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1.

Background

Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree.

Methods

Three groups (n = 100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2 s & 12 s); sustained attention processing was assessed using the Continuous Performance Task—Identical Pairs version.

Results

SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls.

Conclusions

These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP.  相似文献   

2.

Objective

The aim of the study was to assess the associations between self-stigma and temperament and character dimensions.

Methods

One hundred twenty outpatients with diagnosis of schizophrenia, established with Mini International Neuropsychiatric Interview were consecutively included in the study. Self-stigma was assessed with Internalized Stigma of Mental Illness (ISMI), personality dimensions with Temperament and Character Inventory, and psychopathology with Positive and Negative Symptom Scale.

Results

The results showed that higher level of harm avoidance, lower self-directedness, and persistence correlated with ISMI and all its subscales. Self-transcendence correlated with ISMI subscales alienation, discrimination, and stigma resistance. Regression analyses controlling for psychopathology, age, length of illness, and number of hospitalizations revealed that higher level of harm avoidance and low self-directedness predicted internalized stigma.

Conclusion

The finding suggests that the experience of self-stigma is related to personality dimensions. Interpretations of these findings include the possibility that, irrespective of patients' psychopathology or functional characteristics, experience of self-stigma and its consequences might depend on personality dimensions. Further studies are needed.  相似文献   

3.

Introduction

In the present study we investigated the impact of soluble urokinase plasminogen activator receptor (suPAR) as a biomarker in patients with abdominal aortic aneurysm (AAA) in relation to conventional inflammatory markers, aneurysm size, and rupture.

Methods

suPAR and conventional inflammatory markers were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit.

Results

The results support earlier studies suggesting a state of activated inflammatory response in patients with nonruptured AAA as expressed by elevated CRP and IL-6 compared with the controls. In contrast, suPAR showed similar levels in patients with nonruptured AAA compared with the controls. Unexpectedly, all follow-up patients (n = 16) have significant (p < 0.001) elevated suPAR levels three years postoperatively compared preoperatively.

Conclusions

suPAR does not seem to be a useful biomarker in the AAA disease. The role of the postoperative elevation of suPAR needs to be further elucidated.  相似文献   

4.

Introduction

Disturbed interregional functional connectivity has been hypothesized to be a promising marker of schizophrenia. The relationship between working memory (WM) impairment, disturbed functional connectivity, and the characteristic symptoms of schizophrenia, however, remains elusive.

Methods

We used functional MRI (fMRI) to investigate in patients with schizophrenia and matched controls the patterns of functional connectivity during the performance of different tasks selectively engaging subcomponent processes of working memory.

Results

Compared with controls, patients showed reduced connectivity of the prefrontal cortex with the intraparietal cortex and the hippocampus and abnormal negative interactions between the ventrolateral and dorsolateral prefrontal cortex during the non-articulatory maintenance of phonological information. During the maintenance of visuospatial information, patients presented reduced connectivity between regions in the superior parietal and occipital cortex, as well as enhanced positive connectivity of the frontal eye field with visual processing areas.

Discussion

Our findings suggest complex dysregulations within the networks supporting working memory functions in schizophrenia, which manifest as decreased positive and abnormal negative interactions. Correlations between the connection strength and WM performance suggest that these dysregulations may be neurofunctional correlates of the WM deficits seen in schizophrenia. Altered prefronto-hippocampal and parieto-occipital connectivity was further found to be associated with higher positive symptoms, providing a possible explanation for the development of delusions and disorganization symptoms.

Conclusion

The present findings can help to better understand the relationship between altered patterns of synchronized brain activity and the cognitive and clinical symptoms of schizophrenia.  相似文献   

5.

Introduction

In animal studies, long-term prenatal nicotinic exposure alters the development of dopaminergic neurons. To determine whether prenatal smoking exposure was associated with schizophrenia, using a retrospective design study, we compared the prevalence of tobacco use during pregnancy in mothers of subjects with and without schizophrenia.

Methods

One hundred patients with schizophrenia, 100 nonschizophrenic-matched subjects, and their respective mothers were interviewed. The prevalence of smoking was measured in these individuals as well as in their respective mothers during the pregnancy.

Results

Patients with schizophrenia smoked more often compared with controls (73% vs 57%). In contrast, the prevalence of smoking during pregnancy did not differ between the groups of mothers. Indeed, the amount of tobacco used was significantly lower in mothers of patients with schizophrenia vs mothers of nonpsychotic subjects.

Conclusion

This study did not show any association between prenatal tobacco exposure and further development of schizophrenia.  相似文献   

6.

