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1.
Objectives: We studied cognitive function in high‐risk relatives belonging to a single extended family showing linkage of bipolar disorder to a locus on chromosome 4. High‐risk relatives were defined as those that carried the risk haplotype of polymorphic markers, identified in a previous linkage study. This family provided a rare opportunity to characterize a neuropsychological endophenotype in a homogeneous sample of relatives with a common genetic risk factor. Methods: Fifteen family members carrying the risk haplotype (eight diagnosed with bipolar disorder or depression and seven with no psychiatric diagnosis), unrelated patients with bipolar disorder (n = 36) and major depressive disorder (n = 40), and healthy control subjects (n = 33) were administered the California Verbal Learning Test, Verbal Fluency Test, Hayling Sentence Completion Test, and Brixton Spatial Anticipation Test to assess verbal memory, verbal fluency, and executive function. Results: Compared with healthy controls, family members carrying the risk haplotype were impaired in indices of memory and executive function. There were no significant differences between unaffected and affected haplotype‐carrying family members in any cognitive measure. Pronounced deficits in the encoding stage of verbal memory and category verbal fluency were evident in individuals with the risk haplotype. Conclusions: Verbal learning and semantic verbal fluency impairments may represent a cognitive endophenotype for both bipolar disorder and major depression in relatives of bipolar disorder patients, as impairment was also present in high‐risk relatives who had not developed any affective disorder symptoms. These findings suggest that impairment in semantic organization may be linked to the genetic aetiology of bipolar disorder.  相似文献   

2.
OBJECTIVE: Obsessive-compulsive disorder (OCD) is highly heritable. Attempts to delineate precise genetic contributions have met with limited success. There is an ongoing search for intermediate cognitive brain markers (endophenotypes) that may help clarify genetic contributions. The aim was to assess inhibitory control processes in unaffected first-degree relatives of OCD patients for the first time with objective tests. METHOD: The Intradimensional/Extradimensional Shift, Stop-Signal, and Cambridge Gamble tasks were administered to 20 unaffected first-degree relatives, 20 OCD patient probands with washing/checking symptoms, and 20 healthy matched comparison subjects without a family history of OCD. RESULTS: Unaffected first-degree relatives and OCD patient probands showed cognitive inflexibility (extradimensional set shifting) and motor impulsivity (stop-signal reaction times). Decision making (Cambridge Gamble task) was intact. CONCLUSIONS: Deficits in cognitive flexibility and motor inhibition may represent cognitive endophenotypes for OCD. Such measures will play a key role in understanding genotype/phenotype associations for OCD and related spectrum conditions.  相似文献   

3.
Recent research suggests that patients with obsessive–compulsive disorder (OCD) have deficits in the volitional control of saccades. Specific evidence comes from increased latencies of saccadic eye movements when they were volitionally executed but not when they were visually guided. The present study sought to test whether this deviance represents a cognitive endophenotype. To this end, first-degree relatives of OCD patients as genetic risk carriers were compared with OCD patients and healthy controls without a family history of OCD. Furthermore, as volitional response generation comprises selection and initiation of the required response, the study also sought to specify the cognitive mechanisms underlying impaired volitional response generation. Twenty-two unaffected first-degree relatives of OCD patients, 22 unmedicated OCD patients, and 22 healthy comparison subjects performed two types of volitional saccade tasks measuring response selection or only response initiation, respectively. Visually guided saccades were used as a control condition. Our results showed that unaffected first-degree relatives and OCD patients were significantly slowed compared to healthy comparison subjects in volitional response selection. Patients and relatives did not differ from each other. There was no group difference in the visually guided control condition. Taken together, the study provides first evidence that dysfunctional volitional response selection is a candidate endophenotype for OCD.  相似文献   

