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Objective: Rapid cycling (RC) is a feature of bipolar disorder (BD) that has been associated with worse outcome and more severe disability. Our goal was to investigate the association of demographic and clinical factors with RC. Methods: We compared RC and non-rapid cycling (NRC) BD patients from the Brazilian Research Network in Bipolar Disorder (BRN-BD) regarding age at onset of BD; total number of episodes; previous number of manic, depressive, mixed, and hypomanic episodes; polarity of the first episode; gender; number of suicide attempts; number of lifetime hospitalizations and lifetime history of at least one hospitalization; family history of mood disorder; clinical comorbidities such as hypothyroidism, hyperthyroidism, seizures; and current use of medications such as lithium, anticonvulsants, antipsychotics, and antidepressants. Results: We studied 577 patients and found that 100 (17.3%) met the criteria for RC in the year before the investigation. RC patients had earlier age at onset, longer duration of disease, more lifetime depressive and manic episodes, higher number of suicide attempts, and higher rate antidepressant use. Conclusion: The presence of RC in the previous year was associated with specific clinical characteristics closely related to worse outcome in the course of BD.

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Objective: To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls. Methods: Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST). A sub-group of patients with BD (n=21), unaffected siblings (n=14), and healthy controls (n=22) also underwent a battery of neuropsychological tests: California Verbal Learning Test (CVLT), Stroop Color and Word Test, and Wisconsin Card Sorting Test (WCST). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chi-square test; multivariate analysis of covariance was used to examine differences in neuropsychological variables. Results: Patients with BD showed higher FAST total scores (23.90±11.35) than healthy controls (5.86±5.47; p < 0.001) and siblings (12.60±11.83; p 0.001). Siblings and healthy controls also showed statistically significant differences in FAST total scores (p = 0.008). Patients performed worse than healthy controls on all CVLT sub-tests (p < 0.030) and in the number of correctly completed categories on WCST (p = 0.030). Siblings did not differ from healthy controls in cognitive tests. Conclusion: Unaffected siblings of patients with BD may show poorer functional performance compared to healthy controls. FAST scores may contribute to the development of markers of vulnerability and endophenotypic traits in at-risk populations.

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Objective: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls. Methods: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle. Conclusion: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD.

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Objective: Exposure and response prevention (ERP) is effective to treat obsessive-compulsive disorder (OCD), but the lack of tolerance to the aversion nature of exposure techniques results in a high drop-out rate. There have been reports of a generic stress endurance effect of serotonin (5-HT) in the central nervous system (CNS) which might be explained by suppression of defensive fixed action patterns. Previous studies have proposed that higher baseline 5-HT concentration and slow decrease in concentration during drug treatment of OCD were predictors of good clinical response to 5-HT reuptake inhibitors. The objective of this study was to investigate whether pre-treatment platelet rich plasma (PRP) 5-HT concentration is associated with latency of treatment response and final response to an ERP protocol for obsessive-compulsive disorder (OCD). Methods: Thirty adult and treatment-free OCD patients were included in an 8-week, 16-session ERP protocol. 5-HT concentration was determined at baseline and after treatment. Patients with a reduction ≥30% on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at the end of ERP were defined as responders. Results: A positive correlation between baseline 5-HT concentration and reduction of symptoms on the Y-BOCS was observed after 4 weeks. Baseline 5-HT concentration was not correlated with clinical response after 8 weeks of ERP, possibly due to the similar though delayed clinical response of patients with lower (compared to those with higher) baseline 5-HT concentration. Patients with higher 5-HT baseline concentration also showed more improvement in depressive symptoms with treatment. Conclusion: The present results partially support the hypothesis of a stress endurance effect of 5-HT in OCD patients. According to the literature, fast onset responders possibly have more or larger 5-HT containing neurons, higher endogenous 5-HT synthesis or lower monoamine oxidase activity; all these hypotheses remain to be investigated.

