Anticipation and repeat expansion in bipolar disorder

O’Donovan, Michael; Jones, Ian; Craddock, Nicholas John

doi:10.1002/ajmg.c.20009

Cited by 23 publications

(7 citation statements)

References 54 publications

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“…This could explain some of the features of the genetic architecture of this category of disorders 9 – 11 . This includes anticipation, a phenomenon where later generations exhibit more severe symptoms at an earlier age, robustly reported (although not explained) in BPD 12 , and recently highlighted in genetic studies of MDD 13 , 14 .…”

Section: Introductionmentioning

confidence: 83%

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Jong¹,

Diniz²,

Saloma³

et al. 2018

Commun Biol

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Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

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Section: Introductionmentioning

confidence: 83%

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Jong¹,

Diniz²,

Saloma³

et al. 2018

Commun Biol

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“…In contrast, most of their children developed their first BP episode before age 12 years, suggesting the possibility that parents were more perceptive of their children's symptoms early in life or perhaps that BP has more penetrance and manifests earlier in new generations 45,52,55…”

Section: Commentmentioning

confidence: 99%

Lifetime Psychiatric Disorders in School-aged Offspring of Parents With Bipolar Disorder

Birmaher¹,

Axelson²,

Monk³

et al. 2009

Arch Gen Psychiatry

330

311

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Context: Whether offspring of parents with bipolar disorder (BP) are at specifically high risk to develop BP and other psychiatric disorders has not been adequately studied. Objective: To evaluate lifetime prevalence and specificity of psychiatric disorders in offspring of parents with BP-I and BP-II. Design: Offspring aged 6 to 18 years who have parents with BP and community control subjects were interviewed with standardized instruments. All research staff except the statistician were blind to parental diagnoses. Setting: Parents with BP were recruited primarily through advertisement and outpatient clinics. Control parents were ascertained by random-digit dialing and were group matched for age, sex, and neighborhood to parents with BP. Participants: Three hundred eighty-eight offspring of 233 parents with BP and 251 offspring of 143 demographically matched control parents. Main Outcome Measures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) Axis I disorders. Results: Adjusting for demographic factors, living with 1 vs both biological parents, both biological parents' non-BP psychopathology, and within-family correlations, offspring of parents with BP showed high risk for BP spectrum disorders (odds ratio [OR]=13.4; 95% confidence interval [CI], 2.9-61.6) and any mood (OR=5.2; 95% CI, 2.3-11.4), anxiety (OR=2.3; 95% CI, 1.3-4.0), and Axis I (OR=2.2; 95% CI, 1.5-3.3) disorders. Off-spring of parents with BP with high socioeconomic status showed more disruptive behavior disorders and any Axis I disorders than offspring of control parents with high socioeconomic status. Families in which both parents had BP had more offspring with BP than families with only 1 parent with BP (OR=3.6; 95% CI, 1.1-12.2). More than 75.0% of offspring who developed BP had their first mood episode before age 12 years, with most of these episodes meeting criteria for BP not otherwise specified and, to a lesser degree, major depression. Conclusions: Offspring of parents with BP are at high risk for psychiatric disorders and specifically for early-onset BP spectrum disorders. These findings further support the familiality and validity of BP in youth and indicate a need for early identification and treatment.

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“…While there has been some progress in this direction, 59 more research is needed. One promising area of research remaining is the possibility of trinucleotide repeat expansion in AAO regions of the chromosome, leading to anticipation of the disorder 60 . Discovery of such phenomena would again help elucidate the degree of urgency needed for intervention in at‐risk youth.…”

Section: Genetic Markersmentioning

confidence: 99%

Prevention of Pediatric Bipolar Disorder

Chang

Howe

Gallelli

et al. 2006

Annals of the New York Academy of Sciences

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Bipolar disorder (BD) is a prevalent condition in the United States that typically begins before the age of 18 years and is being increasingly recognized in children and adolescents. Despite great efforts in discovering more effective treatments for BD, it remains a difficult-to-treat condition with high morbidity and mortality. Therefore, it appears prudent to focus energies into developing interventions designed to prevent individuals from ever fully developing BD. Such interventions early in the development of the illness might prevent inappropriate interventions that may worsen or hasten development of BD, delay the onset of first manic episode, and/or prevent development of full BD. Studies of populations at high-risk for BD development have indicated that children with strong family histories of BD, who are themselves experiencing symptoms of attention-deficit/hyperactive disorder (ADHD) and/or depression or have early mood dysregulation, may be experiencing prodromal states of BD. Understanding the neurobiological and genetic underpinnings that create risk for BD development would help with more accurate identification of this prodromal population, which could then lead to suitable preventative interventions. Such interventions could be pharmacologic or psychosocial in nature. Reductions in stress and increases in coping abilities through psychosocial interventions could decrease the chance of a future manic episode. Similarly, psychotropic medications may decrease negative sequelae of stress and have potential for neuroprotective and neurogenic effects that may contribute to prevention of fully expressed BD. Further research into the biologic and environmental mechanisms of BD development as well as controlled early intervention studies are needed to ameliorate this significant public health problem.

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Anticipation and repeat expansion in bipolar disorder

Cited by 23 publications

References 54 publications

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Lifetime Psychiatric Disorders in School-aged Offspring of Parents With Bipolar Disorder

Prevention of Pediatric Bipolar Disorder

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