4.
Kulkarni S, Jain S, Janardhan Reddy YC, Kumar KJ, Kandavel T. Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder.
Bipolar Disord 2010: 12: 647–656. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Impairments in executive function and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies, but the findings are inconsistent. In this study, neuropsychological performance in unaffected siblings of probands with family loading for bipolar disorder is compared to that of individually matched healthy controls. We hypothesized that performance on tests of executive functions and memory would be impaired in unaffected siblings of probands with bipolar disorder compared to matched healthy controls. Methods: We evaluated 30 unaffected siblings of probands with bipolar I disorder and 30 individually matched healthy controls using tests of attention, executive function, and memory. Unaffected siblings and healthy control subjects did not differ with respect to gender, age, and years of education. Results: Unaffected siblings performed poorly on the Tower of London test (TOL), the Rey’s auditory verbal learning test (RAVLT), and the Rey’s complex figure test. In the multivariate analysis, significance was noted for the TOL, total number of moves (p = 0.007) and the RAVLT total learning score (p = 0.001). Conclusions: Our study suggests that the deficits in verbal learning and memory and executive functions (planning) could be potential endophenotypes in bipolar disorder. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. Future studies could couple cognitive and imaging strategies and genomics to identify neurocognitive endophenotypes in bipolar disorder.  相似文献   

5.
Cognitive dysfunctions such as inhibitory deficits and visuospatial abnormalities are often found in patients with obsessive-compulsive disorder (OCD). Recent findings in unaffected relatives indicate that response inhibition and other neuropsychological functions may also constitute endophenotypes of OCD. In the present study, 30 OCD patients, 30 first-degree relatives, and 30 healthy control subjects were assessed using a comprehensive neuropsychological test battery. A subsample of 21 subjects of each group also performed an antisaccade task. The samples were matched according to age, gender, education, and verbal intelligence. The OCD patients and the unaffected OCD relatives showed increased antisaccade error rates compared with the healthy control group (p?=?0.003, p?=?0.028, respectively). Significantly prolonged antisaccade latencies as compared to prosaccade latencies were only found in the OCD patients compared with the healthy control group (p?=?0.019). Only OCD patients but not the unaffected OCD relatives were impaired with regard to visuospatial functions, problem-solving, and processing speed. Antisaccade errors did not correlate with severity of OCD or depressive symptoms. This study confirms inhibitory deficits, as indicated by increased antisaccade error rates, as a candidate endophenotype of OCD. In agreement with previous findings from imaging studies, our data suggest that functional abnormalities in frontostriatal and parietal cortical regions form part of the vulnerability for OCD.  相似文献   

6.
The purpose of the present study was to investigate the changes in the cognitive dysfunctions of patients with obsessive-compulsive disorder (OCD) over a 1-year period of pharmacological treatment. Twenty-one OCD patients and 20 normal subjects underwent neuropsychological tests and clinical evaluations on three separate occasions (baseline, 4 months, and 1 year after the start of medications). OCD patients continued to show significant impairments in the following cognitive measures compared with the normal controls: accuracy of immediate and delayed recall on the Rey-Osterrieth complex figure tests, the numbers of responses on the category fluency test, the response time on the trail making test--part A, and the number of perseverative response and perseverative errors on the Wisconsin card sorting test. The findings in this study suggested that impaired performance on cognitive domains, such as visuospatial memory and verbal fluency may underline the pathology of OCD.  相似文献   

7.
The authors aimed to investigate cognitive performance of first-degree relatives of probands with bipolar disorder (BD). They hypothesized that the relatives of BD patients would have impaired performance on cognitive tests of frontal-executive functions. A neuropsychological battery was administered to 34 first-degree relatives of BD probands and 25 control subjects. Relatives showed significant impairment in verbal working memory and executive function. Verbal memory and psychomotor performances of relatives were not different from control subjects. One particular component of executive function, cognitive flexibility, was associated with family history of mood episodes with psychotic features. Verbal working memory and executive function deficits may be useful endophenotypic markers of genetic vulnerability to BD.  相似文献   