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Objectives: To determine changes over time in self and caregiver ratings of quality of life (QoL) in people with dementia (PwD) and to identify factors associated with changes in QoL ratings. Methods: In this longitudinal study, 69 people with mild Alzheimer’s disease and their caregivers were assessed at baseline and after 1 year. We examined the association of QoL ratings with the following variables at the two time points: awareness of disease, cognitive status, mood, functionality, neuropsychiatric symptoms, and caregiver burden. Multivariate regression analyses were conducted to examine the contribution of co-factors. Results: At baseline, PwD self-ratings of QoL were associated with caregiver ratings of PwD QoL (p = 0.001). Caregiver ratings were associated with PwD mood (p = 0.001) and self-rated QoL (p = 0.001). After 1 year, caregiver ratings of PwD QoL changed significantly (p = 0.049, d = -0.27), whereas PwD self-ratings did not (p = 0.89, d = 0.09). PwD awareness of disease changed significantly (p = 0.001) at 1 year, having declined in 25.4% and improved in 12.3% of participants. PwD QoL self-ratings were associated with caregiver ratings (p = 0.001). Caregiver ratings of PwD QoL after 1 year were associated with PwD mood (p = 0.029), self-reported QoL (p = 0.001), and awareness of disease (p = 0.033). Conclusions: The association between self and caregiver ratings of PwD QoL was maintained over 1 year. The primary factors accounting for the change in caregiver ratings were PwD mood and awareness of disease. QoL and cognitive impairment seem to be relatively independent in mild dementia.

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Objective: To prospectively evaluate depressive symptoms, nutritional status, and quality of life (QoL) and search for possible associations in patients with end-stage renal disease undergoing hemodialysis. Methods: A cohort study of 104 adult patients with end-stage renal disease undergoing hemodialysis was conducted. Anthropometric, clinical, and biochemical variables were evaluated after a midweek hemodialysis session. The participants’ body composition was assessed by direct segmental multi-frequency bioimpedance analysis. The WHOQOL-Bref questionnaire was used to evaluate QoL. Participants were separated into two groups - depressive symptoms and no depressive symptoms - at inclusion and evaluated annually for 2 years thereafter using the Beck Depression Inventory. Survival analysis used the Kaplan-Meier method and Cox regression analysis for the goodness of fit of associated factors. All-cause mortality was the outcome of interest. Results: Participants’ mean age was 55.3±15.6 years, 60% were male, and the median time on hemodialysis was 17.5 (8.0-36.8) months. Thirty-two patients had depressive symptoms and a significantly lower QoL compared with the 72 patients in the no depressive symptoms group. The fitted outcome model showed that lean body mass had a protective effect against all-cause mortality (hazard ratio [HR] = 0.89; 95%CI 0.80-0.99; p = 0.038). Conclusion: Depressive symptoms were highly prevalent in the cohort, and correlated with the physical and psychological components of the QoL life questionnaire, as well as with C-reactive protein and phosphorus levels. Lean body mass was protective for the assessed outcome.

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Objective: To investigate empathic abilities in patients with obsessive-compulsive disorder (OCD) compared to control subjects. OCD is characterized by persistent obsessions and compulsions. Previous studies have proposed specific emotion recognition deficits in patients with OCD. The ability to recognize emotion is part of the broad construct of empathy that incorporates mentalizing and experience-sharing dimensions. Methods: Twenty-four subjects with a diagnosis of OCD and 23 control subjects underwent empathic measures. Results: Patients with OCD compared to control subjects showed deficits in all mentalizing measures. They were incapable of understanding the mental and emotional states of other people. On the other hand, in the sharing experience measures, the OCD group was able to empathize with the emotional experience of other people when they expressed emotions with positive valence, but were not able to do when the emotional valence was negative. Conclusion: Our results suggest that patients with OCD show a difficulty in mentalizing ability, whereas the deficit in sharing ability is specific for the negative emotional valence.

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Objective: To evaluate trends in psychiatric bed occupancy by elderly inpatients in the Brazilian public health care system between 2000 and 2010 and to determine the leading psychiatric diagnosis for hospital admissions. Methods: Data from all 895,476 elderly psychiatric admissions recorded in the Brazilian Public Health Care Database (DATASUS) between January 2000 and February 2010 were analyzed. Polynomial regression models with estimated curve models were used to determine the trends. The number of inpatient days was calculated for the overall psychiatric admissions and according to specific diagnoses. Results: A moderate decreasing trend (p < 0.001) in the number of inpatient days was observed in all geriatric psychiatric admissions (R2 = 0.768) and in admissions for organic mental disorders (R2 = 0.823), disorders due to psychoactive substance use (R2 = 0.767), schizophrenia (R2 = 0.680), and other diagnoses (R2 = 0.770), but not for mood disorders (R2 = 0.472). Most admissions (60 to 65%) were due to schizophrenia. Conclusion: There was a decreasing trend in inpatient days for elderly psychiatric patients between 2000 and 2010. The highest bed occupancy was due to schizophrenia, schizotypal, and delusional disorders.