Aim

Limited data are available regarding pharmacological characteristics of effective interventions for psychosis prevention. Enrollment challenges in psychosis prevention trials impede screening diverse interventions for efficacy. Relevant animal models could help circumvent this barrier. We previously described prevention with risperidone of abnormal behavior following neonatal hippocampal lesion. We aimed to extend those findings evaluating risperidone and paliperidone following prenatal immune activation, a developmental model of a schizophrenia risk factor. We evaluated a later developmental time point to determine persistent effects of drug treatment.

Methods

Pregnant Sprague-Dawley rats were injected with poly I:C or saline on gestational day 14. Offspring of poly I:C and saline-treated dams received risperidone (0.45 mg/kg/d), paliperidone (0.05 mg/kg/d), or vehicle from postnatal days 35-70. Locomotor responses to novelty, saline injection, and amphetamine (1 and 5 mg/kg) were determined at three months, i.e., 21 days following antipsychotic discontinuation.

Results

Risperidone and paliperidone had persistent effects on behavioral response to amphetamine (1 mg/kg) at 3 months, ameliorating the impact of prenatal immune activation on offspring of poly I:C-treated dams. Risperidone, but not paliperidone, also exerted persistent effects in offspring of saline-treated dams on locomotor response to saline and amphetamine (5 mg/kg) injection.

Conclusions

Risperidone and paliperidone pre-treatment of poly I:C offspring during peri-pubertal development stabilized response to amphetamine exposure persisting into early adulthood. Prenatal immune activation provides a model for evaluating effects of an environmental risk factor for schizophrenia, and has potential utility for identifying pharmacological approaches to early intervention.  相似文献   

7.

Background

Biomarkers are needed that can distinguish between schizophrenia and schizoaffective disorder to inform the ongoing debate over the diagnostic boundary between these two disorders. Neuromorphometric abnormalities of the thalamus have been reported in individuals with schizophrenia and linked to core features of the disorder, but have not been similarly investigated in individuals with schizoaffective disorder. In this study, we examine whether individuals with schizoaffective disorder have a pattern of thalamic deformation that is similar or different to the pattern found in individuals with schizophrenia.

Method

T1-weighted magnetic resonance images were collected from individuals with schizophrenia (n = 47), individuals with schizoaffective disorder (n = 15), and controls (n = 42). Large-deformation, high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance were used to test for group differences in volume and measures of surface shape.

Results

Individuals with schizophrenia or schizoaffective disorder have similar thalamic volumes. Thalamic surface shape deformation associated with schizophrenia suggests selective involvement of the anterior and posterior thalamus, while deformations in mediodorsal and ventrolateral regions were observed in both groups. Schizoaffective disorder had distinct deformations in medial and lateral thalamic regions.

Conclusions

Abnormalities distinct to schizoaffective disorder suggest involvement of the central and ventroposterior medial thalamus which may be involved in mood circuitry, dorsolateral nucleus which is involved in recall processing, and the lateral geniculate nucleus which is involved in visual processing.  相似文献   

8.

Background

Children and adolescent offspring of schizophrenia patients are at increased risk for schizophrenia and are also characterized by impairments in brain structure and function. To date, few studies have investigated whether functional interactions between brain regions are intact or altered. Using an established verbal working memory paradigm with variable levels of memory load, we investigated the modulatory effect of activity in cognitive control regions of the brain (specifically the dorsal anterior cingulate cortex) on activity in core working memory regions, in particular the dorsal prefrontal cortex and the parietal lobe.

Methods

Forty four subjects participated. An n-back task with two levels of working memory load (1- and 2-back) was employed during fMRI (4 T Bruker MedSpec system). Data were processed with SPM5 and the modulatory effects of the anterior cingulate were investigated using psycho-physiological interaction (PPI).

Results

In spite of only subtle activation differences, and no significant differences in performance accuracy, a significant group x memory load interaction in the parietal lobe, indicated aberrantly increased modulatory inputs to this region under conditions of high working memory load in schizophrenia offspring.

Discussion

Increased modulatory inputs from a central control region like the anterior cingulate presumably reflect relative inefficiency in intra-cortical interactions in the vulnerable brain. This inefficiency may reflect a developmentally mediated impairment in functional brain interactions in this important vulnerable population. It is highly plausible that the resultant effect of these altered interactions is an increased vulnerability to impaired brain development, and therefore to psychiatric disorders including schizophrenia.  相似文献   

9.

