ABSTRACT
Introducción El Trastorno Bipolar es una enfermedad que causa discapacidad física y cognitiva, afectando tanto a hombres como mujeres, con edad de inicio temprano y con un alto componente hereditario. Objetivo Estimar el comportamiento del Trastorno Bipolar, variables sociodemográficas, antecedentes y su relación con los genes CACNA1C (12p13.3) y DAOA (13q34) entre personas de 18 años y más en áreas específicas de la Región de Azuero de Panamá. Metodología La muestra calculada fue de 267 personas de 18 años y más (IC 95%) utilizando un muestreo aleatorio, de distribución proporcional según sexo. Se utilizaron las variables: "trastorno bipolar" medido a través del cuestionario de trastornos del estado de ánimo (Mood Disorder Questionnaire, MDQ por sus siglas en inglés); "genes asociados a la bipolaridad" (genes CACNA1C (12p13.3) y DAOA (13q34)); y un cuestionario de datos sociodemográficos y antecedentes personales familiares. El análisis genético se realizó con PCR (tiempo real). Se utilizaron porcentajes como medida de frecuencia relativa y se consideró significancia estadística para un valor de p ≤ 0.05. Resultados La prevalencia de bipolaridad en la muestra estudiada fue 3.7% (IC 95% 3.5 4.1), siendo mayor en mujeres, 6.0% (IC 95% 5.9 6.3). El 74.2% (IC 95% 73.9 74.4) de los participantes tenía presente el polimorfismo del gen CACNA1C (12p13.3), y 19.1% (IC 95% 18.9 19.4) el del gen DAOA (13q34). Para todas las variables de estudio, la presencia del gen CACNA1C (12p13.3) fue mayor que la del gen DAOA (13q34). De los 10 casos con MDQ+, 3 presentaron el gen CACNA1C. Conclusión Esta es la primera investigación sobre bipolaridad, genes y otros factores asociados en Panamá. El gen CACNA1C fue más prevalente que el DAOA y se asoció más al MDQ +.
Introduction Bipolar disorder is a disease that causes physical and cognitive disability, affecting both men and women, with an early onset age and a high hereditary component. Objective To estimate Bipolar Disorder demeanor, sociodemographic variables, antecedents and its relationship with CACNA1C (12p13.3) and DAOA (13q34) genes among people aged 18 years and over in specific areas of the Azuero Region of Panama. Methodology The calculated sample was 267 people aged 18 and over (95% CI) using random sampling, proportional distribution according to sex. The variables were used: "bipolar disorder" measured through the Mood Disorder Questionnaire (MDQ); "genes associated with bipolarity" (CACNA1C (12p13.3) and DAOA (13q34) genes); and a sociodemographic data questionnaire and personal family background. The genetic analysis was performed with PCR (real time). Percentages were used as a re of relative frequency and statistical significance was considered for a value of p ≤ 0.05. Results The prevalence of bipolarity in the studied sample was 3.7% (CI 95% 3.5 4.1), being higher in women, 6.0% (CI 95% 5.9 6.3). 74.2% (CI 95% 73.9 74.4) of the participants were aware of the polymorphism of the CACNA1C gene (12p13.3), and 19.1% (CI 95% 18.9 19.4) of the DAOA gene (13q34). For all study variables, the presence of the CACNA1C gene (12p13.3) was greater than that of the DAOA gene (13q34). Of the 10 cases with MDQ +, 3 presented the CACNA1C gene. ConclusionThis is the first research on bipolarity, genes and other associated factors in Panama. The CACNA1C gene was more prevalent than DAOA and was more associated with MDQ +.
Subject(s)
Bipolar Disorder , Bipolar Disorder/physiopathology , Bipolar and Related Disorders/epidemiology , Mania , Mental Disorders , Polymorphism, Genetic , Schizophrenia/genetics , Depression/geneticsABSTRACT
Objective: Circadian dysregulation plays an important role in the etiology of mood disorders. Evening chronotype is frequent in these patients. However, prospective studies about the influence of chronotype on mood symptoms have reached unclear conclusions in patients with bipolar disorder (BD). The objective of this study was to investigate relationship between chronotype and prognostic factors for BD. Methods: At the baseline, 80 euthymic BD patients answered a demographic questionnaire and clinical scales to evaluate anxiety, functioning and chronotype. Circadian preference was measured using the Morningness-Eveningness Questionnaire, in which lower scores indicate eveningness. Mood episodes and hospitalizations were evaluated monthly for 18 months. Results: Among the BD patients, 14 (17.5%) were definitely morning type, 35 (43.8%), moderately morning, 27 (33.7%) intermediate (neither) and 4 (5%) moderately evening. Eveningness was associated with obesity or overweight (p = 0.03), greater anxiety (p = 0.002) and better functioning (p = 0.01), as well as with mood episodes (p = 0.04), but not with psychiatric hospitalizations (p = 0.82). This group tended toward depressive episodes (p = 0.06), but not (hypo)mania (p = 0.56). Conclusion: This study indicated that evening chronotype predicts a poor prognostic for BD. It reinforces the relevance of treating rhythm disruptions even during euthymia to improve patient quality of life and prevent mood episodes.
