Perinatal risk factors and subclinical hypomania: A prospective community study.

BACKGROUND: Perinatal risk factors are implicated in the development of psychopathology, but their role in bipolar disorder (BD) and hypomania is unclear. Using data from a prospective community cohort, this is the first study to investigate the association between a range of perinatal risk factors, hypomanic symptoms, and 'high-risk' for BD in the general population. METHODS: Parent report of perinatal events were available for 26,040 eighteen-month-olds from the Twins Early Development Study. Subsequent self-report hypomania was measured at ages 16 (Hypomania Checklist-16; N = 2943) and 26 (Mood Disorders Questionnaire; N = 7748). Participants were categorised as 'high-risk' for BD using established classifications. Linear and logistic regressions were conducted within a generalised estimating equations framework to account for relatedness in the sample. RESULTS: Prenatal alcohol exposure (ß = 0.08, SE = 0.04, p = .0002) and number of alcohol units consumed (ß = 0.09, SE = 0.02, p < .0001) were associated with hypomanic symptoms at age 16, and number of alcohol units (OR = 1.13, 95 % CI:1.06-1.21, p = .0003) and maternal stress (OR = 1.68, 95 % CI:1.21-2.34, p = .002) were associated with 'high-risk' for BD age 16. Prenatal tobacco exposure (ß = 0.10, SE = 0.04, p < .0001) and number of cigarettes smoked (ß = 0.10, SE = 0.01, p < .0001) were associated with hypomanic symptoms and 'high-risk' for BD at age 26, although these result were attenuated controlling for parental psychiatric history. LIMITATIONS: Familial confounding could not be fully adjusted for. Rater reports include some biases. CONCLUSIONS: These findings show perinatal risk factors to be associated with subclinical hypomania and 'high-risk' for BD. Future work should explore the mechanisms underlying these longitudinal associations, which could shed light on prevention and intervention efforts.

A cross-sectional investigation into the role of intersectionality as a moderator of the relation between youth adversity and adolescent depression/anxiety symptoms in the community.

BACKGROUND: Adolescents exposed to adversity show higher levels of depression and anxiety, with the strongest links seen in socially/societally disadvantaged individuals (e.g., females, low socioeconomic status [SES]), as well as neurodivergent individuals. The intersection of these characteristics may be important for the differential distribution of adversity and mental health problems, though limited findings pertain to the extent to which intersectional effects moderate this association. METHODS: Combined depression/anxiety symptoms were measured using the emotional problems subscale of the Strengths and Difficulties Questionnaire in 13-14-year-olds in Cornwall, United Kingdom in 2017-2019. In a cross-sectional design (N = 11,707), multiple group structural equation modeling was used to estimate the effects of youth adversity on depression/anxiety symptoms across eight intersectionality profiles (based on gender [female/male], SES [lower/higher], and traits of hyperactivity/inattention [high/low]). Moderation effects of these characteristics and their intersections were estimated. RESULTS: Youth adversity was associated with higher levels of depression/anxiety (compared to an absence of youth adversity), across intersectional profiles. This effect was moderated by gender (stronger in males; ß = 0.22 [0.11, 0.36]), and SES (stronger in higher SES; ß = 0.26 [0.14,0.40]); with indications of moderation attributable to the intersection between gender and hyperactivity/inattention (ß = 0.21 [-0.02,0.44]). CONCLUSIONS: Youth adversity is associated with heightened depression/anxiety across intersectional profiles in 13-14-year-olds. The stronger effects observed for males, and for higher SES, may be interpreted in terms of structural privilege. Preliminary findings suggest that vulnerability and resilience to the effects of youth adversity may partially depend on specific intersectional effects. Importantly, the current results invite further investigation in this emerging line of inquiry.

Self-directed digital interventions for the improvement of emotion regulation-effectiveness for mental health and functioning in adolescents: protocol for a systematic review.

