Is personal and social functioning associated with subjective quality of life in schizophrenia patients living in the community?

Subjective quality of life (QoL) and psychosocial functioning constitute important treatment outcomes in schizophrenia. We aimed to investigate the relationship between them in schizophrenia patients living in the community. Symptom severity and insight were assessed with the Positive and Negative Syndrome Scale (PANSS) in 76 community schizophrenia patients. Social functioning was measured with the Portuguese version of Personal and Social Performance (PSP) scale, and subjective QoL was measured with the Portuguese version of the WHO Quality of Life Measure-Abbreviated Version (WHOQOL-Bref). The majority of patients were single (78%) and unemployed/inactive (74%). Mean PSP total score was 55.5, and mean scores on WHOQOL-Bref domains ranged from 54.1 to 63.0. Greater symptom severity and worse insight were significantly associated with worse functioning in all PSP domains. Symptoms were more moderately correlated with QoL, with no significant correlations between QoL and positive symptoms and insight levels. Partial correlations controlling for symptom severity revealed no significant associations between social functioning and subjective QoL. Symptom severity may exert a greater influence on social functioning than on subjective QoL; however, social functioning was not associated with subjective QoL. The results suggest these constructs might be independent and should be assessed separately. A broader research approach, with increased attention to social and psychological factors, may help identify treatment targets to improve schizophrenia patients' social functioning and QoL.

The importance of measuring psychosocial functioning in schizophrenia.

BACKGROUND: Schizophrenia is among the most disabling of mental illnesses and frequently causes impaired functioning. We explore issues of definition and terminology, and the relationship between social functioning, cognition, and psychopathology considering relevant research findings. METHODS: The present article describes measures of social functioning and outlines their psychometric properties. It considers their usefulness in research and clinical settings. Treatment aims and objectives are explored in the context of cognitive and social functioning. Finally, we identify areas for developing research and refining the measurement of social functioning. RESULTS: The definition and measurement of social functioning in schizophrenia remains a complex and disputed area. The relationships between symptoms, cognitive functioning and social functioning are complex but we are beginning to understand them better. Scales for measuring functioning in clinical practice must be brief and sensitive to change and the Personal and Social Performance (PSP) scale may offer several advantages in these regards. Brief cognitive assessments focusing upon the domains most commonly affected in schizophrenia, such as verbal memory and executive functions, should be coadministered with measures of functioning. CONCLUSIONS: The use of validated scales for schizophrenia that are sensitive to change over the course of the illness and its treatment, should allow for a better understanding of patients' functional disabilities, enabling better and more comprehensive monitoring and evaluation of both pharmacological and non-pharmacological treatment strategies.

Cognitive function and serum levels of brain-derived neurotrophic factor in patients with bipolar disorder.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) is an important contributor to the pathophysiology of bipolar disorder (BD), and abnormalities in the BDNF-signaling system may be implicated in the cognitive decline observed in BD patients. We aimed to investigate serum BDNF levels in BD patients and its relation to neurocognitive function. METHODS: We measured serum BDNF levels using an enzyme-linked immunosorbent assay method in 65 euthymic type I BD patients and 50 healthy controls, and administered a neuropsychological test battery to assess attention and mental control, perceptual-motor skills, executive functions, verbal fluency and abstraction, visuospatial attention, and memory. RESULTS: We found no significant differences regarding serum BDNF levels in BD patients and healthy controls. We found significant positive associations between serum BDNF levels and illness duration, and manic and depressive episodes in female BD patients only. Serum BDNF levels were lower in patients medicated with antipsychotics and/or lithium, whereas patients on valproate and/or antidepressants showed higher serum BDNF levels. Patients performed significantly worse on 11 out of 16 neurocognitive tests as compared to controls. We found a significant positive association between serum BDNF levels and a test of verbal fluency in both BD patients and controls. CONCLUSIONS: Present results support the hypothesis that BDNF normalizes with mood stabilization and pharmacological treatment. Our findings in young and physically healthy patients with short illness duration and few mood episodes may explain the lack of association between serum BDNF levels and neurocognitive performance, even though cognitive performance in patients was overall significantly worse as compared to healthy controls.

Insight, quality of life and cognitive functioning in euthymic patients with bipolar disorder.

