Understanding the developmental pathways to bipolar disorder

Durdurak, Buse Beril (2025). Understanding the developmental pathways to bipolar disorder. University of Birmingham. Ph.D.

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Abstract

Bipolar Disorder (BD) is a multifactorial condition, with a diversity of trajectories. Existing evidence indicates the presence of significant psychopathology preceding the onset of BD, such as Borderline Personality Disorder (BPD), Attention Deficit Hyperactivity Disorder (ADHD) and depression. However, a more nuanced understanding of these developmental risk trajectories and their relationship to BD are lacking and remain essential to disentangle risks and links.

The overarching aim of this thesis is to develop new knowledge of the developmental pathways to BD, so that people who are vulnerable to developing BD can be more clearly identified so that ultimately targeted interventions can be developed for this group. In doing so the thesis will also review gaps in current knowledge and provide directions for future research.

Three studies were conducted to answer the research aim via examining developmental trajectories of BPD, ADHD, and depression to BD. Firstly, factors that are associated with the early course of BD and BPD symptoms, features, or onset were examined in a priori literature to be able to understand the differences and similarities in developmental pathways to these disorders were examined. To address this aim and take advantage of the recent surge in publications, I conducted a meta-review of systematic reviews evaluating prospective studies investigating these factors. Secondly, the associations between ADHD symptom trajectories (including its subtypes) through childhood and adolescence with clinically significant hypomanic symptoms at age 21-23 years were examined, using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Thirdly, the association between trajectories of depressive symptoms in adolescence and the risk of subsequent clinically significant hypomanic symptoms at 21-23 years and whether atypical depression features and psychotic symptoms potentially mediate any association were investigated, using data from the same UK birth cohort ALSPAC. Findings from the meta-review of reviews demonstrated that family history of psychopathology, affective instability, ADHD, anxiety disorders, depression, sleep disturbances, substance abuse, psychotic symptoms, suicidality, childhood adversity and temperament were common predisposing factors/trajectories across both disorders. Since the detected risk trajectories are non-specific and overlapping, results can advance the field of defining progressive stages in transdiagnostic clinical staging models in youth mental health.

Results from the second study showed that individuals with persistently high and increasing levels of ADHD symptoms had increased odds of hypomanic symptoms compared to persistently low and remitting classes. In separate analyses, persistently high levels of hyperactivity, and increasing levels of inattentive symptoms were also independently associated with hypomanic symptoms. These trajectories in childhood and adolescence may represent distinct phenotypic risk profiles for subsequently developing BD and be clinically significant targets for prevention and treatment of BD.

Results from the third study indicated that adolescents with increasing levels of depression symptoms were more likely to develop clinically significant hypomanic symptoms at 21-23 years, compared to adolescents with persistently low depression symptoms. Both atypical depression features and psychotic symptoms partially mediated the association of increasing depression levels with hypomanic symptoms.
The collective implications and limitations of the findings arising from these three studies, along with future directions are discussed in the final chapter. Overall, these studies advance our understanding and differentiation of emerging trajectories in BD by taking a developmental prospective approach and encouraging early recognition and treatment of emerging syndromal illnesses in youth mental health.

The collective implications and limitations of the findings arising from these three studies, along with future directions are discussed in the final chapter. Overall, these studies advance our understanding and differentiation of emerging trajectories in BD by taking a developmental prospective approach and encouraging early recognition and treatment of emerging syndromal illnesses in youth mental health.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):