid (GABA) cortical neurons can be distinguished by their content of neuropeptides such as somatostatin (SST), or calcium-binding proteins such as calretinin (CR). SST, but not CR, neurons have been reported to be altered in the prefrontal cortex (PFC) of subjects with schizophrenia. Understanding the functional significance of the SST neuron disturbances in schizophrenia requires knowledge of the specialized synaptic circuitry of these neurons relative to that of CR neurons. Consequently, we used immuno-electron microscopy to examine the synaptic type and postsynaptic targets of SST-immunoreactive (IR) axon terminals in monkey PFC and compared these findings with similar data for CR-IR axon terminals. SST-IR axon terminals formed exclusively symmetric synapses and contacted only dendritic shafts (86%) and dendritic spines (14%), whereas CR-IR terminals also formed synapses with cell bodies. The postsynaptic targets of SST-IR axon terminals also differed across layers with synapses onto dendritic spines more frequent in the superficial (20%) than in the deep (8%) layers. Dual-label immunoelectron microscopy revealed that CR-IR axon terminals targeted GABA-IR dendritic shafts with a greater frequency (60%) than did SST-IR axon terminals (21.5%). Conversely, SST-IR axon terminals contacted unlabeled dendritic shafts, presumably belonging to pyramidal neurons, more frequently than did CR-IR axon terminals (57% vs. 19%, respectively). This specialized synaptic circuitry of SST neurons in the primate PFC suggests that the alterations of these neurons in schizophrenia is likely to have distinct functional consequences. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | Cereb. Cortex 2008 Jul 18: 1575-87 |
| PMID | 18203698 |
| Title | Alterations in somatostatin mRNA expression in the dorsolateral prefrontal cortex of subjects with schizophrenia or schizoaffective disorder. |
| Abstract | Alterations in the inhibitory circuitry of the dorsolateral prefrontal cortex (DLPFC) in schizophrenia include reduced expression of the messenger RNA (mRNA) for somatostatin (SST), a neuropeptide present in a subpopulation of gamma-aminobutyric acid (GABA) neurons. However, neither the cellular substrate nor the causal mechanisms for decreased SST mRNA levels in schizophrenia are known. We used in situ hybridization to quantify the compartmental, laminar, and cellular levels of SST mRNA expression in the DLPFC of 23 pairs of schizophrenia or schizoaffective disorder and control subjects. We also explored potential causal mechanisms by utilizing similar methods to analyze SST mRNA expression in 2 animal models. The expression of SST mRNA was significantly decreased in layers 2-superficial 6 of subjects with schizophrenia, but not in layer 1, deep 6 or the white matter. At the cellular level, both the density of cortical SST mRNA-positive neurons and the expression of SST mRNA per neuron were reduced in the subjects with schizophrenia. These alterations were not due to potential confounds and appeared to be a downstream consequence of impaired neurotrophin signaling through the trkB receptor. These findings support the hypothesis that a marked reduction in SST mRNA expression in a subset of GABA neurons contributes to DLPFC dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | Biol. Psychiatry 2009 Jun 65: 1006-14 |
| PMID | 19121517 |
| Title | Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia. |
| Abstract | Prefrontal deficits in gamma-aminobutyric acid (GABA)ergic gene expression, including neuropeptide Y (NPY), somatostatin (SST), and parvalbumin (PV) messenger RNAs (mRNAs), have been reported for multiple schizophrenia cohorts. Preclinical models suggest that a subset of these GABAergic markers (NPY/SST) is regulated by brain-derived neurotrophic factor (BDNF), which in turn is under the inhibitory influence of small noncoding RNAs. However, it remains unclear if these mechanisms are important determinants for dysregulated NPY and SST expression in prefrontal cortex (PFC) of subjects with schizophrenia. Using a postmortem case-control design, the association between BDNF protein, NPY/SST/PV mRNAs, and two BDNF-regulating microRNAs (miR-195 and miR-30a-5p) was determined in samples from the PFC of 20 schizophrenia and 20 control subjects. Complementary studies were conducted in cerebral cortex of mice subjected to antipsychotic treatment or a brain-specific ablation of the Bdnf gene. Subjects with schizophrenia showed deficits in NPY and PV mRNAs. Within-pair differences in BDNF protein levels showed strong positive correlations with NPY and SST and a robust inverse association with miR-195 levels, which in turn were not affected by antipsychotic treatment or genetic ablation of Bdnf. Taken together, these results suggest that prefrontal deficits in a subset of GABAergic mRNAs, including NPY, are dependent on the regional supply of BDNF, which in turn is fine-tuned through a microRNA (miRNA)-mediated mechanism. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | Schizophr. Res. 2009 Dec 115: 261-9 |
| PMID | 19804960 |
| Title | NPY mRNA expression in the prefrontal cortex: Selective reduction in the superficial white matter of subjects with schizoaffective disorder. |
| Abstract | Alterations in the inhibitory circuitry of the dorsolateral prefrontal cortex (DLPFC) in schizophrenia include reduced expression of the messenger RNA (mRNA) for somatostatin (SST), a neuropeptide present in a subpopulation of gamma-aminobutyric acid (GABA) neurons. Neuropeptide Y (NPY) is expressed in a subset of SST-containing interneurons and lower levels of NPY mRNA have also been reported in schizophrenia spectrum disorders. However, whether the alterations in these two transcripts identify the same, particularly vulnerable, subset of GABA neurons has not been examined. We used in situ hybridization to quantify NPY mRNA levels in DLPFC gray and white matter from 23 pairs of subjects with schizophrenia or schizoaffective disorder and matched normal control subjects; results were compared to those from a previous study of SST mRNA expression in the same subjects. In contrast to SST mRNA, NPY mRNA levels were not significantly lower in the gray matter of subjects with schizophrenia or schizoaffective disorder. However, NPY, but not SST, mRNA expression was significantly lower in the superficial white matter of subjects with schizoaffective disorder. These findings suggest that the alterations in SST-containing interneurons in schizophrenia and schizoaffective disorder are selective for the subset that do not express NPY mRNA, and that lower NPY mRNA expression in the superficial white matter may distinguish subjects with schizoaffective disorder from those with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | J Int Neuropsychol Soc 2010 Nov 16: 1064-76 |
| PMID | 20719043 |
| Title | Inhibitory control and psychopathology: a meta-analysis of studies using the stop signal task. |
| Abstract | The Stop Signal Task (SST) is a measure that has been used widely to assess response inhibition. We conducted a meta-analysis of studies that examined SST performance in patients with various psychiatric disorders to determine the magnitude and generality of deficient inhibition. A five-item instrument was used to assess the methodological quality of studies. We found medium deficits in stop signal reaction time (SSRT), reflecting the speed of the inhibitory process, for attention-deficit hyperactivity disorder (ADHD) (g = 0.62), obsessive compulsive disorder (OCD) (g = 0.77) and schizophrenia (SCZ) (g = 0.69). SSRT was less impaired or normal for anxiety disorder (ANX), autism, major depressive disorder (MDD), oppositional defiant disorder/conduct disorder (ODD/CD), pathological gambling, reading disability (RD), substance dependence, and Tourette syndrome. We observed a large SSRT deficit for comorbid ADHD + RD (g = 0.82). SSRT was less than moderately impaired for ADHD + ANX and ADHD + ODD/CD. Study quality did not significantly affect SSRT across ADHD studies. This confirms an inhibition deficit in ADHD, and suggests that comorbid ADHD has different effects on inhibition in patients with ANX, ODD/CD, and RD. Further studies are needed to firmly establish an inhibition deficit in OCD and SCZ. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 16 | Psychiatry Res 2010 Oct 179: 259-66 |