Subject(s)
Humans , Male , Female , Adult , Aged , Young Adult , Anxiety/physiopathology , Bipolar Disorder/physiopathology , Circadian Rhythm/physiology , Prognosis , Psychiatric Status Rating Scales , Quality of Life , Time Factors , Logistic Models , Prospective Studies , Surveys and Questionnaires , Statistics, Nonparametric , Chronobiology Disorders/physiopathology , Hospitalization/statistics & numerical data , Middle AgedABSTRACT
Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.
Subject(s)
Animals , Male , Bipolar Disorder/immunology , Disease Models, Animal , Lisdexamfetamine Dimesylate , Lithium/pharmacology , Anti-Inflammatory Agents/pharmacology , Nerve Growth Factors/drug effects , Time Factors , Bipolar Disorder/physiopathology , Bipolar Disorder/chemically induced , Enzyme-Linked Immunosorbent Assay , Lipopolysaccharides/pharmacology , Reproducibility of Results , Cytokines/blood , Treatment Outcome , Rats, Wistar , Brain-Derived Neurotrophic Factor/blood , Nitric Oxide Synthase Type II/blood , Locomotion/drug effectsABSTRACT
Objective: To evaluate whether exposing rats to individual or combined environmental stressors triggers endophenotypes related to mood and anxiety disorders, and whether this effect depends on the nature of the behavior (i.e., innate or learned). Methods: We conducted a three-phase experimental protocol. In phase I (baseline), animals subjected to mixed schedule of reinforcement were trained to press a lever with a fixed interval of 1 minute and a limited hold of 3 seconds. On the last day of phase I, an open-field test was performed and the animals were divided into four experimental groups (n=8/group). In phase II (repeated stress), each group was exposed to either hot air blast (HAB), paradoxical sleep deprivation (PSD) or both (HAB+PSD group) on alternate days over a 10-day period. Control group animals were not exposed to stressors. In phase III (post-stress evaluation), behavior was analyzed on the first (short-term effects), third (mid-term effects), and fifth (long-term effects) days after repeated stress. Results: The PSD group presented operant hyperactivity, the HAB group presented spontaneous hypoactivity and anxiety, and the HAB+PSD group presented spontaneous hyperactivity, operant hypoactivity, impulsivity, loss of interest, and cognitive impairment. Conclusion: A combination of environmental stressors (HAB and PSD) may induce endophenotypes related to bipolar disorder.
Subject(s)
Animals , Male , Rats , Stress, Psychological/physiopathology , Behavior, Animal , Bipolar Disorder/physiopathology , Cognition Disorders/physiopathology , Anxiety , Sleep Deprivation , Rats, Wistar , Cognition , Disease Models, AnimalABSTRACT
Objective: Few quantitative studies have examined the effect of religious involvement on the course of bipolar disorder (BD). We investigated the effects of religious activity and coping behaviors on the course of depression, mania, and quality of life (QoL) in patients with BD. Methods: Two-year longitudinal study of 168 outpatients with BD. Linear regression was used to examine associations between religious predictors and outcome variables (manic symptoms, depression, QoL), controlling for sociodemographic variables. Results: Among the 158 patients reassessed after 2 years, positive religious coping at T1 predicted better QoL across all four domains: physical (β = 10.2, 95%CI 4.2 to 16.1), mental (β = 13.4, 95%CI 7.1 to 19.7), social (β = 10.5, 95%CI 3.6 to 17.33), and environmental (β = 11.1, 95%CI 6.2 to 16.1) at T2. Negative religious coping at T1 predicted worse mental (β = -28.1, 95%CI -52.06 to -4.2) and environmental (β = -20.4, 95%CI -39.3 to -1.6) QoL. Intrinsic religiosity at T1 predicted better environmental QoL (β = 9.56, 95%CI 2.76 to 16.36) at T2. Negative religious coping at T1 predicted manic symptoms (β = 4.1) at T2. Conclusion: Religiosity/spirituality (R/S) may influence the QoL of patients with BD over time, even among euthymic patients. Targeting R/S (especially positive and negative religious coping) in psychosocial interventions may enhance the quality of recovery in patients with BD.