INTRODUCTION: The relationship between insight, quality of life and cognition in bipolar disorder has not been clearly established. METHOD: A neuropsychological battery assessing attention, mental control, perceptual-motor skills, executive functions, verbal fluency, abstraction and visuo-spatial attention was administered to 70 remitted bipolar patients and 50 healthy controls. Insight was assessed using the Scale to Assess Unawareness of Mental Disorder; Quality of Life was assessed using the Portuguese version of the WHO Quality of Life Assessment--Abbreviated version (WHOQOL-BREF-PT). RESULTS: No differences in QoL and cognitive performance were observed between bipolar patients with 'impaired' and 'preserved' insight. Insight was found to be correlated with poorer psychological and environmental QoL. A multiple regression model showed that depressive symptoms were significant predictors of physical, psychological and environmental QoL. CONCLUSION: The present study adds to the notion that depressive symptoms, even of low intensity, are strong predictors of QoL. The present study suggests that the impact of insight on self-reported QoL may be subtle during remission and may be more substantially affected in the presence of manic symptoms.

Quality of life in bipolar type I disorder and schizophrenia in remission: clinical and neurocognitive correlates.

This cross-sectional study examined the relationships between clinical and neuropsychological variables and self-reported quality of life (QoL) in 30 euthymic bipolar I patients, 23 remitted schizophrenic patients, and 23 healthy controls. Participants were administered the World Health Organization Quality of Life Measure-Abbreviated Version (WHOQOL-BREF) to assess QoL. Moreover, a broad neuropsychological battery was also administered. Bipolar disorder (BD) and schizophrenia patients demonstrated significantly lower scores on the physical, psychological, and social domains of the WHOQOL-BREF compared with controls, but there were no significant differences between the two patient groups on those domains. More symptomatic BD patients reported worse QoL, especially in the physical and environmental domains, which was also associated with worse neurocognitive performance. In schizophrenic patients, neurocognitive performance was not associated with self-reported QoL, but more symptomatic patients reported lower QoL. Substantial impairments in QoL, similar in severity, were found in both patient groups. In patients with schizophrenia, QoL was more strongly related to levels of psychopathology, whereas in BD patients, both psychopathology and neurocognitive deficits were strongly associated with lower QoL. Clinical recovery is essential in schizophrenia and BD. The association between cognitive functioning and QoL in bipolar patients suggests that these patients may also benefit from psychological interventions addressed to improve cognitive deficits and enhance the functional recovery.

The impact of co-morbid alcohol use disorder in bipolar patients.

Alcohol use is highly prevalent in patients with bipolar disorder (BD) and is associated with significant mortality and morbidity. The detrimental effects of each condition are compounded by the presence of the other. The objective of this study was to examine the impact of alcohol abuse and of alcohol dependence in BD in a Brazilian sample, as indicated by clinical severity, functional impairment, and quality of life (QOL). A cross-sectional survey of 186 bipolar outpatients were interviewed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-4th Edition. The primary outcome measures were functioning, as indicated by the Global Assessment of Functioning Scale scores and QOL, as indicated by the World Health Organization Quality of Life Instrument. Secondary outcomes were clinical severity features. Alcohol abuse and dependence were associated with male gender, lower education, earlier age of onset, psychosis within first episode, depressive symptoms, and worse functioning. In addition, the presence of alcohol abuse or dependence was associated with remarkably high rates of suicide attempt. Our findings suggest that the co-occurrence of alcohol abuse/dependence with BD increases the risk for suicide attempt, which may reflect in part the greater severity of symptoms and impaired functioning. This subgroup of bipolar patients requires a treatment tailored to address both conditions.

Role of quetiapine beyond its clinical efficacy in bipolar disorder: From neuroprotection to the treatment of psychiatric disorders (Review).

The aim of the present review was to discuss the following aspects of treatment with quetiapine in psychiatric disorders: i) Neurocognition and functional recovery in bipolar disorder (BD); ii) neuroprotective profile in different models; and iii) potential off-label indications. A PubMed search was conducted of articles published in English between 2000 and 2012 on quetiapine, cross-referenced with the terms 'anxiety', 'attention deficit disorder', 'borderline personality disorder', 'dementia', 'insomnia', 'major depressive disorder' (MDD), 'obsessive-compulsive disorder', 'post-traumatic stress disorder', 'remission', 'cognition', 'neurobiology', 'neuroprotection', 'efficacy' and 'effectiveness'. Articles were selected from meta-analyses, randomized clinical trials and open trials, and the results were summarized. Quetiapine, when studied in off-label conditions, has shown efficacy as a monotherapy in MDD and general anxiety disorder. Quetiapine also appears to exhibit a small beneficial effect in dementia. The review of other conditions was affected by methodological limitations that precluded any definitive conclusions on the efficacy or safety of quetiapine. Overall, the present review shows evidence supporting a potential role for quetiapine in improving cognition, functional recovery and negative symptoms in a cost-effective manner in BD. These benefits of quetiapine are potentially associated with its well-described neuroprotective effects; however, further studies are clearly warranted.

