High dose benzodiazepines prolong reaction times in chronic users who have major depressive and/or anxiety disorders.

AIM: Short term administration of benzodiazepines (BZD) was found to prolong reaction time (RT) in experimental studies. However, studies on long term BZD use did not always adjust for important confounders and showed inconsistent results. We aimed to identify a possible relationship between long term BZD use and RT in BZD users in this large cross-sectional, observational study. METHODS: The RTs of non-users (n = 2404) were compared with low (n = 288), intermediate (n = 74), and high dose BZD users (n = 57) in the Netherlands Study of Depression and Anxiety (NESDA). RTs were obtained from the Implicit Association Test. Analyses were adjusted for sociodemographic characteristics, health indicators, severity of psychopathology and antidepressant use. RESULTS: Of the NESDA participants, 419 subjects (14.8%) used BZDs. A higher dose of BZDs was associated with prolonged RTs (P = 0.01). When comparing the different dose groups, the high dose group, but not the low and medium dose groups, had significantly longer RTs than the non-users. CONCLUSIONS: Tolerance for the RT prolonging effect of relatively high doses of BZDs does not seem to develop. As prolonged RTs can have adverse consequences in daily life, BZDs should be prescribed conservatively at the lowest possible dose.

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 ß = -.062 [p = .003] and ß = -.050 [p = .02], respectively) and an increase in waist circumference (adjusted ß = .060 [p = .01] and ß = .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.

Efficacy versus effectiveness: a direct comparison of the outcome of treatment for mild to moderate depression in randomized controlled trials and daily practice.

BACKGROUND: Results from randomized controlled trials (RCTs) are considered to give the most reliable information on treatment outcome (efficacy). Yet, the generalizability of efficacy results to daily practice (effectiveness) might be diminished by the design of RCTs. The STAR*D trial approached daily practice as much as possible, but still has some properties of an RCT. In this study, we compare results from treatment of major depressive disorder (MDD) in routine clinical practice to those of RCTs and STAR*D. METHODS: Effectiveness in routine clinical practice was compared with efficacy results from 15 meta-analyses on antidepressant, psychotherapeutic and combination treatment and results from STAR*D. Data on daily practice patients and treatments were derived from a routine outcome monitoring (ROM) system. Treatment outcome was defined as proportion of remitters (MADRS ≤10) and within-group effect size. RESULTS: From ROM, 598 patients suffering from a MDD episode according to the MINI-plus were included. Remission percentages were lower in routine practice than in meta-analyses for all treatment modalities (32 vs.40-74%). Differences were less explicit for antidepressants (21 vs. 34-47%) than for individual psychotherapy (27 vs. 34-58%; effect size 0.85 vs. 1.71) and combination therapy (21 vs. 45-63%), since only 60% of the meta-analyses for antidepressants showed significant differences with ROM, while for psychotherapy and combination treatment almost all meta-analyses showed significant differences. No differences in effectiveness were found between routine practice and STAR*D (antidepressants 27 vs. 28%; individual psychotherapy 27 vs. 25%; combination treatment 21 vs. 23%, respectively). CONCLUSIONS: Effectiveness of treatment for mild-to-moderate MDD in daily practice is similar to STAR*D and significantly lower than efficacy results from RCTs.

The generalizability of psychotherapy efficacy trials in major depressive disorder: an analysis of the influence of patient selection in efficacy trials on symptom outcome in daily practice.

BACKGROUND: Treatment guidelines for major depressive disorder (MDD) are based on results from randomized clinical trials, among others in psychotherapy efficacy trials. However, patients in these trials differ from routine practice patients since trials use stringent criteria for patient selection. It is unknown whether the exclusion criteria used in psychotherapy efficacy trials (PETs) influence symptom outcome in clinical practice. We first explored which exclusion criteria are used in PETs. Second, we investigated the influence of commonly used exclusion criteria on symptom outcome in routine clinical practice. METHODS: We performed an extensive literature search in PubMed, PsycInfo and additional databases for PETs for MDD. From these, we identified commonly used exclusion criteria. We investigated the influence of exclusion criteria on symptom outcome by multivariate regression models in a sample of patients suffering from MDD according to the MINIplus from a routine clinical practice setting (n=598). Data on routine clinical practice patients were gathered through Routine Outcome Monitoring. RESULTS: We selected 20 PETs and identified the following commonly used exclusion criteria: 'a baseline severity threshold of HAM-D≤14', 'current or past abuse or dependence of alcohol and/or drugs' and 'previous use of medication or ECT'. In our routine clinical practice sample of patients suffering from MDD (n=598), presence of 'current or past abuse of or dependence on alcohol and/or drugs' had no significant influence on outcome.'Meeting a baseline severity threshold of HAM-D≤14' and 'previous use of medication or ECT' were associated with better outcome, but the explained variance of the models was very small (R2=2-11%). CONCLUSIONS: The most consistently used exclusion criteria are not a major threat to the generalizability of results found in PETs. However, PETs do somewhat improve their results by exclusion of patients with minor depression and patients who used antidepressants prior to psychotherapy.