INTRODUCTION: Research suggests that problems with emotion regulation, that is, how a person manages and responds to an emotional experience, are related to a range of psychological disorders (eg, bipolar disorder, anxiety and depression). Interventions targeting emotion regulation have been shown to improve mental health in adults, but evidence on related interventions for adolescents is still emerging. Increasingly, self-directed digital interventions (eg, mobile apps) are being developed to target emotion regulation in this population, but questions remain about their effectiveness. This systematic review aimed to synthesise evidence on current self-directed digital interventions available to adolescents (aged 11-18 years) and their effectiveness in addressing emotion regulation, psychopathology and functioning (eg, academic achievement). METHODS AND ANALYSIS: Several electronic databases will be searched (eg, MEDLINE, PsycINFO, ACM Digital Library) to identify all studies published any time after January 2010 examining self-directed digital interventions for adolescents, which include an emotion regulation component. This search will be updated periodically to identify any new relevant research from the selected databases. Data on the study characteristics (eg, author(s)) and methodology, participant characteristics (eg, age) and the digital interventions used to address emotion (dys-)regulation (eg, name, focus) will be extracted. A narrative synthesis of all studies will be presented. If feasible, the effectiveness data will be synthesised using appropriate statistical techniques. The methodological quality of the included studies will be assessed with the Effective Public Health Practice Project quality assessment tool. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. Findings will be disseminated widely via peer-reviewed publications and presentations at conferences related to this field. REGISTRATION DETAILS: PROSPERO CRD42022385547.

Youth adversity and trajectories of depression/anxiety symptoms in adolescence in the context of intersectionality in the United Kingdom.

BACKGROUND: Youth adversity is associated with persistence of depression and anxiety symptoms. This association may be greater for disadvantaged societal groups (such as females) compared with advantaged groups (e.g. males). Given that persistent symptoms are observed across a range of disadvantaged, minoritized, and neurodivergent groups (e.g. low compared with high socio-economic status [SES]), the intersection of individual characteristics may be an important moderator of inequality. METHODS: Data from HeadStart Cornwall (N = 4441) was used to assess the effect of youth adversity on combined symptoms of depression and anxiety (Strengths and Difficulties Questionnaire emotional problems subscale) measured at three time-points in 11-14-year-olds. Latent trajectories and regressions were estimated for eight intersectionality profiles (based on gender, SES, and hyperactivity/inattention), and moderating effects of the individual characteristics and their intersections were estimated. RESULTS: Youth adversity was associated with higher average depression/anxiety symptoms at baseline (11-12-years) across all intersectionality profiles. The magnitude of effects differed across profiles, with suggestive evidence for a moderating effect of youth adversity on change over time in depression/anxiety symptoms attributable to the intersection between (i) gender and SES; and (ii) gender, SES, and hyperactivity/inattention. CONCLUSIONS: The detrimental effects of youth adversity pervade across intersectionality profiles. The extent to which these effects are moderated by intersectionality is discussed in terms of operational factors. The current results provide a platform for further research, which is needed to determine the importance of intersectionality as a moderator of youth adversity on the development of depression and anxiety symptoms in adolescence.

Understanding psychosis complexity through a syndemic framework: A systematic review.

Psychotic conditions pose significant challenges due to their complex aetiology and impact on individuals and communities. Syndemic theory offers a promising framework to understand the interconnectedness of various health and social problems in the context of psychosis. This systematic review aims to examine existing literature on testing whether psychosis is better understood as a component of a syndemic. We conducted a systematic search of 7 databases, resulting in the inclusion of five original articles. Findings from these studies indicate a syndemic characterized by the coexistence of various health and social conditions, are associated with a greater risk of psychosis, adverse health outcomes, and disparities, especially among ethnic minorities and deprived populations. This review underscores the compelling need for a new paradigm and datasets that can investigate how psychosis emerges in the context of a syndemic, ultimately guiding more effective preventive and care interventions as well as policies to improve the health of marginalised communities living in precarity.

Experience-based Investigation and Co-design of Psychosis Centred Integrated Care Services for Ethnically Diverse People with Multimorbidity (CoPICS): study protocol.

