Vicent Balanzá-Martínez

Neurocognitive endophenotypes (Endophenocognitypes) from studies of relatives of bipolar disorder subjects: A systematic review

BACKGROUND There is growing interest to research neurocognition as a putative endophenotype for subjects with bipolar disorders (BD). The authors sought to review the available literature focused on relatives of subjects with bipolar disorder (BD-Rels) and identify suitable cognitive candidates to endophenotypes or endophenocognitypes. METHOD A systematic review was conducted in Medline, EMBASE and PsycINFO databases (1980-July 2007), supplemented with a manual search of reference lists. RESULTS Twenty-three cross-sectional papers of discordant twins (4 studies), genetic high-risk subjects (7), and different BD-Rel groups (12) met the inclusion criteria and evaluated 532 BD-Rels. Impairments on the broad domain of verbal learning/memory were found in 6 out of 11 studies (54%), as well as in 3 of 9 reports (33%) of working memory. Moreover, BD-Rels showed deficits in visual-spatial learning and memory (1/6 reports; 17%), alternating attention (1/8; 12.5%), psychomotor speed (2/10; 20%), and abstraction/cognitive flexibility, sustained attention and selective attention (2/8 each; 25%). Scores of general intelligence were lower than those of controls in 2/16 (12.5%) reports, but fell well within the average range in all studies. No study that assessed immediate memory or verbal fluency (6 each) reported impairments in BD-Rels. Finally, language, social cognition, and motor and planning skills are neglected areas of research. CONCLUSIONS Overall, the neurocognitive profile in BD-Rels is still unclear, and the evidence in support of the presence of cognitive deficits seems quite sparse. Verbal learning/memory and verbal working memory seem to be the most suitable endophenocognitypes for BD. Conversely, healthy family members would have an intact performance on immediate memory, verbal fluency, and probably on general intelligence. The possibility that BD-Rels show less cognitive efficiency compared to healthy controls also on other functions must be addressed by future studies with larger samples, comprehensive neuropsychological assessments, and, ideally, longitudinal designs.

Specificity of cognitive deficits in bipolar disorder versus schizophrenia. A systematic review.

Background: More and more epidemiological, genetic and neuroimaging studies show similarities between bipolar disorder (BD) and schizophrenia (SZ). Cognitive functions are known to be highly impaired in SZ and are increasingly studied in BD. When both populations are compared, the conclusions appear to be contradictory. The purpose of this review is to help define the profile of cognitive deficits in BD and in SZ. Methods: A systematic review of the literature of neuropsychological studies comparing BD and SZ was made, beginning in January 1990 and ending in January 2005. Thirty-eight studies met the required quality criteria and were included in this review. Results: Bipolar patients exhibit extensive cognitive abnormalities with a pattern of deficits that is not unique to this disease. However, when compared to schizophrenic patients, bipolar patients demonstrate a lesser degree of deficits, particularly concerning premorbid and current intelligence quotient and perhaps attention, verbal memory and executive functions. When looking into effect sizes, there seem to be different profiles even in studies finding no significant differences. Conclusions: The neuropsychological differences reported between both groups could be due to the presence of psychotic features, to environmental factors (stressful events, duration of the disease and number of hospitalisations) and could also be related to differences during the neurodevelopmental phase. Further studies should confirm whether these results are truly related to different neurobiological backgrounds.

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Nutritional medicine as mainstream in psychiatry

Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health.

Neurocognition in bipolar disorders—A closer look at comorbidities and medications

The last decade has witnessed a growing interest in the neuropsychological study of bipolar disorder (BD). This chronic mood disorder is associated with persistent neurocognitive impairments even during periods of euthymia, particularly in the broad domains of attention, verbal memory and executive functions. More interestingly, cognitive dysfunction seems to predict a poorer functional outcome among BD patients and thus represents an important target for future therapies. The aetiology of cognitive dysfunction is probably multifactorial, including gene-environment interactions with potentially confounding variables as well. Drug-induced cognitive adverse effects represent an important and difficult to examine confounder. This review provides an overview of selected aspects of neurocognition in bipolar disorder with a focus on the relative contributions of medications as well as medical and psychiatric comorbid conditions to cognitive dysfunction. Finally, recommendations for future research in the field are provided including collaborative studies with larger samples, observational follow-up studies, as well as randomized clinical trials comparing head-to-head the neurocognitive impact of different medications.