Subject(s)
Humans , Male , Adult , Middle Aged , Quality of Life/psychology , Religion and Psychology , Bipolar Disorder/psychology , Spirituality , Depression/psychology , Socioeconomic Factors , Bipolar Disorder/physiopathology , Adaptation, Psychological , Prospective Studies , Surveys and Questionnaires , Follow-Up Studies , Longitudinal StudiesABSTRACT
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.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Bipolar Disorder/psychology , Psychiatric Status Rating Scales , Suicide, Attempted/psychology , Suicide, Attempted/statistics & numerical data , Bipolar Disorder/physiopathology , Bipolar Disorder/drug therapy , Bipolar Disorder/epidemiology , Brazil/epidemiology , Comorbidity , Epidemiologic Methods , Age of Onset , Hospitalization , Antidepressive Agents/therapeutic useABSTRACT
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.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Bipolar Disorder/genetics , Aging/genetics , Telomere/genetics , Telomere Shortening/genetics , Bipolar Disorder/physiopathology , DNA/blood , Case-Control Studies , Cellular Senescence/genetics , Real-Time Polymerase Chain ReactionABSTRACT
Objectives: Depressive symptoms are associated with worse outcomes in patients with bipolar disorder (BD). However, scarce data are available regarding neurocognitive profiles across different areas of functioning among BD patients with moderate and severe depression. Our objective was to assess cognition and global functioning in a group of patients with bipolar depression. Methods: Data were available for 100 patients with bipolar depression (78% female) and 70 controls (64% female) paired by age and education level. Cognitive function was assessed with a neuropsychological test battery. Functioning was assessed with the Functioning Assessment Short Test. Results: In patients, severe depression was associated with poorer cognitive performance on measures of executive function. Patients with severe depression showed worse global functioning than those with moderate depression (z = 2.54, p = 0.011). In patients with severe depression, lower global functioning was associated with lower scores in working memory (r = -0.200, p = 0.010), and executive function (r = -0.210, p = 0.007; and r = 0.293, p < 0.001). Conclusion: Our findings suggest cognitive impairment and global functioning impairment are associated with the severity of depressive symptoms in bipolar depression. Intensive treatment of depressive symptoms in patients with BD is crucial to improve cognitive functioning and, consequently, functional outcomes.
Subject(s)
Humans , Male , Female , Adult , Bipolar Disorder/physiopathology , Depression/physiopathology , Cognitive Dysfunction/physiopathology , Psychiatric Status Rating Scales , Severity of Illness Index , Case-Control Studies , Analysis of Variance , Cognition/physiology , Executive Function/physiology , Memory, Short-Term/physiology , Middle Aged , Neuropsychological TestsABSTRACT
Objective: To compare sensory processing, coping strategies, and quality of life (QoL) in unipolar and bipolar patients; to examine correlations between sensory processing and QoL; and to investigate the relative contribution of sociodemographic characteristics, sensory processing, and coping strategies to the prediction of QoL. Methods: Two hundred sixty-seven participants, aged 16-85 years (53.6±15.7), of whom 157 had a diagnosis of unipolar major depressive disorder and 110 had bipolar disorder type I and type II, completed the Adolescent/Adult Sensory Profile, Coping Orientations to Problems Experienced, and 12-item Short-Form Health Survey version 2. The two groups were compared with multivariate analyses. Results: The unipolar and bipolar groups did not differ concerning sensory processing, coping strategies, or QoL. Sensory processing patterns correlated with QoL independently of mediation by coping strategies. Correlations between low registration, sensory sensitivity, sensation avoidance, and reduced QoL were found more frequently in unipolar patients than bipolar patients. Higher physical QoL was mainly predicted by lower age and lower sensory sensitivity, whereas higher mental QoL was mainly predicted by coping strategies. Conclusion: While age may predict physical QoL, coping strategies predict mental QoL. Future studies should further investigate the impact of sensory processing and coping strategies on patients’ QoL in order to enhance adaptive and functional behaviors related to affective disturbances.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Aged , Aged, 80 and over , Young Adult , Quality of Life/psychology , Sensation/physiology , Bipolar Disorder/physiopathology , Adaptation, Psychological/physiology , Depressive Disorder, Major/physiopathology , Psychiatric Status Rating Scales , Psychometrics , Reference Values , Socioeconomic Factors , Multivariate Analysis , Age Factors , Sensation Disorders/physiopathology , Self Report , Middle AgedABSTRACT
ABSTRACT Chronic mania is an under-investigated condition and few reports have associated this disorder with an organic background. The present work examines Kraepelin’s reliable description of chronic mania from a current behavioral neurology viewpoint. Kraepelin had described a cluster of symptoms that are now recognized as core manifestations of the behavioral variant frontotemporal dementia (bvFTD) clinical phenotype. We also carried out additional reviews of original manuscripts from Kraepelin’s peers, in order to find any case reports that might fulfill the current diagnostic proposal for bvFTD. Even though we failed to find an ideal case, we found some scholars who seemed to agree that chronic mania should be considered a special form of dementia. The present work highlights, through historical data, the possible overlapping features between primary psychiatric disorders and neuropsychiatric symptoms secondary to neurodegenerative conditions.