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Objective: To examine association of sociodemographic characteristics, personality traits, social skills, and work variables with anxiety, depression, and alcohol dependence in medical residents. Methods: A total of 270 medical residents completed the following self-report instruments: sociodemographic and work questionnaire, Patient Health Questionnaire-4 (PHQ-4), Alcohol Use Disorders Identification Test-3 (AUDIT-3), Revised NEO-Five Factor Inventory (NEO-FFI-R), and Social Skills Inventory (SSI-Del-Prette). Data were analyzed using descriptive statistics and univariate and multivariate logistic regression analyses. Results: Multivariate analysis showed an association of neuroticism (odds ratio [OR] 2.60, p < 0.001), social skills (OR 0.41, p < 0.01), and number of shifts (OR 1.91, p = 0.03) with anxiety or depression, and of male sex (OR 3.14, p = 0.01), surgical residency (OR 4.40, p = 0.001), extraversion (OR 1.80, p < 0.01), and number of shifts (OR 2.32, p = 0.04) with alcohol dependence. Conclusion: The findings support a multidetermined nature of mental health problems in medical residents, in addition to providing data that may assist in the design of preventive measures to protect the mental health of this group.

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Objective: To assess the relationship of biological rhythms, evaluated by the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), with affective temperaments and schizotypy. Methods: The BRIAN assessment, along with the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) and the Oxford-Liverpool Inventory for Feelings and Experiences (O-LIFE), was administered to 54 patients with remitted bipolar disorder (BD) and 54 healthy control (HC) subjects. Results: The TEMPS-A cyclothymic temperament correlated positively and the hyperthymic temperament correlated negatively with BRIAN scores in both the BD and HC groups, although the correlation was stronger in BD subjects. Depressive temperament was associated with BRIAN scores in BD but not in HC; conversely, the irritable temperament was associated with BRIAN scores in HC, but not in BD. Several positive correlations between BRIAN scores and the schizotypal dimensions of the O-LIFE were observed in both BD and HC subjects, especially with cognitive disorganization and less so with unusual experiences and impulsive nonconformity. A correlation with introversion/anhedonia was found only in BD subjects. Conclusion: Cyclothymic and depressive temperaments predispose to disturbances of biological rhythms in BD, while a hyperthymic temperament can be protective. Similar predispositions were also found for all schizotypal dimensions, mostly for cognitive disorganization.

Resumo em Inglês:

Recently, attention in the field of bipolar disorder (BD) has focused on prevention, including early detection and intervention, as these strategies have the potential to delay, lessen the severity, or even prevent full-blown episodes of BD. Although knowledge of the neurobiology of BD has advanced substantially in the last two decades, most research was conducted with chronic patients. The objective of this paper is to comprehensively review the literature regarding the early stages of BD, to explore recent discoveries on the neurobiology of these stages, and to discuss implications for research and clinical care. The following databases were searched: PubMed, PsycINFO, Cochrane Library, and SciELO. Articles published in English from inception to December 2015 were retrieved. Several research approaches were used, including examination of offspring studies, retrospective studies, prospective studies of clinical high-risk populations, and exploration of the progression after the first manic episode. Investigations with neuroimaging, cognition assessments, and biomarkers provide promising (although not definitive) evidence of alterations in the neural substrate during the at-risk stage. Research on BD should be expanded to encompass at-risk states and aligned with recent methodological progress in neuroscience.

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Objective: Major depressive disorder (MDD) is a prevalent psychiatric condition characterized by multiple symptoms that cause great distress. Uncovering the brain areas involved in MDD is essential for improving therapeutic strategies and predicting response to interventions. This systematic review discusses recent findings regarding cortical alterations in depressed patients during emotional or cognitive tasks, as measured by electroencephalography (EEG). Methods: A search of the MEDLINE/PubMed and Cochrane databases was carried out using the keywords EEG and depression, confined to article title. Results: The studies identified reveal the frontal cortex as an important brain structure involved in the complex neural processes associated with MDD. Findings point to disorganization of right-hemisphere activity and deficient cognitive processing in MDD. Depressed individuals tend to ruminate on negative information and respond with a pattern of relatively higher right frontal activity to emotional stimuli associated with withdrawal and isolation. Conclusion: Patients with MDD may have altered dynamic patterns of activity in several neuroanatomical structures, especially in prefrontal and limbic areas involved in affective regulation. Identification of these alterations might help predict the response of patients to different interventions more effectively and thus maximize the effects both of pharmacotherapeutic and of psychotherapeutic strategies.