Objective

Past reports have found patients with comorbid depression and schizophrenia spectrum disorders exhibit greater deficits in memory and attention compared to schizophrenia spectrum disorder patients without depressive symptoms. However, in contrast to younger schizophrenia patients, the few past studies using cognitive screens to examine the relationship between depression and cognition in inpatient geriatric schizophrenia have found that depressive symptomatology was associated with relatively enhanced cognitive performance. In the current study we examined the relationship between depressive symptoms and cognitive deficits in geriatric schizophrenia spectrum disorder patients (n = 71; mean age = 63.7) on an acute psychiatric inpatient service.

Method

Patients completed a battery of cognitive tests assessing memory, attention and global cognition. Symptom severity was assessed via the PANSS and Calgary Depression Scale for Schizophrenia.

Results

Results revealed that geriatric patients' depression severity predicted enhancement of their attentional and verbal memory performance. Patients' global cognitive functioning and adaptive functioning were not associated with their depression severity.

Conclusion

Contrary to patterns typically seen in younger patients and non-patient groups, increasing depression severity is associated with enhancement of memory and attention in geriatric schizophrenia spectrum disorder patients. Also, diverging from younger samples, depression severity was unassociated with patients adaptive and global cognitive functioning.  相似文献   

10.

Introducion

Paraneoplastic movement disorders are rare. Reported cases frequently describe association with anti-CV2/CRMP5 antibodies.

Case report

We report a case of an 80-year-old man who developed sensorial neuronopathy, following by movement disorders mimicking chorea and obsessive-compulsive and behavioral disorders. These manifestations were first considered to be associated with a prostatic adenocarcinoma but PET and surgical biopsy revealed a mediastinal small cell lung carcinoma classically associated with anti-CV2/CRMP5 antibodies.

Conclusion

This case demonstrates that in a context of paraneoplastic neurological syndrome, search for a classically associated cancer is necessary in order to institute adapted treatment early, even if another tumor is obvious.  相似文献   

11.

Research questions

Separation anxiety disorder (SAD) is one of the most common mental disorders in childhood, and one of the earliest emerging. Little is known about the association between SAD and the hypothalamic-pituitary-adrenocortical (HPA) axis activity. Therefore, the present study aimed at investigating this association in children suffering from separation anxiety compared to healthy controls.

Methods

A total of 31 children with diagnosed SAD (mean age: 8.45; 17 females, 14 males) and 25 healthy controls (HC; mean age: 9.74; 12 females, 13 males) took part in the study. All participants underwent psycho-physiological testing for HPA axis challenge. Testing consisted of a separation and a social exposure paradigm. Saliva samples to assess HPA axis-related cortisol secretion were gathered in parallel.

Results

Compared to healthy controls, children with SAD showed greatly increased HPA axis activity, as reflected by an increased cortisol secretion throughout the entire period of investigation. The rise of cortisol was already observed in anticipation of, but not following the separation paradigm. No gender-related differences of cortisol secretion were observed.

Conclusions

Separation anxiety disorder (SAD) in children is reflected in greatly increased HPA axis activity. Compared to healthy controls, children with SAD showed increased cortisol values from the beginning of, and throughout, the entire investigation. This pattern of results suggests that both the anticipation of a separation and a persistent hyperactivity of the HPA axis system leads to an increased cortisol secretion.  相似文献   

12.

Background

Dissociation is often related to psychologic trauma and is also commonly correlated with posttraumatic stress disorder (PTSD). Schneiderian symptoms occur in dissociative disorder and PTSD, whereas dissociation and trauma are also frequent in patients with schizophrenia. Dissociation and schneiderian symptoms may reflect posttraumatic symptomatology in some patients diagnosed with schizophrenia who might not develop PTSD.

Method

Seventy-one patients completed an interview assessing symptoms of schizophrenia, depression, dissociative disorder, and PTSD. Data were collected using the Positive and Negative Syndrome Scale, the Montgomery-Asberg Depression Rating Scale, the Arbeitsgemeinschaft Methodik und Dokumentation in der Psychiatrie scale for dissociation, and a Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-based questionnaire. Multiple analysis of covariance was used to compare psychopathologic measures between groups with or without PTSD criteria A1 and A2, PTSD, and high and low levels of dissociation, controlling for substance abuse.

Result

Trauma and dissociation were associated with more severe symptoms of schizophrenia. Especially high dissociation was associated with an increase in symptom load, whereas criterion A and PTSD had little or no such effect.

Discussion

In the present study, those with more severe schizophrenic and depressive symptoms were also characterized by high dissociation. The possible relation to trauma and schizophrenic diathesis is discussed along with the limitations of the study.  相似文献   

13.