| PMID | 20537400 |
| Title | Executive control in schizophrenia in task involving semantic inhibition and working memory. |
| Abstract | Executive dysfunctions have been consistently demonstrated in patients with schizophrenia. This study aimed to investigate deficits in specific executive functioning components, namely working memory and inhibition, in schizophrenia. In study 1, a set of neurocognitive function tests was administered to 41 patients with schizophrenia and 25 healthy controls to capture specific components of executive functioning, including semantic inhibition (the Stroop-like paradigm and the Chinese Version of the Hayling Sentence Completion Test (HSC)), working memory (the spatial n-back), and response inhibition (the stop signal task (SST)). Results showed that schizophrenia patients did significantly worse than controls under both working memory and inhibition demands in the Stroop-like paradigm. In particular, patients were impaired when inhibiting a semantically associated response; and performance was correlated with negative symptoms. In study 2, we employed a modified semantic inhibitory error monitoring paradigm to examine whether patients with schizophrenia (n=11) were impaired in semantic inhibitory error monitoring or not as compared to 11 healthy controls. The results suggested that patients with schizophrenia in this study remained intact in semantic inhibition error monitoring. There was no difference in the semantic inhibitory monitoring performance between healthy controls and patients with schizophrenia. Taken together, these results suggested impaired working memory context maintenance and semantic inhibition in schizophrenia patients, and these impairments were related to clinical symptoms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 17 | Eur Arch Psychiatry Clin Neurosci 2010 Jun 260: 305-15 |
| PMID | 19826855 |
| Title | Social skills and neurocognitive individualized training in schizophrenia: comparison with structured leisure activities. |
| Abstract | Cognitive impairment and deficits in social skills have been largely documented in patients with schizophrenia and are increasingly recognized as rate-limiting factors for recovery. Evidence has been provided that cognitive training and social skills training (SST) are effective to treat cognitive and social skills impairment in schizophrenia; however, the translation of improved performance on cognitive or social skills tasks into improved functional outcome is controversial. According to recent reviews, interventions providing cognitive training in conjunction with psychosocial rehabilitation have a greater impact on functional outcome than either intervention alone suggesting that the two treatment approaches may work together in a synergistic fashion. The present pilot study was designed to test the hypothesis that an integrated rehabilitation program, including individualized cognitive and SST, is more effective than the structured leisure activities (SLA) carried out in many Italian Mental Health Departments. The primary outcome measure was subjects' personal and social functioning as assessed by the Interview for the assessment of disability. The study is based on a controlled design including randomization to treatment groups, blind assessments and stable pharmacological treatment. Subjects were recruited among patients attending three psychiatric facilities located in the Italian region Campania. Thirty patients were randomized to the experimental program "social skills and neurocognitive individualized training" (SSANIT), and 30 to SLA. The two programs were matched for the overall duration as well as frequency and duration of the sessions. The two groups of patients did not differ at baseline on psychopathology, neurocognitive and personal/social functioning. After 6 months of treatment, personal and social functioning was significantly better in patients assigned to SSANIT than in those assigned to usual rehabilitation activities practiced in Mental Health Departments. No advantage was observed for either program on psychopathological and cognitive outcome indices. As for other integrated programs, also for SSANIT further studies are needed to verify generalization and persistence of the observed gains, and to clarify most adequate length and doses of the therapeutic intervention as well as the relative contribution of each program component to its impact on subjects' disability. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 18 | Seishin Shinkeigaku Zasshi 2010 -1 112: 439-52 |
| PMID | 20560363 |
| Title | [Schizophrenia and cortical GABA neurotransmission]. |
| Abstract | Individuals with schizophrenia show disturbances in a number of brain functions that regulate cognitive, affective, motor, and sensory processing. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related molecules. First, mRNA levels for the 67-kilodalton isoform of glutamic acid decarboxylase (GAD67), an enzyme principally responsible for GABA synthesis, and the GABA membrane transporter GAT1, which regulates the reuptake of synaptically released GABA, are decreased in a subset of GABA neurons. Second, affected GABA neurons include those that express the calcium-binding protein parvalbumin (PV), because PV mRNA levels are decreased in the prefrontal cortex of subjects with schizophrenia and GAD67 mRNA is undetectable in almost half of PV-containing neurons. These changes are accompanied by decreased GAT1 expression in the presynaptic terminals of PV-containing neurons and by increased postsynaptic GABA-A receptor alpha2 subunit expression at the axon initial segments of pyramidal neurons. These findings indicate decreased GABA synthesis/release by PV-containing GABA neurons and compensatory changes at synapses formed by these neurons. Third, another subset of GABA neurons that express the neuropeptide somatostatin (SST) also appear to be affected because their specific markers, SST and neuropeptide Y mRNAs, are decreased in a manner highly correlated with the decreases in GAD67 mRNA. Finally, mRNA levels for GABA-A receptor subunits for synaptic (alpha1 and gamma2) and extra-synaptic (delta) receptors are decreased, indicating alterations in both synaptic and extra-synaptic GABA neurotransmission. Together, this pattern of changes indicates that the altered GABA neurotransmission is specific to PV-containing and SST-containing GABA neuron subsets and involves both synaptic and extra-synaptic GABA-A receptors. Our recent analyses demonstrated that this pattern exists across diverse cortical areas including the prefrontal, anterior cingulate, primary motor, and primary visual cortices. GABA neurotransmission by PV-containing and SST-containing neurons is important for the generation of cortical oscillatory activities in the gamma (30-100 Hz) and theta (4-7 Hz) bands, respectively. These oscillatory activities have been proposed to play critical roles in regulating the efficiency of information transfer between neurons and neuronal networks in the cortex. Altered cortical GABA neurotransmission appears to contribute to disturbances in diverse functions through affecting the generation of cortical oscillations in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 19 | Neuropeptides 2010 Oct 44: 421-9 |
