Impairment of executive function but not memory in first-degree relatives of patients with bipolar I disorder and in euthymic patients with unipolar depression

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.     

Impaired sustained attention in euthymic bipolar disorder patients and non‐affected relatives: an fMRI study

Sepede G, De Berardis D, Campanella D, Perrucci MG, Ferretti A, Serroni N, Moschetta FS, Del Gratta C, Salerno RM, Ferro FM, Di Giannantonio M, Onofrj M, Romani GL, Gambi F. Impaired sustained attention in euthymic bipolar disorder patients and non‐affected relatives: an fMRI study. Bipolar Disord 2012: 14: 764–779. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Behavioral deficits in sustained attention have been reported during both acute and euthymic phases of type I bipolar disorder (BD‐I) and also in non‐affected relatives of bipolar disorder (BD) patients. In particular, selective failure in target recognition was proposed as a potential trait marker for BD, but there are few studies exploring the neural correlates. The aim of the present study was to analyze the behavioral and functional magnetic resonance imaging (fMRI) response of euthymic BD‐I patients and non‐affected relatives during a sustained attention task. Methods: Twenty‐four euthymic BD‐I patients, 22 non‐affected first‐degree relatives of BD‐I subjects, and 24 matched controls underwent a continuous performance test (CPT) with two levels of difficulty during event‐related fMRI scanning. Results: Both patients and relatives showed a lower accuracy in target detection when compared to controls. The fMRI data analysis revealed between‐group differences in several brain regions involved in sustained attention. During error in target recognition, both patients and relatives showed a larger activation in the bilateral insula and the posterior part of the middle cingulate cortex. By contrast, during correct target response, only patients failed to activate the right insula, whereas relatives showed an increased activation of the left insula and bilateral inferior parietal lobule – limited to the higher attention load – and an augmented deactivation of the posterior cingulate/retrosplenial cortex. Conclusions: A selective impairment in target recognition during a CPT was behaviorally and functionally detectable in both euthymic BD‐I patients and non‐affected first‐degree relatives, suggesting that specific sustained attention deficits may be a potential trait marker for BD‐I.     

Neurocognitive impairment in euthymic young adults with bipolar spectrum disorder and recurrent major depressive disorder

OBJECTIVE: Patients with remitted major depressive disorder (MDD) and bipolar disorder have persistent impairments in executive function and verbal memory that may represent endophenotypic abnormalities. In this study, we examine neurocognitive function in a sample of euthymic young adults with bipolar spectrum disorder (BSD) (Can J Psychiatry 2002; 47: 125-134) and compare this to well-matched samples of young adults with recurrent MDD and controls. METHOD: Twenty-one euthymic young adult patients with BSD were compared with 42 young adult patients with MDD and 33 controls on a neuropsychological battery assessing attention, executive function and verbal memory. RESULTS: Patients with BSD were significantly more impaired than MDD patients and controls on tests of executive function and verbal memory. MDD patients did not differ significantly from controls on verbal memory function but performed less well on a test of executive function. CONCLUSION: Euthymic young adults with BSD had greater impairment on neurocognitive measures associated with prefrontal and hippocampal function than MDD patients and controls. This is a reflection of a strong bipolar diathesis in the BSD group rather than being a consequence of a more severe unipolar illness.     

Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis

OBJECTIVE: Although cognitive deficits are prominent in symptomatic patients with bipolar disorder, the extent and pattern of cognitive impairment in euthymic patients remain uncertain. METHOD: Neuropsychological studies comparing euthymic bipolar patients and healthy controls were evaluated. Across studies, effect sizes reflecting patient-control differences in task performance were computed for the 15 most frequently studied cognitive measures in the literature. RESULTS: Across the broad cognitive domains of attention/processing speed, episodic memory, and executive functioning, medium-to-large performance effect size differences were consistently observed between patients and controls, favoring the latter. Deficits were not observed on measures of vocabulary and premorbid IQ. CONCLUSION: Meta-analytic findings provide evidence of a trait-related neuropsychological deficit in bipolar disorder involving attention/processing speed, memory, and executive function. Findings are discussed with regard to potential moderators, etiologic considerations, limitations, and future directions in neuropsychological research on bipolar disorder.     

