Is processing speed a valid neurocognitive endophenotype in bipolar disorder? Evidence from a longitudinal, family study.

BACKGROUND: Substantial evidence supports the existence of neurocognitive endophenotypes in bipolar disorder (BD), but very few longitudinal studies have included unaffected relatives. In a 5-year, follow-up, family study, we have recently suggested that deficits in manual motor speed and visual memory could be endophenotype candidates for BD. We aimed to explore whether this also applies to processing speed. METHODS: A sample of 348 individuals, including 163 BD patients, 65 unaffected first-degree relatives (BD-Rel) and 120 genetically unrelated healthy controls (HC), was assessed with the Digit Symbol Substitution Test (DSST) on two occasions over a 2-year period (T1, T2). DSST values were controlled for age, years of education, occupational status, and subsyndromic mood symptoms. Differences between groups were evaluated with ANCOVAs. RESULTS: At T1 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.38) and BD-Rel (p < 0.001; Cohen's d = 0.82). BD-Rel showed an intermediate performance with significant differences with HC (p < 0.01; Cohen's d = 0.50). Similarly, at T2 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.44) and BD-Rel (p < 0.01; Cohen's d = 0.51). BD-Rel performance was intermediate and significantly lower than that of HC (p < 0.01; Cohen's d = 0.97). A Repeated Measures ANOVA revealed no significant between-group differences in performance over time (p > 0.05). CONCLUSIONS: The results of this longitudinal, family study suggest that impaired processing speed may represent a suitable cognitive endophenotype for BD. Further research on the field is required to confirm these preliminary findings.

Treatment patterns and appropriateness of antipsychotic prescriptions in patients with schizophrenia.

Schizophrenia is a chronic mental condition presenting a wide range of symptoms. Although it has a low prevalence compared to other mental conditions, it has a negative impact on social and occupational functions. This study aimed to assess the appropriateness of antipsychotic medications administered to schizophrenic patients and describe current treatment patterns for schizophrenia. A retrospective cohort study was conducted in all patients over the age of 15 with an active diagnosis of schizophrenia and treated with antipsychotics between 2008 and 2013 in the Valencia region. A total of 19,718 patients were eligible for inclusion. The main outcome assessed was inappropriateness of the pharmacotherapeutic management, including polypharmacy use. Altogether, 30.4% of patients received antipsychotic polypharmacy, and 6.8% were prescribed three or more antipsychotics. Overdosage affected 318 individuals (1.6%), and 21.5% used concomitant psychotropics without an associated psychiatric diagnosis. Women and people with a comorbid condition like anxiety or depression were less likely to receive antipsychotic polypharmacy. In contrast, increased polypharmacy was associated with concomitant treatment with other psychoactive drugs, and only in user on maintenance therapy, with more visits to the mental health hospital. Overall, we observed a high level of inappropriateness in antipsychotic prescriptions. Greater adherence to guidelines could maximize the benefits of antipsychotic medications while minimizing risk of adverse effects.

Five Interpersonal Factors Are Predictive of the Response to Treatment of Major Depression With Antidepressants in Primary Care.

Introduction: Factors relating to the interpersonal relationship between the patient and their physician and social environment are important components, which contribute to their response to treatment for major depressive disorder. This study aimed to assess the influence of optimism, perfectionism, therapeutic alliance, empathy, social support, and adherence to medication regimen in the response to antidepressant treatments in the context of normal primary care clinical practice. Method: We conducted a prospective study in which 24 primary care physicians administered sertraline or escitalopram to 89 patients diagnosed with major depressive disorder. The response to treatment and remission of the episode was assessed at 4 and 12 weeks by Cox regression. The effect of adherence to the medication regimen was assessed by multiple regression statistical techniques. Results: Adherence to medication (HR = 0.262, 95% CI = 0.125-0.553, p < 0.001) and patient perfectionism (HR = 0.259, 95% CI = 0.017-0.624, p < 0.01) negatively predicted the initial response to treatment, whereas patient optimism (HR = 1.221, 95% CI = 1.080-1.380, p < 0.05) positively predicted it. Patient optimism (HR = 1.247, 95% CI = 1.1-1.4, p < 0.05), empathy perceived by the patient (HR = 1.01, 95% CI = 1001-1002, p < 0.05), and therapeutic alliance (HR = 1.02, 95% CI = 1001-1.04, p < 0.05) positively predicted episode remission, while patient perfectionism (HR = 0.219, 95% CI = 0.093-0.515, p < 0.001) and low adherence to the treatment regimen (HR = 0.293, 95% CI = 0.145-0.595, p < 0.001) negatively predicted it. Finally, social support (p < 0.01) and therapeutic alliance (p < 0.05) predicted adherence to the medication regimen. Conclusions: In addition to taking the antidepressant drug, other factors including the personal interactions between the patient with their primary care physician and with their social environment significantly influenced the patients' initial response and the final rate of episode remission.