| PMID | 20537385 |
| Title | Somatostatin-28 modulates prepulse inhibition of the acoustic startle response, reward processes and spontaneous locomotor activity in rats. |
| Abstract | Somatostatins have been shown to be involved in the pathophysiology of motor and affective disorders, as well as psychiatric disorders, including schizophrenia. We hypothesized that in addition to motor function, somatostatin may be involved in somatosensory gating and reward processes that have been shown to be dysregulated in schizophrenia. Accordingly, we evaluated the effects of intracerebroventricular administration of somatostatin-28 on spontaneous locomotor and exploratory behavior measured in a behavioral pattern monitor, sensorimotor gating, prepulse inhibition (PPI) of the acoustic startle reflex, and brain reward function (measured in a discrete trial intracranial self-stimulation procedure) in rats. Somatostatin-28 decreased spontaneous locomotor activity during the first 10 min of a 60 min testing session with no apparent changes in the exploratory activity of rats. The highest somatostatin-28 dose (10 microg/5 microl/side) induced PPI deficits with no effect on the acoustic startle response or startle response habituation. The somatostatin-induced PPI deficit was partially reversed by administration of SRA-880, a selective somatostatin 1 (SST(1)) receptor antagonist. Somatostatin-28 also induced elevations in brain reward thresholds, reflecting an anhedonic-like state. The non-peptide SST(1) receptor antagonist SRA-880 had no effect on brain reward function under baseline conditions. Altogether these findings suggest that somatostatin-28 modulates PPI and brain reward function but does not have a robust effect on spontaneous exploratory activity. Thus, increases in somatostatin transmission may represent one of the neurochemical mechanisms underlying anhedonia, one of the negative symptoms of schizophrenia, and sensorimotor gating deficits associated with cognitive impairments in schizophrenia patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 20 | Psychiatry Res 2011 Sep 189: 166-72 |
| PMID | 21529970 |
| Title | A virtual reality application in role-plays of social skills training for schizophrenia: a randomized, controlled trial. |
| Abstract | Although social skills training (SST) is an effective approach for improving social skills for schizophrenia, the motivational deficit attenuates its efficacy. Virtual reality (VR) applications have allowed individuals with mental disabilities to enhance their motivation for rehabilitation. We compared SST using VR role-playing (SST-VR) to SST using traditional role-playing (SST-TR). This randomized, controlled trial included 91 inpatients with schizophrenia who were assigned to either SST-VR (n=46) or SST-TR (n=45). Both groups were administered over 10 semiweekly group sessions. An experienced, blinded rater assessed vocal, nonverbal and conversational skills. We also obtained data on motivation for SST and various social abilities. Throughout the 10 sessions, the SST-VR group (n=33) showed greater interest in SST and generalization of the skills than the SST-TR group (n=31). After SST, the SST-VR group improved more in conversational skills and assertiveness than the SST-TR group, but less in nonverbal skills. The VR application in role-plays of SST for schizophrenia may be particularly beneficial in terms of improving the conversational skills and assertiveness, possibly through its advantages in enhancing motivation for SST and generalization of the skills, and thus it may be a useful supplement to traditional SST. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 21 | Neurosci. Lett. 2011 Sep 502: 173-7 |
| PMID | 21827833 |
| Title | Semantic fluency and executive functions as candidate endophenotypes for the early diagnosis of schizophrenia in Han Chinese. |
| Abstract | Neurocognitive de?cits are recognized as core features of schizophrenia. The aim of this study was to compare the cognitive performance of antipsychotic, drug-naive patients with first-episode schizophrenia (FES patients) to their healthy siblings and to healthy controls from the Han Chinese population for exploring potential endophenotypes for the early detection of schizophrenia. A battery of cognitive assessment tools was used to measure seven cognitive domains in matched groups consisting of 56 subjects each. Cognitive tests included the grooved pegboard test (GPT), the category fluency test (CFT), the trail making test A (TMT-A), the Wechsler memory scale-III spatial span test (WMS-III SST), the Hopkins verbal learning test-revised (HVLT-R), the brief visuospatial memory test-revised (BVMT-R), the paced auditory serial addition test (PASAT), and the Wisconsin card sorting test-64 cards version (WCST-64). The performances of FEP patients were inferior to normal controls on all neuropsychological tests, while siblings were lower than healthy controls in many of the same tasks. Patients' performances were lower than siblings' on all tests except for the CFT, the WMS-III SST backward test, and four subtests of the WCST-64. Our data suggest that FEP patients exhibited pronounced impairment of fine motor skills, speed of processing, attention, verbal memory, visual memory, and executive function, while siblings exhibited deficits intermediate between those of schizophrenic patients and the control group. Semantic fluency function and executive function may be potential endophenotypes for the early diagnosis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 22 | Neurosci. Lett. 2011 Sep 502: 173-7 |
| PMID | 21827833 |
| Title | Semantic fluency and executive functions as candidate endophenotypes for the early diagnosis of schizophrenia in Han Chinese. |
| Abstract | Neurocognitive de?cits are recognized as core features of schizophrenia. The aim of this study was to compare the cognitive performance of antipsychotic, drug-naive patients with first-episode schizophrenia (FES patients) to their healthy siblings and to healthy controls from the Han Chinese population for exploring potential endophenotypes for the early detection of schizophrenia. A battery of cognitive assessment tools was used to measure seven cognitive domains in matched groups consisting of 56 subjects each. Cognitive tests included the grooved pegboard test (GPT), the category fluency test (CFT), the trail making test A (TMT-A), the Wechsler memory scale-III spatial span test (WMS-III SST), the Hopkins verbal learning test-revised (HVLT-R), the brief visuospatial memory test-revised (BVMT-R), the paced auditory serial addition test (PASAT), and the Wisconsin card sorting test-64 cards version (WCST-64). The performances of FEP patients were inferior to normal controls on all neuropsychological tests, while siblings were lower than healthy controls in many of the same tasks. Patients' performances were lower than siblings' on all tests except for the CFT, the WMS-III SST backward test, and four subtests of the WCST-64. Our data suggest that FEP patients exhibited pronounced impairment of fine motor skills, speed of processing, attention, verbal memory, visual memory, and executive function, while siblings exhibited deficits intermediate between those of schizophrenic patients and the control group. Semantic fluency function and executive function may be potential endophenotypes for the early diagnosis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 23 | Schizophr. Res. 2011 Sep 131: 11-7 |