Different gene sets contribute to different symptom dimensions of depression and anxiety.

Although many genetic association studies have been carried out, it remains unclear which genes contribute to depression. This may be due to heterogeneity of the DSM-IV category of depression. Specific symptom-dimensions provide a more homogenous phenotype. Furthermore, as effects of individual genes are small, analysis of genetic data at the pathway-level provides more power to detect associations and yield valuable biological insight. In 1,398 individuals with a Major Depressive Disorder, the symptom dimensions of the tripartite model of anxiety and depression, General Distress, Anhedonic Depression, and Anxious Arousal, were measured with the Mood and Anxiety Symptoms Questionnaire (30-item Dutch adaptation; MASQ-D30). Association of these symptom dimensions with candidate gene sets and gene sets from two public pathway databases was tested using the Global test. One pathway was associated with General Distress, and concerned molecules expressed in the endoplasmatic reticulum lumen. Seven pathways were associated with Anhedonic Depression. Important themes were neurodevelopment, neurodegeneration, and cytoskeleton. Furthermore, three gene sets associated with Anxious Arousal regarded development, morphology, and genetic recombination. The individual pathways explained up to 1.7% of the variance. These data demonstrate mechanisms that influence the specific dimensions. Moreover, they show the value of using dimensional phenotypes on one hand and gene sets on the other hand.

Determinants of initiated and continued benzodiazepine use in the Netherlands study of depression and anxiety.

BACKGROUND: Longitudinal research on determinants of initiated and continued benzodiazepine (BZD) use is inconsistent and has identified many possible determinants. It is unclear which of those are most important in the prediction of BZD use. We aimed to identify the most important predictors of initiated and continued BZD use. Therefore, we analyzed the most consistently identified determinants from previous research plus some new determinants. METHODS: We identified baseline and 2-year longitudinal predictors of initiated BZD use (vs nonuse) among 2205 baseline BZD nonusers and of continued use (vs discontinued use) among 369 baseline BZD users in the Netherlands Study of Depression and Anxiety using logistic regression analyses. RESULTS: During follow-up, BZD use was initiated by 4.9% of BZD nonusers at baseline. Initiated use was predicted by insomnia (odds ratio [OR], 1.60), enduring anxiety symptoms (OR, 2.02), entering secondary care during follow-up (OR, 2.85), and past BZD use (OR, 3.57). Positive life events during follow-up reduced the likelihood of BZD initiation (OR, 0.76). Of BZD users at baseline, 54.2% continued use during the entire follow-up period. Continuation of BZD use was predicted by higher age (OR, 1.03), severe anxiety (OR, 1.85), and a long duration of BZD use (OR, 1.54). Leaving secondary care was associated with less continued BZD use (OR, 0.29). CONCLUSION: Insomnia and anxiety were the main risk factors of initiated use, whereas advanced age and anxiety severity were the main risk factors of continued use. Sex, education, pain, and physical health seemed to be less important.

Correlates of (inappropriate) benzodiazepine use: the Netherlands Study of Depression and Anxiety (NESDA).

