The relationship between cognitive dysfunction and stress sensitivity in schizophrenia

The aim of the current study was to replicate the finding that cognitive impairments are not or inversely associated with sensitivity to stress in a sample of 25 patients diagnosed with psychotic disorder. The results indicated that impairments in performance on the Trailmaking Test and the Stroop Color Word Test were inversely associated with sensitivity to stress in daily life, whereas impairment in a subtest of the Behavioral Assessment of Dysexecutive Syndrome (BADS) was not associated with stress-sensitivity. The data thus show that in some instances cognitive functioning is not, and in other instances is inversely associated with momentary sensitivity to stress. Cognitive impairment and affective reactivity thus appear to be independent or mutually exclusive mechanisms in psychosis, suggesting competing causal pathways.     

抑郁症述情障碍与认知应对策略的关系

目的：探讨发作期抑郁症述情障碍与认知应对策略的特征。方法：采用多伦多述情量表（TAS-20）中文版、认知情绪调节问卷中文版（CERQ-C）对143例发作期抑郁症患者进行评定,并与95名健康志愿者（对照组）比较。结果：抑郁症组TAS-20总分及各因子分均显著高于对照组（P均〈0.01）。CERQ-C中责难自己、接受、沉思、灾难化、责怪他人因子分高于对照组,理性分析因子分低于对照组（P〈0.05或P〈0.01）。患者住院与他人交流、与家人的感情等依次进入TAS-20因子I的回归方程;父母的文化程度、经济状况等依次进入TAS-20因子II的回归方程;受教育年限、CERQ接受因子等依次进入TAS-20因子III的回归方程;与他人的交流、与家人的感情等依次进入TAS-20总分的回归方程。结论：抑郁发作患者存在明显的述情障碍与不良的认知应对策略。认知应对策略、性别、受教育年限等为发作期抑郁症患者述情障碍的重要影响因素。     

精神分裂症患者性激素与认知功能的关系

目的:探讨精神分裂症患者性激素与认知功能的关系。方法:精神分裂症患者95例,使用利培酮治疗6周,分别于治疗前和治疗后进行雌二醇(E2)、孕酮(Prog)、睾酮(T)、催乳素(PRL)、促卵泡激素(FSH)、黄体生成素(LH)检测、简明精神病评定量表(BPRS)评定和瑞文标准推理测验。结果:男性患者的E2、T、FSH、LH水平与瑞文测验正确题数、知觉辨别、类同比较、比较推理、系列关系正确题数均正相关;治疗后E2、T水平不再与瑞文推理测验相关。女性患者的E2、Prog、T、FSH、LH水平与瑞文测验正确题数、智商数、类同比较、比较推理、系列关系、抽象推理正确题数均正相关;治疗后E2、LH水平仍与瑞文测验正确题数、智商数、类同比较、比较推理、系列关系、抽象推理正确题数正相关,T水平与瑞文测验正确题数及所有因子正确题数负相关。结论:男女精神分裂症患者性激素对认知功能有不同影响。     

Relationship between coping,cognitive dysfunction and depression in multiple sclerosis

Given its relatively high prevalence, one possible source of stress for patients with multiple sclerosis (MS) is cognitive dysfunction. The authors' study was guided by a new theoretical model suggesting that cognitive dysfunction in MS may be most likely to lead to depression when patients use high levels of avoidance coping and/or low levels of active coping. To test this model, 55 patients with definite MS were administered a neuropsychological battery and measures of depression and coping. Consistent with predictions, regression analyses showed that coping significantly moderated the relationship between cognitive dysfunction and depression. Specifically, cognitive dysfunction was most likely to be associated with depression when patients used either high levels of avoidance or low levels of active coping. Implications of these data for clinical applications and for our theoretical conceptualization are discussed and limitations of the model explored.     

The relationship between coping style and burden in the carers of reatives with schizophrenia

The development of a questionnaire to measure the coping style of people caring for a relative with schizophrenia is described. Data on the psychometric properties of this questionnaire are reported for a sample of 91 carers. It is shown that coping style is associated with carer burden and psychological distress. In particular, the coping styles ‘collusion’, ‘criticism/coercion’,‘overprotectiveness',‘emotional over-involvement’ and‘resignation’ were found to be associated with higher levels of carer burden, and the coping style‘warmth’ was found to be associated with lower levels of carer burden.     

