The Neurobiology and Treatment of Bipolar Disorder

2017 ◽  
Author(s):  
Katherine E. Burdick ◽  
Luz H. Ospina ◽  
Stephen J. Haggarty ◽  
Roy H. Perlis
Keyword(s):  
Bipolar Disorder ◽  
High Risk ◽  
Genetic Risk ◽  
Biological Models ◽  
Increased Risk ◽  
Psychotic Features ◽  
Prodromal Syndrome ◽  
Abnormal Sleep ◽  
Epigenetic Processes ◽  
High Risk Children

Bipolar disorder (BPD) is a severe mood disorder that often has psychotic features. Its most severe forms are more common and significantly more likely to cause disability than originally thought. Studies of high-risk children have found them to be at increased risk for a variety of symptoms and neurobiological abnormalities. In contrast to schizophrenia, there is no formal prodromal syndrome that has been identified, and cognitive abnormalities do not precede the onset of the disorder. Abnormal sleep and circadian rhythms are prominent and have led to intriguing biological models. Neurobiological experiments have primarily focused on candidate pathways and include circadian abnormalities, epigenetic processes including histone modification, WNT/GSK3 signaling, other modulators of neuroplasticity, and mitochondrial dysfunction. Recent data suggest that BPD is a highly polygenic disease and that integration of prior modeling and data with the wide variety of new genetic risk loci will be productive in the future.

The Neurobiology of Bipolar Disorder

2013 ◽  
pp. 355-364
Author(s):  
Katherine E. Burdick ◽  
Stephen J. Haggarty ◽  
Roy Perlis
Keyword(s):  
Bipolar Disorder ◽  
High Risk ◽  
Circadian Rhythms ◽  
Histone Modification ◽  
Mood Disorder ◽  
Genetic Risk ◽  
Increased Risk ◽  
Psychotic Features ◽  
Prodromal Syndrome ◽  
Abnormal Sleep

The focus of this chapter is squarely on bipolar disorder. Bipolar disorder is a severe mood disorder that often has psychotic features. Its most severe forms are more common than thought and significantly more likely to cause disability than originally thought. Studies of high-risk children have found them to be at increased risk for a variety of symptoms and neurobiological abnormalities. In contrast to schizophrenia, there is no formal prodromal syndrome that has been identified and cognitive abnormalities do not precede the onset of the disorder. Abnormal sleep and circadian rhythms are prominent and have led to intriguing biological models. Neurobiological experiments have primarily focused on candidate pathways and include circadian abnormalities, epigenetic processes including histone modification, Wnt/GSK3 signaling, other modulators of neuroplasticity, and mitochondrial dysfunction. Recent data suggest that bipolar disorder is a highly polygenic disease and that integration of prior modeling and data with the wide variety of new genetic risk loci will be productive in the future.

Update on the treatment of bipolar disorder in children and adolescents

2005 ◽  
Vol 20 (2) ◽  
pp. 87-91 ◽  
Author(s):  
Robert L. Findling
Keyword(s):  
Bipolar Disorder ◽  
High Risk ◽  
Genetic Risk ◽  
Pediatric Patients ◽  
Treatment Strategies ◽  
Pharmacological Intervention ◽  
Pediatric Bipolar Disorder ◽  
Symptom Remission ◽  
Affected Parent ◽  
Maintenance Study

AbstractAs the phenomenology of pediatric bipolar disorder has become better delineated, clinicians are now able to more accurately assess and treat young people suffering from this condition. For pediatric patients with bipolar I disorder and symptoms of mania, medication monotherapy has been shown to lead to symptom amelioration. However, this treatment modality oftentimes does not lead to full symptom remission. In an attempt to address this observation, combination treatment strategies have recently been investigated. Recently, a maintenance study has shown that in youths who achieved remission on a combination of lithium and divalproate therapy, either of these agents alone was equally effective as a treatment strategy. In youths identified as being at genetic high risk for bipolarity who also had problematic affective symptomatology, treatment with divalproate was not found to be superior to placebo; however, those with the greatest degree of genetic risk for familial psychopathology remained in the trial longer than those with more modest amounts of familial psychopathology. These data suggest that intervention in youths with only one affected parent may not be a rational prevention strategy for pharmacological intervention in bipolar disorder, and that cohorts more genetically at risk may be a more appropriate group for preventative pharmacotherapy.