Impaired working memory monitoring in euthymic bipolar patients

OBJECTIVES: Converging evidence suggests that patients with remitted bipolar disorder (BD) have a persistent cognitive deficit in the executive control of working memory (WM). However, the component operations that contribute to this deficit remain unclear. The aim of the present study was to further profile the nature and specificity of WM impairment in euthymic BD. METHODS: Fifty DSM-IV-confirmed patients with euthymic BD and demographically matched controls completed a modified version of the Self-Ordered Pointing Task (SOPT) and the Cambridge Neuropsychological Test Automated Battery Pattern Recognition Test along with traditional executive and WM tasks [Stroop, initial letter Verbal Fluency (FAS), Trail-Making, Digits Forwards and Backwards]. Prospective clinical ratings over one month prior to testing confirmed that patients were euthymic at test. Absence of basal hypercortisolaemia was confirmed by serial saliva sampling. RESULTS: Error analysis revealed that whilst patients made more errors on the SOPT overall, they were no more likely to perseverate than controls. Patients' erroneous responses did not proliferate across trials, suggesting that proactive interference did not contribute to their poor performance, but serial position effects were evident where patients' errors clustered towards the end of a trial. No differences were found on the recognition memory test, in WM capacity, or on two of the three traditional executive procedures (FAS and Trail-Making). However, patients' Digits Backwards was impaired. CONCLUSIONS: These data suggest that patients with BD have a deficit in their ability to monitor the contents of WM. This deficit is not an epiphenomenon of mood, but may be due to enduring brain dysfunction, integral to bipolar illness.     

Fronto-limbic circuitry in euthymic bipolar disorder: evidence for prefrontal hyperactivation

Functional magnetic resonance imaging (fMRI) studies of bipolar disorder have revealed fronto-limbic abnormalities in patients during manic and depressive episodes. However, relatively few studies have examined neural activity during euthymia, leaving unanswered questions concerning the impact of mood state on activity in these brain regions. In the present study, we examined 15 remitted bipolar type I patients and 16 demographically matched healthy comparison subjects during performance on an affective face-matching task previously shown to elicit amygdala hyperactivation and prefrontal hypoactivation in manic relative to healthy subjects. In our euthymic sample, amygdala activation did not differ from controls. However, bipolar patients showed hyperactivation in inferior prefrontal cortical regions compared with controls, a finding that contrasts with the hypoactivation previously reported in this region in manic patients. Given the reciprocal relationship between the prefrontal cortex and limbic structures, we propose state-related amygdala activity, similar to that of healthy controls, may be associated with prefrontal hyperactivation when bipolar patients are asymptomatic.     

Evidence for theory of mind deficits in euthymic patients with bipolar disorder

OBJECTIVE: i) To investigate the subtle ToM (theory of mind) deficits in euthymic patients with bipolar disorder. ii) To investigate the impact of non-ToM cognitive deficits on ToM abilities. METHOD: Forty-three euthymic patients with bipolar disorder and 30 healthy control subjects were involved in this study. ToM was assessed by the Eyes test and the Hinting task. Both groups were also evaluated with a comprehensive neuropsychological battery including tasks for basic emotion and face recognition. RESULTS: The patient group was impaired on both of the ToM tasks. The patient group also showed impairment in many cognitive tasks including tasks related to sustained attention. CONCLUSION: Even euthymic patients with bipolar disorder may be impaired in advanced ToM tasks. Executive dysfunction and some other cognitives deficits such as basic emotion recognition may be at least partly responsible for this result.     