Purpose

The author has endeavoured to present a qualitative review of current data on the interest of repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of negative symptoms of schizophrenia, its therapeutic impact and processes that underlie it.

Method

The method consisted in a review of the literature by an extensive consultation of the computerized Medline database.

Results

Despite the small number of controlled studies and the small sample sizes, rTMS appears to be an effective therapeutic method in the treatment of negative symptoms of schizophrenia and also helps understanding the patho-physiologic processes that underlie them (hypofrontality, dopamine hypothesis and responsiveness of the HPA axis).

Conclusion

Before any conclusion may be reached about the effectiveness of this new technology more studies are required using larger parameters for active treatment and optimal placebos (alpha-TMS at least 110 % of the motor threshold, focused on the hypo-active area).  相似文献   

14.

Background

ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients.

Methods

69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2 × 2 analysis of variance.

Results

1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers.2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group.

Limitation

The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated.

Conclusions

The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia.  相似文献   

15.

Introduction

Although the substrates that mediate singing abilities in the human brain are not well understood, invasive brain mapping techniques used for clinical decision making such as intracranial electro-cortical testing and Wada testing offer a rare opportunity to examine music-related function in a select group of subjects, affording exceptional spatial and temporal specificity.

Methods

We studied eight patients with medically refractory epilepsy undergoing indwelling subdural electrode seizure focus localization. All patients underwent Wada testing for language lateralization. Functional assessment of language and music tasks was done by electrode grid cortical stimulation. One patient was also tested non-invasively with functional magnetic resonance imaging (fMRI). Functional organization of singing ability compared to language ability was determined based on four regions-of-interest (ROIs): left and right inferior frontal gyrus (IFG), and left and right posterior superior temporal gyrus (pSTG).

Results

In some subjects, electrical stimulation of dominant pSTG can interfere with speech and not singing, whereas stimulation of non-dominant pSTG area can interfere with singing and not speech. Stimulation of the dominant IFG tends to interfere with both musical and language expression, while non-dominant IFG stimulation was often observed to cause no interference with either task; and finally, that stimulation of areas adjacent to but not within non-dominant pSTG typically does not affect either ability. Functional fMRI mappings of one subject revealed similar music/language dissociation with respect to activation asymmetry within the ROIs.

Conclusion

Despite inherent limitations with respect to strictly research objectives, invasive clinical techniques offer a rare opportunity to probe musical and language cognitive processes of the brain in a select group of patients.  相似文献   

16.

Background

The association between methylenotetrahydrofolate reductase (MTHFR) 677TT and the increased risk of venous thrombosis is uncertain. Studies of this polymorphism in cerebral venous thrombosis (CVT) are inconclusive.

Objectives

With a systematic review, we aimed to collect all case-control studies comparing the frequency of this polymorphism in CVT patients (cases) and healthy controls.

Methods

We used the MEDLINE, Cochrane Library and the ISI web of knowledge electronic databases and reference lists of retrieved articles in order to identify published case-control studies that evaluated the presence of MTHFR 677C>T polymorphism in CVT. Two reviewers independently selected studies. We compared the frequency of 677TT between cases and controls using the Mantel-Haenszel method, a fixed and a random-effects model in the pooled data.

Results

Nine case-control studies were included. The pooled analysis included 382 patients with CVT and 1217 controls. The frequency of 677TT genotype among CVT patients was not significantly higher compared with controls (15.7% versus 14.6%; OR = 1.12, 95% confidence interval (95% CI) 0.80 to 1.58; p = 0.50). There was significant heterogeneity between studies.

Conclusions

This meta-analysis confirmed that there is currently insufficient data supporting that 677TT genotype is a risk factor for CVT. These results imply a continuing searching for the cause of CVT in patients with this polymorphism.  相似文献   

17.

Objective

The ATP-binding cassette transporter A1 (ABCA1) mediates cellular cholesterol efflux through the transfer of cholesterol from the inner to the outer layer of the cell membrane and regulates extracellular cholesterol levels in the central nervous system. Several lines of evidence have indicated lipid and myelin abnormalities in schizophrenia.

Method

Initially, we examined the possible association of the polymorphisms of the ABCA1 gene (ABCA1) with susceptibility to schizophrenia in 506 patients with schizophrenia (DSM-IV) and 941 controls. The observed association was then subject to a replication analysis in an independent sample of 511 patients and 539 controls. We further examined the possible effect of the risk allele on gray matter volume assessed with magnetic resonance imaging (MRI) in 86 patients with schizophrenia (49 males) and 139 healthy controls (47 males).