AIM: Results on determinants of benzodiazepine (BZD) use in general and inappropriate use were inconsistent and mostly univariate. The relative importance of sociodemographic, psychological and physical determinants has never been investigated in a comprehensive, multivariate model. METHODS: We included 429 BZD users and 2423 non-users from the Netherlands Study of Depression and Anxiety (NESDA) in order to investigate sociodemographic, psychological and physical determinants of BZD use and inappropriate use by logistic and linear regression analyses. RESULTS: BZDs were used by a considerable proportion of the 2852 NESDA participants (15.0%). BZD use was independently associated with older age, singleness, unemployment, treatment in secondary care, higher medical consumption (more severe) anxiety, depression (OR [95% CI]=1.95 [1.29, 2.93]), comorbidity, insomnia, SSRI (OR [95% CI]=2.05 [1.55, 2.70]), TCA and other antidepressant (OR [95% CI]=2.44 [1.64, 3.62]) use. Overall, BZD use was rarely in accordance with all guidelines, mainly because most users (82.5%) exceeded the recommended duration of safe use. Inappropriate use was independently associated with older age (ß=0.130) and chronic illnesses (ß=0.120). Higher scores on agreeableness were associated with less inappropriate use. CONCLUSIONS: Mentally or physically vulnerable subjects were most likely to use BZDs. The most vulnerable (i.e. the old and physically ill) BZD users were at highest risk of inappropriate BZD use. Without further evidence of the effectiveness of BZDs in long-term use, caution in initiating BZD prescriptions is recommended, particularly when patients are chronically ill and old, as those are most likely to display inappropriate use.

Long-term benzodiazepine use and salivary cortisol: the Netherlands Study of Depression and Anxiety (NESDA).

BACKGROUND: As benzodiazepines (BZDs) have anxiolytic effects, it is expected that they influence the stress system. During short-term treatment, BZD use was found to suppress cortisol levels. However, little research has been done on the effects of long-term BZD administration on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: The association between long-term BZD use and cortisol levels was investigated in subjects of the Netherlands Study of Depression and Anxiety with a lifetime diagnosis of anxiety or depression (n = 1531). The subjects were categorized as "daily BZD users" (n = 96), "infrequent BZD users" (n = 172), and "nonusers" (n = 1263). Possible associations between characteristics of BZD use (dose, duration, and dependence) and salivary cortisol levels were analyzed. MAIN OUTCOME MEASURE: Subjects provided 7 saliva samples, from which 4 cortisol indicators were calculated: the cortisol awakening response, diurnal slope, evening cortisol, and cortisol suppression after ingestion of 0.5 mg of dexamethasone. RESULTS: Daily users used BZDs for a median duration of 26.5 months and had a median daily dosage of 6.0 mg as measured in diazepam equivalents. Evening cortisol levels were significantly lower in daily users (P = 0.004; effect size: d = 0.24) and infrequent users (P = 0.04; effect size: d = 0.12) compared to nonusers. We did not find significant differences in the cortisol awakening response, diurnal slope, or in the dexamethasone suppression test. CONCLUSIONS: Despite the finding of slightly lower evening cortisol levels in daily and infrequent BZD users compared to nonusers, results indicate that long-term BZD use is not convincingly associated with HPA axis alterations.

Development and validation of a 30-item short adaptation of the Mood and Anxiety Symptoms Questionnaire (MASQ).

The original Mood and Anxiety Symptoms Questionnaire (MASQ) is a 90-item self-report, designed to measure the dimensions of Clark and Watson's tripartite model. We developed and validated a 30-item short adaptation of the MASQ: the MASQ-D30, which is more suitable for large-scale psychopathology research and has a clearer factor structure. The MASQ-D30 was developed through a process of item reduction and grouping of the appropriate subscales in a sample of 489 psychiatric outpatients, using a validated Dutch translation, based on the original English MASQ, as a starting point. Validation was done in two other large samples of 1461 and 2471 subjects, respectively, with an anxiety, somatoform and/or depression diagnosis or no psychiatric diagnosis. Psychometric properties were investigated and compared between the MASQ-D30 and the full (adapted) MASQ. A three-dimensional model (negative affect, positive affect and somatic arousal) was found to represent the data well, indicating good construct validity. The scales of the MASQ-D30 showed good internal consistency (all alphas>0.87) in patient samples. Correlations of the subscales with other instruments indicated acceptable convergent validity. Psychometric properties were similar for the MASQ-D30 and the full questionnaire. In conclusion, the MASQ-D30 is a valid instrument to assess dimensional aspects of depression and anxiety and can easily be implemented in psychopathology studies.

Trauma exposure and hypothalamic-pituitary- adrenal axis functioning in mentally healthy Dutch peacekeeping veterans, 10-25 years after deployment.