The effect of previous psychotic mood episodes on cognitive impairment in euthymic bipolar patients

OBJECTIVES: Cognitive dysfunctions in several domains were proposed to be trait markers of bipolar patients. The aim of this study was to evaluate the effect of previous psychotic features on neuropsychological measures, including sustained attention, in remitted bipolar patients. METHODS: The study participants were 40 euthymic psychotic, 25 non-psychotic bipolar I patients and 30 healthy control subjects. Participants were assessed with a battery of neuropsychological tests targeting attention, executive functions, psychomotor speed, verbal learning and memory. RESULTS: Euthymic psychotic bipolar patients performed worse than controls on most of the measures, after controlling for the confounding effects of education, age and residual symptoms. Non-psychotic patients were also impaired on tasks of attention, fluency and psychomotor speed. 'Number of Wisconsin Card Sorting Test (WCST) categories' achieved was the only measure on which psychotic patients performed significantly worse compared to non-psychotic patients. Differences among patient groups were not explained by illness severity measures. The duration of illness was related to slowness in psychomotor speed tasks. Verbal memory deficits may be related to serum lithium levels and age of onset of disease. CONCLUSIONS: Deficits in cognitive flexibility may be a candidate for being a trait marker of psychotic features among bipolar patients. However, verbal fluency, psychomotor speed and sustained attention deficits may be candidates for vulnerability indicators of bipolar disorder in general.     

Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives psychiatrically and pediatrically referred samples.

We examined 140 probands with attention deficit hyperactivity disorder, 120 normal controls, and their 822 first-degree relatives using "blind" raters and structured diagnostic interviews. Compared with controls, probands with attention deficit hyperactivity disorder were more likely to have conduct, mood, and anxiety disorders. Compared with relatives of controls, relatives of probands with attention deficit hyperactivity disorder had a higher risk for attention deficit hyperactivity disorder, antisocial disorders, major depressive disorder, substance dependence, and anxiety disorders. Patterns of comorbidity indicate that attention deficit hyperactivity disorder and major depressive disorders may share common familial vulnerabilities, that attention deficit hyperactivity disorder plus conduct disorder may be a distinct subtype, and that attention deficit hyperactivity disorder and anxiety disorders are transmitted independently in families. These results extend previous findings indicating family-genetic influences in attention deficit hyperactivity disorder by using both pediatrically and psychiatrically referred proband samples. The distributions of comorbid illnesses in families provide further validation for subgrouping probands with attention deficit hyperactivity disorder by comorbidity.     

Prefrontal and paralimbic metabolic dysregulation related to sustained attention in euthymic older adults with bipolar disorder

Brooks JO III, Bearden CE, Hoblyn JC, Woodard SA, Ketter TA. Prefrontal and paralimbic metabolic dysregulation related to sustained attention in euthymic older adults with bipolar disorder.
Bipolar Disord 2010: 12: 866–874. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objective: Reports of sustained attention deficits in the euthymic phase of bipolar disorder have been variable, and have yet to be related to cerebral metabolism. In the present study, we evaluated relationships between cognitive performance deficits and resting cerebral metabolism in euthymic older adults with bipolar disorder. Methods: Sixteen older (mean age 58.7 years) euthymic outpatients with bipolar disorder (10 type I, 6 type II; 44% female) and 11 age‐matched healthy controls received resting positron emission tomography with ¹⁸fluorodeoxyglucose and, within 10 days, the Conners’ Continuous Performance Test‐II, a commonly used measure of sustained attention and inhibitory control. Results: Bipolar disorder patients had significantly more omission errors (z = 2.53, p = 0.01) and a trend toward more commission errors (z = 1.83, p < 0.07) than healthy controls. Relative to healthy controls, among bipolar disorder subjects commission errors were more strongly related to inferior frontal gyrus [Brodmann area (BA) 45/47] hypometabolism and paralimbic hypermetabolism. In bipolar disorder subjects, relative to controls, omission errors were more strongly related to dorsolateral prefrontal (BA 9/10) hypometabolism and greater paralimbic, insula, and cingulate hypermetabolism. Conclusions: In older adults with bipolar disorder, even during euthymia, resting‐state corticolimbic dysregulation was related to sustained attention deficits and inhibitory control, which could reflect the cumulative impact of repeated affective episodes upon cerebral metabolism and neurocognitive performance. The relative contributions of aging and recurrent affective episodes to these differences in bipolar disorder patients remain to be established.     

