Association of daily-life functioning and obesity in individuals with schizophrenia and controls.

Early weight gain following the diagnosis of schizophrenia (SCZ) has been associated with improved daily functioning. However, in the general population and in other psychiatric conditions such as bipolar disorder, increased body mass index (BMI) has been associated with worse functioning. The data on this association in chronic individuals with SCZ is still scarce. To address this gap in knowledge, our objective was to evaluate the association between BMI and psychosocial functioning in chronic outpatients with SCZ and in healthy individuals. Six-hundred individuals (n = 600), 312 with schizophrenia (SCZ) and 288 individuals with no personal or family history of severe mental illness (CTR), underwent weight, height and psychosocial functioning score (FAST) assessment. Linear regression models tested the association between FAST as dependent variable and BMI as independent variable, controlling for age, sex, use of clozapine and years of illness. In the CTR group, the highest BMI could predict a worse result in FAST, explaining about 22% of the variation found (Model: AdjR2 = 0.225 F(3,284) = 28.79 p < .001; BMI main effect: ß = 0.509 t = 9.240 p < .001). In the SCZ group, there was no statistically significant association. Our findings corroborate the perception that increased BMI is associated with worse functioning status in the general population. In chronic SCZ, whatsoever, there is no association. Our findings suggest that patients with higher BMI in the SCZ group may compensate for the possible impairment of functionality due to increased body weight, through improved adherence and responsiveness to prescribed psychopharmacological treatment, leading to better control of psychiatric symptoms.

A five-year follow-up of the verbal memory performance of individuals with bipolar disorder and schizophrenia: evidence of unchanging deficits under treatment.

OBJECTIVE: Bipolar disorder (BD) and schizophrenia (SZ) are chronic and heterogeneous mental disorders that present cognitive and functional impairments. Verbal memory is considered an important predictor of functioning and a domain vulnerable to the aging process. However, only few studies investigate the progression of memory longitudinally in BD and SZ, especially in lower- and middle-income countries. Therefore, we aim to evaluate the course of verbal memory in individuals with BD and SZ. METHODS: We assessed 31 individuals with BD and 27 individuals with SZ under treatment at outpatient clinics at baseline and after five years. They were assessed through a sociodemographic questionnaire, memory and estimated IQ (eIQ) instruments, and clinical scales. RESULTS: Individuals with SZ showed worse verbal memory performance in comparison to BD, however, we did not observe changes over time within patient groups. Individuals with BD with higher eIQ showed a better verbal memory performance, while no effect of eIQ was found for subjects with SZ. CONCLUSION: Patients with SZ and BD showed different levels of verbal memory impairment, although they had similar unchanging trajectories after 5 years under psychiatric treatment. This finding indicates a relative stable cognitive course for both disorders.

The role of semantic clustering in the relationship between verbal memory and psychosocial functioning in schizophrenia and bipolar disorder: Possible distinct cognitive pathway compared to healthy controls.

BACKGROUND: Verbal memory (VM) is impaired in schizophrenia (SZ) and bipolar disorder (BD), and predicts psychosocial functioning. However, there is a lack of research exploring the role of VM component processes, including semantic clustering, in these disorders. Semantic clustering might impact this association, as effective semantic memory strategies may reflect unimpaired executive control, leading to an adequate functioning. We aimed to investigate VM components in SZ and BD, and the role of semantic clustering in the relationship between VM and functioning. METHODS: We included 495 participants (156 SZ, 172 BD, and 167 healthy controls (HC)) that underwent an assessment using the Hopkins Verbal Learning Test - Revised for VM and the Functioning Assessment Short Test for psychosocial functioning. We compared groups through ANOVAs and investigated the effect of semantic clustering in the relationship between VM total immediate free recall and functioning through linear regression models. RESULTS: SZ had worse overall VM performance compared to BD, which performed worse than HCs. HCs used more semantic clustering than SZ and BD, but there were no differences between the two clinical groups. In HCs, semantic clustering impacted the relationship between VM performance and functioning, while no interaction was observed in SZ or BD. LIMITATIONS: Cross-sectional design; no medication effects or other cognitive functions were assessed. CONCLUSIONS: SZ and BD may use an alternative cognitive pathway in which the relationship between VM and functioning is independent of complex cognitive processes such as semantic clustering, supporting the cognitive remediation targeting of VM in these disorders.

