-
Revista Brasileira de Psiquiatria (Sao... 2016Recently, attention in the field of bipolar disorder (BD) has focused on prevention, including early detection and intervention, as these strategies have the potential... (Review)
Review
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.
Topics: Biomarkers; Biomedical Research; Bipolar Disorder; Cognition Disorders; Disease Progression; Early Diagnosis; Humans; Prospective Studies; Retrospective Studies
PubMed: 27533022
DOI: 10.1590/1516-4446-2016-1975 -
Revista Brasileira de Psiquiatria (Sao... Jun 2011Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine... (Comparative Study)
Comparative Study
OBJECTIVE
Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthymic), and healthy volunteers.
METHOD
Forty-eight bipolar patients were recruited: 18 in the euthymic phase; 17 in the manic phase; and 13 in the depressive phase. The control group comprised 41 healthy volunteers. The phases of bipolar disorder were defined as follows: euthymic-not meeting the DSM-IV criteria for a mood episode and scoring < 8 on the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS); manic-scoring < 7 on the HDRS and > 7 on the YMRS; depressive-scoring > 7 on the HDRS and < 7 on the YMRS. Patients in mixed phases were excluded. Blood samples were collected from all participants.
RESULTS
Creatine kinase levels were higher in the manic patients than in the controls. However, we observed no significant difference between euthymic and depressive patients in terms of the creatine kinase level.
CONCLUSION
Our results suggest that the clinical differences among the depressive, manic, and euthymic phases of bipolar disorder are paralleled by contrasting levels of creatine kinase. However, further studies are needed in order to understand the state-dependent differences observed in serum creatine kinase activity.
Topics: Adult; Biomarkers; Bipolar Disorder; Case-Control Studies; Creatine Kinase; Female; Humans; Male
PubMed: 21829911
DOI: 10.1590/s1516-44462011005000005 -
Psychosomatic Medicine Jul 2009To compare the risk for cardiovascular mortality between bipolar I and bipolar II subtypes and determine correlates of cardiovascular mortality. Bipolar disorder conveys... (Comparative Study)
Comparative Study
OBJECTIVES
To compare the risk for cardiovascular mortality between bipolar I and bipolar II subtypes and determine correlates of cardiovascular mortality. Bipolar disorder conveys an increased risk of cardiovascular mortality.
METHODS
Participants with major affective disorders were recruited for the National Institute of Mental Health Collaborative Depression Study and followed prospectively for up to 25 years. A total of 435 participants met the diagnostic criteria for bipolar I (n = 288) or bipolar II (n = 147) disorder based on Research Diagnostic Criteria at intake and measures of psychiatric symptoms during follow-up. Diagnostic subtypes were contrasted by cardiovascular mortality risk using Cox proportional hazards regression. Affective symptom burden (the proportion of time with clinically significant manic/hypomanic or depressive symptoms) and treatment exposure were additionally included in the models.
RESULTS
Thirty-three participants died from cardiovascular causes. Participants with bipolar I disorder had more than double the cardiovascular mortality risk of those with bipolar II disorder, after controlling for age and gender (hazard ratio = 2.35, 95% Confidence Interval = 1.04-5.33; p = .04). The observed difference in cardiovascular mortality between these subtypes was at least partially confounded by the burden of clinically significant manic/hypomanic symptoms which predicted cardiovascular mortality independent of diagnosis, treatment exposure, age, gender, and cardiovascular risk factors at intake. Selective serotonin uptake inhibitors seemed protective although they were introduced late in follow-up. Depressive symptom burden was not related to cardiovascular mortality.
CONCLUSIONS
Participants with bipolar I disorder may face a greater risk of cardiovascular mortality than those with bipolar II disorder. This difference in cardiovascular mortality risk may reflect manic/hypomanic symptom burden.
Topics: Adult; Bipolar Disorder; Cardiovascular Diseases; Cause of Death; Cohort Studies; Cost of Illness; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Proportional Hazards Models; Prospective Studies; Psychiatric Status Rating Scales; Risk Factors
PubMed: 19561163
DOI: 10.1097/PSY.0b013e3181acee26 -
Frontiers in Bioscience (Elite Edition) Jun 2013Kraepelin's observations of the differences in the course and outcome of dementia praecox and manic depression fundamentally influenced thinking about bipolar disorder... (Review)
Review
Kraepelin's observations of the differences in the course and outcome of dementia praecox and manic depression fundamentally influenced thinking about bipolar disorder (BP) and schizophrenia (SZ) for over a century. In modern times, there is increasing awareness that a greater understanding of the similarities between these two highly prevalent and disabling conditions can teach us as many lessons about the pathophysiology of severe mental disorders as does the pursuit of differentiating factors. We review publications on developmental, genetic, epidemiological, and outcome research that challenges the Kraepelian dichotomy. We highlight the increasing evidence of the overlap in genetic susceptibility. Neuro-developmental studies provide evidence of shared early pathological processes, whilst neurophysiological investigations also suggest that different genes may have a role in the development of both phenotypes. There is also evidence of overlapping neurocognitive phenotypes. It has become increasingly clear that a simple binary classification of these disorders represents an oversimplification. It may be more apposite to think in terms of genetic influences on six continuous symptom dimensions: neurobiological, cognitive, positive, negative, depressive and manic symptoms.