| PMID | 21757324 |
| Title | Theory of Mind in patients at clinical high risk for psychosis. |
| Abstract | Patients with schizophrenia have a decreased ability to interpret the intentions of other individuals, called Theory of Mind (ToM). As capacity for ToM normally advances with brain maturation, research on ToM in individuals at heightened clinical risk for psychosis may reveal developmental differences independent of disease based differences. We examined ToM in at clinical high risk and schizophrenia patients as well as healthy controls: 1) 63 clinical high risk (CHR) patients and 24 normal youths ascertained by a CHR program; and 2) in 13 schizophrenia cases and 14 normal adults recruited through a schizophrenia program. ToM measures included first- and second-order false belief cartoon tasks (FBT) and two "higher order" tasks ("Strange Stories Task" (SST) and the "Reading the Mind in the Eyes" task). In the first study, CHR patients and normal youths were also assessed for cognition, "prodromal" symptoms and social function. Errors on first- and second-order false belief tasks were made primarily by patients. CHR patients and their young comparison group had equivalent performance on higher order ToM, which was not significantly different from the worse ToM performance of schizophrenia patients and the higher performance of normal adult controls. In the combined dataset from both studies, all levels of ToM were associated with IQ, controlling for age and sex. ToM bore no relation to explicit memory, prodromal symptoms, social function, or later transition to psychosis. Higher order ToM capacity was equally undeveloped in high risk cases and younger controls, suggesting that performance on these tasks is not fully achieved until adulthood. This study also replicates the association of IQ with ToM performance described in previous studies of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 24 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2011 Jun 35: 1148-54 |
| PMID | 21466833 |
| Title | Impairments in executive functioning in patients with remitted and non-remitted schizophrenia. |
| Abstract | Although deficits in executive functioning are prominent in schizophrenia, some patients in remission have shown significantly higher levels of neurocognitive functioning than patients not in remission. However, no consensus on the relationship between neurocognitive functioning and the severity of symptoms has been reached. Additionally, previous studies have mainly examined the primary symptom domains of schizophrenia without considering the influence of anxiety symptoms, which are likely to influence neuropsychological performance. The aim of the present study was to compare the executive functioning of normal controls and with that of patients with schizophrenia in acute and remitted states. We further examined associations between impaired executive functioning in patients and anxiety levels. Using a battery of tests assessing executive functioning including subtests of the Cambridge Neuropsychological Automated Test Battery (CANTAB) and the short form of the Korean Wechsler Adult Intelligence Scale (K-WAIS), we assessed 54 patients with schizophrenia and 33 normal controls. Our results showed that patients with non-remitted schizophrenia obtained significantly lower estimated IQ scores than did normal controls. They also exhibited longer reaction times on the Choice Reaction Time (CRT) test and the Stop Signal Test (SST) subtests of CANTAB and a greater number of total errors and errors that occurred before the extradimensional stage (i.e., pre-ED errors) on the Intradimensional/Extradimensional Shift (IED) subtest of CANTAB. Furthermore, those with schizophrenia in acute states showed significantly slower stop signal reaction times (SSRT) on the SST than did those with remitted schizophrenia and healthy controls. Finally, differences in the pre-ED errors and total adjusted errors on the IED became insignificant when scores on the Beck Anxiety Inventory (BAI) were entered as the covariate, whereas other significant differences remained when these scores were entered. Differences in executive functioning exist between patients with schizophrenia and healthy controls; these differences can be largely attributed to the relatively poor performance of patients in an active state. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 25 | Biol. Psychiatry 2011 Jan 69: 63-70 |
| PMID | 20974464 |
| Title | Increased interstitial white matter neuron density in the dorsolateral prefrontal cortex of people with schizophrenia. |
| Abstract | Interstitial white matter neurons (IWMNs) may reflect immature neurons that migrate tangentially to the neocortex from the ganglionic eminence to form cortical interneurons. Alterations of interneuron markers have been detected in gray matter of dorsolateral prefrontal cortex in schizophrenia, and IWMNs are also reported to be altered in schizophrenia. In this study, we considered whether a potential link exists between these two pathological findings. From a cohort of 29 schizophrenia subjects and 37 control subjects, IWMN densities were determined in the dorsolateral prefrontal cortex by counting neuronal nuclear antigen (NeuN) and somatostatin (SST)-positive cells. Double-label immunofluorescence was carried out to determine the overlap between SST+/NeuN+ and SST+/neuropeptide Y + neurons. We found that density of NeuN + IWMNs in superficial white matter is significantly increased in schizophrenia subjects compared with control subjects. There was a significant negative correlation between SST mRNA expression in gray matter and NeuN + IWMN density. In schizophrenic patients with increased NeuN IWMN density, the density of SST-expressing neurons in white matter was also higher compared with control subjects. A subpopulation of SST immunopositive cells also show coexpression of neuropeptide Y. Our study confirmed previous results indicating that the density of NeuN + IWMNs is increased in superficial white matter in schizophrenia. We provide the first evidence that increased IWMN density correlates with a gray matter interneuron deficit, suggesting that migration of interneurons from white matter to the cortex may be deficient in some patients with schizophrenia, consistent with an interneuron deficit in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 26 | Biol. Psychiatry 2011 Jan 69: 63-70 |
| PMID | 20974464 |
| Title | Increased interstitial white matter neuron density in the dorsolateral prefrontal cortex of people with schizophrenia. |
| Abstract | Interstitial white matter neurons (IWMNs) may reflect immature neurons that migrate tangentially to the neocortex from the ganglionic eminence to form cortical interneurons. Alterations of interneuron markers have been detected in gray matter of dorsolateral prefrontal cortex in schizophrenia, and IWMNs are also reported to be altered in schizophrenia. In this study, we considered whether a potential link exists between these two pathological findings. From a cohort of 29 schizophrenia subjects and 37 control subjects, IWMN densities were determined in the dorsolateral prefrontal cortex by counting neuronal nuclear antigen (NeuN) and somatostatin (SST)-positive cells. Double-label immunofluorescence was carried out to determine the overlap between SST+/NeuN+ and SST+/neuropeptide Y + neurons. We found that density of NeuN + IWMNs in superficial white matter is significantly increased in schizophrenia subjects compared with control subjects. There was a significant negative correlation between SST mRNA expression in gray matter and NeuN + IWMN density. In schizophrenic patients with increased NeuN IWMN density, the density of SST-expressing neurons in white matter was also higher compared with control subjects. A subpopulation of SST immunopositive cells also show coexpression of neuropeptide Y. Our study confirmed previous results indicating that the density of NeuN + IWMNs is increased in superficial white matter in schizophrenia. We provide the first evidence that increased IWMN density correlates with a gray matter interneuron deficit, suggesting that migration of interneurons from white matter to the cortex may be deficient in some patients with schizophrenia, consistent with an interneuron deficit in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 27 | J Psychiatr Res 2012 Nov 46: 1464-74 |
