Polygenic Risk and Progression to Bipolar or Psychotic Disorders Among Individuals Diagnosed With Unipolar Depression in Early Life

Musliner, Katherine L.; Krebs, Morten Dybdahl; Albiñana, Clara; Vilhjálmsson, Bjarni J.; Agerbo, Esben; Zandi, Peter P.; Hougaard, David M.; Nordentoft, Merete; Børglum, Anders; Werge, Thomas; Mortensen, Preben Bo; Østergaard, Søren Dinesen

doi:10.1176/appi.ajp.2020.19111195

Cited by 44 publications

(51 citation statements)

References 35 publications

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“…Longitudinal monitoring of cohorts comprising youth with various ‘at risk’ presentations (the so-called ‘close-in’ strategy), indicates that 10–40% of individuals demonstrate subsequent onset of a mental disorder meeting diagnostic criteria over 12–36 months [ 7 , 8 ]. Currently, it is unclear why only some individuals identified as being at risk of developing a mental disorder show transition to caseness and others who appear to be equally at risk do not [ 9 ]. Also, whilst family history of major mental disorders and/or the presence of subthreshold syndromes are associated with the development of full-threshold disorders, there is uncertainty regarding their specificity (e.g.…”

Section: Introductionmentioning

confidence: 99%

Early expressions of psychopathology and risk associated with trans-diagnostic transition to mood and psychotic disorders in adolescents and young adults

Scott

Crouse

et al. 2021

PLoS ONE

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Objectives The heterogeneity and comorbidity of major mental disorders presenting in adolescents and young adults has fostered calls for trans-diagnostic research. This study examines early expressions of psychopathology and risk and trans-diagnostic caseness in a community cohort of twins and non-twin siblings. Methods Using data from the Brisbane Longitudinal Twin Study, we estimated median number of self-rated psychiatric symptoms, prevalence of subthreshold syndromes, family history of mood and/or psychotic disorders, and likelihood of subsequent trans-diagnostic caseness (individuals meeting diagnostic criteria for mood and/or psychotic syndromes). Next, we used cross-validated Chi-Square Automatic Interaction Detector (CHAID) analyses to identify the nature and relative importance of individual self-rated symptoms that predicted trans-diagnostic caseness. We examined the positive and negative predictive values (PPV; NPV) and accuracy of all classifications (Area under the Curve and 95% confidence intervals: AUC; 95% CI). Results Of 1815 participants (Female 1050, 58%; mean age 26.40), more than one in four met caseness criteria for a mood and/or psychotic disorder. Examination of individual factors indicated that the AUC was highest for subthreshold syndromes, followed by family history then self-rated psychiatric symptoms, and that NPV always exceeded PPV for caseness. In contrast, the CHAID analysis (adjusted for age, sex, twin status) generated a classification tree comprising six trans-diagnostic symptoms. Whilst the contribution of two symptoms (need for sleep; physical activity) to the model was more difficult to interpret, CHAID analysis indicated that four self-rated symptoms (sadness; feeling overwhelmed; impaired concentration; paranoia) offered the best discrimination between cases and non-cases. These four symptoms showed different associations with family history status. Conclusions The findings need replication in independent cohorts. However, the use of CHAID might provide a means of identifying specific subsets of trans-diagnostic symptoms representing clinical phenotypes that predict transition to caseness in individuals at risk of onset of major mental disorders.

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Section: Introductionmentioning

confidence: 99%

Early expressions of psychopathology and risk associated with trans-diagnostic transition to mood and psychotic disorders in adolescents and young adults

Scott

Crouse

et al. 2021

PLoS ONE

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“…Although case note follow-up only provides weak evidence, we do think it is worthwhile to get a snapshot of the course and outcome of case series participants. Recent research highlights that about 18% individuals with a family history of BD will develop BD or another major mental disorder during the peak age range for onset of adult pattern conditions (4,6,7,(31)(32)(33)(34). Furthermore, about 10% of those with early expressions of psychopathology and about 30% of those with subthreshold manifestations of BD will develop a full-threshold mood or psychotic disorder over about 2-4 years (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

“…Recent research highlights that about 18% individuals with a family history of BD will develop BD or another major mental disorder during the peak age range for onset of adult pattern conditions (4,6,7,(31)(32)(33)(34). Furthermore, about 10% of those with early expressions of psychopathology and about 30% of those with subthreshold manifestations of BD will develop a full-threshold mood or psychotic disorder over about 2-4 years (31)(32)(33). In those with a family history of BD and a subthreshold presentation of BD, the transition rate may be >50% over 2 years (31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, about 10% of those with early expressions of psychopathology and about 30% of those with subthreshold manifestations of BD will develop a full-threshold mood or psychotic disorder over about 2-4 years (31)(32)(33). In those with a family history of BD and a subthreshold presentation of BD, the transition rate may be >50% over 2 years (31)(32)(33)(34). In this pilot study of a small case series, we found evidence that about 21% could be viewed as having a poor clinical outcome with 7% of participants (one individual) developing BD, 7% a psychotic disorder, and 7% continuing to experience mood problems, but without transition to full-threshold BD (or perhaps transition has been delayed).…”

