Weighing poor immunometabolic health in relatives for severity of affective symptoms:A study of patients with depressive and anxiety disorders and their siblings

BACKGROUND: Affective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic studies have confirmed this link in community and clinical samples, studies in at-risk samples of siblings of persons with affective disorders are lacking. Furthermore, this somatic-mental co-occurrence may be partially explained by familial clustering of the conditions. First, we examined whether the association between a wide range of immunometabolic diseases and related biomarker based risk-profiles with psychological symptoms replicates in at-risk siblings of probands with affective disorders. Second, leveraging on a sibling-pair design, we disentangled and quantified the effect of probands' immunometabolic health on siblings' psychological symptoms and on the association between immunometabolic health and these symptoms in siblings.METHODS: The sample included 636 participants (M age = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and at least one of their sibling(s) (N = 380 proband-sibling pairs). Immunometabolic health included cardiometabolic and inflammatory diseases, body mass index (BMI), and composite metabolic (based on the five metabolic syndrome components) and inflammatory (based on interleukin-6 and C-reactive protein) biomarker indices. Overall affective symptoms and specific atypical, energy-related depressive symptoms were derived from self-report questionnaires. Mixed-effects analyses were used to model familial clustering. RESULTS: In siblings, inflammatory disease (γ = 0.25, p = 0.013), higher BMI (γ = 0.10, p = 0.033) and metabolic index (γ = 0.28, p &lt; 0.001) were associated with higher affective symptoms, with stronger associations for atypical, energy-related depressive symptoms (additionally associated with cardiometabolic disease; γ = 0.56, p = 0.048). Immunometabolic health in probands was not independently associated with psychological symptoms in siblings nor did it moderate the association between immunometabolic health and psychological symptoms estimated in siblings.CONCLUSIONS: Our findings demonstrate that the link between later life immunometabolic health and psychological symptoms is consistently present also in adult siblings at high risk for affective disorders. Familial clustering did not appear to have a substantial impact on this association. Instead, individual lifestyle, rather than familial factors, may have a relatively higher impact in the clustering of later life immunometabolic conditions with psychological symptoms in at-risk adult individuals. Furthermore, results highlighted the importance of focusing on specific depression profiles when investigating the overlap with immunometabolic health.</p

Associations between depressive symptom profiles and immunometabolic characteristics in individuals with depression and their siblings

Objectives: The present study examined associations between immunometabolic characteristics (IMCs) and depressive symptom profiles (DSPs) in probands with lifetime diagnoses of depression and/or anxiety disorders and their siblings.Methods: Data were from the Netherlands Study of Depression and Anxiety, comprising 256 probands with lifetime diagnoses of depression and/or anxiety and their 380 siblings. Measured IMCs included blood pressure, waist circumference, and levels of glucose, triglycerides, HDL cholesterol, CRP, TNF-α and IL-6. DSPs included mood, cognitive, somatic and atypical-like profiles. We cross-sectionally examined whether DSPs were associated with IMCs within probands and within siblings, and whether DSPs were associated with IMCs between probands and siblings.Results: Within probands and within siblings, higher BMI and waist circumference were associated with higher somatic and atypical-like profiles. Other IMCs (IL-6, glucose and HDL cholesterol) were significantly related to DSPs either within probands or within siblings. DSPs and IMCs were not associated between probands and siblings.Conclusions: The results suggest that there is a familial component for each trait, but no common familial factors for the association between DSPs and IMCs. Alternative mechanisms, such as direct causal effects or non-shared environmental risk factors, may better fit these results

Familial risk for depressive and anxiety disorders:associations with genetic, clinical, and psychosocial vulnerabilities

