Bipolar disorder (BD) and unipolar depression (UD) are two severe mood disorders, with BD often misdiagnosed as UD. Given their severity and high rates of misdiagnosis, it is of paramount importance to understand the psychological and neurobiological mechanisms underlying these disorders to enhance our ability to diagnose, treat, and prevent them effectively. Many neuroimaging studies have shown that mood disorders are associated with abnormal reward-related responses, particularly in the ventral striatum (VS). Yet, the link between mood disorders and reward-related responses in other regions remains inconclusive, thus limiting our understanding of the pathophysiology of mood disorders. To provide insights into the neurobiological underpinnings of reward processing dysfunction in mood disorders, two studies were conducted. Study 1 (Chapter 2) is a coordinate-based meta-analysis of 41 whole-brain neuroimaging studies encompassing reward-related responses from a total of 794 patients with major depressive disorder (MDD), and 803 healthy controls (HC). It aims to address inconsistencies in the literature by synthesizing the literature quantitatively. The findings of Study 1 indicate that MDD is associated with opposing abnormalities in the reward circuit: hypo-responses in the VS and hyper-responses in the orbitofrontal cortex (OFC). These findings provide a foundation for Study 2 (Chapter 3) and help to reconceptualize our understanding of reward processing abnormalities in UD by suggesting a role for dysregulated corticostriatal connectivity. Study 2 is the first fMRI study to employ region-of-interest (VS and OFC), whole-brain, activation, connectivity, and network analyses to examine the similarities and differences in reward-related brain activation patterns between 46 children with remitted bipolar I disorder, 48 children with remitted MDD, and 46 HC. The results of Study 2 revealed differential connectivity in corticostriatal circuitry during reward processing among BD, UD, and HC in pre-adolescence. Specifically, BD exhibited increases in OFC-VS connectivity during anticipation of larger reward, whereas UD and HC showed no changes in OFC-VS connectivity across anticipation conditions ranging from large loss to large reward. Furthermore, BD and UD generally showed more abnormal whole-brain responses to reward anticipation in accordance with the valence of the stimuli than HC. These findings suggest that pre-adolescents with BD and UD exhibit reward processing dysfunction during reward anticipation relative to HC even outside of acute periods of illness. Taken together, the dissertation provides novel insight into the nature of reward processing abnormalities in mood disorders in pre-adolescence. As early onset BD or UD often is associated with long treatment delays and a persistently pernicious illness course, this dissertation may aid efforts to ensure early accurate diagnosis, which may improve our ability to intervene with appropriate treatments and result in a more benign prognosis and course of illness over the lifespan. / Psychology

Impulsivity and sleep and circadian rhythm disturbance are two core features of bipolar disorder that are elevated antecedents to bipolar disorder onset and persist even between mood episodes; their pervasive presence in bipolar disorder suggests that they may be particularly relevant to better understanding bipolar disorder etiology, onset, and course. Given considerable research demonstrating bidirectional associations between sleep and circadian rhythm disturbance and impulsivity in healthy individuals, it is surprising that little research has examined how these core features interact to impact bipolar disorder symptomatology, onset, and course. In a sample of late adolescents and young adults (N = 150) at low or high risk for developing bipolar disorder, we employed a naturalistic experiment in the context of an ecological momentary assessment (EMA) design to examine relationships between impulsivity, sleep and circadian rhythm alterations, and mood symptoms in everyday life. Furthermore, we sought to understand how the relationships between sleep and circadian rhythm alterations and mood fluctuation, collected during the EMA study, prospectively predicted mood symptom severity and mood episode onset at a 6-month follow-up. Linear regression, logistic regression, and multi-level modeling (MLM) revealed that higher impulsivity predicted increased mood symptoms during the EMA study, and less total sleep time (measured by actigraphy) predicted increased next-day EMA-assessed mood symptoms. Interaction analyses suggested that dim light melatonin onset time, total sleep time, and sleep onset latency moderated the relationship between impulsivity and mood symptoms (both next-day and at 6-month follow-up). Results are discussed in terms of their contribution to the existing literature. Findings highlight the necessity of multi-method, nuanced examination of the dynamic relationships between impulsivity and sleep and circadian disturbance within bipolar disorder. / Psychology