| PMID | 22954356 |
| Title | A combined analysis of microarray gene expression studies of the human prefrontal cortex identifies genes implicated in schizophrenia. |
| Abstract | Small cohort sizes and modest levels of gene expression changes in brain tissue have plagued the statistical approaches employed in microarray studies investigating the mechanism of schizophrenia. To combat these problems a combined analysis of six prior microarray studies was performed to facilitate the robust statistical analysis of gene expression data from the dorsolateral prefrontal cortex of 107 patients with schizophrenia and 118 healthy subjects. Multivariate permutation tests identified 144 genes that were differentially expressed between schizophrenia and control groups. Seventy of these genes were identified as differentially expressed in at least one component microarray study but none of these individual studies had the power to identify the remaining 74 genes, demonstrating the utility of a combined approach. Gene ontology terms and biological pathways that were significantly enriched for differentially expressed genes were related to neuronal cell-cell signaling, mesenchymal induction, and mitogen-activated protein kinase signaling, which have all previously been associated with the etiopathogenesis of schizophrenia. The differential expression of BAG3, C4B, EGR1, MT1X, NEUROD6, SST and S100A8 was confirmed by real-time quantitative PCR in an independent cohort using postmortem human prefrontal cortex samples. Comparison of gene expression between schizophrenic subjects with and without detectable levels of antipsychotics in their blood suggests that the modulation of MT1X and S100A8 may be the result of drug exposure. In conclusion, this combined analysis has resulted in a statistically robust identification of genes whose dysregulation may contribute to the mechanism of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 28 | J Psychiatr Res 2012 Nov 46: 1464-74 |
| PMID | 22954356 |
| Title | A combined analysis of microarray gene expression studies of the human prefrontal cortex identifies genes implicated in schizophrenia. |
| Abstract | Small cohort sizes and modest levels of gene expression changes in brain tissue have plagued the statistical approaches employed in microarray studies investigating the mechanism of schizophrenia. To combat these problems a combined analysis of six prior microarray studies was performed to facilitate the robust statistical analysis of gene expression data from the dorsolateral prefrontal cortex of 107 patients with schizophrenia and 118 healthy subjects. Multivariate permutation tests identified 144 genes that were differentially expressed between schizophrenia and control groups. Seventy of these genes were identified as differentially expressed in at least one component microarray study but none of these individual studies had the power to identify the remaining 74 genes, demonstrating the utility of a combined approach. Gene ontology terms and biological pathways that were significantly enriched for differentially expressed genes were related to neuronal cell-cell signaling, mesenchymal induction, and mitogen-activated protein kinase signaling, which have all previously been associated with the etiopathogenesis of schizophrenia. The differential expression of BAG3, C4B, EGR1, MT1X, NEUROD6, SST and S100A8 was confirmed by real-time quantitative PCR in an independent cohort using postmortem human prefrontal cortex samples. Comparison of gene expression between schizophrenic subjects with and without detectable levels of antipsychotics in their blood suggests that the modulation of MT1X and S100A8 may be the result of drug exposure. In conclusion, this combined analysis has resulted in a statistically robust identification of genes whose dysregulation may contribute to the mechanism of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 29 | J Autism Dev Disord 2012 Nov 42: 2285-96 |
| PMID | 22361923 |
| Title | Comparison of children with autism spectrum disorder with and without schizophrenia spectrum traits: gender, season of birth, and mental health risk factors. |
| Abstract | Children with autism spectrum disorder (ASD) with and without co-occurring schizophrenia spectrum traits (SST) were examined for differences in co-occurring psychiatric symptoms, background characteristics, and mental health risk factors. Participating mothers and teachers completed a DSM-IV-referenced rating scale and a background questionnaire (mothers only) describing 147 children (6-12 years) with ASD. There was a clear pattern of group differences in co-occurring psychiatric symptom severity (+SST > SST-) and background characteristics. Children with impairing SST had more mental health risk factors. Girls were more likely to be classified SST according to mothers' ratings. Children born in spring-summer were more likely to be classified non-SST by teachers' ratings. Findings provide tentative evidence that SST may be a useful marker of behavioral heterogeneity within the ASD clinical phenotype. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 30 | PLoS ONE 2012 -1 7: e43904 |
| PMID | 22937123 |
| Title | Selective expression of KCNS3 potassium channel ?-subunit in parvalbumin-containing GABA neurons in the human prefrontal cortex. |
| Abstract | The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurotransmission in the subsets of inhibitory neurons that express either parvalbumin (PV) or somatostatin (SST). Identification of molecular mechanisms that operate selectively in these neurons is essential for developing targeted therapeutic strategies that do not influence other cell types. Consequently, we sought to identify, in the human cortex, gene products that are expressed selectively by PV and/or SST neurons, and that might contribute to their distinctive functional properties. Based on previously reported expression patterns in the cortex of mice and humans, we selected four genes: KCNS3, LHX6, KCNAB1, and PPP1R2, encoding K(+) channel Kv9.3 modulatory ?-subunit, LIM homeobox protein 6, K(+) channel Kv?1 subunit, and protein phosphatase 1 regulatory subunit 2, respectively, and examined their colocalization with PV or SST mRNAs in the human prefrontal cortex using dual-label in situ hybridization with (35)S- and digoxigenin-labeled antisense riboprobes. KCNS3 mRNA was detected in almost all PV neurons, but not in SST neurons, and PV mRNA was detected in >90% of KCNS3 mRNA-expressing neurons. LHX6 mRNA was detected in almost all PV and >90% of SST neurons, while among all LHX6 mRNA-expressing neurons 50% expressed PV mRNA and >44% expressed SST mRNA. KCNAB1 and PPP1R2 mRNAs were detected in much larger populations of cortical neurons than PV or SST neurons. These findings indicate that KCNS3 is a selective marker of PV neurons, whereas LHX6 is expressed by both PV and SST neurons. KCNS3 and LHX6 might be useful for characterizing cell-type specific molecular alterations of cortical GABA neurotransmission and for the development of novel treatments targeting PV and/or SST neurons in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 31 | J Psychiatr Res 2012 Jul 46: 913-9 |
