Anhedonia as a phenotype for the Val1??Met COMT polymorphism in relatives of patients with schizophrenia.

The Val1??Met polymorphism of the catechol-O-methyltransferase (COMT) gene has been associated with aspects of schizophrenia that are possibly related to the disorder's pathogenesis. The present study investigated the Val1??Met polymorphism in relation to anhedonia--a construct central to negative schizotypy. Anhedonia and other schizotypal characteristics were assessed in relatives of patients with schizophrenia, relatives of patients with bipolar disorder, and nonpsychiatric controls using the Chapman schizotypy scales and the Schizotypal Personality Questionnaire. Compared with controls, relatives of individuals with schizophrenia had elevated scores on Chapman scales for social anhedonia and physical anhedonia, while relatives of patients with bipolar disorder exhibited only increased scores on the Social Anhedonia Scale. As a group, relatives of patients with schizophrenia who were homozygous for the val allele of the COMT polymorphism showed the highest elevations in self-reported social and physical anhedonia. Associations with the COMT polymorphism were absent in relatives of patients with bipolar disorder and control participants. Findings suggest that anhedonia is manifest in individuals who carry genetic liability for schizophrenia and is associated with the Val1??Met polymorphism of the COMT gene. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive, clinical, and functional characteristics of verbally superior schizophrenia patients.

The existence of small numbers of schizophrenia patients with superior ability in specific cognitive domains is implied by meta-analytic evidence as well as by occasional empirical reports. The authors identified 25 patients with superior (i.e., ≥90th percentile) ability on the Vocabulary subtest of the Wechsler Adult Intelligence Scale 3rd edition (Wechsler, 1997). These cognitively advantaged patients were compared with 22 healthy participants performing at the superior level and with 126 schizophrenia patients and 50 healthy participants scoring below the superior range. Verbally superior schizophrenia patients and verbally superior healthy participants had similar cognitive profiles and life skills performance, but diverged markedly in terms of independent "real-world" functioning. Verbally superior patients significantly outperformed more typical patients in other aspects of cognitive performance, life skills, and support requirements. However, severity of positive and negative symptoms was equivalent in the patient groups. Detailed biobehavioral study of cognitively exceptional patients may offer new insights into mechanisms mediating psychotic disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cofilin Signaling in the CNS Physiology and Neurodegeneration

All eukaryotic cells are composed of the cytoskeleton, which plays crucial roles in coordinating diverse cellular functions such as cell division, morphology, migration, macromolecular stabilization, and protein trafficking. The cytoskeleton consists of microtubules, intermediate filaments, and actin filaments. Cofilin, an actin-depolymerizing protein, is indispensable for regulating actin dynamics in the central nervous system (CNS) development and function. Cofilin activities are spatiotemporally orchestrated by numerous extra- and intra-cellular factors. Phosphorylation at Ser-3 by kinases attenuate cofilin’s actin-binding activity. In contrast, dephosphorylation at Ser-3 enhances cofilin-induced actin depolymerization. Cofilin functions are also modulated by various binding partners or reactive oxygen species. Although the mechanism of cofilin-mediated actin dynamics has been known for decades, recent research works are unveiling the profound impacts of cofilin dysregulation in neurodegenerative pathophysiology. For instance, oxidative stress-induced increase in cofilin dephosphorylation is linked to the accumulation of tau tangles and amyloid-beta plaques in Alzheimer’s disease. In Parkinson’s disease, cofilin activation by silencing its upstream kinases increases α-synuclein-fibril entry into the cell. This review describes the molecular mechanism of cofilin-mediated actin dynamics and provides an overview of cofilin’s importance in CNS physiology and pathophysiology.     

Psychotherapy and recovery from schizophrenia: A review of potential applications and need for future study.

Recovery from schizophrenia has been conceptualized to involve not only symptom remission of symptoms and achievement of psychosocial milestones but also subjective changes in how persons appraise their lives and the extent to which they experience themselves as meaningful agents in the world. In this article we review the potential of individual psychotherapy to address these more subjective aspects of recovery. Literature on the effectiveness of psychotherapy for persons with schizophrenia is discussed, and two different paths by which psychotherapy might modify self-experience are described. First, we detail how psychotherapy could be conceptualized and tailored to help persons with schizophrenia to construct richer and fuller narrative accounts of their lives, including their strengths, challenges, losses, and hopes. Second, we explore how psychotherapy could target the capacity for metacognition or thinking about thinking, assisting persons with psychosis to become able to think about themselves and others in a generally more complex and flexible manner. The needs for future research are discussed along with a commentary on how current evidence- and skill-based treatments may contain key elements that could be considered psychotherapeutic. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrophysiological correlates of emotional responding in schizophrenia.

People with schizophrenia consistently report normal levels of pleasant emotion when exposed to evocative stimuli, suggesting intact consummatory pleasure. However, little is known about the neural correlates and time course of emotion in schizophrenia. This study used a well-validated affective picture viewing task that elicits a characteristic pattern of event-related potentials (ERPs) from early to later processing stages (i.e., P1, P2, P3, and late positive potentials [LPPs]). Thirty-eight stabilized outpatients with schizophrenia and 36 healthy controls viewed standardized pleasant, unpleasant, and neutral pictures while ERPs were recorded and subsequently rated their emotional responses to the stimuli. Patients and controls responded to the pictures similarly in terms of their valence ratings, as well as the initial ERP components (P1, P2, and P3). However, at the later LPP component (500–1,000 ms), patients displayed diminished electrophysiological discrimination between pleasant versus neutral stimuli. This pattern suggests that patients demonstrated normal self-reported emotional experience and intact initial sensory processing of and resource allocation to emotional stimuli. However, they showed a disruption in a later component associated with sustained attentional processing of emotional stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adolescents exhibit behavioral differences from adults during instrumental learning and extinction.

