Arianne K. B. van Reedt Dortland

Increased sympathetic and decreased parasympathetic activity rather than changes in hypothalamic-pituitary-adrenal axis activity is associated with metabolic abnormalities.

CONTEXTnStress is suggested to lead to metabolic dysregulations as clustered in the metabolic syndrome, but the underlying biological mechanisms are not yet well understood.nnnOBJECTIVEnWe examined the relationship between two main str systems, the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, with the metabolic syndrome and its components.nnnDESIGNnThe design was baseline data (yr 2004-2007) of a prospective cohort: the Netherlands Study of Depression and Anxiety (NESDA).nnnSETTINGnThe study comprised general community, primary care, and specialized mental health care.nnnPARTICIPANTSnThis study included 1883 participants aged 18-65 yr.nnnMAIN OUTCOME MEASURESnAutonomic nervous system measures included heart rate, respiratory sinus arrhythmia (RSA; high RSA reflecting high parasympathetic activity), and preejection period (PEP; high PEP reflecting low sympathetic activity). HPA axis measures included the cortisol awakening response, evening cortisol, and a 0.5 mg dexamethasone suppression test as measured in saliva. Metabolic syndrome was based on the updated Adult Treatment Panel III criteria and included high waist circumference, serum triglycerides, blood pressure, serum glucose, and low high-density lipoprotein cholesterol.nnnRESULTSnRSA and PEP were both independently negatively associated with the presence of the metabolic syndrome, the number of metabolic dysregulations as well as all individual components except high-density lipoprotein cholesterol (all P < 0.02). Heart rate was positively related to the metabolic syndrome, the number of metabolic dysregulations, and all individual components (all P < 0.001). HPA axis measures were not related to metabolic syndrome or its components.nnnCONCLUSIONnOur findings suggest that increased sympathetic and decreased parasympathetic nervous system activity is associated with metabolic syndrome, whereas HPA axis activity is not.

Associations Between Serum Lipids and Major Depressive Disorder: Results From the Netherlands Study of Depression and Anxiety (NESDA)

BACKGROUNDnSeveral studies have suggested an association between lipids or lipoproteins and depression, but findings are contradictory. However, previous studies did not always take into consideration potentially mediating factors or heterogeneity of symptoms, which may clarify contradicting findings.nnnMETHODnWe compared levels of serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and triglyceride between 761 subjects with current major depressive disorder (MDD) (Composite International Diagnostic Interview, based on the DSM-IV), 1,071 subjects with remitted MDD, and 629 controls, aged 18 to 65 years. Subjects participated in the baseline assessment of the Netherlands Study of Depression and Anxiety, which lasted from September 2004 to February 2007. We studied the impact of adjustment for sociodemographics, lifestyle-related covariates, and antidepressant use and examined the association between specific psychopathological characteristics and lipid/lipoprotein levels.nnnRESULTSnHDL cholesterol level was lower (P = .007) and triglyceride level was higher (P = .001) in current MDD versus remitted MDD and controls. After adjustment for level of education, body mass index (BMI), smoking status, and alcohol use, dissimilarities lost statistical significance. Depression severity, comorbid dysthymia, and melancholic and atypical features were all associated with lipids/lipoproteins, but most associations attenuated after adjustment for covariates, especially BMI. The association between melancholic features and lower HDL cholesterol (P = .038) and between atypical depression and higher total and LDL cholesterol (P = .004 and P = .002, respectively) persisted after full adjustment.nnnCONCLUSIONSnAdverse lipoprotein patterns were found in patients with MDD. The fact that these associations diminished after adjustment for lifestyle-related factors, especially BMI, suggests that the unfavorable lipid/lipoprotein pattern among depressed subjects is mainly secondary to lifestyle-related factors. However, melancholic features were independently associated with lower HDL cholesterol, and atypical depression was independently associated with higher total and LDL cholesterol.