Heterogeneous trajectories in schizophrenia: insights from neurodevelopment and neuroprogression models

The notion that schizophrenia is a neuroprogressive disorder is based on clinical perception of cumulative impairments over time and is supported by neuroimaging and biomarker research. Nevertheless, increasing evidence has indicated that schizophrenia first emerges as a neurodevelopmental disorder that could follow various pathways, some of them neuroprogressive. The objective of this review is to revisit basic research on cognitive processes and neuroimaging findings in a search for candidate keys to the intricate connections between neurodevelopment and neuroprogression in schizophrenia. In the complete panorama, schizophrenia is a neurodevelopmental disorder, possibly associated with an additional burden over the course of the disease through pathologically accelerated aging, and cognitive heterogeneity may explain the different trajectories of each patient.

Heterogeneous trajectories in schizophrenia: insights from neurodevelopment and neuroprogression models.

OBJECTIVES: The notion that schizophrenia is a neuroprogressive disorder is based on clinical perception of cumulative impairments over time and is supported by neuroimaging and biomarker research. Nevertheless, increasing evidence has indicated that schizophrenia first emerges as a neurodevelopmental disorder that could follow various pathways, some of them neuroprogressive. The objective of this review is to revisit basic research on cognitive processes and neuroimaging findings in a search for candidate keys to the intricate connections between neurodevelopment and neuroprogression in schizophrenia. In the complete panorama, schizophrenia is a neurodevelopmental disorder, possibly associated with an additional burden over the course of the disease through pathologically accelerated aging, and cognitive heterogeneity may explain the different trajectories of each patient.

Bipolar disorder: an association between body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation.

OBJECTIVE: To investigate associations between body mass index (BMI), white matter fractional anisotropy (FA), and C-reactive protein (CRP) in a group of individuals with bipolar disorder (BD) during euthymia and compare them with a control group of healthy subjects (CTR). METHODS: The sample consisted of 101 individuals (BD n = 35 and CTR n = 66). Regions of interest (ROI) were defined using a machine learning approach. For each ROI, a regression model tested the association between FA and BMI, controlling for covariates. Peripheral CRP levels were assayed, correlated with BMI, and included in a mediation analysis. RESULTS: BMI predicted the FA of the right cingulate gyrus in BD (AdjR2 = 0.312 F(3) = 5.537 p = 0.004; ß = -0.340 p = 0.034), while there was no association in CTR. There was an interaction effect between BMI and BD diagnosis (F(5) = 3.5857 p = 0.012; Fchange = 0.227 AdjR2 = 0.093; ß = -1.093, p = 0.048). Furthermore, there was a positive correlation between BMI and CRP in both groups (AdjR2 = 0.170 F(3) = 7.337 p < 0.001; ß = 0.364 p = 0.001), but it did not act as a mediator of the effect on FA. CONCLUSION: Higher BMI is associated with right cingulate microstructure in BD, but not in CTR, and this effect could not be explained by inflammatory mediation alone.

Bipolar disorder: an association between body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation

Abstract Objective To investigate associations between body mass index (BMI), white matter fractional anisotropy (FA), and C-reactive protein (CRP) in a group of individuals with bipolar disorder (BD) during euthymia and compare them with a control group of healthy subjects (CTR). Methods The sample consisted of 101 individuals (BD n = 35 and CTR n = 66). Regions of interest (ROI) were defined using a machine learning approach. For each ROI, a regression model tested the association between FA and BMI, controlling for covariates. Peripheral CRP levels were assayed, correlated with BMI, and included in a mediation analysis. Results BMI predicted the FA of the right cingulate gyrus in BD (AdjR2 = 0.312 F(3) = 5.537 p = 0.004; β = -0.340 p = 0.034), while there was no association in CTR. There was an interaction effect between BMI and BD diagnosis (F(5) = 3.5857 p = 0.012; Fchange = 0.227 AdjR2 = 0.093; β = -1.093, p = 0.048). Furthermore, there was a positive correlation between BMI and CRP in both groups (AdjR2 = 0.170 F(3) = 7.337 p < 0.001; β = 0.364 p = 0.001), but it did not act as a mediator of the effect on FA. Conclusion Higher BMI is associated with right cingulate microstructure in BD, but not in CTR, and this effect could not be explained by inflammatory mediation alone.

Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities.

BACKGROUND: Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear. AIMS: We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed. METHOD: This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model. RESULTS: A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = -0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. CONCLUSIONS: Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.

Adjunctive tianeptine treatment for bipolar disorder: A 24-week randomized, placebo-controlled, maintenance trial.

OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of tianeptine as an adjunctive maintenance treatment for bipolar depression. METHODS: This is a multicenter double-blind randomized placebo-controlled maintenance trial of adjunctive tianeptine 37.5 mg/day. Participants ( n=161) had a Montgomery-Asberg Depression Rating Scale ⩾12 at entry. After eight weeks of open-label tianeptine treatment, those who responded to tianeptine ( n=69) were randomized to adjunctive tianeptine ( n=36) or placebo ( n=33) in addition to usual treatment. Kaplan-Meier estimates and the Mantel-Cox log-rank test were used to evaluate differences in time to intervention for a mood episode between the tianeptine and placebo groups. We also assessed overall functioning, biological rhythms, quality of life, rates of manic switch and serum brain-derived neurotrophic factor levels. RESULTS: There were no differences between adjunctive tianeptine or placebo regarding time to intervention or depression scores in the 24-week double-blind controlled phase. Patients in the tianeptine group showed better performance in the letter-number sequencing subtest from the Wechsler Adult Intelligence Scale at the endpoint ( p=0.014). Tianeptine was well tolerated and not associated with higher risk for manic switch compared to placebo. CONCLUSION: Tianeptine was not more effective than placebo in the maintenance treatment of bipolar depression. There is preliminary evidence suggesting a pro-cognitive effect of tianeptine in working memory compared to placebo.

Volumetric brain magnetic resonance imaging predicts functioning in bipolar disorder: A machine learning approach.

Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Neuroanatomical changes tend to be more pronounced in patients with repeated episodes. Although the role of such changes in cognition and memory is well established, daily-life functioning impairments bulge among the consequences of the proposed progression. The objective of this study was to analyze MRI volumetric modifications in BD and healthy controls (HC) as possible predictors of daily-life functioning through a machine learning approach. Ninety-four participants (35 DSM-IV BD type I and 59 HC) underwent clinical and functioning assessments, and structural MRI. Functioning was assessed using the Functioning Assessment Short Test (FAST). The machine learning analysis was used to identify possible candidates of regional brain volumes that could predict functioning status, through a support vector regression algorithm. Patients with BD and HC did not differ in age, education and marital status. There were significant differences between groups in gender, BMI, FAST score, and employment status. There was significant correlation between observed and predicted FAST score for patients with BD, but not for controls. According to the model, the brain structures volumes that could predict FAST scores were: left superior frontal cortex, left rostral medial frontal cortex, right white matter total volume and right lateral ventricle volume. The machine learning approach demonstrated that brain volume changes in MRI were predictors of FAST score in patients with BD and could identify specific brain areas related to functioning impairment.

Cardiovascular risk and bipolar disorder: factors associated with a positive coronary calcium score in patients with bipolar disorder type 1

Objective: Cardiovascular disease is the leading cause of death in patients with bipolar disorder. The aim of this study was to evaluate the factors associated with positive coronary calcium score (CCS) in individuals with bipolar disorder type 1. Methods: Patients from the Bipolar Disorder Program at Hospital de Clínicas de Porto Alegre, Brazil, underwent computed tomography scanning for calcium score measurement. Clinical and sociodemographic variables were compared between patients according to their CCS status: negative (CCS = 0) or positive (CCS > 0). Poisson regression analysis was used to examine the association of CCS with number of psychiatric hospitalizations. Results: Out of 41 patients evaluated, only 10 had a positive CCS. Individuals in the CCS-positive group were older (55.2±4.2 vs. 43.1±10.0 years; p = 0.001) and had more psychiatric hospitalizations (4.7±3.0 vs. 2.6±2.5; p = 0.04) when compared with CCS- negative subjects. The number of previous psychiatric hospitalizations correlated positively with CCS (p < 0.001). Conclusion: Age and number of psychiatric hospitalizations were significantly associated with higher CCS, which might be a potential method for diagnosis and stratification of cardiovascular disease in bipolar patients. There is a need for increased awareness of risk assessment in this population.

Cardiovascular risk and bipolar disorder: factors associated with a positive coronary calcium score in patients with bipolar disorder type 1.

OBJECTIVE: Cardiovascular disease is the leading cause of death in patients with bipolar disorder. The aim of this study was to evaluate the factors associated with positive coronary calcium score (CCS) in individuals with bipolar disorder type 1. METHODS: Patients from the Bipolar Disorder Program at Hospital de Clínicas de Porto Alegre, Brazil, underwent computed tomography scanning for calcium score measurement. Clinical and sociodemographic variables were compared between patients according to their CCS status: negative (CCS = 0) or positive (CCS > 0). Poisson regression analysis was used to examine the association of CCS with number of psychiatric hospitalizations. RESULTS: Out of 41 patients evaluated, only 10 had a positive CCS. Individuals in the CCS-positive group were older (55.2±4.2 vs. 43.1±10.0 years; p = 0.001) and had more psychiatric hospitalizations (4.7±3.0 vs. 2.6±2.5; p = 0.04) when compared with CCS- negative subjects. The number of previous psychiatric hospitalizations correlated positively with CCS (p < 0.001). CONCLUSION: Age and number of psychiatric hospitalizations were significantly associated with higher CCS, which might be a potential method for diagnosis and stratification of cardiovascular disease in bipolar patients. There is a need for increased awareness of risk assessment in this population.