BACKGROUND: In research and clinical practice, familial risk for depression and anxiety is often constructed as a simple Yes/No dichotomous family history (FH) indicator. However, this measure may not fully capture the liability to these conditions. This study investigated whether a continuous familial loading score (FLS), incorporating family- and disorder-specific characteristics (e.g. family size, prevalence of depression/anxiety), (i) is associated with a polygenic risk score (PRS) for major depression and with clinical/psychosocial vulnerabilities and (ii) still captures variation in clinical/psychosocial vulnerabilities after information on FH has been taken into account. METHODS: Data came from 1425 participants with lifetime depression and/or anxiety from the Netherlands Study of Depression and Anxiety. The Family Tree Inventory was used to determine FLS/FH indicators for depression and/or anxiety. RESULTS: Persons with higher FLS had higher PRS for major depression, more severe depression and anxiety symptoms, higher disease burden, younger age of onset, and more neuroticism, rumination, and childhood trauma. Among these variables, FH was not associated with PRS, severity of symptoms, and neuroticism. After regression out the effect of FH from the FLS, the resulting residualized measure of FLS was still associated with severity of symptoms of depression and anxiety, rumination, and childhood trauma. CONCLUSIONS: Familial risk for depression and anxiety deserves clinical attention due to its associated genetic vulnerability and more unfavorable disease profile, and seems to be better captured by a continuous score that incorporates family- and disorder-specific characteristics than by a dichotomous FH measure

Why some siblings thrive whereas others struggle: A within-family study on recollections of childhood parental bonding and current adult depressive and anxiety symptoms

Background: Brothers and sisters growing up together share a large proportion of their genes and rearing environment. However, some siblings thrive whereas others struggle. This study investigated family-wide childhood bonding experiences with mother and father, in addition to individual-specific recollections, in relation to current depressive and anxiety symptom levels in adulthood. We examined whether extraversion and internal locus of control (iLoC) had a protective effect in this. Methods: The sample consisted of 256 families with at least one lifetime depressed or anxious person (N = 596; ages 20–78). Multilevel modeling with cross-level interactions was used. Results: Adult siblings showed moderate to high agreement in their childhood parental bonding (PB) recollections. Over-and-above the association between individual-specific recollections of PB and adult internalizing symptoms, family-wide poor PB was additionally linked to elevated symptom levels. Within families characterized by poor maternal bonding persons with an iLoC were relatively less anxious (but not less depressed), whereas extraversion was not protective in this context. Limitation: Although evidence exists that poor childhood PB has an impact on (adult) psychopathology, causality cannot be determined and possible recall bias of PB should be noted. Moreover, next to their moderating effects, extraversion and LoC may also act as mediators. Conclusions: Our findings extend prior work by demonstrating the importance of siblings’ childhood PB experiences next to a person\u27s own recollections when investigating adult internalizing symptoms, while also elucidating individual differences within families

Familial risk for depressive and anxiety disorders: Associations with genetic, clinical, and psychosocial vulnerabilities

Background In research and clinical practice, familial risk for depression and anxiety is often constructed as a simple Yes/No dichotomous family history (FH) indicator. However, this measure may not fully capture the liability to these conditions. This study investigated whether a continuous familial loading score (FLS), incorporating family- A nd disorder-specific characteristics (e.g. family size, prevalence of depression/anxiety), (i) is associated with a polygenic risk score (PRS) for major depression and with clinical/psychosocial vulnerabilities and (ii) still captures variation in clinical/psychosocial vulnerabilities after information on FH has been taken into account.MethodsData came from 1425 participants with lifetime depression and/or anxiety from the Netherlands Study of Depression and Anxiety. The Family Tree Inventory was used to determine FLS/FH indicators for depression and/or anxiety.ResultsPersons with higher FLS had higher PRS for major depression, more severe depression and anxiety symptoms, higher disease burden, younger age of onset, and more neuroticism, rumination, and childhood trauma. Among these variables, FH was not associated with PRS, severity of symptoms, and neuroticism. After regression out the effect of FH from the FLS, the resulting residualized measure of FLS was still associated with severity of symptoms of depression and anxiety, rumination, and childhood trauma.ConclusionsFamilial risk for depression and anxiety deserves clinical attention due to its associated genetic vulnerability and more unfavorable disease profile, and seems to be better captured by a continuous score that incorporates family- A nd disorder-specific characteristics than by a dichotomous FH measure

Familial resemblance in mental health symptoms, social and cognitive vulnerability, and personality: A study of patients with depressive and anxiety disorders and their siblings