Affective disorders in the first-degree relatives of bipolar probands: results from the South Island Bipolar Study

The current study was performed to document observed rates of affective disorders in the first degree relatives of probands with bipolar I or II disorder; to determine whether bipolar II probands have an excess of bipolar II relatives; and to determine whether bipolar probands with a history of one or more suicide attempts have more relatives who have also made suicide attempts. Bipolar probands with positive family histories of affective disorder were recruited from a variety of sources for a study on the molecular genetics of bipolar disorder. Probands and relatives were interviewed with the Diagnostic Interview for Genetic Studies (DIGS) and blood was obtained for DNA extraction and genetic analyses. Among 423 first-degree adult relatives of 153 bipolar probands, 7% (29) had bipolar I disorder, 7% had bipolar II disorder, and 7% had bipolar not otherwise specified (NOS) disorder, making 21% of relatives with any bipolar disorder. A further 42% of relatives had a depressive disorder and only 38% had no affective disorder. A suicide attempt by a proband was not associated with any increase in suicide attempts by relatives. We conclude that while unipolar depressive disorders are the most common affective disorders in the first-degree relatives of bipolar probands, extension of the bipolar phenotype to include bipolar spectrum disorders results in 21% of relatives having any bipolar disorder.     

Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients

OBJECTIVE: A systematic evaluation of neuropsychological functioning in individuals with pediatric bipolar disorder is necessary to clarify the types of cognitive deficits that are associated with acutely ill and euthymic phases of the disorder and the effects of medication on these deficits. METHOD: Unmedicated (N=28) and medicated (N=28) pediatric bipolar patients and healthy individuals (N=28) (mean age=11.74 years, SD=2.99) completed cognitive testing. Groups were matched on age, sex, race, parental socioeconomic status, general intelligence, and single-word reading ability. A computerized neurocognitive battery and standardized neuropsychological tests were administered to assess attention, executive function, working memory, verbal memory, visual memory, visuospatial perception, and motor skills. RESULTS: Subjects with pediatric bipolar disorder, regardless of medication and illness status, showed impairments in the domains of attention, executive functioning, working memory, and verbal learning compared to healthy individuals. Also, bipolar subjects with comorbid attention deficit hyperactivity disorder (ADHD) performed worse on tasks assessing attention and executive function than patients with bipolar disorder alone. CONCLUSIONS: The absence of differences in the deficits of neurocognitive profiles between acutely ill unmedicated patients and euthymic medicated patients suggests that these impairments are trait-like characteristics of pediatric bipolar disorder. The cognitive deficits found in individuals with pediatric bipolar disorder suggest significant involvement of frontal lobe systems supporting working memory and mesial temporal lobe systems supporting verbal memory, regardless of ADHD comorbidity.     

Neurocognitive function in unaffected first-degree relatives of patients with bipolar disorder: a preliminary report

OBJECTIVE: Patients with remitted bipolar disorder (BD) have persistent impairments in neuropsychological function, particularly in the domains of executive control and declarative memory [Br J Psychiatry 180 (2002) 293]. If these were the phenotypic expression of genetic vulnerability to BD, then healthy subjects with a genetic predisposition to BD would be expected to display the same deficits. This study, therefore, examined neuropsychological function in healthy first-degree relatives of patients with BD. METHOD: A cross-sectional design was employed to compare the performance of 17 unaffected first-degree relatives of BD patients and 17 demographically matched controls on a range of neuropsychological tests. RESULTS: Relatives were significantly impaired on Backward Digit Span, Spatial Span and on tasks of visuospatial declarative memory in comparison with controls. Psychomotor performance and verbal declarative memory were intact, as were non-working memory aspects of executive performance. CONCLUSION: The selective deficits in executive control and declarative memory exhibited by relatives in this study have previously been reported in euthymic BD patients suggesting they may be useful endophenotypic markers of genetic vulnerability to BD.     

Neurocognitive functions in euthymic bipolar patients

Objective: Meta‐analytic findings support the hypothesis of specific neurocognitive deficits for bipolar patients in the domains of attention, processing speed, memory and executive functions. This study aims to show neurocognitive impairment in euthymic patients with bipolar I disorder compared with healthy controls while detailing the impact of medication side‐effects or illness characteristics on neuropsychological test performance. Method: Forty euthymic patients with bipolar I disorder were compared with 40 healthy controls in a cross‐sectional design. Clinical features and neuropsychological measures of IQ, psychomotor speed, verbal fluency, learning and memory, executive functions and attention were assessed. Results: Patients without antipsychotic drug use did not differ significantly from healthy controls in any neuropsychological measure. Yet patients treated with antipsychotics showed significant underperformance in the domains of semantic fluency, verbal learning and recognition memory as well as executive functions related to planning abilities, even when clinical features were controlled for. Conclusion: The impact of antipsychotic medication needs to be further clarified for euthymic bipolar patients and should be considered when neuropsychological test performance is interpreted.     

