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.

Risk factors for mood disorders among offspring of parents with bipolar disorder: Findings from a discordant-sibling study.

The purpose of this naturalistic, prospective study was to identify risk factors for mood disorders in offspring of parents with bipolar disorder (BPD) using the discordant-sibling design by comparing premorbid psychopathology or symptoms, temperament, personality traits and coping style as well as the perception of family-related characteristics among affected and unaffected siblings within the same family. This approach controls for confounding by unmeasured genetic and environmental factors shared within families. Our sample comprised 24 families of a parent with BPD with at least one child that developed BPD or major depressive disorder (n = 31), and at least one child who did not. Offspring were followed for a mean duration of 16.2 (s.d: 4.6) years. Information was collected from the offspring themselves. Generalized linear mixed models only revealed differences in three dimensions of the Dimension of Temperament Survey-Revised (DOTS-R) version: Offspring with mood disorders scored higher on "Approach-withdrawal", "Rhythmicity for daily habits", and "Task orientation" than their unaffected siblings. The higher scores, and not lower scores as expected, on these temperament dimensions observed in offspring that subsequently developed mood disorders may reflect increased vulnerability, but they could also mirror premorbid mood swings or strategies to cope with them.

How ambient temperature affects mood: an ecological momentary assessment study in Switzerland.

BACKGROUND: Recent research has suggested that an increase in temperature can negatively affect mental health and increase hospitalization for mental illness. It is not clear, however, what factors or mechanisms mediate this association. We aimed to (1) investigate the associations between ambient temperatures and bad daily mood, and (2) identify variables affecting the strength of these associations (modifiers) including the time, the day of the week and the year of the mood rating, socio-demographic characteristics, sleep quality, psychiatric disorders and the personality trait neuroticism in the community. METHODS: Data stemmed from the second follow-up evaluation of CoLaus|PsyCoLaus, a prospective cohort study conducted in the general population of Lausanne (Switzerland). The 906 participants rated their mood level four times a day during seven days using a cell phone app. Mixed-effects logistic regression was used to determine the association between daily maximum temperature and mood level. Participant ID was inserted as a random effect in the model, whereas the time of the day, the day of the week and the year were inserted as fixed effects. Models were controlled for several confounders (socio-demographic characteristics, sleep quality, weather parameters and air pollutants). Stratified analyses were conducted based on socio-demographic characteristics, sleep quality, presence of psychiatric disorders or a high neuroticism. RESULTS: Overall, the probability of having a bad mood for the entire day decreased by 7.0% (OR: 0.93: 95% CI 0.88, 0.99) for each 5 °C increase in maximum temperature. A smaller and less precise effect (-3%; OR: 0.97: 95% CI 0.91, 1.03) was found when controlling for sunshine duration. A higher association was found in participants with bipolar disorder (-23%; OR: 0.77: 95% CI 0.51, 1.17) and in participants with a high neuroticism (-13%; OR: 0.87 95% CI 0.80, 0.95), whereas the association was reversed for participants with anxiety (20%; OR: 1.20: 95% CI 0.90, 1.59), depression (18%; OR: 1.18 95% CI 0.94, 1.48) and schizophrenia (193%; OR: 2.93 95% CI 1.17, 7.73). CONCLUSIONS: According to our findings, rising temperatures may positively affect mood in the general population. However, individuals with certain psychiatric disorders, such as anxiety, depression, and schizophrenia, may exhibit altered responses to heat, which may explain their increased morbidity when exposed to high temperatures. This suggests that tailored public health policies are required to protect this vulnerable population.

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.

On the complex and dimensional relationship of maternal posttraumatic stress disorder during early childhood and child outcomes at school-age.

BACKGROUND: Several studies have shown associations between maternal interpersonal violence-related posttraumatic stress disorder (PTSD), child mental health problems, and impaired socioemotional development. However, the existing literature lacks evidence linking constellations of risk factors such as maternal interpersonal-violence-related PTSD, psychopathology, and interactive behavior with toddlers and outcome measures at school-age. METHODS: This study involved a prospective, longitudinal investigation of 62 mothers and examined the relationship between maternal variables measured when children were in early childhood (mean age 27 months), and child outcomes when children were school-age (age mean = 83.2 months) while retaining a focus on the context of maternal PTSD. To identify and weigh associated dimensions comparatively, we employed sparse canonical correlation analysis (sCCA) aimed at associating dimensions of a dataset of 20 maternal variables in early childhood with that of more than 20 child outcome variables (i.e., child psychopathology, life-events, and socioemotional skills) at school-age. RESULTS: Phase 1 variables with the highest weights were those of maternal psychopathology: PTSD, depressive and dissociative symptoms, and self-report of parental stress. The highest weighted Phase 2 child outcome measures were those of child psychopathology: PTSD, anxiety, and depressive symptoms as well as peer bullying and victimization. CONCLUSIONS: sCCA revealed that trauma-related concepts in mothers were significantly and reliably associated with child psychopathology and other indicators of risk for intergenerational transmission of violence and victimization. The results highlight the dimensional and multifaceted nature-both for mothers as well as children-of the intergenerational transmission of violence and associated psychopathology.

Psychotic features, particularly mood incongruence, as a hallmark of severity of bipolar I disorder.

BACKGROUND: The occurrence of psychotic features within mood episodes in patients with bipolar I disorder (BD I) has been associated in some studies with a more severe clinical and socio-professional profile. In contrast, other studies establishing the associations of psychotic features in BD I, and in particular of mood-congruent (MC) and mood-incongruent (MI) features, with clinical characteristics have yielded contradictory results. However, many pre-existing studies have been affected by serious methodological limitations. Using a sample of thoroughly assessed patients with BD I our aims were to: (1) establish the proportion of those with MI and MC features, and (2) compare BD I patients with and without psychotic features as well as those with MI to those with MC features on a wide array of socio-demographic and clinical characteristics including course, psychiatric comorbidity and treatment. METHODS: A sample of 162 treated patients with BD I (60.5% female, mean age = 41.4 (s.d: 10.2) years) was recruited within a large family study of mood disorders. Clinical, course and treatment characteristics relied on information elicited through direct diagnostic interviews, family history reports and medical records. RESULTS: (1) A total of 96 patients (59.3%) had experienced psychotic features over their lifetime. Among them, 44.8% revealed MI features at least once in their lives. (2) Patients with psychotic features were much less likely to be professionally active, revealed alcohol abuse more frequently and used health care, particularly inpatient treatment, more frequently than those without psychotic features. Within patients with psychotic symptoms, those with MI features showed more clinical severity in terms of a higher likelihood of reporting hallucinations, suicidal attempts and comorbid cannabis dependence. CONCLUSION: Our data provide additional support for both the distinction between BD-I with and without psychotic features as well as the distinction between MI and MC psychotic features. The more severe course of patients with psychotic features, and particularly those with MI psychotic features, highlights the need for thorough psychopathological evaluations to assess the presence of these symptoms to install appropriate treatment.

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.

Families With Violence Exposure and the Intergenerational Transmission of Somatization.

Introduction: Adults who have histories of childhood trauma have been noted to display greater somatization, dissociative symptoms and affect dysregulation. What happens in the parent-child relationship when those traumatized children become parents? A potential link to somatization in the child has been suggested by several prior studies. Children who have early attachment disturbances had more physical complaints if their mothers displayed less maternal sensitivity during observed parent-child interactions. Yet, the intergenerational link between maternal and child somatization has not been sufficiently explored in a longitudinal study in order to understand the potential impact of maternal trauma history and related psychopathology on subsequent child somatization and psychopathology. Methods: This paper examined prospective, longitudinal data of 64 mother-toddler dyads (mean age = 2.4 years, SD = 0.7) who were later studied when children had a mean age of 7 years. Mothers with and without histories of interpersonal violence (IPV; physical/sexual abuse and/or family violence exposure) were included. Mothers with IPV histories were oversampled. Linear and Poisson regression models were used to test the associations between maternal IPV-related post-traumatic stress disorder (PTSD) with maternal somatization severity when children were toddlers, and between maternal somatization and maternal interactive behaviors with child somatization by maternal report and clinician-rated assessment at school-age. Results: Maternal PTSD severity was significantly associated with increased maternal somatization severity (p = 0.031). Maternal somatization severity during the child's early childhood predicted both maternal report of child somatization (p = 0.011) as well as child thought problems (p = 0.007) when children were school-aged. No association was found between maternal somatization and child-reported psychopathology. The study did not find that maternal alexithymia, caregiving behaviors or child exposure to violence contributed significantly to the model examining the association between maternal and child somatization. Conclusion: The results are in line with the hypothesis of intergenerational transmission of somatization in the context of IPV and related maternal PTSD during formative early development. We interpret this as an expression of psychological distress from mother to child, as maternal trauma and pathology affect the caregiving environment and, thus, the parent-child relationship. The authors conclude with a discussion of implications for parent-infant and early childhood intervention.

Mood and anxiety profiles differentially associate with physical conditions in US adolescents.

BACKGROUND: Mood and anxiety are widely associated with physical conditions, but research and treatment are complicated by their overlap, clinical heterogeneity, and manifestation on a spectrum rather than as discrete disorders. In contrast to previous work relying on threshold-level disorders, we examined the association between empirically-derived profiles of mood and anxiety syndromes with physical conditions in a nationally-representative sample of US adolescents. METHODS: Participants were 2,911 adolescents (aged 13-18) from the National Comorbidity Survey-Adolescent Supplement who provided information on physical conditions and reported at least one lifetime mood-anxiety 'syndrome' based on direct interviews with the Composite International Diagnostic Interview Version 3.0. Mood-anxiety syndromes reflected 3-level ratings from subthreshold to severe distress/impairment, and subtyped mood episodes. Stepwise latent profile analysis identified mood-anxiety profiles and tested associations with physical conditions. RESULTS: Three mood-anxiety profiles were identified: "Mood-GAD" (25.6%)-non-atypical depression, mania, generalized anxiety; "Atypical-Panic" (11.3%)-atypical depression, panic; and "Reference" (63.1%)-lower mood and anxiety except specific phobia. Headaches were more prevalent in Mood-GAD and Atypical-Panic than Reference (47.9%, 50.1%, and 37.7%, respectively; p=0.011). Heart problems were more common in Mood-GAD than Atypical-Panic (7.4% v 2.2%, p=0.004) and Reference, with back/neck pain more prevalent in Mood-GAD than Reference (22.5% v 15.3%, p=0.016). LIMITATIONS: Broad categories of physical conditions without information on specific diagnoses; replication regarding specificity is recommended. CONCLUSIONS: Heart problems and pain-related conditions were differentially associated with specific mood-anxiety profiles. Subtyping depression and anxiety-inclusive of subthreshold syndromes-and their patterns of clustering may facilitate etiologic and intervention work in multimorbidity.

The impact of disease severity on the psychological well-being of youth affected by an inborn error of metabolism and their families: A one-year longitudinal study.

BACKGROUND: Inborn errors of metabolism (IEMs) refer to rare heterogeneous genetic disorders with various clinical manifestations that can cause serious physical and psychological sequelae. Results of previous studies on the impact of an IEM on health-related quality of life (HR-QoL) were incongruent and only few studies considered more broadly the psychological well-being of children with IEM and their families. Our objectives were to examine: (1) the impact of the IEM severity on the HR-QoL and psychological functioning of patients and their parents at baseline; and (2) its evolution over time; and (3) the correlation between parental and children's perspectives. Methods: The sample included 69 pediatric patients (mean age = 7.55 y, SD = 4.59) with evaluations at baseline and after one year. We collected data on HR-QoL, child mental health and emotional regulation as well as on parental mood and stress using different validated questionnaires. IEM severity was rated by a clinician through the biological subdomain of the pediatric INTERMED instrument. Results: Two groups of patients based on IEM severity scores were created (n = 31 with low and n = 38 with moderate/high IEM severity). The two groups differed with respect to age, diet and supplement intake. IEM severity had an impact on HR-QoL and behavioral symptoms in children, as well as on HR-QoL and stress in parents. For patients with moderate/high IEM severity, child and parental HR-QoL improved after 1-year of follow-up. We did not observe any significant difference between evaluations by patients versus parents. Conclusions: Our findings demonstrate that moderate/high IEM severity altered child and parental psychological well-being, but also revealed a significant improvement after one-year follow-up. This observation suggests that patients with a moderate/high IEM severity and their families benefit from the care of an interdisciplinary team including a child psychologist specialized in IEMs. Moreover, in patients with higher IEM severity there may also be more room for improvement compared to patients with low IEM severity. Future studies should focus on observations over a larger time span, particularly during adolescence, and should include objective measurements.

Associations Between Maternal Post-traumatic Stress Disorder and Traumatic Events With Child Psychopathology: Results From a Prospective Longitudinal Study.

Introduction: Exposure to interpersonal violence (IPV) can lead to post-traumatic stress disorder (PTSD) in mothers, and in turn adversely affect the mother-child relationship during early development, as well as the mental health of their children. Our objectives are to assess: (1) the association of maternal IPV-PTSD to child psychopathology, (2) the association of maternal IPV independently of PTSD to child psychopathology, and (3) the relationship between child exposure to violence to the psychopathology of these children. Methods: We used data from the longitudinal Geneva Early Childhood Stress Project. The sample included 64 children [mean age at Phase 1 = 2.4 (1.0-3.7) years] of mothers with or without IPV-PTSD. Data on mothers was collected during Phase 1, using the Clinical Administered PTSD Scale (CAPS), the Brief Physical and Sexual Abuse Questionnaire (BPSAQ) and the Conflict Tactics Scale (CTS2). Modules of a semi-structured diagnostic interview, and the Violence Exposure Scale were used to collect information on child at Phase 2, when children were older [mean age = 7.02 (4.7-10)]. Results: A higher CAPS score in mothers when children were toddler-age was associated with an increased risk of symptoms of attention deficit/hyperactivity disorder (ADHD; ß = 0.33, p = 0.014) and PTSD in school-age children. The association between maternal IPV-PTSD and child PTSD (ß = 0.48, p < 0.001) symptoms remained significant after adjustment for potential confounders. Among children, exposure to violence was associated with an increased risk of symptoms of generalized anxiety (ß = 0.37, p = 0.006), major depressive (ß = 0.24, p = 0.039), ADHD (ß = 0.27, p = 0.040), PTSD (ß = 0.52, p < 0.001), conduct (ß = 0.58, p = 0.003) and oppositional defiant (ß = 0.34, p = 0.032) disorders. Conclusion: Our longitudinal findings suggest that maternal IPV-PTSD during the period of child development exert an influence on the development of psychopathology in school-aged children. Mothers' IPV was associated with child psychopathology, independently of PTSD. Child lifetime exposure to violence had an additional impact on the development of psychopathology. Careful evaluation of maternal life-events is essential during early childhood to reduce the risk for the development of child psychopathology. Early efforts to curb exposure to violence in children and early intervention are both needed to reduce further risk for intergenerational transmission of trauma, violence, and related psychopathology.

Years of life lost due to the psychosocial consequences of COVID-19 mitigation strategies based on Swiss data.

BACKGROUND: The pandemic caused by coronavirus disease 2019 (COVID-19) has forced governments to implement strict social mitigation strategies to reduce the morbidity and mortality from acute infections. These strategies, however, carry a significant risk for mental health, which can lead to increased short-term and long-term mortality and is currently not included in modeling the impact of the pandemic. METHODS: We used years of life lost (YLL) as the main outcome measure, applied to Switzerland as an example. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status, and social isolation, as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans. RESULTS: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average of 9.79 YLL. CONCLUSIONS: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

Generalized Anxiety Disorder is Prospectively Associated With Decreased Levels of Interleukin-6 and Adiponectin Among Individuals from the Community.

BACKGROUND: Anxiety disorders have been related to cardiovascular diseases via low-grade inflammation, but longitudinal studies on the association between generalized anxiety disorder (GAD) and inflammatory biomarkers are sparse. Furthermore, no studies have examined the association between GAD and the "cardio-protective" adipocytokine adiponectin in this context so far. METHODS: In a Swiss population-based sample of 2,415 adults participating in baseline and follow-up exams (mean follow-up duration=5.5 years), we diagnosed a total of 55 persons (2.3%) with GAD using a validated semi-structured psychiatric interview. We prospectively examined the relation between GAD and circulating levels of inflammatory biomarkers (i.e., C-reactive protein, interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and adiponectin), in linear regression models, statistically controlled for the baseline inflammatory marker, socioeconomic status, cardiovascular risk factors, health behaviors, and psychiatric disorders. RESULTS: Compared to those without GAD, individuals with GAD had lower IL-6 (ß=-0.249, 95%-CI -0.493-(-0.004), p=0.046), and adiponectin (ß=-0.264, 95%-CI -0.482-(-0.045), p=0.018) levels at follow-up after adjustment for all covariates. Moreover, GAD was unrelated to several other inflammatory measures. CONCLUSION: Individuals with GAD do not seem to exhibit chronic low-grade inflammation, suggesting different underlying biobehavioral mechanisms to those from other anxiety disorders. Low adiponectin levels may be linked to symptoms of GAD through brain areas directly involved in the processing of fear and anxiety.

Major depression subtypes are differentially associated with migraine subtype, prevalence and severity.

OBJECTIVE: Migraine and major depressive disorder show a high rate of comorbidity, but little is known about the associations between the subtypes of major depressive disorder and migraine. In this cross-sectional study we aimed at investigating a) the lifetime associations between the atypical, melancholic, combined and unspecified subtype of major depressive disorder and migraine with and without aura and b) the associations between major depressive disorder and its subtypes and the severity of migraine. METHODS: A total of 446 subjects with migraine (migraine without aura: n = 294; migraine with aura: n = 152) and 2511 controls from the population-based CoLaus/PsyCoLaus study, Switzerland, were included. Associations between major depressive disorder subtypes and migraine characteristics were tested using binary logistic or linear regression. RESULTS: Melancholic, combined and unspecified major depressive disorder were associated with increased frequency of migraine with aura, whereas only melancholic major depressive disorder was associated with increased frequency of migraine without aura. Lifetime and unspecified major depressive disorder were associated with severe migraine intensity among subjects with migraine with aura but not migraine without aura, while combined major depressive disorder was associated with higher migraine frequency independently from migraine subtype. CONCLUSION: This study suggests that melancholic but not atypical major depressive disorder is associated with migraine and migraine subtypes. Future studies exploring pathophysiological mechanisms shared between melancholic depression and migraine are warranted.

Associations of Personality Traits With Chronic Low-Grade Inflammation in a Swiss Community Sample.

Objective: Among the major dimensions of personality, high Neuroticism and low Conscientiousness have frequently been linked to worse health-related behaviors and poor health outcomes. However, studies on the association between personality traits and biomarkers of chronic low-grade inflammation reflecting increased morbidity and mortality risk are sparse; therefore, the aim of this study was to explore this association. Methods: A population-based Swiss sample of 2,182 persons (40-82 years, 42% men) completed a comprehensive personality questionnaire (NEO Five-Factor Inventory-Revised). Circulating levels of inflammatory markers, including C-reactive protein, interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and levels of the "cardioprotective" adipo(cyto)kine adiponectin were also determined. Analyses controlled for sociodemographic factors, traditional cardiovascular risk factors and lifetime psychiatric disorders using a validated semi-structured psychiatric interview. The role of gender as a moderator of the personality-inflammation link was additionally explored. Results: Controlling for all covariates, higher Extraversion (ß = 0.092, 95%CI 0.004-0.180) was positively associated with higher IL-6 levels, and higher Conscientiousness (ß = -0.095, 95%CI -0.180-[-0.009]) were significantly associated with lower IL-6 levels (all p-values < 0.05). Neuroticism and Agreeableness showed no significant association with any inflammatory biomarker. The associations between personality traits and inflammatory markers were not moderated by gender. Conclusions: Conscientiousness seems to be inversely related to chronic low-grade inflammation as measured by IL-6 levels, compatible with protection from the cardiovascular risk. The opposite may apply to Extraversion. Further research is needed to better understand the underlying mechanisms and their impact for health outcomes in the community.

A step beyond the hygiene hypothesis-immune-mediated classes determined in a population-based study.