Differences in parental bonding between schizophrenia and bipolar disorder: Evidence of prodromal symptoms?

BACKGROUND: The Parental Bonding Instrument (PBI) examines parent-child bonds and attachment during the first 16 years. Our study aims to compare PBI scores between patients with schizophrenia and bipolar disorder (BD). METHODS: We analyzed PBI scores in 59 patients with schizophrenia, 36 with BD and 52 healthy controls using ANCOVA, with age, gender and years of education as covariates. Bonferroni correction was used to adjust for multiple comparisons. PBI has maternal and paternal scores, each one with two domains: care and overprotection. RESULTS: In PBI maternal and paternal care domains, patients with schizophrenia showed significantly higher scores when compared with BD patients (p<0.001). However, when compared with healthy controls, patients with schizophrenia only showed significantly higher scores of PBI maternal care domain (p=0.037). BD patients showed significantly lower PBI care scores compared with healthy controls (maternal score: p=0.016; paternal score: p<0.001). In PBI maternal and paternal overprotection domain, BD patients showed significantly higher scores compared with patients with schizophrenia (p=0.004; p=0.021) and healthy controls (p=0.014; p=0.008); while no significant difference was observed between patients with schizophrenia and healthy controls. "P values" are according to Bonferroni correction. CONCLUSION: There are significant differences in the perception of attachment between schizophrenia and BD. This finding may shed some light to better understand the prodromal symptoms of each disorder.

Verbal episodic memory along the course of schizophrenia and bipolar disorder: a new perspective.

Impairment on episodic memory (EM) has been strongly correlated with psychiatric disorders, including schizophrenia (SZ) and bipolar disorder (BD). Morevover, the effects of course and progression of the illness on cognitive functioning have not been well established. The aim of the present study is to assess performance of episodic memory in BD and SZ according to their clinical stages. Subjects who met DSM-IV criteria for bipolar disorder (n=43) and schizophrenia (31), on euthymia or clinical remission, were recruited from the outpatients facilities at Hospital de Clínicas de Porto Alegre (Brazil). They were classified into two clinical stages (early or late for BD, and recent onset or chronic for SZ) and compared to 54 healthy controls. Episodic memory performance was assessed by means the Hopkins Verbal Learning Test-Revised (HVLT-R) that measures verbal learning and episodic memory in both disorders. Our results showed that patients in early stage of BD (EBD) performed better performance on the total immediate free recall (p<0.0001, F=12.060) as well as in delayed free recall (p<0.0001, F=13.914) compared to late stage (LBD) and SZ groups. In the ability to retain words learned, LBD and chronic (CSZ) were more impaired than other groups. Furthermore, the variation of learning (i.e, learning effects) along the 3 trials of immediate free recall was similar between groups. In conclusion, we found a cognitive decline alongside with the progression of BD whereas such impairment was evident in the early of SZ. Despite this, both groups (BD and SZ) seem to maintain the ability to learn. It emphasizes the relevance of studying new therapeutic strategies, in particular, cognitive rehabilitation/remediation techniques as promissory treatment for psychiatric patients, even in those with moderate disabilities.

Daytime sleepiness, sleep disturbance and functioning impairment in bipolar disorder.

OBJECTIVE: To verify the prevalence and clinical impact of excessive daytime sleepiness (EDS) in outpatients with bipolar disorder. METHODS: Eighty-one outpatients with bipolar disorder and 79 healthy control subjects were recruited. Patients were required not to be acutely manic or depressed. We used the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index and the Functioning Assessment Short Test to assess sleepiness, sleep problems and functioning, respectively. RESULTS: Patients had a higher prevalence of sleepiness (40%) than the control group (18%). Sleepiness and sleep disturbance had independent impacts on disability in the multivariable model. CONCLUSIONS: This study suggests that EDS is a relevant clinical dimension in patients with bipolar disorder. It is a frequent symptom that often overlaps with other sleep disturbances. This study also reveals that once present it has the potential to increase functional impairment.