Sustained attention deficits in manic and euthymic patients with bipolar disorder

Sustained attention deficits are proposed to be both state and trait indicators of bipolar disorder. The nature of these deficits and their association with medication and symptoms is not clear yet. The aim of this study was to investigate the impairments in various components of sustained attention task in euthymic and manic patients and was to investigate the relationship between the deficits in the manic state and medication effects. The performances of 37 manic patients, 34 euthymic patients with bipolar disorder and 34 control subjects on eight scores from Conners' CPT II, reflecting three different dimensions of sustained attention were compared. Similar to some recent findings, euthymic patients had decreased target sensitivity (omission errors) and response time inconsistency. The increased false responding (commission errors), perseveration and vigilance deficits were prominent in the manic patients. These state dependent impairments could not be explained by the impact of medication. In contrast, the exacerbation of seemingly trait-related impairments in the manic state can be at least partly explained by the impact of pharmacological therapy.     

Neuropsychological profile in bipolar disorder: a preliminary study of monotherapy lithium-treated euthymic bipolar patients evaluated at a 2-year interval

Objective: To investigate the cognitive impairment of a sample of euthymic bipolar patients treated with lithium monotherapy at baseline in a 2‐year longitudinal study. Method: Fifteen DSM‐IV‐TR bipolar out‐patients and 15 healthy‐matched controls were cognitively assessed twice over a 2‐year follow‐up. All patients underwent lithium monotherapy on the first evaluation, and they were euthymic in both evaluations. Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). Results: Repeated measures multivariate analysis of variance showed that the bipolar disorder group was cognitively impaired in the executive domain, attention and processing speed, and such deficits were maintained over time. Conclusion: Our results showed that executive dysfunction is the main long‐term neuropsychological deficit of bipolar disorder. Also, the persistence of these deficits did not seem to be influenced by any clinical or pharmacological variables.     

A comparison of euthymic bipolar patients with unaffected first-degree relatives and healthy controls in terms of neuropsychological functions

Objective. Cognitive dysfunction in bipolar disorder (BD) is well established in the literature. The neurocognitive deficits have been considered to be endophenotypic markers of BD, and studies have examined whether neurocognitive deficits exist in first-degree relatives of individuals with BD I. We hypothesized that performance in tests of neurocognitive function would be impaired in euthymic BD I patients and their unaffected first-degree relatives compared to that of healthy controls. Methods. We compared the performance of bipolar patients, their first-degree relatives, and healthy controls in a battery of neurocognitive tests to reveal possible endophenotypes of BD. A diagnostic interview and neuropsychological test battery were administered to 30 BD I patients, 55 of their unaffected first-degree relatives and 32 healthy controls. Results. The patients and their first-degree relatives were significantly impaired in executive function assessed using the Wisconsin Card Sorting Test (WCST) and Trail Making Test-B (TMT-B) relative to the controls (WCST; perseverative errors: p < 0.0005, categories completed: p = 0.002, TMT-B; p = 0.002). There were no significant differences between the groups in terms of attention, psychomotor speed, verbal memory, or learning. Conclusion. Our study suggests that the deficits in executive function may be endophenotypic markers of genetic vulnerability to BD I.     

Comorbid bipolar disorder and panic disorder in families with a high prevalence of bipolar disorder.