RESUMO A mania crônica constitui uma condição subinvestigada e alguns trabalhos têm associado esta desordem a um substrato orgânico. O presente manuscrito analisa a descrição fidedigna de Kraepelin de mania crônica a partir de um ponto de vista atual da neurologia comportamental. Concebemos que ele havia descrito um conjunto de sintomas que atualmente é reconhecido como manifestações centrais do fenótipo clínico da variante comportamental da demência frontotemporal (bvFTD). Também realizamos uma revisão adicional de manuscritos originais de pares contemporâneos de Kraepelin, a fim de procurar por um único relato de caso que poderia preencher critério diagnóstico atual de bvFTD. Mesmo que não tenhamos conseguido encontrar um caso perfeitamente exemplar, identificamos que alguns estudiosos da época pareciam concordar que a mania crônica devesse ser considerada uma forma especial de demência. O presente trabalho destaca por meio de dados históricos a sobreposição entre transtornos psiquiátricos primários e sintomas neuropsiquiátricos secundários a doenças neurodegenerativas.
Subject(s)
Humans , History, 19th Century , History, 20th Century , Phenotype , Bipolar Disorder/history , Catatonia/history , Dementia/history , Frontotemporal Dementia/history , Bipolar Disorder/physiopathology , Catatonia/physiopathology , Chronic Disease , Dementia/physiopathology , Frontotemporal Dementia/physiopathologyABSTRACT
Background: People with psychiatric disorders have higher rates of obesity, diabetes mellitus and dyslipidemia. These comorbidities are associated with the underlying psychopathology and drug therapy. Aim: To determine the quality and quantity of carbohydrates and fatty acids in the diet and their association with anthropometric parameters in subjects with schizophrenia and bipolar disorders. Patients and Methods: We studied 30 patients with schizophrenia and bipolar disorders in treatment with atypical antipsychotics or mood stabilizers. Three 24-hour recall dietary surveys were carried out. Glycemic index, intake of carbohydrates and fatty acids (g/day) were calculated, and the ratio of saturated, monounsaturated and polyunsaturated fatty acids was determined. Body mass index, waist circumference (WC) and body fat percentage were evaluated. Results: The average intakes of carbohydrates and fatty acids were 295 ± 111 and 73 ± 38 g/day respectively. The mean glycemic index was 59% ± 5.4, while the ratio of saturated, monounsaturated and polyunsaturated fatty acids was 2: 1.4: 0.6. No association between dietary and anthropometric variables was found. Patients using second-generation antipsychotics had a significantly higher waist circumference than those using mood stabilizing drugs. Conclusions: We found no association between the amount and quality of carbohydrate or fatty acid dietary intake and anthropometric parameters.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Schizophrenia/physiopathology , Bipolar Disorder/physiopathology , Dietary Carbohydrates/analysis , Dietary Fats/analysis , Waist Circumference/physiology , Nutritional Status/physiology , Surveys and Questionnaires , Glycemic Index/physiologyABSTRACT
Objective: To review the available data on diffusion tensor imaging (DTI) of subjects with bipolar disorder (BD), with a particular focus on fractional anisotropy (FA) in white matter (WM) tracts. Methods: The PubMed/MEDLINE database was searched for relevant articles, which were included in a systematic review of the literature. FA reductions and WM abnormalities were divided anatomically into three groups: commissural tracts, association tracts, and projection tracts. Results: Eighteen studies met the inclusion criteria. The corpus callosum was the main impaired commissural tract as demonstrated by FA reductions. Five studies reported FA reductions in the cingulum. Two studies reported decreased FA in the anterior thalamic radiation, and one in the corticospinal tract. Conversely, three studies found increased FA values in WM tracts involved in BD pathophysiology. Conclusion: Despite considerable heterogeneity, these results indicate a direct link between executive cognitive functioning and abnormal WM microstructural integrity of fronto-limbic tracts in patients with remitted BD, providing further evidence of the neuronal disruption that underlies BD symptomatology.