Topics: Biomarkers; Bipolar Disorder; Humans; Schizophrenia
PubMed: 23747901
DOI: 10.2741/e665 -
The FEBS Journal Apr 2012Psychiatric disorders are documented to be associated with a mild pro-inflammatory state. Pro-inflammatory mediators could activate the tryptophan breakdown and... (Review)
Review
Psychiatric disorders are documented to be associated with a mild pro-inflammatory state. Pro-inflammatory mediators could activate the tryptophan breakdown and kynurenine pathway with a shift toward the neurotoxic arm where excitotoxic N-methyl-D-aspartate receptor agonist quinolinic acid is formed. An unbalanced metabolism in terms of neuroprotective and neurotoxic effects, such as reduced kynurenic acid to kynurenine ratio, has been demonstrated in the major psychiatric disorders such as unipolar depression, bipolar manic-depressive disorder and schizophrenia, and in drug-induced neuropsychiatric side effects such as interferon-α treated patients. The changes in serum or plasma are shown to be associated with central changes such as in the cerebrospinal fluid and certain brain areas. While currently available antidepressants and mood stabilizers could not efficiently improve these neurochemical changes within the same period that could induce clinical improvement, some antipsychotic treatments could reverse certain metabolic imbalances. Some of these changes were tested also in animal models. In this review the role of this unbalanced kynurenine metabolism through interactions with other neurochemicals is discussed as a major contributing pathophysiological mechanism in psychiatric disorders. Moreover, the biomarker role of kynurenine metabolites and future therapeutic opportunities are also discussed.
Topics: Animals; Bipolar Disorder; Depressive Disorder, Major; Humans; Kynurenine; Schizophrenia
PubMed: 22404766
DOI: 10.1111/j.1742-4658.2012.08551.x -
PloS One 2017Seasonal variation of manic and depressive symptoms is a controversial topic in bipolar disorder research. Several studies report seasonal patterns of hospital...
Seasonal variation of manic and depressive symptoms is a controversial topic in bipolar disorder research. Several studies report seasonal patterns of hospital admissions for depression and mania and variation in symptoms that appear to follow a seasonal pattern, whereas others fail to report such patterns. Differences in research methodologies, data analysis strategies, and temporal resolution of data may partly explain the variation in findings between studies. The current study adds a novel perspective to the literature by investigating specific meteorological factors such as atmospheric pressure, hours of sunshine, relative humidity, and daily maximum and minimum temperatures as more proximal predictors of self-reported daily mood change in people diagnosed with bipolar disorder. The results showed that daily maximum temperature was the only meteorological variable to predict clinically-relevant mood change, with increases in temperature associated with greater odds of a transition into manic mood states. The mediating effects of sleep and activity were also investigated and suggest at least partial influence on the prospective relationship between maximum temperature and mood. Limitations include the small sample size and the fact that the number and valence of social interactions and exposure to natural light were not investigated as potentially important mediators of relationships between meteorological factors and mood. The current data make an important contribution to the literature, serving to clarify the specific meteorological factors that influence mood change in bipolar disorder. From a clinical perspective, greater understanding of seasonal patterns of symptoms in bipolar disorder will help mood episode prophylaxis in vulnerable individuals.
Topics: Affect; Atmospheric Pressure; Bipolar Disorder; Female; Humans; Humidity; Male; Meteorological Concepts; Middle Aged; Sleep; Temperature; Weather
PubMed: 28278268
DOI: 10.1371/journal.pone.0173431 -
Journal of Medical Genetics Aug 1999Bipolar disorder (also known as manic depressive illness) is a complex genetic disorder in which the core feature is pathological disturbance in mood (affect) ranging... (Review)
Review
Bipolar disorder (also known as manic depressive illness) is a complex genetic disorder in which the core feature is pathological disturbance in mood (affect) ranging from extreme elation, or mania, to severe depression usually accompanied by disturbances in thinking and behaviour. The lifetime prevalence of 1% is similar in males and females and family, twin, and adoption studies provide robust evidence for a major genetic contribution to risk. There are methodological impediments to precise quantification, but the approximate lifetime risk of bipolar disorder in relatives of a bipolar proband are: monozygotic co-twin 40-70%; first degree relative 5-10%; unrelated person 0.5-1.5%. Occasional families may exist in which a single gene plays the major role in determining susceptibility, but the majority of bipolar disorder involves the interaction of multiple genes (epistasis) or more complex genetic mechanisms (such as dynamic mutation or imprinting). Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest identified in linkage studies include 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Chromosome 18 is also of interest but the findings are confusing with up to three possible regions implicated. To date most candidate gene studies have focused on neurotransmitter systems influenced by medication used in clinical management of the disorder but no robust positive findings have yet emerged. It is, however, almost certain that over the next few years bipolar susceptibility genes will be identified. This will have a major impact on our understanding of disease pathophysiology and will provide important opportunities to investigate the interaction between genetic and environmental factors involved in pathogenesis. This is likely to lead to major improvements in treatment and patient care but will also raise important ethical issues that will need to be addressed.