OBJECTIVE: Panic attacks are a common complication of affective disorder, although the etiologic relationship of panic and affective symptoms has not been determined. Evidence from a family study suggests that panic attacks and panic disorder may be related genetically to bipolar disorder. This study used diagnostic data from the NIMH Bipolar Disorder Genetics Initiative to assess in a separate, larger family set the familiality of panic combined with bipolar disorder. METHOD: First-degree relatives (N=966) of probands with bipolar I disorder (N=192) and schizoaffective disorder, bipolar type, (N=11) were included in the study. All subjects were interviewed directly and were assigned best-estimate diagnoses for major affective and other psychiatric disorders. The risk of a family member being diagnosed with panic disorder if the proband with bipolar disorder had panic attacks or panic disorder was calculated with logistic regression analysis with generalized estimating equations that controlled for sex and affective disorder subdiagnosis. RESULTS: More than 90% of the probands and first-degree relatives with panic disorder also had an affective disorder diagnosis. Panic disorder was present in 17% of the relatives with recurrent major affective disorder and in 3% of the relatives without recurrent major affective disorder. Risk of panic disorder in relatives with bipolar disorder was increased significantly if the proband had panic attacks or panic disorder. CONCLUSIONS: Risk for panic disorder with familial bipolar disorder appears to be inherited. Inherited risk for panic disorder with bipolar disorder may indicate a shared genetic etiology for both disorders in some families. The patterns of bipolar disorder and panic disorder comorbidity observed in families imply a complex genetic etiology, which may be elucidated by using endophenotypes.     

Familial aggregation of delusional proneness in schizophrenia and bipolar pedigrees

OBJECTIVE: Clinical, familial, and, more recently, genetic linkage studies suggest that overlapping genetic susceptibility might contribute to both schizophrenia and bipolar disorder. To identify a potential psychotic dimension common to families of both bipolar and schizophrenia probands, the authors tested if delusional proneness was observed among first-degree relatives of bipolar and schizophrenia probands. METHOD: The authors included 32 schizophrenia probands and 61 bipolar probands and their respective first-degree relatives (N=63 and N=59). They were all interviewed with the Diagnostic Interview for Genetic Studies, and delusional proneness was assessed with a self-report questionnaire, the Peters et al. Delusions Inventory. Schizophrenia and bipolar probands were subdivided into subgroups according to the intensity of delusional symptoms assessed by Peters et al. Delusions Inventory scores, and the authors compared delusional proneness in their respective first-degree relatives. RESULTS: Familial aggregation of delusional proneness was demonstrated, since Peters et al. Delusions Inventory scores were higher among nonschizophrenic first-degree relatives of schizophrenia probands with productive symptoms and among first-degree relatives of bipolar probands with psychotic features during their affective episodes. The authors also found an intrafamilial correlation of delusional proneness scores in nonaffected siblings of schizophrenia and bipolar probands. CONCLUSIONS: Delusional proneness appears to be an inherited predisposition common to both schizophrenia and bipolar disorder. In the future, this dimension might be valuable when used as a quantitative phenotype in linkage and association studies.     

Facial emotion recognition in euthymic patients with bipolar disorder and their unaffected first-degree relatives

BackgroundFacial emotion recognition (FER) is an important task associated with social cognition because facial expression is a significant source of non-verbal information that guides interpersonal relationships. Increasing evidence suggests that bipolar disorder (BD) patients present deficits in FER and these deficits may be present in individuals at high genetic risk for BD. The aim of this study was to evaluate the occurrence of FER deficits in euthymic BD patients, their first-degree relatives, and healthy controls (HC) and to consider if these deficits might be regarded as an endophenotype candidate for BD.MethodsWe studied 23 patients with DSM-IV BD type I, 22 first-degree relatives of these patients, and 27 HC. We used the Penn Emotion Recognition Tests to evaluate tasks of FER, emotion discrimination, and emotional acuity. Patients were recruited from outpatient facilities at the Institute of Psychiatry of the University of Sao Paulo Medical School, or from the community through media advertisements, had to be euthymic, with age above 18 years old and a diagnosis of DSM-IV BD type I.ResultsEuthymic BD patients presented significantly fewer correct responses for fear, and significantly increased time to response to recognize happy faces when compared with HC, but not when compared with first-degree relatives. First-degree relatives did not significantly differ from HC on any of the emotion recognition tasks.ConclusionOur results suggest that deficits in FER are present in euthymic patients, but not in subjects at high genetic risk for BD. Thus, we have not found evidence to consider FER as an endophenotype candidate for BD.