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 impact of a history of psychotic symptoms on cognitive function in euthymic bipolar patients: a comparison with schizophrenic patients and healthy controls.

BACKGROUND: About two-thirds of patients with bipolar disorder (BD) have a lifetime history of at least one psychotic symptom. OBJECTIVE: To compare the neurocognitive performance of four groups: BD patients with and without a history of psychotic symptoms (BD HPS+ and BD HPS-, respectively); patients with schizophrenia (SZ); and healthy control (HC) subjects. METHOD: In this cross-sectional study, 35 stabilized patients with SZ, 79 euthymic (44 HPS+ and 35 HPS-) patients with BD, and 50 HC were administered a comprehensive battery of neuropsychological tests. RESULTS: There was worse neurocognitive functioning in both BD and SZ patients compared to HC. Overall, data from both groups of BD patients did not differ on sociodemographic, clinical, or neurocognitive variables. However, BD HPS+ patients had significantly more negative symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS), and showed a trend toward worse performance on executive functions compared to BD HPS- patients. Moreover, both BD groups had better performance on all neurocognitive tests compared to SZ group. CONCLUSIONS: Neurocognitive dysfunction may be more marked in SZ than in BD, yet qualitatively similar. A history of past psychotic symptoms in BD was not associated with more severe cognitive impairment during euthymia. Therefore, BD with psychotic symptoms does not appear to be a distinct neurocognitive phenotype.

Creativity and executive function across manic, mixed and depressive episodes in bipolar I disorder.

INTRODUCTION: Creativity is a complex construct involving affective and cognitive components. Bipolar Disorder (BD) has been associated with creativity and is characterized by a wide range of affective and cognitive symptoms. Although studies of creativity in BD have tended to focus on creativity as a trait variable in medicated euthymic patients, it probably fluctuates during symptomatic states of BD. Since creativity is known to involve key affective and cognitive components, it is plausible to speculate that cognitive deficits and symptoms present in symptomatic BD could interfere with creativity. MATERIAL AND METHODS: Sixty-seven BD type I patients medication free, age 18-35 years and experiencing a maniac, mixed, or depressive episodes, were assessed for creativity, executive functioning, and intelligence. RESULTS: Manic and mixed state patients had higher creativity scores than depressive individuals. Creativity was influenced by executive function measures only in manic patients. Intelligence did not influence creativity for any of the mood episode types. CONCLUSION: We propose that creativity in BD might be linked to the putative hyperdopaminergic state of mania and be dependent on intact executive function. Future studies should further explore the role of dopaminergic mechanisms in creativity in BD.

SHORT COMMUNICATION: Apolipoprotein E genotype and cognition in bipolar disorder.

Apolipoprotein E (APOE) has been extensively studied as a risk factor for sporadic and late onset Alzheimer's Disease (AD). APOE allele (∗)3, the most frequent variant, is not associated to cognitive dysfunction (CD) or to increased AD risk. Differently, the (∗)4 allele is a well-established risk factor for CD, while the (∗)2 allele is associated with survival and longevity. CD is an important feature of Bipolar Disorder (BD) and recent data suggest that CD may be one of its endophenotypes, although controversial results exist. The aim of this research is to study the association of APOE genotype (APOE) and neurocognitive function in a sample of drug free young BD-type I patients. Sample consisted of 25 symptomatic BD (type I) patients (age 18-35 years old). They were submitted to an extensive neuropsychological evaluation and genotyped for APOE. Subjects with allele (∗)2 presented better cognitive performance. The presence of allele (∗)4 was associated with worse performance in a few executive tasks. APOE (∗)3(∗)3 was associated with overall severe dysfunction on cognitive performance. In young individuals with nontreated BD-type I, APOE may predict cognitive performance. Further and larger studies on APOE and cognition in BD are required to clarify whether APOE is a BD cognitive endophenotype.

Serum homocysteine levels and cognitive functioning in euthymic bipolar patients.