8.
Language difficulties have been implicated to be a part of the broad autism phenotype in first-degree relatives of individuals with autism. Phonological processing difficulties in particular have been reported by some, but not all groups studying parents or siblings of probands with autism. In the present study, we examined a broad battery of language tasks and general cognitive abilities in parents of children with autistic disorder. Parents of individuals with autism (n = 22) were compared to matched adult controls on a series of cognitive and language measures. Parents of children with autism exhibited lower performance on the matrix reasoning subtest and total performance IQ than did controls, but did not show differences in verbal IQ measures, when tested with the Wechsler Abbreviated Scale of Intelligence (WASI). In addition, parents of children with autism had lower performance on a nonword repetition task, but did not show differences on tests of figurative language, receptive language, expressive language, and verbal fluency and on a questionnaire assessing history of reading difficulties. Results from this study are generally consistent with the cognitive profiles reported for parents of children with autism. Our finding of nonword repetition difficulties, along with others' previous findings for nonword reading in autism families, suggests that problems in phonological processing might be characteristic of the broad autism phenotype.  相似文献   

9.
To understand the familial relationship between obsessive-compulsive disorder (OCD), other anxiety disorders, and major depressive disorder (MDD), we examined the rates of anxiety disorders and MDD in first-degree relatives of OCD probands and controls, the association between age at onset of OCD and the occurrence of other anxiety disorders and major depressive disorder in relatives of probands, and the co-transmission of specific anxiety disorders, MDD, and OCD within families of probands. Recurrence risks were estimated from 466 first-degree relatives of 100 probands with OCD and 113 first-degree relatives of 33 non-psychiatric controls. Rates of non-OCD anxiety disorders and MDD were comparable in relatives of OCD probands and controls. Rates of anxiety disorders and MDD were higher among case relatives with OCD than among case relatives without OCD and control relatives. Fifty percent of case relatives with OCD had at least one comorbid anxiety disorder. Early age at onset (<10 years) in probands was associated with higher rates of anxiety and depression comorbidity among case relatives with OCD but not among case relatives without OCD. The occurrence of specific anxiety disorders and MDD in case relatives was independent of the same comorbid diagnosis in the OCD probands. OCD, panic disorder, generalized anxiety disorder, and MDD occurred together more often than expected by chance among individuals with OCD. Furthermore, age at onset in probands is associated with specific anxiety and affective comorbidity among case relatives. These findings support the hypothesis that early- and late-onset OCD represent different etiologic variants.  相似文献   

10.
ObjectiveStudies investigating the cognitive function of healthy relatives of patients with bipolar disorder are conflicting, and the neurocognitive profile of relatives of bipolar disorder probands is still unclear. We aimed to evaluate executive function in unaffected parents of familial and sporadic patients with bipolar disorder.MethodsThe study included 24 unaffected familial parents (FP) of patients with bipolar disorder, 26 unaffected sporadic parents (SP) of patients with bipolar disorder and 26 controls matched with the parents for gender, age and duration of education (76 subjects in total). All of the subjects were interviewed with the Structured Clinical Interview for DSM-IV-Axis I. Executive function was assessed using the California Verbal Learning Test (CVLT), the Trail Making Test (TMT), the Wisconsin Card Sorting Test (WCST) and the Stroop test.ResultsIn comparison to their respective matched controls, FP performed significantly worse on the CVLT, TMT, WCST and Stroop test, whereas SP performed significantly worse only on WCST perseverative errors and Stroop color test. FP performed significantly worse than SP on the CVLT, TMT, and WCST.ConclusionThe present study investigated relatives with and without a family history of bipolar disorder separately and found that executive function was impaired in parents with a positive family history of bipolar disorder. These findings bring more evidence suggesting that deficits in prefrontal executive function and verbal memory are associated with familial vulnerability to bipolar disorder and that executive function and verbal memory impairments may represent a potential endophenotype of bipolar disorder.  相似文献   