Section: Discussionmentioning

confidence: 99%

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Brief Research Report: A Pilot Study of Cognitive Behavioral Regulation Therapy (CBT-REG) for Young People at High Risk of Early Transition to Bipolar Disorders

Scott

Meyer²

2021

Front. Psychiatry

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Attempts to increase early identification of individuals in the early stages of bipolar disorders (i.e., individuals at high risk of bipolar disorders and/or experiencing a subthreshold syndrome with bipolar symptoms) have highlighted the need to develop high benefit-low risk interventions. We suggest that any new psychological therapy should (i) be acceptable to young people seeking help for the first time, (ii) be applicable to “at risk” conditions and sub-syndromal states and (iii) consider pluripotent factors that may be linked to illness progression not only for bipolar disorders specifically but also for other potential disease trajectories. However, evidence indicates that current interventions for youth with emerging mood disorders mainly represent approaches abbreviated from “disorder-specific” therapies used with older adults and are primarily offered to first episode cases of bipolar disorders who are also receiving psychotropic medication. This brief report discusses empirical findings used to construct core targets for therapeutic interventions that might reduce or delay transition to full-threshold bipolar disorders. We describe an intervention that includes strategies for problem-solving, reducing sleep-wake cycle disturbances, self-management of rumination and that addresses the needs of individuals with “sub-threshold” presentations who are probably at risk of developing a bipolar or other major mental disorders. Outcome data from a case series of 14 youth indicates that the intervention appears to demonstrate a relatively high benefit-to-risk ratio, promising levels of engagement with the therapy modules, and the therapy appears to be acceptable to a wide range of help-seeking youth with early expressions of bipolar psychopathology.

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“…environmental variables). We applied this model to the study of interaction one or more PD with the psychosocial environment 27 , Nitrogen Dioxide 28 , Unipolar Depression in Early Life 29 , substance use disorders 30 , voter turnout 31 and Parental Socioeconomic Status coupled with history of PD 32…”

Section: Introductionmentioning

confidence: 99%

The iPSYCH2015 Case-Cohort sample: updated directions for unravelling genetic and environmental architectures of severe mental disorders

Bybjerg‐Grauholm

Pedersen

Bækvad‐Hansen

et al. 2020

Preprint

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The Lundbeck Foundation Integrative Psychiatric Research (iPSYCH) consortium has almost doubled its Danish population-based Case-Cohort sample (iPSYCH2012). The newly updated cohort, named iPSYCH2015, expands the study base with 56,233 samples, to a combined total of 141,265 samples. The cohort is nested within the Danish population born between 1981 and 2008 and is a Case-cohort design including 50,615 population controls. We added more cases to the existing phenotypes identified with, schizophrenia (Nnew=4,131/Ntotal=8,113), autism (Nnew=8,056 / Ntotal=24,975), attention-deficit/hyperactivity disorder (Nnew=10,026/Ntotal=29,668) and affective disorder (Nnew=13,999/Ntotal=40,482) of which a subset has bipolar affective disorder (N-new=1,656/Ntotal=3,819). We also added two additional focus phenotypes, schizophrenia spectrum disorder (N=16,008) and post-partum disorder (N=3,421). In total, the expanded iPSYCH2015 sample consists of 93,608 unique individuals in the case groups and 50,615 population controls. For the sample expansion, DNA was extracted and amplified from dried blood spots samples stored within the Danish Neonatal Screening Biobank and genotyped using the Illumina Global Screening Array. The Biobank sample retrieval rate was 95%, and the genotyping success rate was 92% (97% of retrieved). We expanded the follow-up period by three years, including data such as longitudinal information on health, prescribed medicine, social and socioeconomic information.

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Polygenic Risk and Progression to Bipolar or Psychotic Disorders Among Individuals Diagnosed With Unipolar Depression in Early Life

Cited by 44 publications

References 35 publications

Early expressions of psychopathology and risk associated with trans-diagnostic transition to mood and psychotic disorders in adolescents and young adults

Early expressions of psychopathology and risk associated with trans-diagnostic transition to mood and psychotic disorders in adolescents and young adults

Brief Research Report: A Pilot Study of Cognitive Behavioral Regulation Therapy (CBT-REG) for Young People at High Risk of Early Transition to Bipolar Disorders

The iPSYCH2015 Case-Cohort sample: updated directions for unravelling genetic and environmental architectures of severe mental disorders

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