Longitudinal assessment of coping abilities at exacerbation and stabilization in schizophrenia

BACKGROUND: Coping strategies play an important role in one's ability to adapt to stressful life conditions such as schizophrenia. To better understand the nature of various coping mechanisms at various stages in schizophrenia, this study examined task-, emotion-, and avoidance-oriented coping strategies and explored associated clinical factors at exacerbation and stabilization phases of the illness. METHOD: Patients with schizophrenia were examined twice (at exacerbation phase, N = 237 and at stabilization phase, N = 148) with the Coping Inventory for Stressful Situations, and standardized measures of psychopathology and emotional distress severity, side effects, insight, self-constructs, social support, and quality of life. Multiple regression analysis was performed with coping strategies as dependent variables at exacerbation and stabilization including analysis of any change during the 16-month follow-up period. RESULTS: Analysis indicated that emotion coping strategies were used more at exacerbation than at stabilization phase. Regression analysis demonstrated emotional distress to be a strong predictor of emotion-oriented coping, with self-efficacy and social support being the best predictors of task and avoidance coping strategies, respectively. Individual changes in these variables also appear to be important predictors for fluctuations of these coping strategies over time. Severity of symptoms accounted for 3.5% and 5.5% to 9% of the total variance of emotion- and task-oriented coping strategies, respectively. CONCLUSIONS: Emotion, task, and avoidance coping strategies and their predictors are influenced and may vary over the course of schizophrenia illness. Experienced emotional distress, self-efficacy, and social support are the best predictors of coping strategies both at exacerbation and stabilization phases of illness.     

分裂症听感觉加工障碍与较高程度功能障碍的关系

目的 用失匹配负波(MMN)和P300去评定分裂症听信息加工中听感觉加工障碍与较高程度功能障碍的相关性.方法 52例分裂症患者和44例正常对照组采用事件相关脑电位检查,测量MMN和P300潜伏期和波幅,并采用SPSS和结构方程模型进行分析.结果 患者组产生的MMN的潜伏期、波幅与正常对照组比较差异有统计学意义(t=6.18,P＜0.01;t=2.42,P＜0.05),患者组产生的P300的波幅与正常对照组比较差异有统计学意义(t=2.64,P=0.01),患者组产生的P300的潜伏期与正常对照组比较差异无统计学意义(t=1.71,P＞0.05).结构方程模型评定显示Group(疾病过程)和MMN波幅及Group和P300波幅显示出有显著路径的内相关(B=-1.01,P=0.015;B=-0.60,P -0.039),MMN波幅与P300波幅显示出有显著路径的内相关(B=0.17,P=0.015).结论 分裂症听信息加工中听感觉加工的障碍直接影响着较高程度的功能障碍.     

Insight,cognitive dysfunction and symptomatology in schizophrenia

Lack of insight is frequent in schizophrenia and usually influences negatively both patient’s treatment and prognosis. This study aimed to investigate the relationship between insight, symptomatology and cognitive dysfunctions in schizophrenia using the PANSS five-factor model (modified from Gaag et al. in Schizophr Res 85:280–287, 2006). Forty patients diagnosed with chronic schizophrenia (DSM-IV) were evaluated with the scale to assess unawareness of mental disorder (SUMD), the PANSS and a neuropsychological battery. Spearman correlation and linear regression analyses were performed to investigate the relationship between clinical, neurocognitive and insight measures. The SUMD current and past awareness of symptoms score showed a correlation with WCST indices (correct answers and non-persevering errors). The negative and disorganization factor of the PANSS showed a positive correlation with current and past awareness of symptoms. However, when submitted to a linear regression model only the disorganization factor emerged as significant contributor for insight. Considering that the core items of the “disorganization factor” of the PANSS are related to cognition (e.g., poor attention, difficult in abstract thinking), insight is associated cognitive symptoms although no direct relationship between insight and neuropsychological tests was observed.     