INTRODUCTION: Ethnic minorities (also called racialised groups) are more likely to experience severe mental illness (SMI). People with SMI are more likely to experience multimorbidity (MM), making psychosis among racialised groups more likely to lead to MM, poor outcomes, disability and premature mortality. METHODS AND ANALYSIS: This National Institute for Health and Care Research-funded study (151887) seeks to use innovative participatory methods including photovoice and biographical narrative interviews in urban and rural areas of England to assemble experience data. These data will be subjected to polytextual thematic analysis, and alongside pictures and captions, will inform an experienced-based co-design of interventions, the implementation of which will be evaluated. There will be an economic analysis and a process evaluation of the implementation. ETHICS AND DISSEMINATION: This programme of work has received ethical (IRAS 322421; Newcastle North Tyneside Research Ethics Committee 23/NE/0143) and sponsor approval. The findings will be disseminated in galleries showing the creative work, as lay and academic summaries and infographics; as practice briefings for practitioners, commissioners and policy makers; peer-reviewed publications. TRIAL REGISTRATION NUMBER: https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/649c08111c037d0027b17d17/.

Interplay between polygenic risk for mood disorders and stressful life events in bipolar disorder.

BACKGROUND: Although genetic and environmental factors are involved in the aetiology of bipolar disorder [BD], studies focused on their interplay are lacking. The current investigation examines interactions and correlations between polygenic risk scores [PRS] for BD and major depressive disorder [MDD] with stressful life events [SLEs] in liability for BD. METHODS: This study used data from 1715 participants (862 bipolar cases and 853 controls) taken from UK and Canadian samples. The List of Threatening Experiences Questionnaire recorded SLEs that occurred 6 months before interview for controls and 6 months prior to the first (Canadian sample) and worst (UK sample) depressive and manic episodes for bipolar cases. PRS-BD and PRS-MDD were calculated from the Psychiatric Genomics Consortium. RESULTS: For the worst depressive episode, the PRS-MDD was significantly correlated with total number of SLEs (ß = 0.13, 95 % CI:0.04-0.22, p = 0.003) and dependent SLEs (ß = 0.09, 95 % CI:0.02-0.16, p = 0.007). After correction for multiple testing nominally significant correlations were detected for PRS-BD with total number of SLEs (ß = 0.11, 95 % CI:0.02-0.20, p = 0.015) and dependent SLEs (ß = 0.08, 95 % CI:0.01-0.15, p = 0.019). Among bipolar cases, these associations were slightly stronger but were only of nominal significance for total number of SLEs (PRS-MDD: ß = 0.19, 95 % CI:0.04-0.35, p = 0.015; PRS-BD: ß = 0.16, 95 % CI:0.01-0.32, p = 0.042) and dependent SLEs (PRS-MDD: ß = 0.14, 95 % CI:0.03-0.26, p = 0.015; PRS-BD: ß = 0.12, 95 % CI:0.004-0.24, p = 0.043). No other significant gene-environment correlations or interactions were found. LIMITATIONS: Use of a larger sample size would be beneficial. CONCLUSIONS: The relationship between SLEs and genetic risk for mood disorders may be best explained through correlations rather than interactions.

Barriers to and facilitators of success for early and Mid-Career professionals focused on bipolar disorder: A global needs survey by the International Society for Bipolar Disorders.

INTRODUCTION: The International Society for Bipolar Disorders created the Early Mid-Career Committee (EMCC) to support career development of the next generation of researchers and clinicians specializing in bipolar disorder (BD). To develop new infrastructure and initiatives, the EMCC completed a Needs Survey of the current limitations and gaps that restrict recruitment and retention of researchers and clinicians focused on BD. METHODS: The EMCC Needs Survey was developed through an iterative process, relying on literature and content expertise of workgroup members. The survey included 8 domains: navigating transitional career stages, creating and fostering mentorship, research activities, raising academic profile, clinical-research balance, networking and collaboration, community engagement, work-life balance. The final survey was deployed from May to August 2022 and was available in English, Spanish, Portuguese, Italian, and Chinese. RESULTS: Three hundred participants across six continents completed the Needs Survey. Half of the participants self-identified as belonging to an underrepresented group in health-related sciences (i.e., from certain gender, racial, ethnic, cultural, or disadvantaged backgrounds including individuals with disabilities). Quantitative results and qualitative content analysis revealed key barriers to pursuing a research career focused on BD with unique challenges specific to scientific writing and grant funding. Participants highlighted mentorship as a key facilitator of success in research and clinical work. CONCLUSION: The results of the Needs Survey are a call to action to support early- and midcareer professionals pursuing a career in BD. Interventions required to address the identified barriers will take coordination, creativity, and resources to develop, implement, and encourage uptake but will have long-lasting benefits for research, clinical practice, and ultimately those affected by BD.