Neurobiological theories of bipolar spectrum disorder (BSD) propose that the emotional dysregulation characteristic of BSD stems from disrupted prefrontal control over subcortical limbic structures (Strakowski et al., 2012; Depue & Iacono, 1989). However, existing neuroimaging research on functional connectivity between frontal and limbic brain regions remains inconclusive, and is unable to adequately characterize global functional network dynamics. Graph theoretical analysis provides a framework for understanding the local and global connections of the brain and comparing these connections between groups (Sporns et al., 2004). The purpose of this study was to investigate resting state functional connectivity in individuals at low and high risk for BSD based on moderate versus high reward sensitivity, both with and without a BSD diagnosis, using graph theoretical network analysis. Results demonstrated decreased connectivity in a cognitive control region (dorsolateral prefrontal cortex), but increased connectivity of a brain region involved in the detection and processing of reward (bilateral orbitofrontal cortex), among participants at high risk for BSD. Participants with BSD showed increased inter-module connectivity of the dorsal anterior cingulate cortex (ACC). Reward sensitivity was associated with decreased global and local efficiency, and interacted with BSD risk group status to predict inter-module connectivity. Findings are discussed in relation to neurobiological theories of BSD. / Psychology

Little to no research has evaluated factors that explain the manifestation and maintenance of bipolar disorder-anxiety disorder (BD-AD) comorbidity. The literature has shown that disruption of social and circadian rhythms is associated with mood episode onset. This association is especially pronounced among individuals who have a sensitive behavioral approach system (BAS). Inasmuch as anxiety sensitivity and trait anxiety have been associated both with BD and social rhythm disruption, it is worth examining whether anxiety sensitivity and trait anxiety confer risk for mood episode onset. The aims of this project were to: 1) evaluate trait anxiety and anxiety sensitivity as predictors of social rhythm disruption and BD-AD comorbidity, 2) examine social rhythm disruption (SRD) as a mediator of the association between trait anxiety and anxiety sensitivity and BD-AD comorbidity status, and 3) explore behavioral approach system sensitivity in these processes as contributing to the vulnerability to BD-AD comorbidity. A sample of 156 young adults participated in a multi-wave study in which they completed diagnostic interviews, symptom measures, and life event interviews which assessed the occurrence of positive and negative life events and the degree of SRD following these events every six months. Partial support for the hypotheses was found. Initial anxiety sensitivity, but not trait anxiety, positively predicted SRD for rewarding life events and follow-up bipolar symptoms. Additionally, SRD following positive life events predicted increases in depressive symptoms, but not hypomanic symptoms. SRD mediated the relationship between anxiety sensitivity and depressive symptoms. Furthermore, this relationship was stronger for healthy controls than for those with a bipolar disorder (BD) diagnosis or at-risk for developing BD. Moreover, individuals with a comorbid BD-AD diagnosis tended to have greater social rhythm disruption following negative life events than BD only or healthy individuals. Unexpectedly, individuals with comorbid BD-AD did not exhibit greater anxiety sensitivity or trait anxiety. Overall, the results suggest that anxiety sensitivity is a factor that may help to identify individuals who are vulnerable to bipolar symptoms. Furthermore, SRD is a mechanism that may partially explain this relationship. / Psychology

Yes / Current NHS policy encourages an integrated approach to provision of mental and physical care for individuals with long term mental health problems. The 'PARTNERS2' complex intervention is designed to support individuals with psychosis in a primary care setting. The trial will evaluate the clinical and cost-effectiveness of the PARTNERS2 intervention. This is a cluster randomised controlled superiority trial comparing collaborative care (PARTNERS2) with usual care, with an internal pilot to assess feasibility. The setting will be primary care within four trial recruitment areas: Birmingham & Solihull, Cornwall, Plymouth, and Somerset. GP practices are randomised 1:1 to either (a) the PARTNERS2 intervention plus modified standard care ('intervention'); or (b) standard care only ('control'). PARTNERS2 is a flexible, general practice-based, person-centred, coaching-based intervention aimed at addressing mental health, physical health, and social care needs. Two hundred eligible individuals from 39 GP practices are taking part. They were recruited through identification from secondary and primary care databases. The primary hypothesis is quality of life (QOL). Secondary outcomes include: mental wellbeing, time use, recovery, and process of physical care. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action, and look for unintended consequences. An economic evaluation will estimate its cost-effectiveness. Intervention delivery and follow-up have been modified during the COVID-19 pandemic. The overarching aim is to establish the clinical and cost-effectiveness of the model for adults with a diagnosis of schizophrenia, bipolar, or other types of psychoses. / PARTNERS2 is funded by the National Institute for Health Research (NIHR) under its Programme Grant for Applied Research Programme (grant number: RP-PG- 200625). This research was also supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust.