| PMID | 22551660 |
| Title | Exploration of the associations between neurocognitive function and neuroleptics side effects. |
| Abstract | The etiology of side effects of antipsychotic medications can be conceptualized as involving both specific pharmacological actions of a drug and any mental and physical states attributed by the patient. Both factors are likely to be linked with neurocognitive functioning which may largely affect the subjective experience of side effects in patients with schizophrenia. In this study, we examined whether baseline neurocognitive functions, such as IQ, attention, executive functioning, and short-term memory, are associated with baseline and 6-month follow-up measures of self-reported Liverpool University Neuroleptics Side Effects Scale (LUNSERS) and clinician-rated Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). At the baseline, anxiety and depression were significantly associated with LUNSERS red herring (RH) and total side effects (SE) but not with DIEPSS. There was no association between LUNSERS and DIEPSS. Controlling for anxiety and depression, IQ was significantly correlated with DIEPSS, while choice reaction time (CRT) and stop signal task (SST) direction errors correlated with RH, and intra-extradimensional set-shifting (IED) total errors and pre-extradimensional set-shifting (pre-EDs) errors correlated with SE. The baseline SST direction errors further correlated significantly with RH and SE and DIEPSS total score of 6-month follow-up, and CRT mean and SD correct latency also correlated with DIEPSS. The correlations between the 6-month changes (?) in the same side effects measures and baseline neurocognitive measures were also significant, except that between RH and SST direction errors. Such evidences supported association between both self-rated and clinician-rated side effects and selective impairments in attention and executive functioning. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 32 | Exp Brain Res 2012 Jun 219: 363-8 |
| PMID | 22532165 |
| Title | Modulating behavioral inhibition by tDCS combined with cognitive training. |
| Abstract | Cognitive training is an effective tool to improve a variety of cognitive functions, and a small number of studies have now shown that brain stimulation accompanying these training protocols can enhance their effects. In the domain of behavioral inhibition, little is known about how training can affect this skill. As for transcranial direct current stimulation (tDCS), it was previously found that stimulation over the right inferior frontal gyrus (rIFG) facilitates behavioral inhibition performance and modulates its electrophysiological correlates. This study aimed to investigate this behavioral facilitation in the context of a learning paradigm by giving tDCS over rIFG repetitively over four consecutive days of training on a behavioral inhibition task (stop signal task (SST)). Twenty-two participants took part; ten participants were assigned to receive anodal tDCS (1.5 mA, 15 min), 12 were assigned to receive training but not active stimulation. There was a significant effect of training on learning and performance in the SST, and the integration of the training and rIFG-tDCS produced a more linear learning slope. Better performance was also found in the active stimulation group. Our findings show that tDCS-combined cognitive training is an effective tool for improving the ability to inhibit responses. The current study could constitute a step toward the use of tDCS and cognitive training as a therapeutic tool for cognitive control impairments in conditions such as attention-deficit hyperactivity disorder (ADHD) or schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 33 | Neuropharmacology 2012 Mar 62: 1598-605 |
| PMID | 21215273 |
| Title | Lamina- and cell-specific alterations in cortical somatostatin receptor 2 mRNA expression in schizophrenia. |
| Abstract | Disturbed cortical ?-aminobutyric acid (GABA) neurotransmission in schizophrenia is evident from lamina- and cell type- specific alterations in presynaptic markers. In the dorsolateral prefrontal cortex (DLPFC), these alterations include lower transcript expression of glutamic acid decarboxylase (GAD67) and somatostatin (SST), a neuropeptide expressed in the Martinotti subpopulation of GABA neurons whose axons innervate the distal apical dendrites of pyramidal neurons. However, whether the alterations in SST-containing interneurons are associated with changes in post-synaptic receptors for SST has not been examined. Thus, we used in situ hybridization to quantify the mRNA expression levels of SST receptors subtype 1 (SSTR1) and subtype 2 (SSTR2) in DLPFC area 9 from 23 matched pairs of subjects with schizophrenia and normal comparison subjects. We also assessed the effects of potential confounding variables within the human subjects and in brain specimens from macaque monkeys with long term exposure to antipsychotic drugs. SSTR1 mRNA levels did not differ between subject groups. In contrast, mean cortical SSTR2 mRNA levels were significantly 19% lower in the subjects with schizophrenia. Laminar and cellular level analyses revealed that lower SSTR2 mRNA levels were localized to pyramidal cells in cortical layers 5-6. Expression of SSTR2 mRNA did not differ between monkeys exposed chronically to high doses of haloperidol or olanzapine and control animals, or between subjects with schizophrenia on or off antipsychotic medications at the time of death. However, levels of SSTR2 mRNA were significantly 37.6% lower in monkeys exposed chronically to low dose haloperidol, suggesting that the lower levels of SSTR2 mRNA selectively in pyramidal neurons in DLPFC layers 5-6 in schizophrenia should be interpreted with caution. In concert with prior findings of lower SST mRNA expression in the same subjects, the results of this study suggest the convergence of pre- and post-synaptic mechanisms to reduce inhibitory inputs to pyramidal neurons in the infragranular layers of the DLPFC. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 34 | Seishin Shinkeigaku Zasshi 2013 -1 115: 413-20 |
| PMID | 23789324 |
| Title | [How cognitive dysfunction affects the offender's social life in a case involving the Medical Treatment and Supervision Act]. |
| Abstract | The objective of psychiatric treatment is to enable patients to regain social competence and participate in society according to their desires. Cognitive dysfunction has recently garnered increased attention due to the prevailing view that it is closely related to the social functioning and strongly affects the functional prognosis in patients with schizophrenia. However, measures for improving the social function of patients with psychiatric disorders do not appear to be widely implemented in routine psychiatric treatment. During the present symposium,"SST for enhancing social life: Focus on cognitive dysfunction", we reported a case involving the Medical Treatment and Supervision Act with a description of how cognitive dysfunction affected the offender's social life and led to offenses, and stated that cognitive dysfunction greatly affects social functioning and that measures to improve cognitive dysfunction are thus necessary in routine treatment. We also reported that the compliance of patients is crucial when implementing these measures, and that it is therefore important to make efforts to "motivate" patients and continue to nurture their "eagerness". |