11.
目的 探讨精神分裂症未患病的一级亲属认知功能的特点。方法 对110例精神分裂症患者未患病一级亲属(亲属组)及50例正常对照(对照组)进行认知功能测验,包括持续注意力测试(CPT)、威斯康星卡片分类测试(WCST)、修订版韦氏记忆量表(WMS-RC)的逻辑记忆和词语流畅性测试。结果 精神分裂症患者一级亲属在WMS-RC逻辑记忆中的即刻逻辑记忆、延迟逻辑记忆,词语流畅性测试中的词语总数、词语正确数,CPT中的视觉漏报、视觉平均反映时间1和2、听觉漏报数、听觉平均反应时间1和2的成绩均差于对照组(P〈0.05)。结论 精神分裂症未患病的一级亲属存在一定程度的认知功能损害,提示认知损害可能是精神分裂症的内表型指标之一。  相似文献   

12.

Background

Impairments in executive functions and non-verbal memory are considered potential endophenotype markers of obsessive–compulsive disorder (OCD). For the neuropsychological deficits to be considered endophenotypes, they should be demonstrable in unaffected family members.

Aim

To compare the neuropsychological performance in unaffected siblings of probands with familial OCD with that of individually matched healthy controls.

Methods

Twenty-five unaffected siblings of OCD probands with familial OCD, and 25 individually matched healthy controls were assessed with tests of attention, executive function, memory and intelligence.

Results

Unaffected siblings showed significant deficits in tests of decision making and behavioural reversal i.e., the Iowa Gambling Task (IGT) and the Delayed Alternation Test (DAT) respectively, but performed adequately in other tests.

Conclusions

Our study suggests that the deficits in decision making and behavioural reversal could be potential endophenotypes in OCD. These deficits are consistent with the proposed neurobiological model of OCD involving the orbitofrontal cortex. Future studies could couple cognitive and imaging strategies to identify neurocognitive endophenotypes in homogenous samples of OCD.  相似文献   

13.
AIM: Because of the heterogeneity of schizophrenia, this study researched different cognitive patterns in distinct subtypes of schizophrenic patients. METHODS: Thirty-five Diagnostic and Statistical Manual IV (DSM IV) schizophrenic patients and 35 healthy controls were included. Patients were categorized into deficit, disorganized and positive subtypes with the schedule for the deficit syndrome (SDS) and the positive and negative syndrome scale (PANSS). Executive/attentional functions were assessed with the modified card sorting test (MCST), a test of verbal fluency, the trail making test (TMT) and the Stroop color-word test (Stroop test). Episodic memory was explored through the California verbal learning test (CVLT). RESULTS: The positive subtype had some executive/attentional (fluency and Stroop tests) and mnesic performances in the normal range, suggesting the preservation of good cognitive skills. In contrast, the deficit and disorganized subtypes had major mnesic and executive/attentional dysfunctions compared to healthy subjects. The deficit subtype compared to the control group performed predominantly worse on the MCST and fluency, whereas the disorganized subtype had the lowest scores on the TMT and the Stroop test. CONCLUSION: This study showed distinct cognitive patterns in deficit, disorganized and positive patients in comparison with the controls, suggesting a heterogeneous cognitive dysfunction in schizophrenia.  相似文献   