The impact of stress systems and lifestyle on dyslipidemia and obesity in anxiety and depression

BACKGROUNDnDyslipidemia and obesity have been observed in persons with severe anxiety or depression, and in tricyclic antidepressant (TCA) users. This likely contributes to the higher risk of cardiovascular disease (CVD) in anxiety and depressive disorders. We aimed to elucidate whether biological stress systems or lifestyle factors underlie these associations. If so, they may be useful targets for CVD prevention and intervention.nnnMETHODSnWithin 2850 Netherlands Study of Depression and Anxiety (NESDA) participants, we evaluated the explaining impact of biological stress systems (i.e., the hypothalamic-pituitary-adrenal [HPA] axis, autonomic nervous system [ANS] and inflammation) and lifestyle factors (i.e., tobacco and alcohol use, and physical activity) on adverse associations of anxiety and depression severity and TCA use with high and low-density lipoprotein cholesterol, triglycerides, body mass index and waist circumference. Through linear regression analyses, percentual change (%Δ) in β was determined and considered significant when %Δ>10.nnnRESULTSnThe inflammatory marker C-reactive protein had the most consistent impact (explaining 14-53% of the associations of anxiety and depression severity and TCA use with lipid and obesity levels), followed by tobacco use (explaining 34-43% of the associations with lipids). The ANS mediated all associations with TCA use (explaining 32-61%). The HPA axis measures did not explain any of the associations.nnnCONCLUSIONSnIncreased dyslipidemia and (abdominal) obesity risk in patients with more severe anxiety disorders and depression may be partly explained by chronic low-grade inflammation and smoking. TCAs may increase metabolic risk through enhanced sympathetic and decreased parasympathetic ANS activity. That the HPA axis had no impact in our sample may reflect the possibility that the HPA axis only plays a role in acute stress situations rather than under basal conditions.

Longitudinal Relationship of Depressive and Anxiety Symptoms With Dyslipidemia and Abdominal Obesity

Objective Previous research indicates that patients with severe symptoms of depression or anxiety are prone toward the development of dyslipidemia and abdominal obesity. We sought to study these associations longitudinally. Methods Among 2126 Netherlands Study of Depression and Anxiety participants, we studied whether severity of depressive (Inventory of Depressive Symptoms) or anxiety (Beck Anxiety Inventory) symptoms at baseline was associated with changes in lipids (i.e., total, high-density lipoprotein [HDL] or low-density lipoprotein cholesterol, and triglycerides) or waist circumference during a 2-year follow-up period. We also examined whether changes in severity of symptoms were associated with changes in lipid or waist circumference levels over these 2 years. Multivariate linear regression analyses were adjusted for age, sex, education, and tobacco consumption. Results Baseline symptoms of depression or anxiety predicted a decrease in HDL cholesterol (adjusted &bgr; = −.062 [p = .003] and &bgr; = −.050 [p = .02], respectively) and an increase in waist circumference (adjusted &bgr; = .060 [p = .01] and &bgr; = .053 [p = .02], respectively) for 2 years. Reduction of symptoms of depression or anxiety over time did not coincide with an amelioration of lipid or waist circumference values. Conclusions People with initially severe symptoms of depression or anxiety showed a subsequent decrease in HDL cholesterol levels and an increase in abdominal obesity over time, independent of a potential reduction in symptom severity in this period. Therefore, such people are at elongated and increasing risk for dyslipidemia and obesity, predisposing them to cardiovascular disease.

Symptom dimensions of depression and anxiety and the metabolic syndrome

Objective: To investigate the association between depression and anxiety symptoms and the metabolic syndrome (MetSyn), using a dimensional approach. The association between depression and anxiety, on the one hand, and the MetSyn as a cluster or its individual components, on the other hand, is equivocal. The categorical nature of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition might partly explain the inconsistent findings. Methods: In 2,433 Netherlands Study of Depression and Anxiety participants (mean age, 42.3 years; 33.1% male), three symptoms dimensions—lack of positive affect (PA, depression specific); negative affect (NA, aspecific); and somatic arousal (SA, anxiety specific)—were assessed by a shortened adaptation of the Mood and Anxiety Symptom Questionnaire. The association between symptom dimensions and MetSyn components (waist circumference, triglycerides, high-density lipoprotein cholesterol, glucose, and mean blood pressure) was analyzed, using linear regression analysis. Results: The occurrence rate of the MetSyn was 20.1% (n = 490). SA, but not PA and NA, was strongly associated with four out of five MetSyn components, especially waist circumference, triglycerides, and blood pressure (&bgr; = 0.046, p = .01; &bgr; = 0.077, p < .001; and &bgr; = 0.069, p < .001, respectively), and with the total number of MetSyn components (&bgr; = 0.098, p < .001). Conclusions: Our results demonstrate a strong association of most of the MetSyn components with the SA dimension, but not with the NA and PA scales. MetSyn = metabolic syndrome; NESDA = Netherlands Study of Depression and Anxiety; PA = positive affect; NA = negative affect; SA = somatic arousal; MASQ = Mood and Anxiety Symptom Questionnaire; HDL = high-density lipoprotein.