| SCZ Keywords | schizophrenia, schizophrenic |
| 35 | Seishin Shinkeigaku Zasshi 2013 -1 115: 399-405 |
| PMID | 23789322 |
| Title | [Social life improvement by social skills training (SST)--intervention with a view to neurocognitive function impairment]. |
| Abstract | Neurocognitive function impairment attracts much attention as an important factor affecting the level of social functioning in patients with severe mental disorders such as schizophrenia. It forms the basis of learning disability and thus poses a major threat to psychosocial intervention. In this report, we classify 13 intervention methods corresponding to specific cognitive disorders. We also indicate the importance of individual assessment prior to psychosocial interventions, commenting on the reality of the "social functioning interview," a semistructured pre-intervention interview in social skills training (SST). Referring to the fact that most of the 13 intervention methods are implemented in SST, a psychosocial intervention, some of these methods are introduced in the context of the "basic training model." Furthermore, four possible inventions that can be incorporated into SST are described. Given that many of the interventions described in this report are also applicable to clinical settings (e.g., personal interviews), we hope that applications will not be limited to SST, but extended to routine clinical practice for improvements in patients with cognitive disorders, eventually leading to improvements in their social lives. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 36 | Clin Psychol Rev 2013 Dec 33: 914-28 |
| PMID | 23988452 |
| Title | Psychosocial treatments for negative symptoms in schizophrenia: current practices and future directions. |
| Abstract | schizophrenia can be a chronic and debilitating psychiatric disorder. Though advancements have been made in the psychosocial treatment of some symptoms of schizophrenia, people with schizophrenia often continue to experience some level of symptoms, particularly negative symptoms, throughout their lives. Because negative symptoms are associated with poor functioning and quality of life, the treatment of negative symptoms is a high priority for intervention development. However, current psychosocial treatments primarily focus on the reduction of positive symptoms with comparatively few studies investigating the efficacy of psychosocial treatments for negative symptoms. In this article, we review and evaluate the existing literature on three categories of psychosocial treatments--cognitive behavioral therapy (CBT), social skills training (SST), and combined treatment interventions--and their impact on the negative symptoms of schizophrenia. Of the interventions reviewed, CBT and SST appear to have the most empirical support, with some evidence suggesting that CBT is associated with maintenance of negative symptom improvement beyond six months after treatment. It remains unclear if a combined treatment approach provides improvements above and beyond those associated with each individual treatment modality. Although psychosocial treatments show promise for the treatment of negative symptoms, there are many unanswered questions about how best to intervene. We conclude with a general discussion of these unanswered questions, future directions and methodological considerations, and suggestions for the further development of negative symptom interventions. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 37 | Eur. J. Neurosci. 2013 Sep 38: 2941-5 |
| PMID | 23551272 |
| Title | From gene to brain to behavior: schizophrenia-associated variation in AMBRA1 alters impulsivity-related traits. |
| Abstract | Recently, genome-wide association between schizophrenia and an intronic variant in AMBRA1 (rs11819869) was reported. Additionally, in a reverse genetic approach in adult healthy subjects, risk allele carriers showed a higher medial prefrontal cortex blood oxygen level-dependent (BOLD) response during a flanker task examining motor inhibition as an aspect of impulsivity. To test whether this finding can be expanded to further aspects of impulsivity, we analysed the effects of the rs11819869 genotype on impulsivity-related traits on a behavioral, temperament and neural level in a large sample of healthy adolescents. We consider this reverse genetic approach specifically suited for use in a healthy adolescent sample, as these individuals comprise those who will eventually develop mental disorders in which impulsivity is implicated. Healthy adolescents from the IMAGEN study were included in the neuropsychological analysis (n = 848) and a functional magnetic resonance imaging (fMRI) task (n = 512). Various aspects of impulsivity were assessed using the Temperament and Character Inventory-Revised, the Substance Use Risk Profile Scale, the Cambridge Cognition Neuropsychological Test Automated Battery, and the Stop Signal Task (SST) in the fMRI paradigm. On a behavioral level, increased delay aversion was observed in risk allele carriers. Furthermore, risk allele carriers showed a higher BOLD response in an orbito-frontal target region during the SST, which declined to trend status after Family Wise Error correction. Our findings support the hypothesis that the schizophrenia-related risk variant of rs11819869 is involved in various aspects of impulsivity, and that this involvement occurs on a behavioral as well as an imaging genetics level. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 38 | Schizophr. Res. 2013 Feb 143: 327-36 |
| PMID | 23235141 |
| Title | A brief cognitive-behavioural social skills training for stabilised outpatients with schizophrenia: a preliminary study. |
| Abstract | Achieving social functioning and achieving social competence are two main objectives of psychosocial interventions for people suffering from schizophrenia. The present preliminary study presents a novel approach of social skills training (SST) based on the proposals of Kopelowicz et al. (Kopelowicz, A., Liberman, R. P., and Zarate, R., 2006. Schizophr. Bull. 32 (1): S12-23) that link the treatment to seven specific target behaviours: social perception, social information processing, responding and sending skills, affiliative skills, interactional skills, and behaviour governed by social norms. Thirty-one stabilised outpatients were randomly assigned to one of two groups, SST (n=13) or treatment-as-usual (n=18) (TAU; case management, medication adherence, psychotherapy, leisure engagement, and family support) and were assessed at baseline in cognitive performance, clinical symptomatology, social cognition, and psychosocial functioning. These outcomes were evaluated across post-treatment and at the 6-month follow-up appointment. SST subjects showed improvements in psychopathology, social discomfort, social cognition (self-regulation statements during interactions), social withdrawal, interpersonal communication, and quality of life compared with the TAU group. At the 6-month follow-up, results were maintained for negative symptoms, social discomfort, and some functioning outcomes. Neuropsychological variables were also examined, as mediators of benefit from skills training. Results support the efficacy of the brief SST for outpatients with schizophrenia and show the need to implement empirically supported interventions in mental health services to enhance patients' social functioning and quality of life. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 39 | J Behav Ther Exp Psychiatry 2014 Mar 45: 81-9 |
