V. Balanzá-Martínez

Neurocognitive and clinical predictors of functional outcome in patients with schizophrenia and bipolar I disorder at one-year follow-up.

OBJECTIVE Many studies have reported that cognitive ability may be predictive of the functional outcome for patients with schizophrenia. However, no study has prospectively examined these aspects in schizophrenia and bipolar disorders simultaneously. The present study attempted to analyze if neurocognition and clinical status predicts the real-life functioning for patients with schizophrenia or bipolar I disorder, using a longitudinal design. METHOD Forty-seven schizophrenic and 43 bipolar I outpatients were assessed twice with a neurocognitive battery (Executive Functions, Working Memory, Verbal Memory, Visual Memory, Visual-Motor Processing, Vigilance, Vocabulary and Motor Speed tasks), clinical scales (the Positive and Negative Symptom Scale, the Hamilton Rating Scale for Depression and the Clinician Administered Rating Scale for Mania) and functional outcome measures (the Global Assessment of Functioning Scale, the WHOs Disability Assessment Scale and occupational adaptation level) over a one-year follow-up period. The cognitive performance of the patients was compared, at baseline and one year later, with that of 25 healthy subjects. RESULTS In schizophrenia patients, global functioning one year later was predicted by a composite neurocognitive score and three specific domain (verbal memory, motor speed, vocabulary). Symptoms appeared to explain less of the variance in functioning. In bipolar I patients, changes in the composite neurocognitive score over one year, deficits in the visual/motor processing domain, severity of symptoms (psychotic, excitatory and affective symptoms) and premorbid adjustment at the first assessment were the variables that better predicted functioning or disability changes over follow-up period. CONCLUSIONS Although the relationships between cognition, symptoms and functional capacity differ for schizophrenia or bipolar I patients, neuropsychological performance seems to be a principal longitudinal predictor of functioning in both disorders. Baseline neurocognition and cognitive changes over 12 months predicted changes in functioning over the same period, but only in bipolar I patients. These cognitive domains could be potential neurocognitive endophenotypes (endophenocognitypes) with regard to bipolar I disorder.

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta‐analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view.

Persistent Cognitive Dysfunctions in Bipolar I Disorder and Schizophrenic Patients: A 3-Year Follow-Up Study

Background: Neurocognitive impairment has consistently been considered a central and stable feature in schizophrenia. As this possibility has been far less studied in bipolar disorder, we aimed to prospectively investigate the stability and specificity of cognitive performance in bipolar disorder compared to schizophrenia. Methods: Fifteen DSM-IV bipolar type I patients and 15 schizophrenic patients were assessed twice with a comprehensive neuropsychological battery and the Positive and Negative Syndrome Scale over a 3-year follow-up. The cognitive performance of the groups was compared at baseline and 3 years later as a mean with that of 26 healthy volunteers. Endpoint and baseline assessments were also compared for each patient group in order to evaluate the stability of cognitive impairment. Results: At both time points, bipolar and schizophrenic patients showed significant deficits on most of the cognitive tasks compared to healthy subjects. Overall, the cross-sectional cognitive profile was similar for both patient groups. Moreover, after controlling for age and length of illness, the two groups’ cognitive function did not differ over time in any test. With the exception of the Stroop color-word interference task, performance at baseline for each test but neither length of illness nor diagnostic category predicted the endpoint performance. Conclusion: This preliminary study suggests that cognitive impairment is also mainly stable over time in bipolar I disorder and thus not specific to schizophrenia.

Staging systems in bipolar disorder: an International Society for Bipolar Disorders Task Force Report.

We discuss the rationale behind staging systems described specifically for bipolar disorders. Current applications, future directions and research gaps in clinical staging models for bipolar disorders are outlined.

Pharmacological approaches in bipolar disorders and the impact on cognition: a critical overview

Dias VV, Balanzá‐Martinez V, Soeiro‐de‐Souza MG, Moreno RA, Figueira ML, Machado‐Vieira R, Vieta E. Pharmacological approaches in bipolar disorders and the impact on cognition: a critical overview.

Effects of atypical antipsychotics on neurocognition in euthymic bipolar patients.

BACKGROUND Different factors may influence cognitive functioning in bipolar disorder such as the effect of subsyndromal symptoms, the history of psychotic symptomatology or substance abuse, negative symptomatology, chronicity, sleep disturbances, and hormonal factors. The effect of pharmacologic treatment on cognition is still uncertain because of an insufficient number of studies examining this issue. OBJECTIVE The aims of this study were to compare neuropsychologic performance of treated bipolar patients with that of controls, including unmedicated patients and healthy subjects, as well as to evaluate possible neurocognitive differences among 3 different atypical antipsychotics. RESEARCH DESIGN AND METHODS A total of 119 subjects were included in the study. Of 79 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition euthymic bipolar patients, 68 were treated with one atypical antipsychotic, quetiapine (n = 12), olanzapine (n = 26), or risperidone (n = 30). Sixteen patients were drug-free. The 4 groups were compared with a sample of drug-naïve patients and a healthy control group (n = 35) on several clinical and neuropsychologic variables, especially on the domains of attention, verbal memory, and executive functions. Euthymia was defined by a score of 6 or less at the Young Mania Rating Scale and a score of 8 or less at the Hamilton Depression Rating Scale for at least 6 months. RESULTS The 5 groups did not differ in age, years of education, sex distribution, or estimated premorbid IQ. The 4 patients groups did not differ in chronicity, age of onset, total number of episodes, and number of hospitalizations. No differences were found regarding antipsychotic dosages between the groups. Bipolar patients performed poorly on most neuropsychologic measures as compared with healthy controls. After controlling for Hamilton Depression Rating Scale symptoms, no significant change in the results was observed. Because many patients with antipsychotic treatment had a history of psychotic symptoms, we performed multivariate analysis of covariance controlling for this variable. Bipolar patients taking 1 of the 3 antipsychotics presented with dose-independent significant deficits in most cognitive tasks compared with healthy controls. After several head-to-head group comparisons, the patients receiving quetiapine showed a better performance in learning task, short-term memory, and recognition task assessed with the California Verbal Learning Test and verbal fluency (P < .05). CONCLUSIONS Our results confirm the findings of previous studies of cognitive deficits in bipolar disorder. Untreated euthymic patients showed better cognitive performance than did patients on atypical antipsychotics. Some iatrogenic-pharmacologic effect, therefore, cannot be excluded, but quetiapine seemed to be less associated with impairment in measures of verbal memory than olanzapine or risperidone. We suggest to use drugs in bipolar disorder with a lower risk of cognitive adverse effects. However, randomized controlled trials are urgently needed to give a definite answer to this critical problem.