Hippocampal complexin proteins and cognitive dysfunction in schizophrenia

BACKGROUND: Converging neuroimaging and postmortem evidence indicates synaptic terminals are abnormal in schizophrenia. A putative molecular mechanism implicates abnormalities of proteins involved in the presynaptic secretory machinery, including the modulator proteins complexin I and complexin II. OBJECTIVES: To determine the amount and distribution of complexin proteins in the hippocampus of subjects with schizophrenia, in parallel with markers for excitatory and inhibitory nerve terminals. The functional implications were also investigated. DESIGN: We used immunocytochemistry to study complexin I and complexin II proteins in hippocampus, as well as the vesicular transporters for gamma-aminobutyric acid (GABA) and for glutamate. Immunocytochemical findings were correlated with cognitive function assessed through medical record review. To further explore the implications of the human findings, we studied rats exposed to haloperidol, amphetamine, and ketamine as well as rats trained in memory tasks. SUBJECTS: We studied hippocampal sections from 12 subjects with schizophrenia and 12 subjects with no known neuropsychiatric disorder. RESULTS: The absolute values and ratio of the hippocampal presynaptic proteins complexin II-complexin I were lower in subjects with schizophrenia. Disturbances in the complexin proteins in subjects with schizophrenia were greater than those observed for vesicular gamma-aminobutyric acid or vesicular glutamate transporters. The lower complexin II-complexin I ratio in several hippocampal subfields in subjects with schizophrenia was inversely correlated with the severity of antemortem cognitive impairment. In contrast, the hippocampal complexin II-complexin I ratio was higher in rats trained in a memory task compared with untrained rats. Treatment of rats with antipsychotic drugs or with the psychotomimetic drugs amphetamine or ketamine did not alter the complexin II-complexin I ratio. CONCLUSIONS: The pathology of hippocampal complexin proteins might play an important role in schizophrenia, especially concerning cognitive disturbances.     

Lateralized cognitive dysfunction and psychotic symptoms in schizophrenia

Our understanding of hemispheric asymmetries in schizophrenia can be attributed to extensive neuropsychological and neuroimaging research on this topic; however, it has yet to be determined whether lateralized cognitive dysfunction represents a single core trait in schizophrenia or whether the lateralized impairments are domain specific. To test whether lateralized deficits are core features in schizophrenia we examined performance across a wide range of lateralized cognitive domains including attention, fluency, recognition memory, perception, and arousal. We also examined the relationship between lateralized impairments and psychotic and affective symptoms to determine whether abnormal hemispheric asymmetries were possibly state-related. The sample consisted of 43 subjects with schizophrenia and 66 normal healthy comparison subjects without psychiatric illness. Schizophrenia subjects exhibited abnormal right hemisphere performance on a test of recognition memory and abnormal left hemisphere performance on a measure of arousal. These findings suggest that lateralized cognitive disturbances in schizophrenia do not represent a single core lateralized deficit. Regarding the symptom analyses, severity of positive symptoms was related to right hemisphere cognitive impairment (including fluency and recognition memory), whereas severity of negative symptoms was related to left hemisphere cognitive impairment (including fluency). Overall, our findings suggest that lateralized dysfunction can occur in both hemispheres in schizophrenia, and that the positive psychotic symptoms may relate more to right hemisphere impairment, whereas negative psychotic symptoms may related more to left hemisphere impairment.     

Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia

Deficits in cognitive control, a core disturbance of schizophrenia, appear to emerge from impaired prefrontal gamma oscillations. Cortical gamma oscillations require strong inhibitory inputs to pyramidal neurons from the parvalbumin basket cell (PVBC) class of GABAergic neurons. Recent findings indicate that schizophrenia is associated with multiple pre- and postsynaptic abnormalities in PVBCs, each of which weakens their inhibitory control of pyramidal cells. These findings suggest a new model of cortical dysfunction in schizophrenia in which PVBC inhibition is decreased to compensate for an upstream deficit in pyramidal cell excitation. This compensation is thought to rebalance cortical excitation and inhibition, but at a level insufficient to generate the gamma oscillation power required for high levels of cognitive control.     

Treating cognitive dysfunction in patients with schizophrenia

Cognitive dysfunction is a common, chronically disabling component of schizophrenia. It has been proposed that many of the symptoms of schizophrenia can be understood as a result of disruption of fundamental cognitive processes. This paper reviews treatment strategies aimed at improving cognitive function in patients with schizophrenia. Nonpharmacologic interventions include instruction in the performance of tasks such as the Wisconsin Card Sorting Test. Mixed results have been achieved, but it appears that instruction methods involving reinforcement of information held in working memory are more successful. Computer-aided remediation has also been used with variable success. Novel antipsychotic drugs appear to have an advantage over conventional antipsychotic drugs in terms of their effect on cognitive function. The development of more precisely tailored methods of remedial teaching, along with optimal pharmacologic treatment, may lead to more effective treatment of cognitive dysfunction in patients with schizophrenia.     