Results

In the initial association study, the 1587 K allele (rs2230808) was significantly more common in male patients with schizophrenia than in male controls. Although such a significant difference was not observed in the second sample alone, the increased frequency of the 1587 K allele in male patients remained to be significant in the combined male sample of 556 patients and 594 controls. Male schizophrenia patients carrying the 1587 K allele had a smaller amount of gray matter volume than those who did not carry the allele.

Conclusion

Our data suggest a male-specific association of the 1587 K allele of ABCA1 with susceptibility to schizophrenia and smaller gray matter volume in schizophrenia.  相似文献   

18.

Background

Cardiac mortality is known to be increased in patients with major depression. Several studies have reported an imbalance within the autonomic nervous system (ANS) of patients with major depressive disorder (MDD) as one putative cause. Since a heritability of autonomic modulation was demonstrated in healthy subjects, we aimed to investigate autonomic modulation in first-degree relatives of patients with MDD to find potential autonomic imbalances.

Methods

We included 30 patients with MDD, 30 of their first-degree relatives (siblings or offspring) and 30 matched healthy controls in our study. We obtained a high resolution electrocardiogram and beat to beat blood pressure measurements for 30 min at rest. Linear and nonlinear parameters of heart rate variability (HRV) and baroreflex sensitivity (BRS) were calculated.

Results

Parameters of HRV and BRS did not differ significantly between relatives and controls. We found significant differences between patients and controls for some HRV and BRS parameters confirming results of previous studies.

Discussion

Findings of our study suggest that an imbalance of autonomic function is related to patients with depression and not to first-degree relatives. Thus, a genetic background for autonomic dysfunction is rather unlikely.  相似文献   

19.

Background

Several studies have found a reduction in hippocampal volume in borderline personality disorder (BPD) patients.

Methods

In order to investigate the degree to which comorbid posttraumatic stress disorder (PTSD) could account for reduction in hippocampal volume in these patients, we conducted a systematic review and meta-analysis of studies that compared hippocampal volume in BPD patients with and without PTSD relative to healthy controls.

Results

Seven articles, involving 124 patients and 147 controls, were included. We found a statistically significant reduction for the left and right hippocampus. Data from the four studies that discriminated BPD patients with and without PTSD indicate that hippocampal volumes were reduced bilaterally in BPD patients with PTSD, relative to healthy controls, but that results were mixed for BPD patients without PTSD, relative to healthy controls.

Conclusions

Results from this meta-analysis suggest that hippocampal volumes are reduced in patients with BPD, relative to healthy controls, but particularly in cases in which patients are diagnosed with comorbid PTSD.  相似文献   

20.

Background

The aim of this study was to investigate the association among aggressive behavior, neuropsychological function, and the Val66Met functional polymorphism of brain-derived neurotrophic factor (BDNF) gene in male schizophrenic patients.

Methods

We examined 51 male patients with schizophrenia who had committed homicide (ie, H-SCZ), 50 male patients with schizophrenia who had not committed homicide (ie, NH-SCZ), and 50 healthy male controls. Patients were evaluated using the Positive and Negative Syndrome Scale, Life History of Aggression, and the Overt Aggression Scale. In addition, patients were given neurocognitive function tests, including Korean-Wechsler Adult Intelligence Scale short form, the Korean version of the Rey Memory Test, the Stroop Test, and the Wisconsin Card Sorting Test. The Val66Met polymorphism of the BDNF gene was also genotyped in all schizophrenic patients.

Results

We observed no significant difference between patients in the H-SCZ and NH-SCZ groups, with regard to Positive and Negative Syndrome Scale scores. Total Life History of Aggression (P < .01) and Overt Aggression Scale scores for the most severe episode (P < .01) or for the previous month (P < .05) were higher in the H-SCZ group than in the NH-SCZ group. There were no significant differences in the genotype distribution or allelic frequency of the Val66Met polymorphism between the schizophrenic groups. In addition, we observed no significant differences between H-SCZ and NH-SCZ groups with regard to performance on neuropsychological tests. The Met allele of the Val66Met polymorphism was associated with poor intelligence quotient, memory quotient), learning, and delayed recall in the H-SCZ group. However, genotype did not seem to influence neurocognitive function in schizophrenic patients who had committed homicide.

Conclusions

The neurocognitive tests used in our study were unable to distinguish between violent and nonviolent schizophrenic patients. Furthermore, the Val66Met polymorphism was not associated with aggressiveness in patients with schizophrenia.  相似文献   

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