Comparative study of neurocognitive function in euthymic bipolar patients and stabilized schizophrenic patients

Few studies have compared neurocognitive performance in euthymic patients with bipolar disorder (BD), stabilized patients with schizophrenia (SC) and normal controls (NC) using a comprehensive neuropsychological battery, and those that have been conducted have yielded discrepant results. We evaluated the neurocognitive profile shown by 73 euthymic patients with BD, 89 stabilized patients with SC and 67 NC. All participants completed a cognitive battery in which the domains evaluated were executive functioning, sustained attention, and verbal and visual memory. Individuals with BD were administered the Quality of Life Scale (QLS). Patients with BD manifested dysfunction in executive functioning (moderate-to-large effect size), sustained attention (moderate effect size) and verbal/visual memory (large effect size) compared with NC. Verbal memory deficit in patients with BD was related to poor functional outcome on the QLS and Global Assessment of Functioning (GAF). Patients with BD performed significantly better than patients with SC on the Trail Making Test (TMT) part B, backward digit span, and California Verbal Learning Test (CVLT) learning trials. Other neuropsychological measures showed no significant differences between the two patient groups. These findings support the notion that euthymic BD patients suffer from an extensive neurocognitive deficit that affects all cognitive domains and is qualitatively similar to that in SC patients. Persistent verbal memory impairment in BD has clinical relevance because it is associated with poor psychosocial function.

Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies

Background: There is a lack of scientific consensus about cancer comorbidity in people with central nervous system (CNS) disorders. This study assesses the co-occurrence of cancers in patients with CNS disorders, including Alzheimers disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders, Downs syndrome (DS), Huntingtons disease (HD), multiple sclerosis (MS), Parkinsons disease (PD) and schizophrenia (SCZ). Method: Comprehensive search in PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published before March 2013. We identified 51 relevant articles from 2,229 discrete references, 50 of which contained data suitable for quantitative synthesis (577,013 participants). Pooled effect sizes (ES) were calculated using multiple random-effects meta-analyses. Sources of heterogeneity and uncertainty were explored by means of subgroup and sensitivity analyses, respectively. Results: The presence of CNS disorders was associated with a reduced co-occurrence of cancer (ES = 0.92; 95% confidence interval, CI: 0.87-0.98; I2 = 94.5%). A consistently lower overall co-occurrence of cancer was detected in patients with neurodegenerative disorders (ES = 0.80; 95% CI: 0.75- 0.86; I2 = 82.8%), and in those with AD (ES = 0.32; 95% CI: 0.22-0.46; I2 = 0.0%), PD (ES = 0.83; 95% CI: 0.76-0.91; I2 = 80.0%), MS (ES = 0.91; 95% CI: 0.87-0.95; I2 = 30.3%) and HD (ES = 0.53; 95% CI: 0.42-0.67; I2 = 56.4%). Patients with DS had a higher overall co-occurrence of cancer (ES = 1.46; 95% CI: 1.08-1.96; I2 = 87.9%). No association was observed between cancer and ALS (ES = 0.97; 95% CI: 0.76-1.25; I2 = 0.0%) or SCZ (ES = 0.98; 95% CI: 0.90-1.07; I2 = 96.3%). Patients with PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower co-occurrence of other specific cancers (e.g. lung, prostate and colorectal cancers in PD; lung and prostate cancers in MS; and melanoma and prostate cancer in SCZ). Conclusion: Increased and decreased co-occurrence of cancer in patients with CNS disorders represents an opportunity to discover biological and non-biological connections between these complex disorders.

Symptomatic remission in schizophrenia patients: Relationship with social functioning, quality of life, and neurocognitive performance

PURPOSE To investigate whether symptomatic remission relates to better outcomes in schizophrenia. METHODS Seventy-six schizophrenia patients were assessed using measures of cross-sectional symptomatic remission, social functioning, subjective quality of life (QoL), and cognition. RESULTS Most patients (53; 69.7%) were not in remission. Remitted patients presented significantly better social functioning, better self-reported QoL, insight, and lower levels of depressive symptoms. They also showed a non-significant trend for better executive function, processing speed and verbal memory. CONCLUSIONS Symptomatic remission may be a good indicator of better clinical status, social functioning and QoL, but not so much for cognitive functioning.

The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper’s blending of experimental trials with observational research is particularly appropriate and effective.

Psychiatric Comorbidity at the Time of Diagnosis in Adults With ADHD: The CAT Study

Objective: The CAT (Comorbilidad en Adultos con TDAH) study aimed to quantify and characterize the psychiatric comorbidity at the time of diagnosis of ADHD in adult outpatients. Method: Cross-sectional, multicenter, observational register of adults with ADHD diagnosed for the first time. Results: In this large sample of adult ADHD (n = 367), psychiatric comorbidities were present in 66.2% of the sample, and were more prevalent in males and in the hyperactive-impulsive and combined subtypes. The most common comorbidities were substance use disorders (39.2%), anxiety disorders (23%), and mood disorders (18.1%). In all, 88.8% patients were prescribed pharmacological treatment for ADHD (in 93.4% of cases, modified release methylphenidate capsules 50:50). Conclusion: A high proportion of psychiatric comorbidity was observed when adult outpatients received a first-time diagnosis of ADHD. The systematic registering of patients and comorbidities in clinical practice may help to better understand and manage the prognostic determinants in adult ADHD.