Adolescence is associated with the development of brain regions linked to cognition and emotion. Such changes are thought to contribute to the behavioral and neuropsychiatric vulnerabilities of this period. We compared adolescent (Postnatal Days 28–42) and adult (Postnatal Day 60+) rats as they performed a simple instrumental task and extinction. Rats were trained to poke into a hole for a food-pellet reinforcer. After six days of training, rats underwent extinction sessions in which the previously rewarded behavior was no longer reinforced. During extinction, we examined the effects of continued presentation of a cue light and food restriction. Adults and adolescents exhibited similar performance during training, although adolescents made more task-irrelevant pokes, consistent with increased exploration. Adults made more premature pokes, which could indicate a more exclusive focus on the task. During extinction, adolescents made more perseverative (previously reinforced) pokes than adults. This behavior was strongly modulated by the combination of motivational factors present (food restriction and cue light), indicating that adolescents were differentially sensitive to them. Furthermore, food restriction induced greater open-field activity in adolescents but not in adults. Thus, as the neural circuitry of motivated behavior develops substantially during adolescence, so too does the behavioral sensitivity to motivational factors. Understanding how such factors differently affect adolescents may shed light on mechanisms that lead to the development of disorders that are manifested during this period. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

氨磺必利治疗精神分裂症疗效以及安全性研究

目的: 本研究主要探讨氨磺必利对照利培酮治疗精神分裂症的疗效以及安全性。方法: 共90例精神分裂症患者被随机分入氨磺必利组和利培酮组,各45例。在治疗前以及治疗后第2、4、8周末,使用阳性和阴性症状量表（positive and negative syndrome scale,PANSS）对病例精神症状进行评定,病情的严重程度采用临床大体疗效量表 疾病严重程度（clinical global impressions severity of illness scale,CGI-S）评定,通过比较量表评分前后变化来评价疗效;副反应量表（TESS）评定不良反应的发生率以评价安全性。结果: 两组在各时点PANSS评分的总分和各因子分相比基线时均有显著性降低,且差异有统计学意义（P<0.05）;与利培酮相比,氨磺必利组阴性症状评分明显下降,差异有统计学意义（P<0.05）;两组间PANSS评分的总分、阳性症状和精神病理症状分在各时点比较差异无统计学意义（P>0.05）。与利培酮组相比,氨磺必利组CGI-S评分较基线时均有显著降低,差异有统计学意义(P<0.01),两组间CGI-S评分比较差异无统计学意义（P>0.05）。至研究结束,两组都没有发生严重的不良反应,经统计学检验,两组各种不良反应的发生率差异无统计学意义（P>0.05）。结论: 氨磺必利治疗精神分裂症疗效明显,能显著改善患者的阳性症状、阴性症状、一般病理症状,其疗效与利培酮相当,在改善阴性症状上优于利培酮。氨磺必利治疗精神分裂症耐受性好,未发生严重的不良反应。     

精神分裂症患者工作记忆EEG功能网络属性分析

精神分裂症与一些认知障碍如信息处理、工作记忆等联系紧密,研究工作是记忆任务中精神分裂症患者与正常人的多通道脑电在各个阶段、各个频段存在哪些显著性差异,可为精神分裂症的诊断提供依据。使用相位锁值（Phase Locking Value,PLV）来量化任意两个电极通道之间的相位同步性,构建脑功能网络的关联矩阵,计算不同稀疏度下脑网络的全局属性以及局部属性曲线下面积,在同一阶段、同一频段下对精神分裂症患者和正常人得到的属性值进行非参数检验,找出差异显著的属性及节点,将对应值作为特征训练SVM分类器,进而将精神分裂症患者和正常人分类。属性分析结果表明,工作记忆任务中[θ]和[α]频段发挥主要作用的脑区集中在右侧额叶区和枕叶区,[γ]频段相关的脑区集中在顶叶区;精神分裂症患者额叶右侧区域与枕叶区电极间[θ、][α]波相关性低于正常人,而其顶叶区电极间[γ]波的相关性高于正常人。     

Low-level temporal coding impairments in psychosis: Preliminary findings and recommendations for further studies.

The authors investigated whether difficulties with temporal event coding, previously reported in patients with schizophrenia, are already present during first-episode psychosis (FEP). In this experiment, the subjective judgments of the simultaneity of visually presented stimuli were compared between 11 healthy controls, 9 patients with chronic schizophrenia (CSZ), and a sample of 11 FEP patients. Participants were asked to indicate whether 2 vertical bars appeared at the same time or at different times on a computer monitor. CSZ patients' thresholds were elevated, and the FEP sample showed higher thresholds relative to controls. Although preliminary, these findings indicate a generalized disturbance in event-structure coding at early stages of psychosis and question the specificity of its disturbance. Considering the proposed relationship between event-structure coding and the experience of time in general, this study recommends that future studies refocus on psychosis in general, rather than on schizophrenia as a particular case of abnormal temporal processing. In addition, it is suggested that the relevant psychopathology will be best determined by means of a comprehensive analysis of low-level temporal coding performance in different types of psychosis. (PsycINFO Database Record (c) 2011 APA, all rights reserved)