This text is an Anzaldúan autohistoria-teoría, a genre that blends the autoethnographic with poetry, fiction, visuals, and theories rooted in narrative identity. Specifically, this dissertation is modeled after Anzaldúa’s own incomplete doctoral dissertation, Luz en el oscuro/Light in the Dark. In Anzaldúa’s final text, she continues her exploration of the new mestiza, but she tempers it with nuanced views on the particulars of identity, alongside deeply personal explorations of her understanding of herself as a chicana, an academic, and a person in an aging body. As with much of her work, she blends creative elements with her theory, including poetry, memoir, and drawings she made to illustrate her theoretical concepts (the autohistoria-teoría). In addition to this, I use Cherrie Moraga’s theory-in-the-flesh (a concept wherein theory is built on particular experience) to provide theoretical justification. I also borrow from Jaques Derrida, Edward Said, Gayarti Spivak, and Roland BarthesBy using Moraga’s and Anzaldúa’s ideas as a roadmap for my own writing, I place myself firmly within a feminist and queer framework, with a focus on decolonial and disability rhetorics. For this dissertation, I use autohistoria-teoría to explore historical traumas through a personal lens, as well as personal trauma through a historical lens. I propose four concepts in narrative identity in order to explore these ideas: los zorros (decolonial metis), pishtaco/Inkarri (decolonial hauntology), el tumi (disability metis), and el retablo (pedagogical concerns). / English

Bipolar disorder (BD) is a serious mental illness characterized by dramatically differing mood states and marked costs for the individual and society, making it important to find factors associated with the condition. Deficits in emotion regulation have been found across a wide range of mental health disorders and may represent an important risk factor for BD. Literature in this area has large methodological inconsistencies and many conclusions are mixed. Therefore, the current study sought to conduct a meta-analytic review of literature related to emotion regulation in BD. Results suggest that people with BD broadly report more frequent use of maladaptive emotion regulation strategies and less frequent use of adaptive emotion regulation strategies than healthy controls. Of these strategies, the largest effect sizes were found for risk-taking, rumination, impulsivity, catastrophizing, and self-blame. Comparisons to other clinical groups suggest that emotion regulation in BD is largely similar to major depressive disorder and less severely impaired than borderline personality disorder. Moderator analyses of BD samples in different mood states suggest mood state plays a limited role in emotion regulation strategy usage, although some maladaptive strategies may be more common in samples with depressive symptoms. Among emotion regulation strategies, increased positive rumination and suppression may be uniquely characteristic of BD. Findings of this review support the importance of targeting emotion regulation in assessment and treatment of BD. Notably, psychotherapeutic interventions focused on emotion regulation, such as cognitive therapies, may be a key factor in reducing BD risk and episode recurrence.

Sammanfattning Bakgrund: Att leva med bipolär sjukdom är besvärligt för många. Sjukdomen ger upphov till allvarliga förändringar i känsloläget. Medicinering är en viktig del i behandlingen av bipolär sjukdom men när detta ger upphov till allvarliga biverkningar som viktökning kan det leda till lidande hos denna patientgrupp. Syftet med studien var att beskriva hur patienter med bipolär sjukdom upplever mediciners biverkningar i samband med viktuppgång och deras erfarenheter av att hantera det samt upplevelser av stödet och deras förväntningar på sjukvården inom aktuellt området. Metod: En kvalitativ och deskriptiv design användes.  Undersökningsgruppen bestod av fem kvinnliga och en manlig patient från ett sjukhus i Mellansverige. Huvudresultatet visade att deltagarna upplevde en stark påverkan på välbefinnande och hälsa av medicinbiverkningar i form av viktökning. Genomgående led deltagarna av biverkningar som påverkade både det fysiska och psykiska måendet. Samtliga deltagare hade gått igenom svåra kamper för att hantera viktökning och det krävdes mycket av deras egna krafter. Vidare betonade de att de inte blivit sedda av sjukvården och deras viktproblem inte tagits på allvar. Deltagarna upplevde starka känslor och lidanden av medicinbiverkningar och viktökning och det framkom förväntningar på att få stöd och information samt kontinuerlig vård för att kunna känna sig trygg i behandlingen och få uppleva en bättre livskvalitet. Slutsatsen visar att personer med bipolär sjukdom lider mycket av viktökning i samband med medicinbiverkningar. Det belyser att viktproblem är svårhanterbart och förbisett av sjukvården, vilket gör att livskvalitén blir svår att bevara. Att problem tas på allvar och att få information samt stöd inom det aktuella området ansågs vara nödvändigt för att kunna lindra vårdlidande Nyckelord: Bipolär sjukdom, Medicin biverkningar, Patientupplevelse, Stöd, Viktökning. / Abstract. Background: Living with bipolar disorder is difficult for many. The disease causes severe changes in emotional state. Medication is an important component in the treatment of bipolar disorder, but when this gives rise to serious side effects such as weight gain, it can lead to suffering of this population. The purpose of the study was to describe how bipolar patients experienced the medication's side effects associated with weight gain and their experience of dealing with it and the experiences of support as well as their expectations of health care within the current range. Method: A qualitative and descriptive design was used. The study group consisted of five women and one male patient from a hospital in central Sweden. The main result showed that participants experienced a great impact on the wellbeing and health of medication side effects such as weight gain. Through the participants suffered from the side effects that affected both the physical and mental health. All participants had gone through difficult struggles to manage weight gain and it took a lot of their own powers. Furthermore, they stressed that they had not been seen by the healthcare and their weight problems were not taken seriously. The participants experienced strong feelings and suffering from the medication side effects and weight gain, and there were expectations of getting support and information as well as continuous care to be able to feel safe in the treatment and experience and to have a better quality of life. The conclusion shows that people with bipolar disorder suffer a lot of the weight gain associated with medication side effects. It highlights that weight problems are difficult to manage and overlooked by the healthcare, making the quality of life of the patient difficult to maintain. That the problems are taken seriously and to get information and support in the area concerned was considered necessary in order to alleviate the suffering of care. Keywords: Bipolar disorder, Medicine side effects, Patient experience, Support, Weight gain.