Neurocognitive impairment and psychosocial functioning in bipolar II disorder.

Solé B, Bonnin CM, Torrent C, Balanzá‐Martínez V, Tabarés‐Seisdedos R, Popovic D, Martínez‐Arán A, Vieta E. Neurocognitive impairment and psychosocial functioning in bipolar II disorder.

Functional impairment in bipolar II disorder: Is it as disabling as bipolar I?

INTRODUCTION It is well established that patients with bipolar disorder experience functional impairment even in remission. Nevertheless, bipolar II disorder remains understudied because most investigations to date include only bipolar I patients or just a small sample of bipolar II patients, without explicitly comparing both subtypes of disorder. The main objective of the current report is to evaluate overall and multiple domains of functioning, specifically in bipolar II disorder compared to patients with bipolar I disorder and healthy subjects. METHODS 233 subjects from 3 groups were compared: bipolar I patients (n=106), bipolar II patients (n=66) and healthy controls (n=61). Bipolar patients meeting criteria of remission were recruited at the Hospital Clinic of Barcelona and at different study sites in Argentina. All participants were assessed with 17-item Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS) and the Functioning Assessment Short Test (FAST). Clinical and sociodemographic data were also recorded. RESULTS Both subgroups of patients, bipolar I and bipolar II, showed lower overall functioning (p<0.001) and in each domain of the FAST scale (all, p<0.001) when compared to the healthy control group. Tukey post hoc test revealed that bipolar II patients scored worse in the cognitive domain compared to bipolar I patients. However, after controlling for potential confounding variables, this difference disappeared and only older age (p<0.005) and HAM-D scores (p<0.001) remained significant. CONCLUSIONS Our results suggest that bipolar II patients are as disabled as bipolar I patients. This may be explained, in part, because bipolar II patients experience greater lifetime residual depressive symptoms than the bipolar I subgroup, which may have particular impact on cognitive domains of functioning.

Specific executive/attentional deficits in patients with schizophrenia or bipolar disorder who have a positive family history of psychosis

Neurocognitive impairments are well documented in patients with schizophrenia and their healthy first-degree biological relatives. Less is known about neuropsychological performance in bipolar disorders, but some studies indicate that, compared to schizophrenia, bipolar disorder displays a similar profile pattern with less severe deficits. The genetic and environmental contributions to the development of neurocognitive deficits are also unclear. This study explored the effect of a family history (FH) of psychotic disorders in first-degree relatives on a variety of cognitive domains (abstraction and flexibility, verbal fluency, verbal memory, motor activity and visual-motor processing/attention) in 30 patients with schizophrenia, and 24 type I bipolar patients. After adjusting the results for age, gender, education level and pre-morbid intelligence, patients with schizophrenia or bipolar disorder with positive FH (n=18) performed significantly worse than patients with negative FH (n=36) on the visual-motor processing/attention domain. These findings were independent of the specific diagnosis. Moreover, when logistic regression analysis was performed, poor Digit Symbol performance was the only predictor of belonging to the positive FH group. Our results are compatible with the existence of some common genetic factors between the illnesses, as well as the involvement of identical, or at least similar, disordered brain systems in both disorders. These findings are discussed within the context of the continuum model of psychosis.

High cognitive reserve in bipolar disorders as a moderator of neurocognitive impairment

BACKGROUND Cognitive reserve (CR) reflects the capacity of the brain to endure neuropathology, minimize clinical manifestations and successfully complete cognitive tasks. The present study aims to determine whether high CR may constitute a moderator of cognitive functioning in bipolar disorder (BD). METHODS 102 patients with BD and 32 healthy controls were enrolled. All patients met DSM-IV criteria for I or II BD and were euthymic (YMRS≤6 and HDRS≤8) during a 6-month period. All participants were tested with a comprehensive neuropsychological battery, and a Cerebral Reserve Score (CRS) was estimated. Subjects with a CRS below the group median were classified as having low CR, whereas participants with a CRS above the median value were considered to have high CR. RESULTS Participants with BD with high CR displayed a better performance in measures of attention (digits forward: F=4.554, p=0.039); phonemic and semantic verbal fluency (FAS: F=9.328, p=0.004; and Animal Naming: F=8.532, p=0.006); and verbal memory (short cued recall of California Verbal Learning Test: F=4.236, p=0.046), after multivariable adjustment for potential confounders, including number of admissions and prior psychotic symptoms. LIMITATIONS The cross-sectional design of the study does not allow the establishment of causal inferences. Additionally, the small size of the sample may have limited some results. CONCLUSIONS High cognitive reserve may therefore be a valuable construct to explore for predicting neurocognitive performance in patients with BD regarding premorbid status.