Subject(s)
Humans , Bipolar Disorder/diagnostic imaging , Diffusion Tensor Imaging , Bipolar Disorder/physiopathology , Anisotropy , Executive Function/physiology , White Matter/physiopathology , White Matter/diagnostic imaging , Neural Pathways/physiopathologyABSTRACT
Objective: Approximately one-half of all patients affected by bipolar disorder present with psychotic features on at least one occasion. Several studies have found that alterations in the activity of mesolimbic and prefrontal regions are related to aberrant salience in psychotic patients. The aim of the present study was to investigate the structural correlates of a history of hallucinations in a sample of euthymic patients with bipolar I disorder (BD-I). Methods: The sample consisted of 21 euthymic patients with BD-I and no comorbid axis I DSM-IV-TR disorders. Voxel based morphometry (VBM) was used to compare patients with and without a lifetime history of hallucinations. Preprocessing was performed using the Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra (DARTEL) algorithm for VBM in SPM8. Images were processed using optimized VBM. Results: The main finding of the present study was a reduction in gray matter volume in the right posterior insular cortex of patients with BD-I and a lifetime history of hallucinations, as compared to subjects with the same diagnosis but no history of hallucinations. Conclusions: This finding supports the presence of abnormalities in the salience network in BD patients with a lifetime history of hallucinations. These alterations may be associated with an aberrant assignment of salience to the elements of one’s own experience, which could result in psychotic symptoms.
Subject(s)
Humans , Male , Female , Adult , Young Adult , Bipolar Disorder/physiopathology , Gray Matter/pathology , Hallucinations/physiopathology , Organ Size , Bipolar Disorder/complications , Bipolar Disorder/diagnostic imaging , Magnetic Resonance Imaging , Cerebral Cortex/physiopathology , Cerebral Cortex/diagnostic imaging , Cross-Sectional Studies , Gray Matter/diagnostic imaging , Hallucinations/complications , Middle AgedABSTRACT
Objective:To conduct a systematic review of the literature about the symptom of rumination in bipolar disorder (BD).Methods:We searched the MEDLINE (PubMed), ISI Web of Knowledge, PsycINFO, and SciELO databases using the descriptors “rumination” and “bipolar disorder” and no time limits. This strategy yielded 105 references, of which 74 were selected. Inclusion criteria were studies involving patients with BD and the use of at least one validated scale for the assessment of rumination. Review articles were excluded. Seventeen articles were ultimately analyzed and included in the review.Results:Rumination is present in all BD phases, is a stable interepisodic symptom, is associated with symptoms of depression, anxiety, and hypomania, and may occur in response to both positive and negative affect. There is no research on rumination and neurobiological findings in patients with BD.Conclusions:Rumination seems to be independent of mood state, but shows close relationship with it. It is possible that rumination has a negative impact on cognitive and executive functions, particularly inhibitory control. Finally, rumination is an important symptom in both phases of BD, and, therefore, may be a useful target for further exploration as a dimensional domain and a transdiagnostic phenomenon in Research Domain Criteria (RDoC) projects.