BACKGROUND: Studies have found elevated plasma homocysteine (Hcy) levels in bipolar disorder (BD). We investigated serum Hcy levels in euthymic BD patients, and its relationship with cognitive and psychosocial functioning. METHODS: Sixty-five BD type I euthymic patients and 49 healthy controls were assessed using a neuropsychological test battery. Hcy levels were measured using an HPLC method with fluorescence detection. RESULTS: The mean Hcy levels were 1.37 mg/L for BD patients and 1.30 mg/L for healthy controls (P=0.342), male patients showing higher Hcy levels as compared to females (P=0.009). Older patients, those with later illness onset, and patients taking more medications showed higher Hcy levels, but no significant correlation was found with psychosocial functioning. Patients with "elevated" Hcy levels performed significantly worse on all neurocognitive tests, and in patients we found significant associations between Hcy levels and number of perseverations on the SCT (r=0.248, P=0.047), and number of moves on the ToH (r=0.265, P=0.033); however, a linear regression model revealed that Hcy was not a significant predictor of neurocognitive test performance. CONCLUSIONS: Our findings suggest that increased homocysteinemia may play a role in the pathophysiology of neurocognitive deficits in BD, with a higher impact among older patients, or who had a delayed onset of illness.

The potential use of biomarkers as an adjunctive tool for staging bipolar disorder.

Recent data show that biomarkers differ in early and late-stage bipolar disorder (BD). Here we propose a model of staging for bipolar disorder that emphasizes the potential use of biomarkers for differentiating early and late-stage BD patients in the inter-episodic period. The proposed model includes a Latent phase: patients at "ultra-high-risk" for developing BD, characterized by a family history of BD, temperament traits, mood, and anxiety symptoms as well as genetic vulnerability for developing the disorder; Stage I: patients who return to their baseline level of functioning when mood episodes resolve; Stage II: biomarkers and functioning impairment are related to comorbidities or rapid-cycling presentations; Stage III: persistent cognitive and functioning impairment in the inter-episode period as well as changes in biomarkers; and Stage IV: same findings as in Stage III associated with extreme cognitive and functioning impairment, to the point that patients are unable to live autonomously. Empirical testing will determine the ability of the present model to inform patients and clinicians about both prognosis and response to treatment.

Clinical implications of a staging model for bipolar disorders.

A model of staging in the field of bipolar disorder (BD) should offer a means for clinicians to predict response to treatment and more general outcome measures, such as the level of functioning and autonomy. The present staging model emphasizes the assessment of patients in the interepisodic period and includes: latent phase: individuals who present mood and anxiety symptoms and increased risk for developing threshold BD; Stage I--patients with BD who present well established periods of euthymia and absence of overt psychiatric morbidity between episodes; Stage II--patients who present rapid cycling or current axis I or II comorbidities; Stage III--patients who present a clinically relevant pattern of cognitive and functioning deterioration, as well as altered biomarkers; and Stage IV--patients who are unable to live autonomously and present altered brain scans and biomarkers. Such a model implies a longitudinal appraisal of clinical variables, as well as assessment of neurocognition and biomarkers in the interepisodic period. Staging facilitates understanding of the mechanisms underlying progression of the disorder, assists in treatment planning and prognosis and, finally, underscores the imperative for early intervention.

Cognitive performance and quality of life in bipolar disorder.

OBJECTIVE: In patients with bipolar disorder (BD), quality of life (QOL) scores have been largely attributed to mood symptoms. However, impairments in QOL may occur even in euthymia, and differential factors have been put forward as important determinants of QOL. Our study was designed to assess the role of cognitive performance in self-reported QOL in patients with BD. METHOD: In this cross-sectional study, we examined the relation between cognitive variables and self-reported QOL in 55 bipolar I euthymic patients and 50 healthy subjects. Participants were administered the World Health Organization Quality of Life Assessment--Abbreviated version and a battery of neuropsychological tests. RESULTS: BD patients showed lower scores in all QOL domains as compared with control subjects. Poorer self-reported QOL correlated significantly with worse cognitive performance, especially on tests of executive functioning and verbal abstraction. A linear regression model revealed that all QOL domains were significantly predicted by cognitive variables, with variances ranging from 12% to 37%, and from 24% to 54% when clinical variables were added to the model. CONCLUSIONS: Deficits in executive functioning and verbal abstraction were strong predictors of poor self-reported QOL. Our findings suggest that, along with mood stabilization, adequate cognitive functioning is desirable for achieving better QOL. These findings suggest that cognitive rehabilitation may be an important factor for restoring QOL to baseline levels among BD patients.

[Neurocognitive functioning in euthymic patients with bipolar type I disorder]. / Funcionamento neurocognitivo em doentes bipolares tipo I eutímicos.