Inflammatory and Metabolic Dysregulation and the 2-Year Course of Depressive Disorders in Antidepressant Users

Scarce evidence suggests that inflammatory and metabolic dysregulation predicts poor response to antidepressants, which could result in worse depression outcome. This study prospectively examined whether inflammatory and metabolic dysregulation predicted the 2-year course of depressive disorders among antidepressant users. Data were from the Netherlands Study of Depression and Anxiety, including 315 persons (18–65 years) with a current depressive disorder (major depressive disorder, dysthymia) at baseline according to the DSM-IV criteria and using antidepressants. Inflammatory (C-reactive protein, interleukin-6 (IL-6), tumor-necrosis factor-α) and metabolic (waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, fasting glucose) factors were measured at baseline. Primary outcome for course of depression was indicated by whether or not a DSM-IV depressive disorder diagnosis was still/again present at 2-year follow-up, indicating chronicity of depression. Elevated IL-6, low HDL cholesterol, hypertriglyceridemia, and hyperglycemia were associated with chronicity of depression in antidepressant users. Persons showing ⩾4 inflammatory or metabolic dysregulations had a 1.90 increased odds of depression chronicity (95% CI=1.12–3.23). Among persons who recently (ie, at most 3 months) started antidepressant medication (N=103), having ⩾4 dysregulations was associated with a 6.85 increased odds of depression chronicity (95% CI=1.95–24.06). In conclusion, inflammatory and metabolic dysregulations were found to predict a more chronic course of depressive disorders among patients using antidepressants. This could suggest that inflammatory and metabolic dysregulation worsens depression course owing to reduced antidepressant treatment response and that alternative intervention treatments may be needed for depressed persons with inflammatory and metabolic dysregulation.

Personality traits and childhood trauma as correlates of metabolic risk factors: The Netherlands Study of Depression and Anxiety (NESDA)

OBJECTIVEnPersonality and childhood trauma may affect cardiovascular disease (CVD) risk. However, evidence for an association with metabolic risk factors for CVD is limited and ambiguous. Moreover, despite their interrelatedness, personality and childhood trauma were not yet studied simultaneously. Therefore, we aimed to explore whether personality and childhood trauma are correlates of metabolic risk factors.nnnMETHODSnAmong 2755 participants of the Netherlands Study of Depression and Anxiety (NESDA), we investigated through linear regression models whether Big Five personality traits (i.e., extraversion, openness, agreeableness, neuroticism and conscientiousness) and childhood trauma type (i.e., emotional neglect, and psychological, physical and sexual abuse) were correlates of metabolic risk factors (i.e., lipids, waist circumference (WC), glucose and blood pressure). Basic covariates (i.e., age, sex and income level), lifestyle, severity of depressive symptoms and years of education were taken into account.nnnRESULTSnOpenness was the most robust favorable correlate, and sexual abuse was the most robust unfavorable correlate of lipids and WC, and of overall metabolic risk (β=-.070; p<.001 and β=.035; p=.04, respectively).nnnCONCLUSIONSnPeople with a low openness trait and those who experienced childhood sexual abuse are at higher risk of dyslipidemia and abdominal obesity.

Serum cholesterol, apolipoprotein E genotype and depressive symptoms in elderly European men: The FINE study

BACKGROUNDnCohort and case-control studies found that lower serum total cholesterol is associated with depression. It is, however, unclear whether low cholesterol or its lipoprotein fractions are causally related to depression. Using a Mendelian randomization design, the potential association between apolipoprotein E (APOE) genotype (affecting lifetime cholesterol levels) and depressive symptoms was studied.nnnMETHODSnIn the longitudinal Finland, Italy, the Netherlands Elderly (FINE) Study 1089 men were included in 1985. The 435 men from Finland, 418 men from The Netherlands, and 236 men from Italy (aged 65-84 years) were free of myocardial infarction, stroke, diabetes mellitus and cancer at all time points. They were prospectively studied around 1985 (n=658), 1990 (n=668), 1995 (n=327), and 2000 (n=82). Associations between serum cholesterol, lipoprotein fractions and APOE genotype, with depressive symptoms (by Zung self-rating depression scale [SDS]) were analyzed using multilevel regression models.nnnRESULTSnSerum total cholesterol was inversely associated with the Zung SDS (-0.61 points per 1 mmol/L increase in cholesterol; 95% confidence interval: -1.05 to -0.17; P=0.007), after adjustment for country, age, body mass index, smoking, and alcohol intake. However, none of the cholesterol lipoprotein fractions were associated with the Zung SDS. The APOE genotypes epsilon4/4, epsilon4/3; epsilon3/3; epsilon4/2, and epsilon3/2 or epsilon2/2 were associated with decreasing levels of serum total and LDL cholesterol (Ps<0.001), but not with increasing depressive symptoms (P=0.67).nnnLIMITATIONSnAPOE genotype was assessed through protein isoforms and not actual DNA-based typing.nnnCONCLUSIONSnThere was a modest inverse relationship between depression scores and serum total cholesterol in elderly men, but no associations with lipoprotein fractions or with the APOE genotype.