Involviert in Netzwerke für das episodische Gedächtnis sowie als Bestandteil des Hypothalamus und des limbischen Systems stellen sich die im Zwischenhirn gelegenen Mamillarkörper als Zielstruktur im Kontext affektiver Störungen dar. Bislang waren die Mamillarkörper diesbezüglich lediglich in einer postmortem durchgeführten Studie Gegenstand der Forschung; es liegen keine Untersuchungen mit Hilfe der 7 Tesla-Magnetresonanztomografie vor. Um diese neuen Möglichkeiten der in vivo-Volumetrie im Submillimeterbereich auszuschöpfen, wurde auf Grundlage einer farbkodierten Darstellung ein detaillierter Algorithmus entwickelt, der sich als Hauptergebnis der vorliegenden Arbeit als hoch reliabel erwies. In der vorliegenden Pilotstudie wurde darüber hinaus das Mamillarkörper-Volumen von 14 Patientinnen und Patienten mit einer Bipolaren Störung und 20 gesunden Kontrollpersonen anhand von hochaufgelösten T1-gewichteten MRT-Bildern bestimmt. Ein signifikanter Unterschied zwischen den beiden Gruppen konnte nicht nachgewiesen werden, ebenso kein Unterschied zwischen den Geschlechtern. Es konnte gezeigt werden, dass das Volumen der Mamillarkörper signifikant invers mit dem Alter der ProbandInnen korreliert. Des Weiteren wurde eine signifikante positive Korrelation mit dem Gesamthirnvolumen der ProbandInnen festgestellt. Krankheitsschwere und Episodenzahl hingegen hatten keinen Einfluss auf das Mamillarkörper-Volumen. Die Ergebnisse dieser Pilotstudie sollten anhand einer größeren Stichprobe überprüft werden.

Objectives: Adherence to psychotropic medication is poor among individuals with bipolar disorder (BD). To understand treatment experiences and associated adherence among these individuals, we developed a novel construct of Clinical Net Benefit (CNB) using psychiatric symptoms, adverse effects and overall functioning assessments. We tested whether adherence differed across classes of CNB, whether individuals transitioned between classes over time, and whether these transitions were differentially associated with adherence. Methods: Data come from individuals aged 18+ during five years of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Latent class analysis identified groups of CNB. Latent transition analysis determined probabilities of transitioning between classes over time. Adherence was defined as taking 75%+ of medications as prescribed. Associations between CNB and adherence were tested using multiple logistic regression adjusting for sociodemographic characteristics. Results: Five classes of CNB were identified during the first two years (high, moderately high, moderate, moderately low, low), and four classes (removing moderately high) during the last three years. Adherence did not differ across classes or time points. Medication regimens differed by class; those with higher CNB taking fewer medications had lower odds of adherence while those with lower CNB taking more medications had higher odds of adherence compared with monotherapy. Probability of transitioning from higher to lower CNB, and lower to higher CNB was greatest over time. Conclusions: CNB is heterogeneous in individuals treated for BD, and movement between classes is not uncommon. Understanding why individuals adhere despite suboptimal CNB may provide novel insights into aspects influencing adherence.