The relationship between cognitive insight, clinical insight, and depression in patients with schizophrenia

Despite comorbid depression being relatively common even in subjects with schizophrenia, to the best of our knowledge, there is, to date, no report in the literature specifically and detailed examining the cognitive and clinical insight in subjects with schizophrenia and a comorbid depressive syndrome. Hence, in this study, we sought to compare the cognitive and clinical insight in our subjects with schizophrenia with and without a comorbid depressive syndrome. We found that participants in the depressive group scored significantly higher on self-reflectiveness and the reflectiveness-certainty (R-C) index scores than those in the nondepressive group. There was no significant difference among groups on the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and clinical insight scores assessed by the Scale to Assess Unawareness of Mental Disorder. In addition, self-reflectiveness scores significantly correlated with depression, observed depression, hopelessness, and suicidality subscores of the Calgary Depression Scale for Schizophrenia. A better understanding of the cognitive component of insight in schizophrenia with comorbid depression may contribute to develop more efficient cognitive strategies, thus improving patient outcome. However, clinicians should be aware of the possibility of exacerbating a sense of hopelessness and suicide risk during the interventions that improve cognitive insight.     

The relationship between antisaccades, smooth pursuit, and executive dysfunction in first-episode schizophrenia.

BACKGROUND: Both oculomotor and neuropsychologic deficits have been used to support the hypothesis that schizophrenia is associated with prefrontal cortex dysfunction, but studies that have specifically investigated the relationships between these deficits have produced inconsistent findings. METHODS: We measured both smooth pursuit and antisaccade performance in a large group (n = 109) of patients with first-episode schizophrenia and a group of matched control subjects (n = 59) and investigated the relationship between performance on these tasks and performance on a range of executive tasks. We additionally explored the relationship between these variables and measures of psychopathology at presentation and duration of untreated psychosis. RESULTS: Antisaccade errors were significantly correlated with spatial working memory performance. Smooth pursuit gain did not correlate with any neuropsychologic measure. There were no reliable correlations between either oculomotor variables and measures of psychopathology and duration of untreated psychosis. CONCLUSIONS: These findings suggest that in schizophrenia working memory and antisaccade performance reflect the same abnormal prefrontal substrates and that smooth pursuit is mediated by a separate neural abnormality.     

The relationship between risk of hospitalization for schizophrenia, SES, and cognitive functioning

Although most studies find low socioeconomic status (SES) to be associated with prevalence of schizophrenia, incidence studies do not generally support this, and some even report an inverse association. The objective of the current historical prospective study was to examine the relationship between SES, cognitive functioning, and risk of hospitalization for schizophrenia in a population-based sample of Israeli adolescents. Subjects were 811 487 adolescents, assessed by the Israeli military draft board for socio-demographic factors and cognitive functioning. Data on later hospitalization for schizophrenia were obtained from a population-based hospitalization registry. Findings indicated that when simply examining SES and schizophrenia, lower SES was associated with greater risk of hospitalization for schizophrenia (Hazard Ratio [HR] = 1.193, 95% CI = 1.091-1.303). When dividing the cohort into low, average, and high cognitive functioning, SES did not influence the risk for schizophrenia among individuals with high and average cognitive functioning, whereas among individuals with low cognitive functioning, high SES was found to slightly increase the risk for schizophrenia (HR = 1.21, 95% CI = 1.03-1.42). One possible explanation for this finding might be that among individuals from low socioeconomic backgrounds, low IQ may reflect decreased opportunities related to SES, whereas among individuals from high SES backgrounds, low IQ might reflect risk for later psychopathology.     

Molecular targets for treating cognitive dysfunction in schizophrenia

Cognitive impairment is a core feature of schizophrenia as deficits are present in the majority of patients, frequently precede the onset of other positive symptoms, persist even with successful treatment of positive symptoms, and account for a significant portion of functional impairment in schizophrenia. While the atypical antipsychotics have produced incremental improvements in the cognitive function of patients with schizophrenia, overall treatment remains inadequate. In recent years, there has been an increased interest in developing novel strategies for treating the cognitive deficits in schizophrenia, focusing on ameliorating impairments in working memory, attention, and social cognition. Here we review various molecular targets that are actively being explored for potential drug discovery efforts in schizophrenia and cognition. These molecular targets include dopamine receptors in the prefrontal cortex, nicotinic and muscarinic acetylcholine receptors, the glutamatergic excitatory synapse, various serotonin receptors, and the gamma-aminobutyric acid (GABA) system.