High BDNF serum levels are associated to good cognitive functioning in bipolar disorder.

BACKGROUND: Neurotrophins such as brain-derived neurotrophic factor (BDNF), inflammation and oxidative damage may contribute to the pathophysiology of bipolar disorder (BD) in terms of illness activity. To date, there is a lack of studies linking the cognitive impairment observed in BD with these neurobiological mechanisms. This study aimed to investigate the role of these neurobiological factors in clinical and cognitive outcomes in a sample of bipolar individuals. METHODS: We measured serum BDNF, cytokines and oxidative stress markers in a sample of 133 individuals: 52 euthymic bipolar patients, 32 manic patients and 49 healthy controls. They were all assessed with a comprehensive cognitive battery. Sociodemographic and clinical data were collected. Multiple linear regression models were built to study associations of neurotrophins and inflammatory and oxidative measures with cognitive functioning. RESULTS: BDNF levels were decreased in euthymic (p = 0.039) and manic (p < 0.001) individuals. Conversely, inflammatory (interleukin 6 (IL-6)) (p = 0.019) and oxidative stress (p = 0.003) measures were increased in bipolar individuals compared to controls. BDNF levels were associated with executive functioning (ß = 0.01, p = 0.02) and verbal memory (ß = 0.013, p = 0.005), together with other demographic variables. In particular, verbal memory was also associated with obesity (ß=-0.04, p = 0.005). Neither inflammatory markers, oxidative stress markers nor other relevant clinical variables showed any association with cognitive outcome. CONCLUSIONS: Of all the peripheral neurobiological factors analysed, BDNF was the only one significantly associated with cognitive dysfunction in bipolar disorder individuals. This study emphasizes the role of BDNF not only across mood phases but also in cognitive functioning.

The Impact of Obesity on Cognitive Functioning in Euthymic Bipolar Patients: A Cross-Sectional and Longitudinal Study.

OBJECTIVE: To determine the influence of body mass index (BMI) on cognition in euthymic bipolar patients and healthy matched controls in a post hoc study of 2 cross-sectional and longitudinal exploratory studies. METHOD: A total sample of 121 individuals was examined, which included 52 euthymic bipolar disorder I or II patients (DSM-IV-TR criteria) and 69 healthy controls matched by age and gender, categorized in 2 subgroups in terms of body mass index (BMI-factor): normal weight (BMI: 18.5-24.9 kg/m²) versus overweight-obesity (overweight, BMI: 25.0-29.9 kg/m²; and obese, BMI ≥ 30 kg/m²). Demographic, clinical, cognitive, and psychosocial functioning data were collected from 2003 until 2011. Cognitive domains studied were executive function, attention, processing speed, verbal memory, and visual memory. Fifty-four subjects (28 bipolar and 26 healthy controls) were reevaluated after 6 years of follow-up. RESULTS: Obesity and bipolar disorder showed a significant effect on cognition in cross-sectional and long-term MANOVA analyses (F7,111 = 2.54, P = .018 and F19,23 = 2.25, P = .033, respectively). In the cross-sectional linear regression model, global cognitive functioning was predicted by the interaction of BMI-factor by group (ß = -0.44, SE = 0.14, P = .002), current age (ß = -0.44, P < .0001), and premorbid IQ (ß = 0.28, P = .0002), which explained 56% of variance (F5,115 = 29.6, P < .0001). Change in cognitive functioning over time was predicted by the interaction of BMI-factor by group (ß = -0.8, SE = 0.33, P = .022) and cognition at baseline (ß = -0.46, SE = 0.15, P = .004), which explained 27.65% of variance (F6,40 = 2.548, P = .0349). Generalized estimating equations analysis showed that interaction of group by BMI (Wald χ²1 = 5.37, P = .02), age (Wald χ²1 = 22.08, P < .0001), and premorbid IQ (Wald χ²1 = 25.65, P < .0001) were the significant predictors. CONCLUSIONS: Obesity was significantly associated with cognitive impairment in euthymic bipolar patients, and it also appeared to affect cognition in the long term.

Are patients with bipolar disorder and comorbid attention-deficit hyperactivity disorder more neurocognitively impaired?