14.
OBJECTIVES: To determine whether juvenile obsessive-compulsive disorder (OCD) is familial and whether the rate of Tourette syndrome (TS) and tic disorders is higher among relatives of patients with OCD than among relatives of controls subjects. METHOD: We assessed first-degree relatives of 35 juvenile OCD probands (aged 16 years or less) and 34 matched, psychiatrically unaffected control subjects, using the Diagnostic Interview for Children and Adolescents-Revised (DICA-R) (unpublished), a Questionnaire for tic disorders, the Children's Version of Leyton's Obsessional Inventory (CV-LOI), and the Children's Version of the Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Similarly, we assessed adult relatives, using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Leyton's Obsessional Inventory (LOI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and a Questionnaire for tic disorders. The diagnoses were determined by consensus, using DSM-III-R criteria. We calculated age-corrected morbid risk, using Weinberg's method. RESULTS: The morbid risk for OCD among the relatives of OCD probands was 4.96%, while none of the relatives of unaffected control subjects had OCD. We did not diagnose TS in any of the relatives of either OCD probands or control subjects. We diagnosed chronic motor tic disorders in only 1 of the relatives of OCD probands, while none of the relatives of control subjects had any tic disorder. CONCLUSION: Most juvenile cases of OCD are nonfamilial and unrelated to tic disorders, while only a few are familial. There is a need to re-examine the issue of familiality in cases of OCD, as well as its relation to TS, using larger community samples to better understand the hypotheses of familial transmission and comorbidity with tic disorders.  相似文献   

15.
OBJECTIVE: The clinical overlaps between schizophrenia and obsessive-compulsive disorder (OCD) seem to be related to thought disorders involving obsessions, overvalued ideas, and delusions. Overvalued ideas are beliefs falling in between obsessions and delusions and are stronger than obsessions but weaker than delusions. The goal of the present study was to compare patients with OCD to those with schizophrenia in terms of cognitive functions and to relate cognition and overvalued ideas in OCD. METHODS: Twenty three patients with OCD (free of depression), 24 patients with schizophrenia, and 22 healthy subjects matched to patients in age, gender, education, and hand dominance were included in the study. All subjects were administered neurocognitive tests assessing verbal learning-memory, executive functions, verbal fluency, attention and verbal working memory. RESULTS: Patients with schizophrenia showed worse performance on cognitive tests than the OCD and control groups. The severity of overvalued ideas was significantly correlated to cognitive functions in the OCD group. There were no significant differences in cognitive functions between schizophrenia group and the OCD patients who had higher scores on the Overvalued Ideas Scale (OVIS). CONCLUSION: Overvalued ideas in OCD may be related to cognitive dysfunctions in OCD and this subtype of OCD may have similar characteristics to schizophrenia in terms of cognition.  相似文献   

16.
Attentional and executive impairments have been found both in patients with schizophrenia and in their unaffected first-degree relatives, suggesting that they might be considered as familial vulnerability markers. Several studies have shown that the performance of bipolar patients does not significantly differ from that of schizophrenic patients, so that executive and attentional deficits might not be specific to schizophrenia. In the present study, we aimed to identify executive dysfunctions in schizophrenia and bipolar disorder that might be vulnerability trait markers specific to one or common to both of these diseases. We assessed cognitive performance of euthymic bipolar and schizophrenic patients, their unaffected first-degree relatives and a healthy control group, using neuropsychological tasks to test different components of executive function: the Verbal Fluency Test, the Stroop Word Colour Test, the Wisconsin Card Sorting Test and the Trail Making Test. The two groups of patients and their unaffected relatives demonstrated disproportionately increased slowness on the Stroop test in comparison to the normal healthy group. Patients with schizophrenia performed poorly on all the tests in comparison to the normal healthy subjects, while no other impairment was observed in the bipolar patients and in the relatives of schizophrenic and bipolar patients. Enhanced susceptibility to interference and reduced inhibition could be transnosographical markers for a shared familial vulnerability common to schizophrenia and bipolar disorders.  相似文献   

17.
Aim:  Cognitive deficits have been presupposed to be endophenotypic markers in bipolar disorder, but few studies have ascertained the cognitive deficits in healthy relatives of bipolar disorder patients. The aim of the present study was to assess the cognitive functions of first-degree relatives of patients with bipolar disorder and compare them with healthy controls.
Methods:  Ten first-degree apparently healthy relatives of patients with bipolar disorder were compared with 10 age- and education-matched control subjects on computer-based cognitive tests.
Results:  As compared to the control group, the relatives group performed significantly poorly on tests for executive function and vigilance, while on the test for working memory the performance was not significantly different on most of the parameters.
Conclusions:  Executive functioning and vigilance could be potential markers of the endophenotype in bipolar patients.  相似文献   