Metabolic Syndrome and Cardiovascular Risk in People Treated with Long-Acting Injectable Antipsychotics.

BACKGROUND: People with schizophrenia and other severe mental disorders have an increased mortality mainly attributed to natural causes, specifically cardiovascular disease and cancer. The metabolic syndrome and the Framingham Risk Score are epidemiologic tools related to long-term cardiovascular disease risk and they are increased in people with severe mental disorders. This increase has been attributed both to the disorder itself and to the use of antipsychotic drugs. OBJECTIVE: To quantify the cardiovascular risk in a group of people treated with long-acting injectable antipsychotics. METHODS: This is a cross-sectional study developed in an outpatient mental health clinic in which the prevalence of metabolic syndrome was estimated and the cardiovascular risk was measured using the Framingham Risk Score. All the analyses were separated by gender. RESULTS: 130 people (81 men) were recruited. According to the International Diabetes Federation criteria, 60 participants (46,2%) had metabolic syndrome. The individual criterion most often met in both genders was obesity. The mean Framingham Risk Score for the sample was moderate, 7,7 (SD: 6,3). For women, the risk was lower (mean 5,7, SD: 4,9) than for men (mean=9, SD: 6,7). There were no significant differences in the prevalence of metabolic syndrome and Framingham Risk Scores by longacting injectable antipsychotic or years of treatment. CONCLUSION: The prevalence of metabolic syndrome and the cardiovascular risk are high in people with psychosis treated with long acting injectable antipsychotics. To better address this vulnerability, the recommendations involve both behavioral and pharmacological interventions.

[Evolution of the use of antidepressants, anxiolytics and hypnotics in Valencia. Period 2000-2010]. / Evolución de la utilización de antidepresivos, ansiolíticos e hipnóticos en la Comunitat Valenciana. Período 2000-2010.

OBJECTIVE: To describe the evolution in the use of antidepressants (AD), anxiolytics (A) and hypnotics (H) in the Comunitat Valenciana (CV) between 2000 and 2010, their expenditure, and the cost of the defined daily dose (DDD). DESIGN: Retrospective observational study. SETTING: Prescriptions covered by the health public service of the CV during the period 2000-2010. MEASUREMENTS: Consumption of the therapeutic groups N06A (antidepressants), N05B (anxiolytics) and N05C (hypnotics) from the pharmacy database of the public Valencian Health Agency measured in defined daily dose per 1.000 inhabitants. RESULTS: During the period of study the use of AD increased by 81.2% and A and H, 11.7%. Selective serotonin reuptake inhibitors were the most prescribed AD and Selective serotonin and norepinephrine reuptake inhibitors experienced the higher rise (386.8%). The increase of escitalopram was 1.013%. Lorazepam, alprazolam and diazepam, accounted for the 80.4% of the anxyolitics, and lormetazepam and zolpidem the 88.7% of the hypnotics. The expenditure rise of AD was by 78.2% and that of the A and H was 14.5%; the cost of the DDD of both decreased by 29%. CONCLUSIONS: Antidepressant utilization has experienced a remarkable rise between 2000 and 2010 while that of A and H has been mild even though they are still more consumed than AD. In spite of the reduction of the DDD cost in both therapeutic groups, the whole expenditure on AD in the CV is still growing.

The Spanish version of the Wisconsin Personality Disorders Inventory-IV (WISPI-IV): tests of validity and reliability.

Personality disorders (PD) are a prevalent class of mental disorders that interfere with functioning and cause subjective distress while increasing the intensity and duration of Axis I clinical syndromes, and therefore assessing PD is important even when PDs are not the focus of treatment. The purpose of these studies was to develop and test a new Spanish version of a self-report measure of PD, the Wisconsin Personality Inventory-IV (WISPI-IV) that would be psychometrically equivalent to the English version while also maintaining the same interpersonal content, which is based on Benjamin's analysis of the PD criteria using her Structural Analysis of Social Behavior (SASB) model (1974). Study 1 participants completed the WISPI-IV twice over a two-week interval. For Study 2, participants from two sites in Spain and one site in Argentina completed Spanish versions of the WISPI-IV and other personality measures. SASB-analysis of the translated items showed high correspondence between the interpersonal content of the English version and the Spanish version demonstrating theoretical validation in relation to other PD measures. The Spanish WISPI-IV showed satisfactory reliability based on test-retest correlations and alphas for internal consistency. Study 2 showed the Spanish WISPI-IV had good convergent validity with the Spanish versions of the IIP and SCID-II and performed similarly to the English versions of these measures. Our goal in translating the WISPI-IV was to extend this measure to Spanish-speakers in language that would be understood by different Hispanic sub-groups, however research team members and subjects had a variety of suggestions for changes in item wording. This reflects the difficulty with creating a "neutral" Spanish version of any assessment given regional differences.

The switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of cognitive deficits. A pilot study in individuals with schizophrenia.

BACKGROUND: Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs) on cognitive performance over time. METHODS: In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13) or novel antipsychotics (n = 26) at baseline and at two years after. RESULTS: Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics. CONCLUSIONS: Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.

[Open narcissism, covered narcissism and personality disorders as predictive factors of treatment response in an out-patient Drug Addiction Unit]. / Narcisismo manifiesto, narcisismo encubierto y trastornos de personalidad en una Unidad de Conductas Adictivas: validez predictiva de respuesta a tratamiento.

INTRODUCTION: Although a high prevalence of personality disorders has been reported in substance users, the literature on their value for predicting treatment response is controversial. On the other hand, while the predictive validity of personality traits as predictors of response to drug abuse or dependence has been studied, research on the validity of narcissistic personality traits is scarce. OBJECTIVES: To study the predictive value of personality disorders, narcissistic personality traits and self-esteem for predicting treatment response. METHOD: We assessed 78 patients attended at an addiction treatment unit using personality disorder diagnoses and measures of self-esteem, narcissism and covert (hypersensitive) narcissism. These variables were used in a Cox survival model as predictive variables of time to relapse into drug use. RESULTS: Hypersensitive (covert) narcissism and borderline and passive-aggressive personality disorders were risk factors for relapse into drug use, while open narcissism was a protective factor. Self-esteem did not show predictive validity. CONCLUSIONS: Personality disorders characterized by impulsivity-instability and passivity-resentfulness show higher risk of relapse into drug abuse. Personality traits characterized by high sensitivity to humiliation increase the risk of relapse, whereas pride and self-confidence are protective factors.

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.

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 WHO's 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.

Posttraumatic stress disorder in primary care with special reference to personality disorder comorbidity.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a common and disabling disturbance in primary care. Few studies have been carried out in primary care samples and none have taken into consideration the association between PTSD and personality disorder. AIM: To describe prevalence and risk factors of PTSD and its comorbidity with personality disorder. SETTING: General practice centre in Valencia (Spain). METHOD: Patients who had experienced at least one traumatic event in their lives were selected from a random sample attending a primary healthcare centre in Valencia and blindly assessed by trained professionals. Patients suffering from PTSD were compared with those who were not. PTSD and personality disorder diagnoses were established using CIDI and SCID-II interviews respectively. Sex, age at the time of experiencing trauma, frequency, multiplicity and type of trauma, dissociative symptoms, personality disorder and severity of PTSD were subjected to multivariate analysis to estimate the probability of developing PTSD and its duration. RESULTS: Life prevalence rate was 14% and current prevalence 9%. Dissociative symptoms and personality disorder were significantly associated with PTSD. Cluster analysis based on age, frequency and type of trauma revealed the existence of one subgroup composed mainly of women who had experienced frequent body-contact trauma at an early age, developed severe PTSD and suffer from a variety of personality disorders, particularly paranoid personality disorder. Time to the complete disappearance of symptoms was only explained by the initial severity of PTSD. CONCLUSION: PTSD is a frequent disorder in general practice and it is often associated with personality disorder. Women who experienced high frequency body-contact traumatic events at an early age often suffer from personality disorder and present a particularly severe form of PTSD deserving referral to specialised care.

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.

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.

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.

Abnormal motor asymmetry only during bimanual movement in schizophrenic patients compared with healthy subjects.

In schizophrenia, research on motor asymmetry has focused on the direction and the degree of handedness using unimanual motor tests and tasks. However, typically both hands collaborate in the production of most manual movements. This study explored motor asymmetry exhibited during unimanual and bimanual tasks in schizophrenic and healthy subjects using a new experimental motor battery. Specifically, the authors investigated the motor indices of laterality during finger-tapping and hand-turning tasks in four unimanual and four bimanual conditions in 84 schizophrenic and 31 healthy subjects, all right-handed. The schizophrenic patients showed reduced motor asymmetries only during bimanual tapping compared with healthy subjects due to reduction in right-hand performance. These results stress the importance of considering bimanual conditions in the assessment of motor asymmetries, and suggest that it is necessary to use bimanual tasks to test hypotheses about abnormal motor lateralization in schizophrenia.