| PMID | 24063993 |
| Title | A virtual reality-integrated program for improving social skills in patients with schizophrenia: a pilot study. |
| Abstract | Social skills training (SST) intervention has shown its efficacy to improve social dysfunction in patients with psychosis; however the implementation of new skills into patients' everyday functioning is difficult to achieve. In this study, we report results from the application of a virtual reality (VR) integrated program as an adjunct technique to a brief social skills intervention for patients with schizophrenia. It was predicted that the intervention would improve social cognition and performance of patients as well as generalisation of the learned responses into patient's daily life. Twelve patients with schizophrenia or schizoaffective disorder completed the study. They attended sixteen individual one-hour sessions, and outcome assessments were conducted at pre-treatment, post-treatment and four-month follow-up. The results of a series of repeated measures ANOVA revealed significant improvement in negative symptoms, psychopathology, social anxiety and discomfort, avoidance and social functioning. Objective scores obtained through the use of the VR program showed a pattern of learning in emotion perception, assertive behaviours and time spent in a conversation. Most of these gains were maintained at four-month follow-up. The reported results are based on a small, uncontrolled pilot study. Although there was an independent rater for the self-reported and informant questionnaires, assessments were not blinded. The results showed that the intervention may be effective for improving social dysfunction. The use of the VR program contributed to the generalisation of new skills into the patient's everyday functioning. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 40 | Psychol Med 2015 -1 45: 2557-69 |
| PMID | 25817407 |
| Title | Expression quantitative trait loci (eQTLs) in microRNA genes are enriched for schizophrenia and bipolar disorder association signals. |
| Abstract | schizophrenia (SZ) and bipolar disorder (BD) have substantial negative impact on the quality of human life. Both, microRNA (miRNA) expression profiling in SZ and BD postmortem brains [and genome-wide association studies (GWAS)] have implicated miRNAs in disease etiology. Here, we aim to determine whether significant GWAS signals observed in the Psychiatric Genetic Consortium (PGC) are enriched for miRNAs. A two-stage approach was used to determine whether association signals from PGC affect miRNAs: (i) statistical assessment of enrichment using a Simes test and sum of squares test (SST) and (ii) biological evidence that quantitative trait loci (eQTL) mapping to known miRNA genes affect their expression in an independent sample of 78 postmortem brains from the Stanley Medical Research Institute. A total of 2567 independent single nucleotide polymorphisms (SNPs) (R2 > 0.8) were mapped locally, within 1 Mb, to all known miRNAs (miRBase v. 21). We show robust enrichment for SZ- and BD-related SNPs with miRNAs using Simes (SZ: p ? 0.0023, BD: p ? 0.038), which remained significant after adjusting for background inflation in SZ (empirical p = 0.018) and approached significance in BD (empirical p = 0.07). At a false discovery rate of 10%, we identified a total of 32 eQTLs to influence miRNA expression; 11 of these overlapped with BD. Our approach of integrating PGC findings with eQTL results can be used to generate specific hypotheses regarding the role of miRNAs in SZ and BD. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 41 | Schizophr. Res. 2015 Mar 162: 35-41 |
| PMID | 25640526 |
| Title | Social skills training and computer-assisted cognitive remediation in schizophrenia. |
| Abstract | A growing body of research shows that cognitive remediation (COG REM), consisting of drill-and-practice and/or strategy training in neurocognitive functions, produces moderate improvements in neurocognition. These improvements generalize to functioning when COG REM is provided with other rehabilitation interventions (Wykes et al., 2011). The number of studies using COG REM as an adjunct to other behavioral-based rehabilitation interventions however remains small and consists of widely varying interventions with few active control conditions. This study compared the effects of an extended (6-month), standardized, computer-assisted cognitive remediation intervention, administered along with a standardized program of social skills-training (SST), with those of an active control condition that included participation in the same SST program and a computer skills training program (Computer Skills). Sixty-four individuals with schizophrenia recruited from two treatment sites were randomly assigned to one of two conditions and were assessed by blinded raters on neurocognitive measures, performance-based measures of social skill, and ratings of psychosocial function before and after treatment. Results revealed that the COG REM group improved significantly more in attention, working memory, and empathy than the Computer Skills group, but there were no differences between groups on other measures of psychosocial functioning or skills. Taken together, these findings suggest that COG REM used in the context of other evidence-based psychosocial interventions (SST) improves working memory in schizophrenia and suggests that this effect may generalize to improved empathy. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 42 | Biol. Psychiatry 2016 Apr -1: -1 |
| PMID | 27259817 |
| Title | Decreased Numbers of Somatostatin-Expressing Neurons in the Amygdala of Subjects With Bipolar Disorder or Schizophrenia: Relationship to Circadian Rhythms. |
| Abstract | Growing evidence points to a key role for somatostatin (SST) in schizophrenia (SZ) and bipolar disorder (BD). In the amygdala, neurons expressing SST play an important role in the regulation of anxiety, which is often comorbid in these disorders. We tested the hypothesis that SST-immunoreactive (IR) neurons are decreased in the amygdala of subjects with SZ and BD. Evidence for circadian SST expression in the amygdala and disrupted circadian rhythms and rhythmic peaks of anxiety in BD suggest a disruption of rhythmic expression of SST in this disorder. Amygdala sections from 12 SZ, 15 BD, and 15 control subjects were processed for immunocytochemistry for SST and neuropeptide Y, a neuropeptide partially coexpressed in SST-IR neurons. Total numbers (Nt) of IR neurons were measured. Time of death was used to test associations with circadian rhythms. SST-IR neurons were decreased in the lateral amygdala nucleus in BD (Nt, p = .003) and SZ (Nt, p = .02). In normal control subjects, Nt of SST-IR neurons varied according to time of death. This pattern was altered in BD subjects, characterized by decreases of SST-IR neurons selectively in subjects with time of death corresponding to the day (6:00 am to 5:59 pm). Numbers of neuropeptide Y-IR neurons were not affected. Decreased SST-IR neurons in the amygdala of patients with SZ and BD, interpreted here as decreased SST expression, may disrupt responses to fear and anxiety regulation in these individuals. In BD, our findings raise the possibility that morning peaks of anxiety depend on a disruption of circadian regulation of SST expression in the amygdala. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 43 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2016 Feb 65: 118-26 |
| PMID | 26385575 |
| Title | Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia. |
| Abstract | Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |