Understanding priorities and needs for child and adolescent mental health in Greece from multiple informants: an open resource dataset.

The Child and Adolescent Mental Health Initiative (CAMHI) aims to enhance mental health care capacity for children and adolescents across Greece. Considering the need for evidence-based policy, the program developed an open-resource dataset for researching the field within the country. A comprehensive, mixed-method, community-based research was conducted in 2022/2023 assessing the current state, needs, barriers, and opportunities according to multiple viewpoints. We surveyed geographically distributed samples of 1,756 caregivers, 1,201 children/adolescents, 404 schoolteachers, and 475 health professionals using validated instruments to assess mental health symptoms, mental health needs, literacy and stigma, service use and access, professional practices, training background, and training needs and preferences. Fourteen focus groups were conducted with informants from diverse populations (including underrepresented minorities) to reach an in-depth understanding of those topics. A dataset with quantitative and qualitative findings is now available for researchers, policymakers, and society [ https://osf.io/crz6h/ and https://rpubs.com/camhi/sdashboard ]. This resource offers valuable data for assessing the needs and priorities for child and adolescent mental health care in Greece. It is now freely available to consult, and is expected to inform upcoming research and evidence-based professional training. This initiative may inspire similar ones in other countries, informing methodological strategies for researching mental health needs.

Association Between Electronic Diary-Rated Sleep, Mood, Energy, and Stress With Incident Headache in a Community-Based Sample.

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the diurnal links between average and changes in average levels of prospectively rated mood, sleep, energy, and stress as predictors of incident headache in a community-based sample. METHODS: This observational study included structured clinical diagnostic assessment of both headache syndromes and mental disorders and electronic diaries that were administered 4 times per day for 2 weeks yielding a total of 4,974 assessments. The chief outcomes were incident morning (am) and later-day (pm) headaches. Generalized linear mixed-effects models were used to evaluate the average and lagged values of predictors including subjectively rated mood, anxiety, energy, stress, and sleep quality and objectively measured sleep duration and efficiency on incident am and pm headaches. RESULTS: The sample included 477 participants (61% female), aged 7 through 84 years. After adjusting for demographic and clinical covariates and emotional states, incident am headache was associated with lower average (ß = -0.206*; confidence intervals: -0.397 to -0.017) and a decrease in average sleep quality on the prior day (ß = -0.172*; confidence interval: -0.305, -0.039). Average stress and changes in subjective energy levels on the prior day were associated with incident headaches but with different valence for am (decrease) (ß = -0.145* confidence interval: -0.286, -0.005) and pm (increase) (ß = 0.157*; confidence interval: 0.032, 0.281) headache. Mood and anxiety disorders were not significantly associated with incident headache after controlling for history of a diagnosis of migraine. DISCUSSION: Both persistent and acute changes in arousal states manifest by subjective sleep quality and energy are salient precursors of incident headaches. Whereas poorer sleep quality and decreased energy on the prior day were associated with incident morning headache, an increase in energy and greater average stress were associated with headache onsets later in the day. Different patterns of predictors of morning and later-day incident headache highlight the role of circadian rhythms in the manifestations of headache. These findings may provide insight into the pathophysiologic processes underlying migraine and inform clinical intervention and prevention. Tracking these systems in real time with mobile technology provides a valuable ancillary tool to traditional clinical assessments.

Subtypes of major depressive disorders and objectively measured physical activity and sedentary behaviors in the community.

BACKGROUND: Lack of physical activity (PA) and high sedentary behavior (SB) may enhance mental health problems, including depression, and are associated with increased mortality. Aside from a large body of research on major depressive disorder (MDD) assessed as an entity and either PA or SB, few studies have examined associations among subtypes of MDD and both PA and SB simultaneously derived from wrist-worn accelerometers. Accordingly, our aim was to explore the associations among MDD subtypes (atypical, melancholic, combined atypical-melancholic and unspecified) and four actigraphy-derived behaviors combining the levels of PA and SB. METHODS: The sample stemmed from CoLaus|PsyCoLaus, a population-based cohort study, consisting of 2375 participants (55.1% women; mean age: 62.4 years) who wore an accelorometer for 14 days after a physical exam and subsequently completed a semi-structured psychiatric interview. Activity behaviors were defined according to the combination of the levels of moderate-to-vigorous intensity PA and SB. Associations of remitted MDD subtypes, current MDD and physical inactivity behaviors were assessed using multinomial logistic regression, adjusted for socio-demographic characteristics, a history of anxiety, alcohol and drug use disorders and cardiovascular risk factors. RESULTS: In the fully adjusted model, participants with the remitted combined atypical-melancholic subtype had a higher risk of being more physically inactive. CONCLUSIONS: Our findings suggest that low PA and high SB are not restricted to the duration of depressive episodes in people with atypical and melancholic episodes. The lack of PA and high SB in this group of depressive patients exposes them to an additional long-term cardiovascular risk and measures to increase PA may be particularly fruitful in this MDD subgroup.

Similarity-based multimodal regression.

To better understand complex human phenotypes, large-scale studies have increasingly collected multiple data modalities across domains such as imaging, mobile health, and physical activity. The properties of each data type often differ substantially and require either separate analyses or extensive processing to obtain comparable features for a combined analysis. Multimodal data fusion enables certain analyses on matrix-valued and vector-valued data, but it generally cannot integrate modalities of different dimensions and data structures. For a single data modality, multivariate distance matrix regression provides a distance-based framework for regression accommodating a wide range of data types. However, no distance-based method exists to handle multiple complementary types of data. We propose a novel distance-based regression model, which we refer to as Similarity-based Multimodal Regression (SiMMR), that enables simultaneous regression of multiple modalities through their distance profiles. We demonstrate through simulation, imaging studies, and longitudinal mobile health analyses that our proposed method can detect associations between clinical variables and multimodal data of differing properties and dimensionalities, even with modest sample sizes. We perform experiments to evaluate several different test statistics and provide recommendations for applying our method across a broad range of scenarios.

Inequalities in the Incidence of Psychotic Disorders Among Racial and Ethnic Groups.

OBJECTIVE: The authors examined recent trends in incidence of psychotic disorders, demographic characteristics, and comorbid psychiatric and medical conditions among six racial/ethnic groups. METHOD: A retrospective cohort study design was used to examine the incidence of psychotic disorders across race/ethnicity groups and comorbid psychiatric and medical conditions among members of Kaiser Permanente Northern California from 2009 to 2019 (N=5,994,758). Poisson regression was used to assess changes in annual incidence, and Cox proportional hazards and logistic regression models adjusted for age and sex were used to test correlates and consequences. RESULTS: Overall, the incidence of nonaffective psychotic disorders decreased slightly over the study period. Compared with White members, the risk of nonaffective psychosis diagnosis was higher among Black (hazard ratio=2.13, 95% CI=2.02-2.24) and American Indian or Alaskan Native (AIAN) (hazard ratio=1.85, 95% CI=1.53-2.23) members and lower among Asian (hazard ratio=0.72, 95% CI=0.68-0.76) and Hispanic (hazard ratio=0.91, 95% CI=0.87-0.96) members, as well as those whose race/ethnicity was categorized as "other" (hazard ratio=0.92, 95% CI=0.86-0.99). Compared with White members, the risk of affective psychosis diagnosis adjusted for age and sex was higher among Black (hazard ratio=1.76, 95% CI=1.62-1.91), Hispanic (hazard ratio=1.09, 95% CI=1.02-1.16), and AIAN (hazard ratio=1.38, 95% CI=1.00-1.90) members and lower among Asian (hazard ratio=0.77, 95% CI=0.71-0.83), Native Hawaiian or other Pacific Islander (hazard ratio=0.69, 95% CI=0.48-0.99), and "other" (hazard ratio=0.86, 95% CI=0.77-0.96) members. Psychotic disorders were associated with significantly higher odds of suicide (odds ratio=2.65, 95% CI=2.15-3.28), premature death (odds ratio=1.30, 95% CI=1.22-1.39), and stroke (odds ratio=1.64, 95% CI=1.55-1.72) and lower odds of health care utilization (odds ratio=0.44, 95% CI=0.42-0.47). CONCLUSIONS: This study demonstrates racial and ethnic variation in incident psychotic disorder diagnoses in the United States, compared with non-Hispanic Whites. Individuals diagnosed with psychosis face a greater burden of other negative health outcomes and lower odds of health care utilization, reflecting personal and economic impacts. Identifying risk factors for elevated rates and protective influences in subgroups can inform strategies for prevention and interventions to ameliorate severe consequences of psychotic syndromes.

Specificity of affective dynamics of bipolar and major depressive disorder.

OBJECTIVE: Here, we examine whether the dynamics of the four dimensions of the circumplex model of affect assessed by ecological momentary assessment (EMA) differ among those with bipolar disorder (BD) and major depressive disorder (MDD). METHODS: Participants aged 11-85 years (n = 362) reported momentary sad, anxious, active, and energetic dimensional states four times per day for 2 weeks. Individuals with lifetime mood disorder subtypes of bipolar-I, bipolar-II, and MDD derived from a semistructured clinical interview were compared to each other and to controls without a lifetime history of psychiatric disorders. Random effects from individual means, inertias, innovation (residual) variances, and cross-lags across the four affective dimensions simultaneously were derived from multivariate dynamic structural equation models. RESULTS: All mood disorder subtypes were associated with higher levels of sad and anxious mood and lower energy than controls. Those with bipolar-I had lower average activation, and lower energy that was independent of activation, compared to MDD or controls. However, increases in activation were more likely to perpetuate in those with bipolar-I. Bipolar-II was characterized by higher lability of sad and anxious mood compared to bipolar-I and controls but not MDD. Compared to BD and controls, those with MDD exhibited cross-augmentation of sadness and anxiety, and sadness blunted energy. CONCLUSION: Bipolar-I is more strongly characterized by activation and energy than sad and anxious mood. This distinction has potential implications for both specificity of intervention targets and differential pathways underlying these dynamic affective systems. Confirmation of the longer term stability and generalizability of these findings in future studies is necessary.

Objectively assessed sleep and physical activity in depression subtypes and its mediating role in their association with cardiovascular risk factors.

The aims of this study were to investigate the associations of major depressive disorder (MDD) and its subtypes (atypical, melancholic, combined, unspecified) with actigraphy-derived measures of sleep, physical activity and circadian rhythms; and test the potentially mediating role of sleep, physical activity and circadian rhythms in the well-established associations of the atypical MDD subtype with Body Mass Index (BMI) and the metabolic syndrome (MeS). The sample consisted of 2317 participants recruited from an urban area, who underwent comprehensive somatic and psychiatric evaluations. MDD and its subtypes were assessed via semi-structured diagnostic interviews. Sleep, physical activity and circadian rhythms were measured using actigraphy. MDD and its subtypes were associated with several actigraphy-derived variables, including later sleep midpoint, low physical activity, low inter-daily stability and larger intra-individual variability of sleep duration and relative amplitude. Sleep midpoint and physical activity fulfilled criteria for partial mediation of the association between atypical MDD and BMI, and physical activity also for partial mediation of the association between atypical MDD and MeS. Our findings confirm associations of MDD and its atypical subtype with sleep and physical activity, which are likely to partially mediate the associations of atypical MDD with BMI and MeS, although most of these associations are not explained by sleep and activity variables. This highlights the need to consider atypical MDD, sleep and sedentary behavior as cardiovascular risk factors.

The science of child and adolescent mental health in Greece: a nationwide systematic review.

Evidence-based information is essential for effective mental health care, yet the extent and accessibility of the scientific literature are critical barriers for professionals and policymakers. To map the necessities and make validated resources accessible, we undertook a systematic review of scientific evidence on child and adolescent mental health in Greece encompassing three research topics: prevalence estimates, assessment instruments, and interventions. We searched Pubmed, Web of Science, PsycINFO, Google Scholar, and IATPOTEK from inception to December 16th, 2021. We included studies assessing the prevalence of conditions, reporting data on assessment tools, and experimental interventions. For each area, manuals informed data extraction and the methodological quality were ascertained using validated tools. This review was registered in protocols.io [68583]. We included 104 studies reporting 533 prevalence estimates, 223 studies informing data on 261 assessment instruments, and 34 intervention studies. We report the prevalence of conditions according to regions within the country. A repository of locally validated instruments and their psychometrics was compiled. An overview of interventions provided data on their effectiveness. The outcomes are made available in an interactive resource online [ https://rpubs.com/camhi/sysrev_table ]. Scientific evidence on child and adolescent mental health in Greece has now been cataloged and appraised. This timely and accessible compendium of up-to-date evidence offers valuable resources for clinical practice and policymaking in Greece and may encourage similar assessments in other countries.

Does circadian dysrhythmia drive the switch into high- or low-activation states in bipolar I disorder?

OBJECTIVES: Emerging evidence suggests a role of circadian dysrhythmia in the switch between "activation" states (i.e., objective motor activity and subjective energy) in bipolar I disorder. METHODS: We examined the evidence with respect to four relevant questions: (1) Are natural or environmental exposures that can disrupt circadian rhythms also related to the switch into high-/low-activation states? (2) Are circadian dysrhythmias (e.g., altered rest/activity rhythms) associated with the switch into activation states in bipolar disorder? (3) Do interventions that affect the circadian system also affect activation states? (4) Are associations between circadian dysrhythmias and activation states influenced by other "third" factors? RESULTS: Factors that naturally or experimentally alter circadian rhythms (e.g., light exposure) have been shown to relate to activation states; however future studies need to measure circadian rhythms contemporaneously with these natural/experimental factors. Actigraphic measures of circadian dysrhythmias are associated prospectively with the switch into high- or low-activation states, and more studies are needed to establish the most relevant prognostic actigraphy metrics in bipolar disorder. Interventions that can affect the circadian system (e.g., light therapy, lithium) can also reduce the switch into high-/low-activation states. Whether circadian rhythms mediate these clinical effects is an unknown but valuable question. The influence of age, sex, and other confounders on these associations needs to be better characterised. CONCLUSION: Based on the reviewed evidence, our view is that circadian dysrhythmia is a plausible driver of transitions into high- and low-activation states and deserves prioritisation in research in bipolar disorders.

Association between COVID-19 risk-mitigation behaviors and specific mental disorders in youth.

BACKGROUND: Although studies of adults show that pre-existing mental disorders increase risk for COVID-19 infection and severity, there is limited information about this association among youth. Mental disorders in general as well as specific types of disorders may influence the ability to comply with risk-mitigation strategies to reduce COVID-19 infection and transmission. METHODS: Youth compliance (rated as "Never," "Sometimes," "Often," or "Very often/Always") with risk mitigation was reported by parents on the CoRonavIruS Health Impact Survey (CRISIS) in January 2021. The sample comprised 314 female and 514 male participants from the large-scale Child Mind Institute Healthy Brain Network, a transdiagnostic self-referred, community sample of children and adolescents (ages 5-21). Responses were summarized using factor analysis of risk mitigation, and their associations with lifetime mental disorders (assessed via structured diagnostic interviews) were identified with linear regression analyses (adjusted for covariates). All analyses used R Project for Statistical Computing for Mac (v.4.0.5). RESULTS: A two-factor model was the best-fitting solution. Factor 1 (avoidance behaviors) included avoiding groups, indoor settings, and other peoples' homes; avoidance scores were higher among youth with any anxiety disorder (p = .01). Factor 2 (hygiene behaviors) included using hand sanitizer, washing hands, and maintaining social distance; hygiene scores were lower among youth with ADHD (combined type) (p = .02). Mask wearing was common (90%), did not load on either factor, and was not associated with any mental health disorder. CONCLUSION AND RELEVANCE: Although most mental disorders examined were not associated with risk mitigation, youth with ADHD characterized by hyperactivity plus inattention may need additional support to consistently engage in risk-mitigation behaviors. Enhancing risk-mitigation strategies among at-risk groups of youth may help reduce COVID-19 infection and transmission.

Assessing the Validity of the Ask Suicide-Screening Questions in Black Youth.

BACKGROUND: Given the increasing rates of suicide and nonfatal suicide attempts among Black youth in the United States, it is crucial that screening tools are valid in identifying Black youth at risk of suicide. OBJECTIVE: This study assessed the validity of the Ask Suicide-Screening Questions (ASQ) among Black youth. METHODS: This analysis used pooled data from 3 ASQ validation studies of pediatric medical patients aged 10-21 years. All participants completed the ASQ and the gold standard Suicidal Ideation Questionnaire. RESULTS: Of the 1083 participants, 330 (30.5%) were non-Hispanic Black and 753 (69.5%) were non-Hispanic White. ASQ psychometric properties for Black and White participants were equivalent (sensitivity = 94% vs. 90.9%; specificity = 91.4% vs. 91.8%, respectively). CONCLUSIONS: There were no significant differences in ASQ psychometric properties between Black and White youth, indicating that the ASQ is valid for screening Black youth at risk of suicide.

Within-day bidirectional associations between physical activity and affect: A real-time ambulatory study in persons with and without depressive and anxiety disorders.

BACKGROUND: Ambulatory assessments offer opportunities to study physical activity level (PAL) and affect at the group and person-level. We examined bidirectional associations between PAL and affect in a 3-h timeframe and evaluated whether associations differ between people with and without current or remitted depression/anxiety. METHODS: Two-week ecological momentary assessment (EMA) and actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) Composite International Diagnostic Interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Positive affect (PA) and negative affect (NA) were assessed by EMA 5 times per day. Average PAL between EMA assessments were calculated from actigraphy data. RESULTS: At the group-level, higher PAL was associated with subsequent higher PA (b = 0.109, p < .001) and lower NA (b = -0.043, p < .001), while higher PA (b = 0.066, p < .001) and lower NA (b = -0.053, p < .001) were associated with subsequent higher PAL. The association between higher PAL and subsequent lower NA was stronger for current depression/anxiety patients than controls (p = .01). At the person-level, analyses revealed heterogeneity in bidirectional associations. CONCLUSIONS: Higher PAL may improve affect, especially among depression/anxiety patients. As the relationships vary at the person-level, ambulatory assessments may help identify who would benefit from behavioral interventions.

Association between COVID-19 Risk-Mitigation Behaviors and Specific Mental Disorders in Youth.

Background : Although studies of adults show that pre-existing mental disorders increase risk for COVID-19 infection and severity, there is limited information about this association among youth. Mental disorders in general as well as specific types of disorders may influence their ability to comply with risk-mitigation strategies to reduce COVID-19 infection and transmission. Methods : Youth compliance (rated as "Never," "Sometimes," "Often," or "Very often/Always") with risk mitigation was reported by parents on the CoRonavIruS Health Impact Survey (CRISIS) in January 2021. Responses were summarized using factor analysis of risk mitigation, and their associations with lifetime mental disorders (assessed via structured diagnostic interviews) were identified with linear regression analyses (adjusted for covariates). All analyses used R Project for Statistical Computing for Mac (v.4.0.5). Results : A two-factor model was the best-fitting solution. Factor 1 (avoidance behaviors) included avoiding groups, indoor settings, and other peoples' homes; avoidance was more likely among youth with any anxiety disorder (p=.01). Factor 2 (hygiene behaviors) included using hand sanitizer, washing hands, and maintaining social distance; practicing hygiene was less likely among youth with ADHD (combined type) (p=.02). Mask wearing, which did not load on either factor, was not associated with any mental health disorder. Conclusion and Relevance : Findings suggest that education and monitoring of risk-mitigation strategies in certain subgroups of youth may reduce risk of exposure to COVID-19 and other contagious diseases. Additionally, they highlight the need for greater attention to vaccine prioritization for individuals with ADHD.

Comorbidity and Coaggregation of Major Depressive Disorder and Bipolar Disorder and Cannabis Use Disorder in a Controlled Family Study.

Importance: Cannabis use disorder (CUD) is increasing in the US. Clarification of the potential mechanisms underlying the comorbidity between mood disorders and CUD may help prevent CUD. Objective: To examine co-occurrence and familial aggregation of CUD and mood disorder subtypes. Design, Setting, and Participants: In this cross-sectional, community-based study in the Washington, DC, metropolitan area, semistructured diagnostic interviews and family history reports assessed lifetime DSM-IV disorders in probands and relatives. Familial aggregation and coaggregation of CUD with mood disorders were estimated via mixed-effects models, adjusting for age, sex, recruitment source, and comorbid mood, anxiety, and other substance use disorders. A total of 586 adult probands (186 with bipolar disorder; 55 with CUD) and 698 first-degree relatives (91 with bipolar disorder; 68 with CUD) were recruited from a community screening of the greater Washington, DC, metropolitan area from May 2004 to August 2020. Inclusion criteria were ability to speak English, and availability and consent to contact at least 2 living first-degree relatives. Main Outcomes and Measures: Lifetime CUD in first-degree relatives. Results: Of 586 probands, 395 (67.4%) were female; among 698 relatives, 437 (62.6%) were female. The mean (SD) age was 47.5 (15.2) years for probands and 49.6 (18.0) years for relatives. In the proband group, 82 participants (14.0%) self-identified as African American or Black, 467 (79.7%) as White, and 37 (6.3%) as American Indian or Alaska Native, Asian, more than one race, or another race or ethnicity or declined to respond. In the relative group, 53 participants (7.6%) self-identified as African American or Black, 594 (85.1%) as White, and 51 (7.3%) as American Indian or Alaska Native, Asian, more than one race, or another race or ethnicity or declined to respond. These groups were combined to protect privacy owing to small numbers. CUD in probands (55 [9.4%]) was associated with an increase in CUD in relatives (adjusted odds ratio [aOR], 2.64; 95% CI, 1.20-5.79; P = .02). Bipolar disorder II (BP-II) in probands (72 [12.3%]) was also associated with increased risk of CUD in relatives (aOR, 2.57; 95% CI, 1.06-6.23; P = .04). However, bipolar disorder I (114 [19.5%]) and major depressive disorder (192 [32.8%]) in probands were not significantly associated with CUD in relatives. Among relatives, CUD was associated with BP-II (aOR, 4.50; 95% CI, 1.72-11.77; P = .002), major depressive disorder (aOR, 3.64; 95% CI, 1.78-7.45; P < .001), and mean (SD) age (42.7 [12.8] years with CUD vs 50.3 [18.3] years without CUD; aOR, 0.98; 95% CI, 0.96-1.00; P = .02). Familial coaggregation of BP-II with CUD was attenuated by the inclusion of comorbid anxiety disorders. Further, rates of CUD were highest in relatives with both a familial and individual history of BP-II (no familial or individual history of BP-II: 41 [7.2%]; familial history but no individual history of BP-II: 13 [19.1%]; individual history but no familial history of BP-II: 10 [22.2%]; familial and individual history of BP-II: 4 [28.6%]; Fisher exact test, P < .001). The onset of mood disorder subtypes preceded CUD in probands and relatives in most cases. Conclusions and Relevance: The findings confirmed a familial aggregation of CUD. The increase in risk of CUD among relatives of probands with BP-II suggests that CUD may share a common underlying diathesis with BP-II. Taken together with the temporal precedence of depression and mania with respect to CUD onset, these findings highlight a potential role for BP-II intervention as CUD prevention.

Toward a Digital Future in Bipolar Disorder Assessment: A Systematic Review of Disruptions in the Rest-Activity Cycle as Measured by Actigraphy.

Background: Disruptions in rest and activity patterns are core features of bipolar disorder (BD). However, previous methods have been limited in fully characterizing the patterns. There is still a need to capture dysfunction in daily activity as well as rest patterns in order to more holistically understand the nature of 24-h rhythms in BD. Recent developments in the standardization, processing, and analyses of wearable digital actigraphy devices are advancing longitudinal investigation of rest-activity patterns in real time. The current systematic review aimed to summarize the literature on actigraphy measures of rest-activity patterns in BD to inform the future use of this technology. Methods: A comprehensive systematic review using PRISMA guidelines was conducted through PubMed, MEDLINE, PsycINFO, and EMBASE databases, for papers published up to February 2021. Relevant articles utilizing actigraphy measures were extracted and summarized. These papers contributed to three research areas addressed, pertaining to the nature of rest-activity patterns in BD, and the effects of therapeutic interventions on these patterns. Results: Seventy articles were included. BD was associated with longer sleep onset latency and duration, particularly during depressive episodes and with predictive value for worsening of future manic symptoms. Lower overall daily activity was also associated with BD, especially during depressive episodes, while more variable activity patterns within a day were seen in mania. A small number of studies linked these disruptions with differential patterns of brain functioning and cognitive impairments, as well as more adverse outcomes including increased suicide risk. The stabilizing effect of therapeutic options, including pharmacotherapies and chronotherapies, on activity patterns was supported. Conclusion: The use of actigraphy provides valuable information about rest-activity patterns in BD. Although results suggest that variability in rhythms over time may be a specific feature of BD, definitive conclusions are limited by the small number of studies assessing longitudinal changes over days. Thus, there is an urgent need to extend this work to examine patterns of rhythmicity and regularity in BD. Actigraphy research holds great promise to identify a much-needed specific phenotypic marker for BD that will aid in the development of improved detection, treatment, and prevention options.

Comorbidity and familial aggregation of back/neck pain in the NIMH Family Study of Affective Spectrum Disorders.

OBJECTIVE: Back pain is associated with substantial Global Burden of Disease and is highly comorbid with mood and anxiety symptoms and syndromes. However, mechanisms underlying this association have not been well-elucidated. Here we apply data from the NIMH Family Study of Affective Spectrum Disorders to investigate the comorbidity, familial aggregation, and cross-aggregation of back/neck pain with mood disorder subtypes. METHODS: The sample includes 519 probands and 560 interviewed first-degree relatives. Lifetime DSM-IV Bipolar I, Bipolar II, and Major Depressive Disorder [MDD] were derived from semi-structured diagnostic interviews. Lifetime history of back or neck pain and its age of onset were self-reported retrospectively. Familial aggregation and cross-aggregation were estimated via mixed effects models in probands and interviewed first-degree relatives, while heritability and co-heritability (endophenotypic ranking value [ERV]) were estimated using full pedigrees. RESULTS: Over 45% of participants endorsed a history of back/neck pain. Back/neck pain was familial (adjusted odds ratio [aOR] 1.5, p = 0.04; h2 = 0.24, p = 0.009). Back/neck pain in probands was associated with MDD in relatives (aOR 1.5, p = 0.04; ERV = 0.17, p = 0.024), but not with bipolar disorder. Onset of back/neck pain occurred earlier in those with bipolar disorder compared to controls. CONCLUSION: Findings suggest common familial risk factors underlying back/neck pain with MDD, whereas there was within-individual comorbidity of bipolar with back/neck pain. Future studies that identify common factors that lead to either back/neck pain or MDD can inform prevention and interventions.

Environmental factors in offspring of parents with mood disorders and their role in parent-child transmission: findings from a 14-year prospective high-risk study.

BACKGROUND: The factors involved in the transmission of mood disorders are only partially elucidated. Aside from genes, the family environment might play a crucial role in parent-child transmission. Our goals were to (1) assess the associations of parental bipolar disorder (BPD) and Major Depressive Disorder (MDD) with individual or shared family environmental factors, including traumatic events in offspring, parental separation, family cohesion and parental attitudes; and 2) test whether these factors were mediators of the association between exposure to parental mood disorders and the onset of these disorders in offspring. METHODS: The sample stems from an ongoing family high-risk study of mood disorders conducted in the French-speaking part of Switzerland. Given the strong impact of the age of onset of parental disorders on their transmission to children, parental disorders were dichotomized according to the onset (cut-off 21 years). Probands with early-onset (n = 30) and later-onset BPD (n = 51), early-onset (n = 21) and later-onset MDD (n = 47) and controls (n = 65), along with their spouses (n = 193) and offspring (n = 388; < 18 years on study inclusion), were assessed over a mean follow-up duration of 14 years (s.d: 4.6). The environmental measures were based on reports by offspring collected before the onset of their first mood episode. RESULTS: Offspring of probands with later-onset BPD and offspring of probands with both early-onset and later-onset MDD reported traumatic events more frequently than comparison offspring, whereas exposure to parental separation was more frequent in all groups of high-risk offspring. Moreover, several familial environment scores including parenting attitudes differed between offspring of probands with BPD and comparison offspring. However, none of these factors were mediators of the parent-child transmission of BPD. Among the environmental factors, traumatic events were shown to be modest mediators of the transmission of early-onset MDD. CONCLUSIONS: Our data do not support the implication of the assessed environmental factors in the parent-child transmission of BPD. In contrast to BPD, traumatic events partially mediate the parent-child transmission of early-onset MDD, which has important implications for intervention and prevention. Early therapeutic efforts in offspring exposed to these events are likely to reduce their deleterious impact on the risk of subsequent MDD.

Association between COVID-19 Risk-Mitigation Behaviors and Specific Mental Disorders in Youth.

Importance: Although studies of adults show that pre-existing mental disorders increase risk for COVID-19 infection and severity, there is limited information about this association among youth. Mental disorders in general as well as specific types of disorders may influence their ability to comply with risk-mitigation strategies to reduce COVID-19 infection and transmission. Objective: To examine associations between specific mental disorders and COVID-19 risk-mitigation practices among 314 female and 514 male youth. Design: Youth compliance (rated as "Never," "Sometimes," "Often," or "Very often/Always") with risk mitigation was reported by parents on the CoRonavIruS Health Impact Survey (CRISIS) in January 2021. Responses were summarized using factor analysis of risk mitigation, and their associations with lifetime mental disorders (assessed via structured diagnostic interviews) were identified with linear regression analyses (adjusted for covariates). All analyses used R Project for Statistical Computing for Mac (v.4.0.5). Setting: The Healthy Brain Network (HBN) in New York City Participants. 314 female and 514 male youth (ages 5-21). Main Outcomes and Measures: COVID-19 risk mitigation behaviors among youth. Results: A two-factor model was the best-fitting solution. Factor 1 (avoidance behaviors) included avoiding groups, indoor settings, and other peoples' homes; avoidance was more likely among youth with any anxiety disorder (p=.01). Factor 2 (hygiene behaviors) included using hand sanitizer, washing hands, and maintaining social distance; practicing hygiene was less likely among youth with ADHD (combined type) (p=.02). Mask wearing, which did not load on either factor, was not associated with any mental health disorder. Conclusion and Relevance: Findings suggest that education and monitoring of risk-mitigation strategies in certain subgroups of youth may reduce risk of exposure to COVID-19 and other contagious diseases. Additionally, they highlight the need for greater attention to vaccine prioritization for individuals with ADHD. Key Points: Question: Are mental disorders among youth associated with COVID-19 risk-mitigation behaviors?Findings: Based on the parent CoRonavIruS Health Impact Survey (CRISIS) of 314 females and 514 males aged 5-21, youth with anxiety disorders were more likely to avoid high-risk exposure settings, and those with ADHD (combined type) were less likely to follow hygiene practices. In contrast, mask wearing was not associated with youth mental disorders.Meaning: Specific types of disorders in youth may interfere with their ability to employ risk-mitigation strategies that may lead to greater susceptibility to COVID-19.

Sleep and circadian informatics data harmonization: a workshop report from the Sleep Research Society and Sleep Research Network.

The increasing availability and complexity of sleep and circadian data are equally exciting and challenging. The field is in constant technological development, generating better high-resolution physiological and molecular data than ever before. Yet, the promise of large-scale studies leveraging millions of patients is limited by suboptimal approaches for data sharing and interoperability. As a result, integration of valuable clinical and basic resources is problematic, preventing knowledge discovery and rapid translation of findings into clinical care. To understand the current data landscape in the sleep and circadian domains, the Sleep Research Society (SRS) and the Sleep Research Network (now a task force of the SRS) organized a workshop on informatics and data harmonization, presented at the World Sleep Congress 2019, in Vancouver, Canada. Experts in translational informatics gathered with sleep research experts to discuss opportunities and challenges in defining strategies for data harmonization. The goal of this workshop was to fuel discussion and foster innovative approaches for data integration and development of informatics infrastructure supporting multi-site collaboration. Key recommendations included collecting and storing findable, accessible, interoperable, and reusable data; identifying existing international cohorts and resources supporting research in sleep and circadian biology; and defining the most relevant sleep data elements and associated metadata that could be supported by early integration initiatives. This report introduces foundational concepts with the goal of facilitating engagement between the sleep/circadian and informatics communities and is a call to action for the implementation and adoption of data harmonization strategies in this domain.

TWO-SAMPLE TESTS FOR MULTIVARIATE REPEATED MEASUREMENTS OF HISTOGRAM OBJECTS WITH APPLICATIONS TO WEARABLE DEVICE DATA.

Repeated observations have become increasingly common in biomedical research and longitudinal studies. For instance, wearable sensor devices are deployed to continuously track physiological and biological signals from each individual over multiple days. It remains of great interest to appropriately evaluate how the daily distribution of biosignals might differ across disease groups and demographics. Hence, these data could be formulated as multivariate complex object data, such as probability densities, histograms, and observations on a tree. Traditional statistical methods would often fail to apply, as they are sampled from an arbitrary non-Euclidean metric space. In this paper we propose novel, nonparametric, graph-based two-sample tests for object data with the same structure of repeated measures. We treat the repeatedly measured object data as multivariate object data, which requires the same number of repeated observations per individual but eliminates any assumptions on the errors of the repeated observations. A set of test statistics are proposed to capture various possible alternatives. We derive their asymptotic null distributions under the permutation null. These tests exhibit substantial power improvements over the existing methods while controlling the type I errors under finite samples as shown through simulation studies. The proposed tests are demonstrated to provide additional insights on the location, inter- and intra-individual variability of the daily physical activity distributions in a sample of studies for mood disorders.