Background: Investigating siblings of probands with affective disorders enables the identification of psychopathology-related risk features. Leveraging data from an older adult sample, as compared to most previous sibling studies, enabled us to study more definitive clinical profiling across the lifespan. We examined prevalence of depressive/anxiety disorders in siblings, proband-sibling resemblance in psychopathology-related features, and whether unaffected siblings showed higher levels of these features than healthy controls. Methods: The sample (N=929; Mage=50.6) consisted of 256 probands with lifetime depressive and/or anxiety disorders, their 380 siblings, and 293 healthy controls without affected relatives. Fifteen psychopathology-related features were investigated across four domains: mental health symptoms, social vulnerabilities, cognitive vulnerabilities, and personality. Results: Lifetime disorders were present in 50.3% of siblings. Prevalence was 2-3 times higher than Dutch population frequencies. We found small to medium probandsibling resemblance across psychopathology-related features (ρ=0.10-0.32). Unaffected siblings reported poorer interpersonal functioning and more negative life events, childhood trauma, and rumination than healthy controls. Limitations: Due to the cross-sectional study design, the directionality of effects cannot be determined. No inferences can be made about potential differences in familial resemblance in psychopathology-related features between high- and low-risk families. Conclusions: Siblings of probands with affective disorders are at higher risk for depressive/anxiety disorders. Even when unaffected, still show higher psychosocial vulnerability than healthy controls. Nevertheless, the only modest proband-sibling resemblance across psychopathology-related features suggests that individual mechanisms differentiate clinical trajectories across the lifespan. Identification of these mechanisms is crucial to improve resilience in subjects with familial risk

Weighing psychosocial factors in relatives for the risk of psychopathology: a study of patients with depressive and anxiety disorders and their siblings

Purpose: Siblings of probands with depressive and anxiety disorders are at increased risk for psychopathology, but little is known about how risk factors operate within families to increase psychopathology for siblings. We examined the additional impact of psychosocial risk factors in probands—on top of or in combination with those in siblings—on depressive/anxious psychopathology in siblings. Methods: The sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and their sibling(s) (N = 380 proband-sibling pairs). Sixteen psychosocial risk factors were tested. In siblings, depressive and anxiety disorders were determined with standardized psychiatric interviews; symptom severity was measured using self-report questionnaires. Analyses were performed with mixed-effects models accounting for familial structure. Results: In siblings, various psychosocial risk factors (female gender, low income, childhood trauma, poor parental bonding, being single, smoking, hazardous alcohol use) were associated with higher symptomatology and likelihood of disorder. The presence of the same risk factor in probands was independently associated (low income, being single) with higher symptomatology in siblings or moderated (low education, childhood trauma, hazardous alcohol use)—by reducing its strength—the association between the risk factor and symptomatology in siblings. There was no additional impact of risk factors in probands on likelihood of disorder in siblings. Conclusion: Our findings demonstrate the importance of weighing psychosocial risk factors within a family context, as it may provide relevant information on the risk of affective psychopathology for individuals

Associations between depressive symptom profiles and immunometabolic characteristics in individuals with depression and their siblings

Objectives: The present study examined associations between immunometabolic characteristics (IMCs) and depressive symptom profiles (DSPs) in probands with lifetime diagnoses of depression and/or anxiety disorders and their siblings. Methods: Data were from the Netherlands Study of Depression and Anxiety, comprising 256 probands with lifetime diagnoses of depression and/or anxiety and their 380 siblings. Measured IMCs included blood pressure, waist circumference, and levels of glucose, triglycerides, HDL cholesterol, CRP, TNF-α and IL-6. DSPs included mood, cognitive, somatic and atypical-like profiles. We cross-sectionally examined whether DSPs were associated with IMCs within probands and within siblings, and whether DSPs were associated with IMCs between probands and siblings. Results: Within probands and within siblings, higher BMI and waist circumference were associated with higher somatic and atypical-like profiles. Other IMCs (IL-6, glucose and HDL cholesterol) were significantly related to DSPs either within probands or within siblings. DSPs and IMCs were not associated between probands and siblings. Conclusions: The results suggest that there is a familial component for each trait, but no common familial factors for the association between DSPs and IMCs. Alternative mechanisms, such as direct causal effects or non-shared environmental risk factors, may better fit these results