Ethnic inequality, multimorbidity and psychosis: can a syndemic framework resolve disputed evidence?

Syndemic theory is described as population-level clustering or co-occurrence of health conditions in the context of shared aetiologies that interact and can act synergistically. These influences appear to act within specific places of high disadvantage. We suggest ethnic inequality in experiences and outcomes of multimorbidity, including psychosis, may be explained through a syndemic framework. We discuss the evidence for each component of syndemic theory in relation to psychosis, using psychosis and diabetes as an exemplar. Following this, we discuss the practical and theoretical adaptations to syndemic theory in order to apply it to psychosis, ethnic inequality and multimorbidity, with implications for research, policy, and practice.

Reliability and convergent validity of retrospective reports of childhood maltreatment by individuals with bipolar disorder.

Childhood maltreatment is associated with the etiology and clinical course of bipolar disorder. Most studies employ retrospective maltreatment self-reports which are vulnerable to bias, raising questions about their validity and reliability. This study examined the test-retest reliability over 10 years, the convergent validity and the impact of current mood on retrospective reports of childhood maltreatment in a bipolar sample. 85 participants with bipolar I disorder completed the Childhood Trauma Questionnaire [CTQ] and the Parental Bonding Instrument [PBI] at baseline. Beck Depression Inventory and Self Report Mania Inventory assessed depressive and manic symptoms, respectively. 53 participants completed the CTQ at baseline and 10-year follow-up. Good levels of convergent validity were observed between the CTQ and PBI. Correlations ranged from rs= -0.35 (CTQ emotional abuse and PBI paternal care) to rs= -0.65 (CTQ emotional neglect and PBI maternal care). Good agreement between CTQ reports at baseline and 10-year follow-up were found (range: κ=0.41 for physical neglect to κ=0.83 for sexual abuse). Higher depression and mania scores were recorded among participants who reported abuse (but not neglect) compared to those without such reports. These findings support using this method in research and clinical practice, though current mood should be taken into account.

The association between childhood bullying victimisation and childhood maltreatment with the clinical expression of bipolar disorder.

Adverse childhood experiences are significantly associated with a worse clinical expression of bipolar disorder, however, the literature has mainly focused on childhood maltreatment (abuse and neglect) with little attention paid to other forms of adversity, such as childhood bullying victimisation (referred to here as bullying), although this is known to have a negative impact on different psychiatric illnesses. The current study aimed to investigate the association between bullying victimisation and the clinical expression of bipolar disorder individually and in combination with childhood maltreatment. This investigation consisted of 63 individuals with a diagnosis of bipolar disorder (mean age 61.4 years) who completed the Retrospective Bullying Questionnaire and the Childhood Trauma Questionnaire to measure exposure to bullying and childhood maltreatment, respectively. The clinical expression variables were assessed using self-report instruments, these were: the Cardiff Anomalous Perceptions Scale (psychotic symptoms), Suicide Behaviours Questionnaire, Self-Report Manic Inventory, Beck Anxiety and Depression Inventories. The results showed that exposure to bullying was significantly associated with more suicidal behaviours (F(1,61) = 11.02, p < .01, η2 = 0.15) and psychotic symptoms (F(1,61) = 4.21, p < .05, η2 = .06). When bullying and childhood maltreatment histories were combined, the results showed that individuals with a history of both adversity types reported significantly more suicidal behaviours (F(2,60) = 6.59, p < .01, R2=.18) compared to those with a history of one or neither form of adversity. The sample size, age and gender distribution, limit the generalisability of the findings. However, the current results underscore the need to account for bullying victimisation when considering the adverse childhood experiences-bipolar disorder relationship, especially its clinical expression.

The moderation effect of secure attachment on the relationship between positive events and wellbeing.