BACKGROUND: Comorbidity patterns of childhood infections, atopic diseases, and adverse childhood experiences (ACE) are related to immune system programming conditions. The aim of this study was to make a step beyond the hygiene hypothesis and to comprehensively classify these patterns with latent class analysis (LCA). A second aim was to characterize the classes by associations with immunological, clinical, and sociodemographic variables. METHODS: LCA was applied to data from the CoLaus|PsyCoLaus study (N = 4874, age range 35-82 years) separately for men and women. It was based on survey information on chickenpox, measles, mumps, rubella, herpes simplex, pertussis, scarlet fever, hay fever, asthma, eczema, urticaria, drug allergy, interparental violence, parental maltreatment, and trauma in early childhood. Subsequently, we examined how immune-mediated classes were reflected in leukocyte counts, inflammatory markers (IL-1ß, IL-6, TNF-α, hsCRP), chronic inflammatory diseases, and mental disorders, and how they differed across social classes and birth cohorts. RESULTS: LCA results with five classes were selected for further analysis. Latent classes were similar in both sexes and were labeled according to their associations as neutral, resilient, atopic, mixed (comprising infectious and atopic diseases), and ACE class. They came across with specific differences in biomarker levels. Mental disorders typically displayed increased lifetime prevalence rates in the atopic, the mixed, and the ACE classes, and decreased rates in the resilient class. The same patterns were apparent in chronic inflammatory diseases, except that the ACE class was relevant specifically in women but not in men. CONCLUSIONS: This is the first study to systematically determine immune-mediated classes that evolve early in life. They display characteristic associations with biomarker levels and somatic and psychiatric diseases occurring later in life. Moreover, they show different distributions across social classes and allow to better understand the mechanisms beyond the changes in the prevalence of chronic somatic and psychiatric diseases.

Association between mood disorders and BMI/overweight using a family study approach.

BACKGROUND: We previously demonstrated the specificity of familial transmission of the atypical subtype of depression, primarily characterized by overeating and oversleeping. However, the specific components of this subtype that are familial have not been established. The aim of this paper is to examine whether the familial specificity of atypical depression can be attributed to the association between Body Mass Index (BMI) and overweight/obesity with mood disorders. METHODS: The sample included 293 probands recruited from the community and their 544 adult first-degree relatives. Diagnostic assignment was based on a direct semi-structured interview. Mixed effect models were employed to test the familial aggregation and the familial cross-aggregation of mood disorders and BMI/overweight. RESULTS: There were significant within-individual associations between overweight and the atypical subtype of depression (p-value = 0.003). There was also an association for BMI/overweight between probands and relatives (ß = 0.23, p-value < 0.001; odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.02-2.43, respectively). Atypical depression in probands was significantly associated with BMI and overweight in relatives (ß = 0.001, p-value = 0.040; OR = 2.79, 95%CI = 1.20-6.49, respectively). LIMITATIONS: The cross-sectional design impedes our ability to evaluate the direction of these associations. Other potential risk factors, such as diabetes, physical activity and unhealthy diet were not considered. CONCLUSIONS: These findings imply that overweight may be either a precursor or consequence of atypical depression rather than a manifestation of a common diathesis underlying depression in families. Clinicians should pay particular attention to this subtype that could be at increased risk for the development of cardiovascular risk factors and diseases.

Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community.