Neuropsychological Evaluation of High-Risk Children from Birth to Seven Years of Age

2012 ◽  
Vol 15 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Judith Nogueira Cruz ◽  
Carolina Laynez Rubio ◽  
Francisco Cruz Quintana ◽  
Miguel Perez Garcia
Keyword(s):  
High Risk ◽  
Psychological Status ◽  
Abnormal Development ◽  
Healthy Children ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Current Psychological ◽  
Development Objectives ◽  
High Risk Children

High Risk Children (HRC) are those with an increased risk of abnormal development due to any factor affecting neurological growth. Those factors have been the focus of most studies in this area. However, little is known about their long-term consequences over the course of child development. Objectives: the goal was to study the cognitive, emotional and academic outcomes of 7-year-old children diagnosed as HRC at birth. Method: We compared 14 HRC and 20 healthy children using the WISC-IV, BASC and Brunet-Lezine tests. Results: HRC showed cognitive, emotional and academic deficits compared with healthy children. However, Brunet-Lezine scores obtained over the course of development (6, 12, 18 and 24 months) were not predictive of the children's' current psychological status. Conclusions: long-term follow-up with HRC should be maintained until 7 years of age, at which point an appropriate treatment should be implemented.

scholarly journals Fatty Acid Desaturase Gene Polymorphisms and Metabolic Measures in Schizophrenia and Bipolar Patients Taking Antipsychotics

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kyle J. Burghardt ◽  
Kristen N. Gardner ◽  
Joshua W. Johnson ◽  
Vicki L. Ellingrod
Keyword(s):  
Insulin Resistance ◽  
Bipolar Disorder ◽  
Fatty Acid ◽  
Side Effects ◽  
High Risk ◽  
Atypical Antipsychotics ◽  
Fatty Acid Desaturase ◽  
Metabolic Side Effects ◽  
Increased Risk ◽  
Bipolar Patients

Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1) and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n=226) or bipolar disorder (n=94) were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

scholarly journals The developmental trajectory of bipolar disorder

2014 ◽  
Vol 204 (2) ◽  
pp. 122-128 ◽  
Author(s):  
Anne Duffy ◽  
Julie Horrocks ◽  
Sarah Doucette ◽  
Charles Keown-Stoneman ◽  
Shannon McCloskey ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
High Risk ◽  
Psychotic Disorders ◽  
Familial Risk ◽  
Childhood Anxiety ◽  
Developmental Trajectory ◽  
Developmental Approach ◽  
Increased Risk ◽  
Clinical Stages

BackgroundBipolar disorder is highly heritable and therefore longitudinal observation of children of affected parents is important to mapping the early natural history.AimsTo model the developmental trajectory of bipolar disorder based on the latest findings from an ongoing prospective study of the offspring of parents with well-characterised bipolar disorder.MethodA total of 229 offspring from families in which 1 parent had confirmed bipolar disorder and 86 control offspring were prospectively studied for up to 16 years. High-risk offspring were divided into subgroups based on the parental long-term response to lithium. Offspring were clinically assessed and DSM-IV diagnoses determined on masked consensus review using best estimate procedure. Adjusted survival analysis and generalised estimating equations were used to calculate differences in lifetime psychopathology. Multistate models were used to examine the progression through proposed clinical stages.ResultsHigh-risk offspring had an increased lifetime risk of a broad spectrum of disorders including bipolar disorder (hazard ratio (HR) = 20.89; P = 0.04), major depressive disorder (HR = 17.16; P = 0.004), anxiety (HR = 2.20; P = 0.03), sleep (HR = 28.21; P = 0.02) and substance use disorders (HR = 2.60; P = 0.05) compared with controls. However, only offspring from lithium non-responsive parents developed psychotic disorders. Childhood anxiety disorder predicted an increased risk of major mood disorder and evidence supported a progressive transition through clinical stages, from non-specific psychopathology to depressive and then manic or psychotic episodes.ConclusionsFindings underscore the importance of a developmental approach in conjunction with an appreciation of familial risk to facilitate earlier accurate diagnosis in symptomatic youth.