Positive events can reduce depression as well as enhance wellbeing. The role of secure attachment style in moderating the relationship between positive events and wellbeing is examined to further understand wellbeing models. Participants (n = 490) included two midlife groups and a student group from the UK. They completed the online Computerized Life Event Assessment Record (CLEAR), a measure of life events, the Vulnerable Attachment Style Questionnaire (VASQ), and the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS). Age was associated with higher rates of wellbeing and secure attachment style. A significant relationship was found between number of positive events and wellbeing, number of people close, and secure attachment score. Hierarchical multiple regression indicated a significant interaction between secure attachment style, number of positive life events, and wellbeing. Simple slopes analysis demonstrated the association between positive life events and wellbeing was significant for secure attachment (B = 1.27, p = .003) but not insecure attachment (B = 0.04, non-significant). This suggests securely attached individuals are better able to take advantage of positive life events than insecurely attached individuals and experience a greater increase in wellbeing.

Association of Etiological Factors for Hypomanic Symptoms, Bipolar Disorder, and Other Severe Mental Illnesses.

Importance: Subsyndromal hypomanic symptoms are relatively common in the general population and are linked to the onset of bipolar disorder. Little is known about their etiology and whether this is shared with the etiology of bipolar disorder or other mental illnesses. Objective: To examine the genetic and environmental architecture of hypomanic symptoms in a nonclinical youth sample and compare estimates at varying severity levels and their association with diagnosed bipolar disorder. Design, Setting, and Participants: This cohort study used phenotypic and genetic data from the Child and Adolescent Twin Study in Sweden and included individuals with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis of psychiatric disorders from national registries for residents of Sweden. Associations between hypomania and polygenic risk scores for bipolar disorder, major depressive disorder and schizophrenia were also investigated. Analysis began November 2018 and ended October 2021. Main Outcomes and Measures: Hypomanic symptoms were assessed using the parent-rated Mood Disorders Questionnaire when the twins were aged 18 years. Bipolar disorder diagnosis and/or lithium prescription were ascertained from national registries for residents of Sweden. Polygenic risk scores for psychiatric disorders were calculated using independent discovery genetic data. Results: A total of 8568 twin pairs aged 18 years (9381 [54.7%] female) were included in the study. The hypomania heritability estimate was 59% (95% CI, 52%-64%) for male individuals and 29% (95% CI, 16%-44%) for female individuals. Unique environmental factors accounted for 41% (95% CI, 36%-47%) of the hypomania variance in male individuals and 45% (95% CI, 40%-50%) in female individuals. Shared environmental factors were only detected for female individuals and explained 26% (95% CI, 13%-38%) of the variance. The heritability estimates were fairly consistent across different hypomania severity groups. Moderate genetic (0.40; 95% CI, 0.21-0.58) and shared environmental (0.41; 95% CI, 0.03-0.75) correlations between hypomania and diagnosed bipolar disorder were found. Hypomania was significantly associated with the polygenic risk scores for schizophrenia (ß = 0.08; SE = 0.026; P = .002) and major depressive disorder (ß = 0.09; SE = 0.027; P = .001) but not bipolar disorder (ß = 0.017; SE = 0.03; P = 0.57) (bipolar disorder I [ß = 0.014; SE = 0.029; P = .64] or bipolar disorder II [ß = 0.045; SE = 0.027; P = .10]). Conclusions and Relevance: Higher heritability for hypomania was found for male compared with female individuals. The results highlight the shared etiologies between hypomanic symptoms, bipolar disorder, major depression, and schizophrenia in youths. Future research should focus on identifying specific shared genetic and environmental factors. These findings support a possible dimensional model of bipolar disorder, with hypomania representing a continuous trait underlying the disorder.

Life events, depression and supportive relationships affect academic achievement in university students.

BackgroundStudents often simultaneously deal with shifting support networks, stressful life changes and psychological distress which may affect academic achievement. Methods: 285 students completed the General Health Questionnaire (GHQ-12) to assess depression and the Computerized Life Events Assessment Record (CLEAR), to establish life events and supportive relationships. Module grades were used to measure academic achievement. A general linear model was used with student grade as the dependent variable and life events, depression and supportive relationships as independent variables. Confounding variables included age and sex. Results: A three-way interaction between life events, depression and lack of supportive relationships was found. It indicated the performance of depressed students depended on whether they had supportive relationships and that this interaction also depended on whether they had experienced a life event in the past year. Conclusions: Universities need to provide more support to students with life stress as they transition into university life.

Early neurophysiological stimulus processing during a performance-monitoring task differentiates women with bipolar disorder from women with ADHD.

Adults with attention-deficit/hyperactivity disorder (ADHD) or bipolar disorder (BD) may display similar cognitive impairments and clinical symptoms, which might reflect shared mechanisms. Initial evidence indicates disorder-specific and overlapping neurophysiological alterations using event-related potentials (ERPs) in individuals with BD or ADHD during attentional tasks, but it is unknown whether impairments generalize across other processes and tasks. We conduct the first comparison between women with ADHD (n = 20), women with BD (n = 20) and control women (n = 20) on ERPs from a performance-monitoring flanker task. The BD group showed a significantly attenuated frontal ERP of conflict monitoring (N2) compared to the ADHD group across both low-conflict (congruent) and high-conflict (incongruent) task conditions, and compared to controls in the high-conflict condition. However, when controlling for an earlier attentional ERP (frontal N1), which was significantly reduced in participants with BD compared to participants with ADHD and controls, N2 group differences were no longer significant. These results indicate that ERP differences in conflict monitoring may be attributable to differences in earlier attentional processes. These findings identify neural differences in early attention between BD and ADHD which precede conflict monitoring processes, potentially pointing to distinct neural mechanisms implicated in the two disorders.

Examining the association between childhood autistic traits and adolescent hypomania: a longitudinal twin study.

BACKGROUND: There is evidence that autism spectrum disorders (ASDs) co-occur with bipolar disorder (BD) relatively frequently. Individuals with BD often report symptoms of mania and hypomania during adolescence, prior to the age of onset for BD. It is unknown whether these symptoms are associated with ASDs. We examined whether diagnoses of ASDs and autistic traits were associated with hypomania in a large, population-based Swedish twin sample. METHODS: Parental structured interviews assessed autistic traits, and were used to assign screening diagnoses of ASDs, when twins were aged 9 or 12 (N = 13 533 pairs). Parents then completed questionnaires assessing hypomania when the twins were aged 15 and 18 (N = 3852 pairs at age 15, and 3013 pairs at age 18). After investigating the phenotypic associations between these measures, we used the classical twin design to test whether genetic and environmental influences on autistic traits influence variation in adolescent hypomania. RESULTS: Autistic traits and ASD diagnoses in childhood were associated with elevated scores on the measures of adolescent hypomania. Twin analyses indicated that 6-9% of the variance in hypomania was explained by genetic influences that were shared with autistic traits in childhood. When repeating these analyses for specific autistic trait domains, we found a stronger association between social interaction difficulties and hypomania than for other autistic trait domains. CONCLUSIONS: These results indicate a genetic link between autistic traits and hypomania in adolescence. This adds to the growing evidence base of genetic factors associated with ASDs showing links with psychiatric outcomes across childhood and into adulthood.

Genome-wide association study of suicidal behaviour severity in mood disorders.

OBJECTIVE: Suicide is a major public health problem and it has a prominent genetic component. We performed a genome-wide association study (GWAS) of suicidal behaviour severity. METHODS: Suicide behaviour severity was assessed within the Schedules for Clinical Assessment in Neuropsychiatry in our mood disorder sample (n = 3506) for the GWAS. We also performed polygenic risk score analyses to explore genetic sharing between suicidal behaviour severity and a number of phenotypes, including bipolar disorder, major depressive disorder, alcoholism, post-traumatic stress disorder, impulsivity, insomnia, educational attainment, loneliness, maltreatment, and amygdala volume. RESULTS: We did not detect genome-wide significant findings at the single-marker or gene level. We report a number of suggestive single-marker and gene-based findings. Our polygenic risk score analyses did not yield significant findings with these phenotypes. CONCLUSIONS: Larger sample sizes are required to detect moderate effects.