OBJECTIVE: The complex relationship between psychosocial stress over the lifetime, psychological factors, and cardiometabolic risk is still poorly understood. Accordingly, our aims were (1) to independently assess the associations between childhood adversity, life-event stress in remote (earlier than the last 5 years), and recent adulthood and cardiometabolic risk, and (2) to determine the role of psychological factors including personality, coping, and depression in these associations. METHODS: The sample included 2674 adults, aged 35 to 66 years, randomly selected from urban area. Participants underwent a physical examination including the assessment of obesity markers, blood pressure, and blood lipid and glucose levels. Stress during adulthood was determined using the severity scores of 52 stressful life events. Information on adverse childhood experiences and major depressive disorders was collected using semistructured interviews, whereas personality traits and coping mechanisms were evaluated through questionnaires. RESULTS: Both childhood adversity and stress in remote adulthood were associated with elevated body mass index (ß [95% confidence interval {CI}] = 0.249 [0.029 to 0.468]; 0.020 [0.006 to 0.034]), waist circumference (ß [95% CI] = 0.061 [0.024 to 0.099]; 0.08 [0.04 to 0.11]), and the global cardiometabolic risk score (ß [95% CI] = 0.278 [0.017 to 0.540]; 0.017 [0.001 to 0.033]) after adjustment for sociodemographic, lifestyle, and psychological factors. In addition, childhood adversity was associated with low high density lipoprotein levels (ß [95% CI] = -0.021 [-0.042 to 0.000]), as well as increased fat mass and systolic blood pressure levels (ß [95% CI] = 0.506 [0.165 to 0.846]; 0.952 [0.165 to 1.740]) and stress in remote adulthood with apolipoprotein B levels (ß [95% CI] = 0.607 [0.312 to 0.901]). Psychological factors did not account for these associations and were not effect modifiers. CONCLUSIONS: Our data demonstrate that psychosocial stress during childhood and remote adulthood favor adiposity and abnormal lipid metabolism.

Factorial structure and familial aggregation of the Hypomania Checklist-32 (HCL-32): Results of the NIMH Family Study of Affective Spectrum Disorders.

BACKGROUND: There is substantial evidence that bipolar disorder (BD) manifests on a spectrum rather than as a categorical condition. Detection of people with subthreshold manifestations of BD is therefore important. The Hypomania Checklist-32 (HCL-32) was developed as a tool to identify such people. PURPOSE: The aims of this paper were to: (1) investigate the factor structure of HCL-32; (2) determine whether the HCL-32 can discriminate between mood disorder subtypes; and (3) assess the familial aggregation and cross-aggregation of hypomanic symptoms assessed on the HCL with BD. PROCEDURES: Ninety-six probands recruited from the community and 154 of their adult first-degree relatives completed the HCL-32. Diagnosis was based on semi-structured interviews and family history reports. Explanatory factor analysis and mixed effects linear regression models were used. FINDINGS: A four-factor ("Activity/Increased energy," "Distractibility/Irritability", "Novelty seeking/Disinhibition, "Substance use") solution fit the HCL-32, explaining 11.1% of the total variance. The Distractibility/Irritability score was elevated among those with BP-I and BP-II, compared to those with depression and no mood disorders. Higher HCL-32 scores were associated with increased risk of BD-I (OR = 1.22, 95%CI 1.14-1.30). The "Distractibility/Irritability" score was transmitted within families (ß = 0.15, p = 0.040). However, there was no familial cross-aggregation between mood disorders and the 4 HCL factors. CONCLUSIONS: Our findings suggest that the HCL-32 discriminates the mood disorder subtypes, is familial and may provide a dimensional index of propensity to BD. Future studies should explore the heritability of symptoms, rather than focusing on diagnoses.

The bidirectional relationship between anxiety disorders and circulating levels of inflammatory markers: Results from a large longitudinal population-based study.

BACKGROUND: Although there has been abundant research on chronic low-grade inflammation as a potential mechanism underlying the link between mood disorders and cardiovascular risk, less is known about the role of inflammatory factors and anxiety disorders. The aim of this paper is to evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP) with anxiety disorders and its subgroups. METHODS: The sample consisted of 3,113 participants (53.7% women; mean age: 51.0, S.D. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, S.D. 0.6). Anxiety disorders were assessed with semistructured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. RESULTS: After adjustment for potential confounders, current anxiety disorders (ß = 0.09, 95% CI 0.00-0.17) and agoraphobia (ß = 0.25, 95% CI: 0.07-0.43) at baseline were associated with a steeper increase of hsCRP levels over the follow-up period. Current posttraumatic stress disorder (PTSD) was associated with a lower increase of IL-6 levels over the follow-up period (ß = -0.52, 95% CI: -1.00/-0.04). There was no evidence for an association between inflammation markers at baseline and anxiety disorders at follow-up. CONCLUSIONS: The prospective association between agoraphobia at baseline and hsCRP levels over the follow-up period suggests that chronic low-grade inflammation may be a consequence of this condition. The decrease in IL-6 in PTSD also requires further investigation. No evidence was found for chronic low-grade inflammation as a predictor of future anxiety disorders.