Hypothalamic-pituitary-adrenal (HPA) axis alterations have been found in veterans with posttraumatic stress disorder (PTSD). It is unclear whether trauma exposure during adulthood in the absence of psychopathology is also associated with HPA-axis dysregulation. Thirty-six trauma-exposed peacekeepers, 23 nonexposed peacekeepers, and 25 nonexposed civilians, all without lifetime psychopathology were studied. Basal HPA-axis functioning was assessed with salivary cortisol samples obtained over 2 days. HPA-axis reactivity was assessed with the dexamethasone/corticotropin-releasing hormone test. Lower afternoon salivary cortisol levels were found in both veteran groups versus controls after adjustment for confounders. The authors concluded that this study does not support the idea that HPA-axis functioning is durably altered by trauma exposure during adulthood in men.

Does trauma cause lasting changes in HPA-axis functioning in healthy individuals?

Although the majority of people who are exposed to traumatic events do not develop psychopathology, trauma has often been associated with increased vulnerability to psychiatric disorders. In addition, alterations in the HPA-axis have been demonstrated in patients with trauma-related psychiatric disorders. We hypothesize that trauma causes dysregulation of the HPA-axis. Therefore, we will compare HPA-axis functioning of traumatized and non-traumatized healthy individuals from the same gender and age from two categories: military and railroad personnel. In addition, a group of women with a history of childhood trauma was included. We will investigate for the putative role of attachment style and psychological resilience factors such as coping. In this article, we present the rationale for this study.

Mental health of Dutch peacekeeping veterans 10-25 years after deployment.

OBJECTIVE: This report describes the mental health of Dutch peacekeeping veterans, 10--25 years after deployment, and its association with deployment-related traumatic events. METHOD: We randomly selected a group of 1046 peacekeeping veterans, who participated in military missions in Lebanon, former Yugoslavia, and various other missions between 1979 and 1997. We sent a questionnaire assessing current levels of psychological distress (Brief Symptom Inventory--BSI), and a questionnaire assessing trauma related to deployment. RESULTS: Psychological data were available for 729 veterans. In 83% of the veterans, no significant psychological distress was found, whereas 17% scored above the BSI cut-off for psychopathology. Interestingly, this percentage was equal to that in a non-patient norm group. CONCLUSION: From this finding we concluded that 10--25 years post-deployment, Dutch peacekeeping veterans do not show more psychological distress than the general Dutch population. In addition, we did not find a significant association between trauma exposure 10--25 years ago and current BSI scores. Moreover, trauma-exposure explained only 9% of the variance in psychological distress. Thus, although military peacekeeping operations may have a strong impact on the lives of soldiers, in this group of veterans they do not seem to have caused severe psychological distress10--25 years after deployment.

CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis.

Chemokines mediate selective recruitment of leukocyte subsets into the CNS during inflammatory episodes. We hypothesised that functional polymorphisms in CCR5 and CCL5 influence perivascular leukocyte infiltration, inflammation, axonal loss, and remyelination, and disease course. Therefore, we determined genotypes at four possibly functional polymorphisms in CCR5 and CCL5 for 637 patients and 92 brain donors with multiple sclerosis (MS). For a subset of 192 patients, MRI data were available. We found that low-producer allele CCL5-403*G was associated with reduced risk of severe axonal loss, whereas high-producer allele CCL5-403*A was associated with a worse clinical disease course measured by the MS Functional Composite Score and MS Severity Score. Low-producer allele CCR5+303*G was associated with reduced T2 hyperintense and T1 hypointense lesion volumes on MRI, and high-producer allele CCR5+303*A with early age at onset. Furthermore, low-producer allele CCR5Delta32 was associated with reduced T2 lesion volume, lower black hole ratio on MRI, and with a higher percentage of lesions with signs of remyelination, histopathologically. In summary, our multifaceted study supports the notion that polymorphisms in CCL5 and CCR5 modify the course of MS.

Characteristics of suicidal outpatients with mood, anxiety and somatoform disorders: The role of childhood abuse and neglect.

BACKGROUND: The most prevalent psychiatric disorders are mood, anxiety and somatoform (MAS) disorders which show high mutual comorbidity, childhood trauma and elevated risk of suicidality. So far, no studies have compared suicide risk in a secondary care population with comorbid MAS disorders. This gap was taken as starting point for the study. AIMS: In comparing suicidal and non-suicidal MAS patients, the following was examined: suicide risk in the three disorder groups, socio-demographic and clinical characteristics, occurrence of childhood trauma types and contribution of childhood trauma to suicidality. METHODS: This cross-sectional study compared suicidal (n = 316) versus non-suicidal comorbid MAS outpatients (n = 929) by means of the Mini-International Neuropsychiatric Interview Plus (MINI-Plus), Brief Symptom Inventory (BSI), Short Form Health Survey 36 (SF-36), Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF) and Childhood Trauma Questionnaire (CTQ). RESULTS: Compared to non-suicidal MAS patients, suicidal MAS patients mostly had mood disorders (single/comorbid), multiple diagnoses, worse functioning, more personality pathology (self-harm) and more childhood neglect and abuse. CONCLUSION: Especially (comorbid) depressed patients are at risk for suicide, and routine screening and monitoring of childhood trauma and suicidality in them are recommended, along with the timely deployment of appropriate trauma-focused psychotherapy.