INTRODUCTION: Bipolar disorder (BD) is a chronic mental disorder that affects 1-3% of the population, and is characterized by affective episodes that alternate with periods of euthymia. Although traditionally patients were thought to return to premorbid functioning levels during the inter-episode periods, recent evidence suggests that cognitive deficits persist even during periods of euthymia, and may impair patients working and functioning status. OBJECTIVES: The present study aimed to characterize the neurocognitive and psychosocial functioning in a sample of Portuguese bipolar type I patients. METHODS: Sixty-five BD type I patients were compared to 50 healthy controls with an extensive neuropsychological battery to assess to assess attention and mental control, speed of processing, executive functions, and verbal memory. Mood symptoms were assessed with the Hamilton Depression Rating Scale and with the Young Mania Rating Scale, and psychosocial functioning was assessed with the Global Assessment of Functioning (GAF). RESULTS: BD patients performed overall significantly worse on neurocognitive tests as compared to healthy controls, but especially on verbal memory and executive functions, even after controlling for educational level and mood symptomatology, showing moderate to large effect sizes on these domains. BD patients scored significantly lower on the GAF as compared to healthy controls, and psychosocial functioning was significantly correlated with performance on all neurocognitive tests. Although there were less BD patients active and working, and more patients inactive and/or retired, working status did not correlate significantly with neurocognitive performance. CONCLUSIONS: The results of our study support the hypothesis that BD type I patients present global cognitive deficits even whilst in euthymia, especially in the domains of verbal memory and executive functions. These cognitive deficits correlate with the functional difficulties that many patients present in the course of the disease, but their impact on working status is still not clear.

The impact of a history of psychotic symptoms on cognitive function in euthymic bipolar patients: a comparison with schizophrenic patients and healthy controls / O impacto da história de sintomas psicóticos na função cognitiva de doentes bipolares eutímicos: comparação com doentes esquizofrênicos e controles saudáveis

BACKGROUND: About two-thirds of patients with bipolar disorder (BD) have a lifetime history of at least one psychotic symptom. Objective: To compare the neurocognitive performance of four groups: BD patients with and without a history of psychotic symptoms (BD HPS+ and BD HPS-, respectively); patients with schizophrenia (SZ); and healthy control (HC) subjects. METHOD: In this cross-sectional study, 35 stabilized patients with SZ, 79 euthymic (44 HPS+ and 35 HPS-) patients with BD, and 50 HC were administered a comprehensive battery of neuropsychological tests. RESULTS: There was worse neurocognitive functioning in both BD and SZ patients compared to HC. Overall, data from both groups of BD patients did not differ on sociodemographic, clinical, or neurocognitive variables. However, BD HPS+ patients had significantly more negative symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS), and showed a trend toward worse performance on executive functions compared to BD HPS- patients. Moreover, both BD groups had better performance on all neurocognitive tests compared to SZ group. CONCLUSIONS: Neurocognitive dysfunction may be more marked in SZ than in BD, yet qualitatively similar. A history of past psychotic symptoms in BD was not associated with more severe cognitive impairment during euthymia. Therefore, BD with psychotic symptoms does not appear to be a distinct neurocognitive phenotype.

INTRODUÇÃO: Cerca de dois terços dos pacientes com Transtorno Bipolar (TB) apresentam sintomas psicóticos ao longo da vida. OBJETIVO: Comparar o desempenho neurocognitivo de quatro grupos: pacientes com TB, com e sem histórico de sintomas psicóticos (HPS+ ou HPS-, respectivamente); pacientes esquizofrénicos; e grupo controle (GC) com indivíduos saudáveis. MÉTODOS: Estudo transversal no qual 35 pacientes com esquizofrenia (EZ), 79 pacientes com TB na fase eutímica (44 HPS+ e 35 HPS-) e 50 GC foram submetidos a extensa avaliação neuropsicológica. RESULTADOS: Observou-se pior funcionamento neurocognitivo em pacientes com TB e com EZ quando comparados ao GC. Os dois grupos de pacientes TB não diferiram em dados demográficos, clínicos ou variáveis neurocognitivas. Entretanto o grupo HPS+ teve mais sintomas negativos mensurados pela Positive and Negative Syndrome Scale (PANSS) e apresentou uma tendência a pior performance nas funções executivas comparativamente aos pacientes HPS-. Além disso ambos os grupos de pacientes TB tiveram melhor desempenho em todos testes neurocognitivos quando comparados aos pacientes com EZ. CONCLUSÕES: A disfunção neurocognitiva é mais marcada nos pacientes com EZ do que com TB, apesar de ser qualitativamente similar. Um histórico de sintomas psicóticos no TB não associou esta amostra de pacientes eutímicos a um maior prejuízo neurocognitivo. Assim sendo, o TB com sintomas psicóticos parece não possuir um fenótipo neurocognitivo diferenciado.