OBJECTIVE: Research on neurocognitive impairment in adult patients with comorbid bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) is very scarce. This study assessed the neurocognitive profile of a comorbid group (BD+ADHD) compared with that of pure BD (pBD) group, pure ADHD (pADHD) group and healthy controls (HCs). METHODS: This was a three-site study comprising 229 subjects: 70 patients with pBD, 23 with BD+ADHD, 50 with pADHD, and 86 HCs. All patients with BD had been euthymic for at least 6 months. Neuropsychological performance was assessed using a comprehensive neurocognitive battery. RESULTS: Our results showed that all the clinical groups had poorer performance than the HCs in all the neurocognitive domains except for executive functions. No significant differences were observed between the pBD and BD+ADHD groups in any of the cognitive domains, with these two groups showing greater impairment than the pADHD group in executive functions and visual memory. CONCLUSIONS: Our results, although preliminary, suggest that the BD+ADHD group showed the same neurocognitive profile as pBD patients, most likely reflecting the same neurobiological basis. On the other hand, the pADHD group showed a more selective moderate impairment in attention.

The influence of cognitive reserve on psychosocial and neuropsychological functioning in bipolar disorder.

Cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain pathology in order to minimize symptomatology. CR was initially investigated in dementia and acute brain damage, but it is being applied to other neuropsychiatric conditions. The present study aims at examining the fit of this concept to a sample of euthymic bipolar patients compared with healthy controls in order to investigate the role of CR in predicting psychosocial and cognitive outcome in bipolar disorder (BD). The sample included 101 subjects: 52 patients meeting DSM-IV-TR criteria for BD type I or II and 49 healthy controls (HC) matched for age and gender. They were all assessed with a cognitive battery tapping into executive and memory functioning. CR was obtained using three different proxies: education-occupation, leisure activities and premorbid IQ. Psychosocial functioning was evaluated by means of the Functioning Assessment Short Test (FAST). MANCOVAs were performed to determine differences in cognitive and functioning variables. Linear regression analyses were carried out to predict neuropsychological and psychosocial outcomes. Euthymic bipolar patients showed worse neuropsychological performance and psychosocial functioning than HC. The linear regression models revealed that CR was significantly predictive of FAST score (ß = -0.47, p < 0.0001), Executive Index (ß = 0.62, p < 0.0001) and Visual Memory Index (ß = 0.44, p = 0.0004), indicating that CR is a significant predictor of cognitive and psychosocial functioning in euthymic bipolar outpatients. Therefore, CR may contribute to functional outcome in BD and may be applied in research and clinical interventions to prevent cognitive and functional impairment.

Comparison of immigrant and native-born population adherence to antipsychotic treatment in a Spanish health region.

Previous studies report that immigrants underuse psychiatric hospitalization services and are less exposed to antipsychotic medication. The objective of this study is to determine whether immigrant and Spanish native groups with psychotic disorder adhere differently to antipsychotic drugs. Retrospective study including two matched samples of 47 immigrants and 47 native-born patients with psychotic disorder admitted to a psychiatric Unit (2006-2007). Adherence was measured after one-year follow-up. Only 30 % of patients adhered to treatment (40.4 % of native-born, and 19.1 % of immigrants). The lowest rate of adherence was found in sub-Saharans. Fifty per cent of non-adherents were readmitted after 12 months, compared with 21.4 % of adherents, the effect was observed in both native and immigrants. This alarmingly poor adherence in immigrant patients with psychosis underlines the need for preventive strategies to minimize the negative clinical, social and economic outcomes.

The impact of general intellectual ability and white matter volume on the functional outcome of patients with Bipolar Disorder and their relatives.

BACKGROUND: There is substantial evidence that cognitive deficits and brain structural abnormalities are present in patients with Bipolar Disorder (BD) and in their first-degree relatives. Previous studies have demonstrated associations between cognition and functional outcome in BD patients but have not examined the role of brain morphological changes. Similarly, the functional impact of either cognition or brain morphology in relatives remains unknown. Therefore we focused on delineating the relationship between psychosocial functioning, cognition and brain structure, in relation to disease expression and genetic risk for BD. METHODS: Clinical, cognitive and brain structural measures were obtained from 41 euthymic BD patients and 50 of their unaffected first-degree relatives. Psychosocial function was evaluated using the General Assessment of Functioning (GAF) scale. We examined the relationship between level of functioning and general intellectual ability (IQ), memory, attention, executive functioning, symptomatology, illness course and total gray matter, white matter and cerebrospinal fluid volumes. LIMITATIONS: Cross-sectional design. RESULTS: Multiple regression analyses revealed that IQ, total white matter volume and a predominantly depressive illness course were independently associated with functional outcome in BD patients, but not in their relatives, and accounted for a substantial proportion (53%) of the variance in patients' GAF scores. There were no significant domain-specific associations between cognition and outcome after consideration of IQ. CONCLUSIONS: Our results emphasise the role of IQ and white matter integrity in relation to outcome in BD and carry significant implications for treatment interventions.