Manuel Gómez-Beneyto

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.

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.

No paradox, no progress: inverse cancer comorbidity in people with other complex diseases

In the past 5 years, several leading groups have attempted to explain why individuals with Downs syndrome have a reduced risk of many solid tumours and an increased risk of leukaemia and testicular cancer. Niels Bohr, the Danish physicist, noted that a paradox could initiate progress. We think that the paradox of a medical disorder protecting against cancer could be formalised in a new model of inverse cancer morbidity in people with other serious diseases. In this Personal View, we review evidence from epidemiological and clinical studies that supports a consistently lower than expected occurrence of cancer in patients with Downs syndrome, Parkinsons disease, schizophrenia, diabetes, Alzheimers disease, multiple sclerosis, and anorexia nervosa. Intriguingly, most comorbidities are neuropsychiatric or CNS disorders. We provide a brief overview of evidence indicating genetic and molecular connections between cancer and these complex diseases. Inverse comorbidity could be a valuable model to investigate common or related pathways or processes and test new therapies, but, most importantly, to understand why certain people are protected from the malignancy.

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.

A short message service (SMS)-based strategy for enhancing adherence to antipsychotic medication in schizophrenia

BACKGROUND The aim of this study was to assess the impact of a short message service (SMS)-based strategy on adherence to antipsychotic treatment. METHODS A multicentre, randomised, open-label, controlled, 6-month study with clinically stabilised outpatients with schizophrenia was conducted. The patients assigned to the intervention received daily SMS reminders to take their medication for 3 months. Self-reported medication adherence was determined using the Morisky Green Adherence Questionnaire (MAQ). Secondary outcomes were severity of illness, attitude towards medication, insight into illness and health-related quality of life. RESULTS A total of 254 patients were analysed. A significantly greater improvement in adherence was observed among patients receiving SMS text messages compared with the control group. The mean change in MAQ total score from baseline to month 3 was -1.0 (95% confidence interval (CI) -1.02, -0.98) and -0.7 (95%CI -0.72, -0.68), respectively (P=0.02). Greater improvement in negative, cognitive and global clinical symptoms at month 3 was observed. Attitude towards medication also significantly improved across the study in the intervention group versus the controls. CONCLUSIONS An SMS-based intervention seems feasible and acceptable for enhancing medication adherence. Further studies are needed to confirm whether this kind of intervention could be a complementary strategy to optimise adherence in schizophrenia.

Psychometric properties of the parental bonding instrument in a Spanish sample.

SummaryThe Parental Bonding Instrument was translated into Spanish and administered to a sample of 205 Spanish primiparae 3 days after childbirth. Reliability, factorial structure and predictive validity for affective disorders were evaluated. The Spanish version of the PBI has psychometric features similar to those described in other cultures. However, the results suggest that in future research the predictive power of the “Control” factor in affective disorders might be improved by splitting it into two subfactors: “Overprotection” and “Restraint”.

Efficacy and effectiveness of individual family intervention on social and clinical functioning and family burden in severe schizophrenia: a 2-year randomized controlled study

BACKGROUND Empirical evidence of the efficacy and effectiveness of psychosocial family intervention and of the specificity of its effects on the course of schizophrenia is limited. The aim was to study the efficacy and effectiveness of psychosocial family intervention with regard to clinical and social functioning and family burden after controlling for compliance and several prognostic factors. METHOD A 2-year randomized controlled trial with blind assessments. Fifty patients with DSM-IV schizophrenia and persistent positive symptoms and/or previous clinical relapse were allocated to psychosocial family intervention, individual counselling and standard treatment versus individual counselling and standard treatment. RESULTS Family intervention was associated with fewer clinical relapses, hospitalizations and major incidents, and an improvement in positive and negative symptoms, social role performance, social relations, employment and family burden. The reduction in hospitalizations in the family intervention group was significantly greater than that observed in the group of patients who refused to participate but this was not the case for the control group. The effects of family intervention were independent of compliance and prognostic factors. CONCLUSIONS Family intervention is effective in severe schizophrenia independently of compliance and prognostic factors.

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.

Unmet needs in the management of schizophrenia.

Studies on unmet needs during the last decades have played a significant role in the development and dissemination of evidence-based community practices for persistent schizophrenia and other severe mental disorders. This review has thoroughly considered several blocks of unmet needs, which are frequently related to schizophrenic disorders. Those related to health have been the first block to be considered, in which authors have examined the frequent complications and comorbidities found in schizophrenia, such as substance abuse and dual diagnosis. A second block has been devoted to psychosocial and economic needs, especially within the field of recovery of the persistently mentally ill. Within this block, the effects of the current economic difficulties shown in recent literature have been considered as well. Because no patient is static, a third block has reviewed evolving needs according to the clinical staging model. The fourth block has been dedicated to integrated evidence-based interventions to improve the quality of life of persons with schizophrenia. Consideration of community care for those reluctant to maintain contact with mental health services has constituted the fifth block. Finally, authors have aggregated their own reflections regarding future trends. The number of psychosocial unmet needs is extensive. Vast research efforts will be needed to find appropriate ways to meet them, particularly regarding so-called existential needs, but many needs could be met only by applying existing evidence-based interventions. Reinforcing research on the implementation strategies and capacity building of professionals working in community settings might address this problem. The final aim should be based on the collaborative model of care, which rests on the performance of a case manager responsible for monitoring patient progress, providing assertive follow-up, teaching self-help strategies, and facilitating communication among the patient, family doctor, mental health specialist, and other specialists.