Metabolic syndrome in patients with bipolar disorder: comparison with major depressive disorder and non-psychiatric controls.

OBJECTIVEnWe aimed to investigate the prevalence of the metabolic syndrome (MetS) and its individual components in subjects with bipolar disorder (BD) compared to those with major depressive disorder (MDD) and non-psychiatric controls.nnnMETHODSnWe examined 2431 participants (mean age 44.3±13.0, 66.1% female), of whom 241 had BD; 1648 had MDD; and 542 were non-psychiatric controls. The MetS was ascertained according to NCEP ATP III criteria. Multivariable analyses were adjusted for age, sex, ethnicity, level of education, smoking status and severity of depressive symptoms, and in the case of BD subjects, also for psychotropic medication use.nnnRESULTSnSubjects with BD had a significantly higher prevalence of MetS when compared to subjects with MDD and non-psychiatric controls (28.4% vs. 20.2% and 16.5%, respectively, p<0.001), also when adjusted for sociodemographic and lifestyle factors (OR 1.52, 95% CI: 1.09-2.12, p=0.02 compared to MDD; OR 1.79, 95% CI: 1.20-2.67, p=0.005 compared to non-psychiatric controls). The differences between BD subjects with controls could partly be ascribed to a higher mean waist circumference (91.0 cm vs. 88.8, respectively, p=0.03). In stratified analysis, the differences in the prevalence of MetS between patients with BD and MDD were found in symptomatic but not in asymptomatic cases.nnnCONCLUSIONnThis study confirms a higher prevalence of MetS in patients with BD compared to both MDD patients and controls. Specifically at risk are patients with a higher depression score and abdominal obesity.

Assessment of Biopsychosocial Complexity and Health Care Needs: Measurement Properties of the INTERMED Self-Assessment Version

Objective The INTERMED Self-Assessment questionnaire (IMSA) was developed as an alternative to the observer-rated INTERMED (IM) to assess biopsychosocial complexity and health care needs. We studied feasibility, reliability, and validity of the IMSA within a large and heterogeneous international sample of adult hospital inpatients and outpatients as well as its predictive value for health care use (HCU) and quality of life (QoL). Methods A total of 850 participants aged 17 to 90 years from five countries completed the IMSA and were evaluated with the IM. The following measurement properties were determined: feasibility by percentages of missing values; reliability by Cronbach &agr;; interrater agreement by intraclass correlation coefficients; convergent validity of IMSA scores with mental health (Short Form 36 emotional well-being subscale and Hospital Anxiety and Depression Scale), medical health (Cumulative Illness Rating Scale) and QoL (Euroqol-5D) by Spearman rank correlations; and predictive validity of IMSA scores with HCU and QoL by (generalized) linear mixed models. Results Feasibility, face validity, and reliability (Cronbach &agr; = 0.80) were satisfactory. Intraclass correlation coefficient between IMSA and IM total scores was .78 (95% CI = .75–.81). Correlations of the IMSA with the Short Form 36, Hospital Anxiety and Depression Scale, Cumulative Illness Rating Scale, and Euroqol-5D (convergent validity) were −.65, .15, .28, and −.59, respectively. The IMSA significantly predicted QoL and also HCU (emergency department visits, hospitalization, outpatient visits, and diagnostic examinations) after 3- and 6-month follow-up. Results were comparable between hospital sites, inpatients and outpatients, as well as age groups. Conclusions The IMSA is a generic and time-efficient method to assess biopsychosocial complexity and to provide guidance for multidisciplinary care trajectories in adult patients, with good reliability and validity across different cultures.