scholarly journals Assessing the Magnitude of Risk for ADHD in Offspring of Parents with ADHD: A Systematic Literature Review and Meta-Analysis

2020 ◽  
pp. 108705472095081
Author(s):  
Mai Uchida ◽  
Haley Driscoll ◽  
Maura DiSalvo ◽  
Aarya Rajalakshmim ◽  
Marco Maiello ◽  
...  
Keyword(s):  
High Risk ◽  
Early Identification ◽  
Meta Analysis ◽  
The Body ◽  
Adhd Symptoms ◽  
Exclusion Criteria ◽  
Hyperactivity Disorder ◽  
Body Of Knowledge ◽  
Increased Risk ◽  
High Risk Children

The main aim of this study was to examine the body of knowledge on the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) in “high-risk” children whose parents are diagnosed with ADHD. This knowledge could aid early identification for children presenting with ADHD symptoms at a young age. We conducted a systematic search of the literature assessing high-risk children. Included were original articles published in English with the main aim to assess prevalence of ADHD in high risk children. In addition, a meta-analysis was conducted to examine this prevalence. Four articles met our inclusion and exclusion criteria all suggesting an increased prevalence of ADHD in children of parents with ADHD. The meta-analysis also confirmed the increased prevalence of ADHD in high-risk children. The literature indicates that children of ADHD parents have an increased risk of developing ADHD compared to control children.

scholarly journals Prediction of Venous Thromboembolism Based on Clinical and Genetic Factors

2020 ◽  
Author(s):  
David A. Kolin ◽  
Scott Kulm ◽  
Olivier Elemento
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Genetic Risk ◽  
Genetic Factors ◽  
Hazard Ratio ◽  
Low Risk ◽  
Clinical Risk Factors ◽  
Clinical Risk ◽  
Increased Risk

BACKGROUNDBoth clinical and genetic factors drive the risk of venous thromboembolism. However, whether clinically recorded risk factors and genetic variants can be combined into a clinically applicable predictive score remains unknown.METHODSUsing Cox proportional-hazard models, we analyzed the association of risk factors with the likelihood of venous thromboembolism in U.K. Biobank, a large prospective cohort. We created a novel ten point clinical score using seven established clinical risk factors for venous thromboembolism. We also generated a polygenic risk score of 21 single nucleotide polymorphisms to quantify genetic risk. The genetic score was categorized into high risk (top two deciles of scores), intermediate risk (deciles three to eight), and low risk (lowest two deciles). The discrete clinical score led to the following approximate decile categorizations: high risk (5 to 10 points), intermediate risk (3 to 4 points), and low risk (0 to 2 points).RESULTSAmongst the 502,536 participants in the U.K. Biobank, there were 4,843 events of venous thromboembolism. Analyses of established clinical risk factors and the most commonly used medications revealed that participants were at decreased risk of venous thromboembolism if they had ever used oral contraceptive pills (hazard ratio, 0.88; 95% confidence interval [CI], 0.79 to 0.99) or if they currently used bendroflumethiazide (hazard ratio, 0.84; 95% CI, 0.74 to 0.95), cod liver oil capsules (hazard ratio, 0.87; 95% CI, 0.77 to 0.99), or atenolol (hazard ratio, 0.79; 95% CI, 0.68 to 0.91). Participants were at significantly increased risk of venous thromboembolism if they were at high clinical risk (hazard ratio, 5.98; 95% CI, 5.43 to 6.59) or high genetic risk (hazard ratio, 2.28; 95% CI, 2.07 to 2.51) relative to participants at low clinical or genetic risk, respectively. Combining clinical risk factors with genetic risk factors produced a model that better predicted risk of venous thromboembolism than either model alone (P<0.001). Participants at high clinical and genetic risk in the combined score had over an eightfold increased risk of venous thromboembolism relative to participants at low risk (hazard ratio, 8.27; 95% CI 7.59 to 9.00).CONCLUSIONSBy assessing venous thromboembolic events in over 500,000 participants, we identified several known and novel associations between risk factors and venous thromboembolism. Participants in the high risk group of a combined score, consisting of clinical and genetic factors, were over eight times more likely to experience venous thromboembolism than participants in the low risk group.