Neurocognitive Training in Patients with Bipolar Disorders: Current Status and Perspectives

The main objective here is to study the current status of research in cognitive training/rehabilitation in patients with BD. The second aim is to discuss the suitability of current cognitive training programs in SCH for use in BD. Finally, some recommendations to increase the effectiveness of cognitive training for BD patients will be outlined. Papers were identified through a comprehensive literature search restricted to human studies but without language restrictions. Electronic searches covering the period from 2000 to March 2011 were performed in Medline and PsycINFO databases. To start with, a search was performed in Medline using the search string: ‘bipolar disorder’ AND ‘cognitive remediation’ OR ‘neurocognitive remediation’ OR ‘neuropsychological remediation’ OR ‘cognitive training’ OR ‘neurocognitive training’ OR ‘neuropsychological training’ OR ‘cognitive rehabilitation’ OR ‘neurocognitive rehabilitation’ OR ‘neuropsychological rehabilitation’. This resulted initially in 13 hits but 1 was discarded because it did not refer to BD, leaving 12 references. Next we performed the same search in PsycINFO databases using the identical search string. This returned 10 hits but only 2 were new as 8 had already been found in our initial search, so our final result was a total of 14 references. Additional searches in other databases (EBSCO Host, ProQuest) did not modify results. Electronic searches identified 14 references, and 2 more [19, 20] were found in their reference lists, therefore 16 potentially relevant articles were included. Eleven of them actually only emphasize the potential relevance that cognitive training might have, pointing out that it may become a very important part of treatment in BD. However, those papers did not involve any cognitive training program. Interesting observations from these studies are: (1) research on SCH could serve to guide studies needed in BD [21, 22] ; (2) a more comprehensive approach to BD treatment with cognitive remediation therapy is necessary [23, 24] ; (3) there is a need for formal assessment of cognition by using standard cognitive test batteries [25, 26] ; (4) improvement in cognition should translate into better social and functional outcome [27–31] . Out of the 5 remaining papers, 4 are examples of cognitive training with heterogeneous samples including some patients with BD together with patients with other diagnoses (with psychotic disorders and other mood disorders) [19, 20, 32, 33] . However, these studies have additional methodological problems, such as small samples and the lack of a control group. Moreover, these empirical studies are not considering important information arising from areas such as cognitive remediation in SCH or patients with brain injury [26] . Finally, the only empirical study with a homogeneous sample of BD patients suggested that improvements in occupational and psychosocial functioning in individuals with BD may be achieved by targeting residual depressive symptoms and cognitive impairment [34] . However, beneficial effects of remediation on cognitive functioning may be confused with those on mood state. Overall, It has been estimated that between 30 and 60% of bipolar disorder (BD) patients have psychosocial dysfunctions, as measured by impairment in occupational and social functioning [1] . Even those who achieve full clinical remission have difficulty in making a complete functional recovery [2–7] . In a recent review, the functional outcome of BD has been associated with several demographic, clinical, pharmacological, psychological and social variables [8, 9] . Cognitive dysfunction is included in this set of variables. Approximately 60% of BD patients are cognitively impaired at a level deemed to be clinically relevant, even during periods of clinical remission [10] . Recent longitudinal reports [10–12] indicated that cognitive disturbances might predict a poorer psychosocial adjustment in the longer term. Specifically, baseline deficits in fluency and attention/psychomotor speed [13] , and in verbal memory, executive and attentional functions were independent predictors of functional recovery 1 year later [10] . A global index of cognition was more predictive of functional outcome than clinical factors in both schizophrenia and BD [11] . Similarly, other studies also reported that subthreshold depressive symptoms and verbal memory problems explained 36% of the variance in functioning at the 4-year follow-up [14] . This data highlights the importance of using suitable interventions to improve neurocognitive dysfunctions in patients with BD [12, 15] . Cognitive training aims to improve neurocognitive abilities such as memory, learning, attention and executive functioning [16] . Compared to schizophrenia (SCH), BD has been historically regarded as a disease with a better prognosis and outcome, so psychosocial outcomes in patients with BD have generally received less attention than those of patients with SCH [17, 18] . Received: May 3, 2011 Accepted after revision: December 11, 2011 Published online: June 1, 2012