Subject(s)
Adult , Child , Female , Humans , Male , Bipolar Disorder/psychology , Feeding and Eating Disorders of Childhood/psychology , Affect/physiology , Anxiety Disorders/physiopathology , Anxiety Disorders/psychology , Bipolar Disorder/physiopathology , Cognition/physiology , Depressive Disorder/physiopathology , Depressive Disorder/psychology , Feeding and Eating Disorders of Childhood/physiopathology , Psychiatric Status Rating ScalesABSTRACT
INTRODUCTION: A growing body of evidence suggests that bipolar disorder (BD) is a progressive disease according to clinical, biochemical and neuroimaging findings. This study reviewed the literature on the relationship between specific biomarkers and BD stages. METHODS: A comprehensive literature search of MEDLINE and PubMed was conducted to identify studies in English and Portuguese using the keywords biomarker, neurotrophic factors, inflammation, oxidative stress, neuroprogression and staging models cross-referenced with bipolar disorder. RESULTS: Morphometric studies of patients with BD found neuroanatomic abnormalities, such as ventricular enlargement, grey matter loss in the hippocampus and cerebellum, volume decreases in the prefrontal cortex and variations in the size of the amygdala. Other studies demonstrated that serum concentrations of neurotrophic factors, inflammatory mediators and oxidative stress may be used as BD biomarkers. CONCLUSIONS: The analysis of neurobiological changes associated with BD progression and activity may confirm the existence of BD biomarkers, which may be then included in staging models that will lead to improvements in treatment algorithms and more effective, individually tailored treatment regimens. Biomarkers may also be used to define early interventions to control disease progression. .
INTRODUÇÃO: Níveis crescentes de evidência sugerem que o transtorno bipolar (TB) exibe um caráter progressivo, em nível tanto clínico, quanto bioquímico e neuroimagiológico. Este estudo revisa a literatura existente sobre a relação entre biomarcadores específicos e estágios do TB. MÉTODOS: Uma busca extensa da literatura nas bases de dados MEDLINE e PubMed foi conduzida para identificar estudos publicados em inglês e em português utilizando as palavras-chave biomarker (biomarcador), neurotrophic factors (fatores neurotróficos), inflammation (inflamação), oxidative stress (estresse oxidativo), neuroprogression (neuroprogressão) e staging models (modelos de estadiamento), em referência cruzada com o termo bipolar disorder (transtorno bipolar). RESULTADOS: Estudos morfométricos em doentes bipolares mostraram a existência de alterações neuroanatômicas, tais como o alargamento dos ventrículos, a perda de substância cinzenta no hipocampo e no cerebelo, a diminuição do volume de determinadas áreas do córtex pré-frontal e variações no tamanho da amígdala. Além disso, outros estudos apontam para a potencialidade do uso dos valores séricos dos fatores neurotróficos, de mediadores inflamatórios e de estresse oxidativo como biomarcadores do TB. CONCLUSÕES: O conhecimento das alterações neurobiológicas, associadas à progressão e atividade do TB, é fundamental para a identificação de biomarcadores. A incorporação de biomarcadores nos modelos de estadiamento do TB poderá permitir um aperfeiçoamento dos algoritmos terapêuticos, possibilitando a elaboração de esquemas de tratamento mais personalizados e eficazes, com destaque para a importância da intervenção precoce na atenuação da progressão da doença. .
Subject(s)
Humans , Bipolar Disorder/diagnosis , Bipolar Disorder/physiopathology , Biomarkers/metabolism , Bipolar Disorder/pathology , Disease ProgressionABSTRACT
La función ejecutiva se ve involucrada en la mayor parte de las actividades que realizamos a diario, repercutiendo en la calidad de vida de las personas. Los rendimientos ejecutivos en el trastorno bipolar tipo I pueden fluctuar en función de la fase clínica en la que se encuentra el paciente. El objetivo de este trabajo se centra en revisar los hallazgos encontrados respecto a la función ejecutiva durante la fase asintomática del trastorno bipolar tipo I. Se han analizado 37 artículos científicos que abordan el rendimiento ejecutivo de pacientes eutímicos con trastorno bipolar tipo I. Se puede concluir que la mayoría de los estudios reportan dificultades ejecutivas en estos pacientes, aunque no parece existir consenso en los diferentes trabajos al indicar el tipo de déficit. Esta falta de acuerdo podría ser debida a aspectos metodológicos de los estudios y a distintas variables clínicas y farmacológicas. Las alteraciones ejecutivas en la eutimia son menores que en las fases agudas del trastorno y afectan sobre todo a la velocidad de procesamiento de la información. Los déficits ejecutivos de los pacientes podrían estar vinculados a posibles alteraciones funcionales a nivel de la corteza prefrontal, así como al propio efecto de los psicofármacos utilizados. Sería de especial relevancia que el tratamiento de estos pacientes incorporase estas alteraciones, lo que podría conseguirse mediante un enfoque neurocognitivo dentro de un abordaje terapéutico integrado...