Topics: Bipolar Disorder; Epidemiologic Methods; Female; Genetic Linkage; Genetic Techniques; Humans; Male; Risk; Twin Studies as Topic; X Chromosome
PubMed: 10465107
DOI: 10.1136/jmg.36.8.585 -
Brain Imaging and Behavior Jun 2018Bipolar disorder is characterized by recurring episodes of depression and mania. Defining differences in brain function during these states is an important goal of...
Bipolar disorder is characterized by recurring episodes of depression and mania. Defining differences in brain function during these states is an important goal of bipolar disorder research. However, few imaging studies have directly compared brain activity between bipolar mood states. Herein, we compare functional magnetic resonance imaging (fMRI) responses during a flashing checkerboard stimulus between bipolar participants across mood states (euthymia, depression, and mania) in order to identify functional differences between these states. 40 participants with bipolar I disorder and 33 healthy controls underwent fMRI during the presentation of the stimulus. A total of 23 euthymic-state, 16 manic-state, 15 depressed-state, and 32 healthy control imaging sessions were analyzed in order to compare functional activation during the stimulus between mood states and with healthy controls. A reduced response was identified in the visual cortex in both the depressed and manic groups compared to euthymic and healthy participants. Functional differences between bipolar mood states were also observed in the cerebellum, thalamus, striatum, and hippocampus. Functional differences between mood states occurred in several brain regions involved in visual and other sensory processing. These differences suggest that altered visual processing may be a feature of mood states in bipolar disorder. The key limitations of this study are modest mood-state group size and the limited temporal resolution of fMRI which prevents the segregation of primary visual activity from regulatory feedback mechanisms.
Topics: Adult; Affect; Bipolar Disorder; Brain; Brain Mapping; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Photic Stimulation; Visual Perception
PubMed: 28674759
DOI: 10.1007/s11682-017-9741-8 -
Psychiatry and Clinical Neurosciences Apr 2020This systematic review and meta-analysis evaluated whether bright light therapy (BLT) is an effective and safe treatment for manic/depressive symptoms and a preventive... (Meta-Analysis)
Meta-Analysis
AIM
This systematic review and meta-analysis evaluated whether bright light therapy (BLT) is an effective and safe treatment for manic/depressive symptoms and a preventive measure for recurrent mood episodes in patients with bipolar disorder.
METHODS
A literature search of major electronic databases was conducted in June 2019, including all published articles up to that date. Two researchers independently selected relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria.
RESULTS
Six randomized controlled trials (RCT) evaluated the efficacy of BLT for bipolar depression. A meta-analysis found no significant differences between BLT and placebo for the following outcomes: (i) rates of remission from depressive episodes (risk ratio [RR]: 1.81, 95% confidence interval [CI]: 0.43 to 7.64, P = 0.42); (ii) depressive symptom scores (standardized mean difference: -0.25, 95%CI: -0.74 to 0.23, P = 0.30); and (iii) rates of manic switching (RR: 1.00, 95%CI: 0.28 to 3.59, P = 0.26). The sensitivity analysis for studies with low overall indirectness did show a significant antidepressant effect for BLT (RR: 3.09, 95%CI: 1.62 to 5.90, P = 0.006). No RCT investigated the effect of BLT in preventing the recurrence of mood episodes in the euthymic state or in improving manic symptoms in the manic state. No severe adverse events were reported.
CONCLUSION
While a meta-analysis was unable to demonstrate the efficacy of BLT for bipolar depression, a sensitivity analysis did show a significant effect. Further well-designed studies are needed to clarify the effectiveness of BLT, not only for the depressive state but also for other states, in the treatment of bipolar disorder.
Topics: Bipolar Disorder; Depression; Humans; Phototherapy
PubMed: 31917880
DOI: 10.1111/pcn.12976 -
Revue Medicale de Liege 2012Bipolar disorder is a multifactorial disease with a strong genetic component. However, environmental factors also play a role in the onset of the disease and in manic... (Review)
Review
Bipolar disorder is a multifactorial disease with a strong genetic component. However, environmental factors also play a role in the onset of the disease and in manic and depressive recurrence. The onset of the disorder is the consequence of a complex interaction between genetic and environmental factors. This gene-environment interaction is well illustrated by the influence of childhood trauma on the clinical expression of the disease in terms of age of onset, comorbidity and suicide. The complexity and heterogeneity of bipolar disorder require the identification of homogenous sub-groups with the use of biomarkers that could help reduce the etiological heterogeneity and better target the therapeutical options.
Topics: Animals; Bipolar Disorder; Causality; Disease Susceptibility; Environment; Gene-Environment Interaction; Humans; Risk Factors
PubMed: 22891492
DOI: No ID Found