18.
The N1 component of the auditory evoked potential (AEP) is a robust and easily recorded metric of auditory sensory-perceptual processing. In patients with schizophrenia, a diminution in the amplitude of this component is a near-ubiquitous finding. A pair of recent studies has also shown this N1 deficit in first-degree relatives of schizophrenia probands, suggesting that the deficit may be linked to the underlying genetic risk of the disease rather than to the disease state itself. However, in both these studies, a significant proportion of the relatives had other psychiatric conditions. As such, although the N1 deficit represents an intriguing candidate endophenotype for schizophrenia, it remains to be shown whether it is present in a group of clinically unaffected first-degree relatives. In addition to testing first-degree relatives, we also sought to replicate the N1 deficit in a group of first-episode patients and in a group of chronic schizophrenia probands. Subject groups consisted of 35 patients with schizophrenia, 30 unaffected first-degree relatives, 13 first-episode patients, and 22 healthy controls. Subjects sat in a dimly lit room and listened to a series of simple 1,000-Hz tones, indicating with a button press whenever they heard a deviant tone (1,500 Hz; 17% probability), while the AEP was recorded from 72 scalp electrodes. Both chronic and first-episode patients showed clear N1 amplitude decrements relative to healthy control subjects. Crucially, unaffected first-degree relatives also showed a clear N1 deficit. This study provides further support for the proposal that the auditory N1 deficit in schizophrenia is linked to the underlying genetic risk of developing this disorder. In light of recent studies, these results point to the N1 deficit as an endophenotypic marker for schizophrenia. The potential future utility of this metric as one element of a multivariate endophenotype is discussed.  相似文献   

19.
OBJECTIVE: Visual-spatial and executive functions deficits have been reported in obsessive-compulsive disorder (OCD). We investigated their specificity comparing cognitive function in OCD, panic disorder with agoraphobia (PD/A) and controls by a comprehensive neuropsychological battery. METHOD: Fifty-five subjects (25 OCD, 15 PD/A, 15 controls) without current depressive episode underwent structured clinical interview for DSM-IV, Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale. Neuropsychological battery assessed: executive functions, visual discrimination, spatial memory and learning, verbal memory, general intellectual functioning. RESULTS: OCD showed controlled fluency, visual-spatial construction, learning and memory deficits; PD/A spatial learning impairment. OCD was discriminated from PD/A and controls by three tests scores, predicting group membership for 76.4% of the cases. CONCLUSION: Visual-constructive and controlled fluency deficits seem specific in OCD, while the spatial learning deficit, shared with PD patients, may not be disorder-specific, but anxiety-related. Results support the proposed ventral frontal-striatal circuit involvement in OCD.  相似文献   

20.
OBJECTIVE: The authors' goal was to characterize cognitive flexibility and verbal learning in relatives of patients with bipolar disorder and in euthymic patients with recurrent major depression. METHOD: The intradimensional/extradimensional shift task and California Verbal Learning Test were administered to 27 first-degree relatives of probands with bipolar I disorder, 15 euthymic outpatients with recurrent unipolar depression, and 47 healthy comparison subjects. RESULTS: The relatives of patients with bipolar I disorder and the euthymic patients with unipolar depression were more likely to fail the intradimensional/extradimensional shift task than the healthy comparison subjects. The impairments at the extradimensional shift stage were pronounced. Verbal learning, delayed recall, and recognition were unimpaired in all groups. CONCLUSIONS: Attentional set shifting may represent an endophenotype in mood disorder, related to underlying vulnerability rather than the actual disease phenotype.  相似文献   

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