Abstract 18093: Bleeding Events in Clopidogrel-Treated Patients with STEMI is Associated with a Genetic Risk Score Based on High-Risk Genetic Polymorphisms

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jia-Hui Zhang ◽  
Jin-Qing Yuan ◽  
Xian-Min Meng ◽  
Xiao-Fang Tang ◽  
Jing Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Major Bleeding ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Multivariate Logistic Regression Analysis ◽  
Bleeding Events ◽  
Genetic Score ◽  
Clinical Safety ◽  
Increased Risk

Introduction: Gene polymorphisms of ABCB1, CYP2C19, PON1 and P2Y12 may influence pharmacodynamics and clinical events of clopidogrel treatment. Hypothesis: We assessed the hypothesis that a genetic risk score based on identified high-risk single nucleotide polymorphisms (SNPs) would be associated with bleedings in clopidogrel-treated Chinese STEMI patients after percutaneous coronary intervention (PCI). Methods: A total of 503 consecutive patients with STEMI who received an uneventful PCI and were exposed to clopidogrel treatment for 12 months, were enrolled in the single-center registry. There were 38 tag SNPs selected from ABCB1, CYP2C19, PON1 and P2Y12 genes, which were detected by the ligase detection reaction. The primary clinical safety endpoint was the incidence of major bleeding events. Major bleeding was quantified according to bleeding academic research consortium definition (BARC) criteria, including type 3 and 5 in the analysis. The follow-up period was 12 months. Results: Overall, 46 BARC≥3 bleeding events (9.1%) occurred, which included 11 (2.1%) cases of BARC 3b bleedings and 35 (7.0%) cases of BARC 3a bleedings. After adjustment for traditional clinical risk factors, multivariate logistic regression analysis identified SNPs significantly associated with bleedings were ABCB1 (rs1045642, rs2235047, rs7779562), P2Y12 (rs6809699) and CYP2C19*17. A genetic risk score was constructed by summing the number of risk alleles. Bleedings were significantly associated with increased genetic risk score tertile. Patients in the top tertile of the genetic score were estimated to have a 3.268-fold (95%CI=1.198-8.929, p=0.021) increased risk of bleedings compared with those in the bottom tertile. As a continuous variable, the risk score resulted in an OR of 1.326 per unit increase in score (95%CI=1.098-1.601, p=0.003). Conclusions: This genetic score was significantly associated with bleedings after PCI in our study population.

scholarly journals The association between self-reported and clinically determined hypomanic symptoms and the onset of major mood disorders

BJPsych Open ◽  
2017 ◽  
Vol 3 (2) ◽  
pp. 71-77 ◽  
Author(s):  
Sarah Margaret Goodday ◽  
Martin Preisig ◽  
Mehdi Gholamrezaee ◽  
Paul Grof ◽  
Jules Angst ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
High Risk ◽  
Major Depression ◽  
Young People ◽  
Mood Disorders ◽  
Clinical Interviews ◽  
Increased Risk ◽  
Ultra High Risk ◽  
Clinically Significant ◽  
And Control

BackgroundHypomanic symptoms may be a useful predictor of mood disorder among young people at high risk for bipolar disorder.AimsTo determine whether hypomanic symptoms differentiate offspring of parents with bipolar disorder (high risk) and offspring of well parents (control) and predict the development of mood episodes.MethodHigh-risk and control offspring were prospectively assessed using semi-structured clinical interviews annually and completed the Hypomania Checklist-32 Revised (HCL-32). Clinically significant sub-threshold hypomanic symptoms (CSHS) were coded.ResultsHCL-32 total and active or elated scores were higher in control compared with high-risk offspring, whereas 14% of high-risk and 0% of control offspring had CSHS. High-risk offspring with CSHS had a fivefold increased risk of developing recurrent major depression (P=0.0002). The median onset of CSHS in high-risk offspring was 16.4 (6–31) years and was before the onset of major mood episodes.ConclusionsCSHS are precursors to major mood episodes in high-risk offspring and could identify individuals at ultra-high risk for developing bipolar disorder.

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