Executive function is present in most of dairy activities, so it influences in quality of life. Executive performances in bipolar disorder type I can change in function of clinical phase that patient is. The aim of this work is to review the studies that have investigated executive function during asymptomatic phase in bipolar disorder type I. It has been analyzed 37 scientific articles that examine executive performance in euthymic patients with bipolar disorder type I. It can be concluded that bipolar patients in asymptomatic phase suffer executive difficulties, but it doesnt seem to exist consensus regarding the type of deficits. This lack of agreement could be due to methodological diversity in studies, as well as the influence of different clinical or pharmacological variables. Executive alterations in euthymic phase are lower than the acute phases in bipolar disorder and affect mainly to processing speed. Executive deficits in patients could be linked to possible functional alterations in prefrontal cortex, as well as the psychopharmacological effect. It would be specially relevant treatment in bipolar disorder keep in mind this alterations, which it can get it with a neurocognitive approach within integrate treatment...
Subject(s)
Humans , Executive Function , Bipolar Disorder/physiopathology , Bipolar Disorder/therapyABSTRACT
There is limited data regarding the cognitive profile from screening tests of older adults with bipolar disorder (BD) with dementia. Objective To investigate the Clock Drawing Test (CDT) among older adults with BD with and without Alzheimer’s disease (AD). Method 209 older adults (79 with BD without dementia and 70 controls; 60 with AD, being 27 with BD) were included to evaluate the performance of three CDT scoring scales, beyond the Mini-Mental State Examination (MMSE) and verbal fluency (VFT). Results Patients with BD without dementia presented with lower scores in MMSE, VF and one CDT scoring scale than controls. Patients with BD and AD presented with lower scores in VF and CDT scoring scales than patients with only AD. All CDT scales presented similar sensitivity and specificity for BD and non-BD groups. Conclusion Elderly subjects with BD showed greater impairment in CDT in both groups of normal cognition and AD. .
Há dados limitados sobre o perfil cognitivo de idosos com transtorno bipolar (TAB) e demência. Previamente, testes de rastreio cognitivo comuns foram pouco estudados. Objetivo Investigar o Teste do Desenho do Relógio (CDT) entre idosos com TAB com e sem doença de Alzheimer (DA). Método Foram incluídos 209 idosos (79 pacientes com TAB sem demência e 70 controles; 60 indivíduos com DA leve, sendo 27 com TAB) para avaliar três escalas de pontuação do TDR, além do Mini-Mental State Examination (MMSE) e fluência verbal (FV). Resultados Pacientes com TAB sem demência apresentaram menores escores no MMSE, FV e uma escala de TDR que controles. Pacientes com TAB e DA apresentaram escores mais baixos na FV e em todos os TDR comparados aos apenas com DA. As escalas de CDT apresentaram sensibilidade e especificidade semelhantes para os grupos com e sem TAB. Conclusão Idosos com TAB apresentaram maior comprometimento no TDR em ambos grupos com cognição normal e DA. .
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Alzheimer Disease/physiopathology , Bipolar Disorder/physiopathology , Cognition/physiology , Neuropsychological Tests , Cross-Sectional Studies , Cognition Disorders/physiopathology , Educational Status , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Statistics, NonparametricABSTRACT
Objective: To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5, in bipolar disorder (BD). Methods: Forty patients with type I BD (18 in remission and 22 in mania) and 25 healthy controls matched for age, gender, and educational attainment were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview; the Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked immunosorbent assay (ELISA). Results: BD patients in mania presented decreased NT-4/5 plasma levels in comparison with controls (p < 0.05). There were no significant differences in NT-3 plasma levels between BD patients and controls. Conclusion: These findings corroborate the view that neurotrophin dysfunction is associated with mood states in patients with BD. .
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Bipolar Disorder/blood , Nerve Growth Factors/blood , Biomarkers/blood , Bipolar Disorder/physiopathology , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , /blood , Psychiatric Status Rating Scales , Reference Values , Statistics, NonparametricABSTRACT
Objective: This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. Methods: Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. Results: There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502); household activities and superoxide dismutase (r = 0.501); participation in social activities and nitric oxide (r = 0.414); hobbies and leisure time activities and total glutathione (r = -0.567), superoxide dismutase (r = 0.667), and neurotrophin 4 (r = 0.450); and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597). There was no correlation between other domains of psychosocial functioning and oxidative stress markers. Conclusion: These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker. .