The impact of glucocorticoid receptor gene polymorphisms on glucocorticoid sensitivity is outweighted in patients with multiple sclerosis.

Glucocorticoid (GC) sensitivity varies considerably in healthy controls as well as in patients with chronic inflammatory diseases like multiple sclerosis (MS). We investigated whether polymorphisms in the glucocorticoid receptor (N363S, ER22/23EK, and the BclI) were responsible for altered GC sensitivity. In healthy controls we found an association between the N363S allele of the GR and a reduced peripheral GC sensitivity. In MS patients neither the variant N363S, the BclI RFLP nor the ER22/23EK allele were found to be associated with GC sensitivity. GC sensitivity is probably in part genetically influenced in healthy controls, but in MS patients other factors seem to have more impact on GC sensitivity.

CTLA-4 and CD28 gene polymorphisms in susceptibility, clinical course and progression of multiple sclerosis.

The balance between CD28 and CTLA-4 signalling is important for regulation of the immune response. We were interested whether a genetically mediated disturbance of this balance could be related to susceptibility or severity of multiple sclerosis (MS). We examined three polymorphisms in these genes, CTLA-4-318, CTLA-4+49 and CD28-I3+17, in 514 patients with MS and 181 controls. As the loci cannot be assumed independent of each other, we analysed the effects of each of the three polymorphisms corrected for the presence of the other two. We found no association between carriership of any of the alleles either with susceptibility to MS or with clinical features. For a subgroup of patients, longitudinal magnetic resonance imaging (MRI) data were available. We observed no effects of the polymorphisms on brain and lesion volumes. These data suggest that the polymorphisms under investigation do not affect the risk of developing MS and have no influence on the course of disease.

The use of symptom dimensions to investigate the longitudinal effects of life events on depressive and anxiety symptomatology.

BACKGROUND: Findings on the association between life events and depression have been quite inconsistent. This could be due to the heterogeneity of traditionally used depression outcomes. The aim of this study was to investigate whether specific symptom dimensions can be used as an alternative to detect more specific life event effects. METHODS: Participants with/without psychiatric diagnoses were included (n=2252). Dimensions of the tripartite model (General Distress [GD], Anhedonic Depression [AD] and Anxious Arousal [AA]) were assessed at baseline, 1-year and 2-year follow-up. Life events occurring between measurements were assessed retrospectively. Longitudinal associations between life events and dimensional scores were analysed with Linear Mixed Models. RESULTS: Occurrence of negative life events was associated with increasing GD and AA, and less with AD. Positive life events were associated with decreasing GD and AD, but not with AA. The association between negative life events and AD was larger in the absence of previous psychiatric problems, lending support to a dimension-specific 'kindling' effect. Also, the negative association between negative life events and GD was stronger in those with high neuroticism. Multivariable analyses with individual life events showed that a few strong independent effects remained for each dimension. LIMITATIONS: Life event reports were retrospective; only three outcome dimensions were used. CONCLUSIONS: These results show that the effects of life events and modifying factors depend, to an extent, on the symptom domain that is considered as outcome, illustrating the need to account for symptom heterogeneity in etiological life event research.

A comparative analysis of personality pathology profiles among patients with pure depressive-, pure anxiety-, and pure somatoform disorders.

BACKGROUND: Depressive-, anxiety-, and somatoform disorders are among the most common psychiatric disorders. The assessment of comorbid personality pathology or traits in these disorders is relevant, because it can lead to the exacerbation of them or to poorer remission rates. To date, no research findings have been published on the comparison of these three prevalent patient groups with regard to comorbid dimensional personality pathology. METHODS: Data of participants (18-60 years) came from a web-based Routine Outcome Monitoring (ROM) programme. The present study used baseline data and was designed to compare personality pathology profiles between three separate outpatient groups: pure anxiety disorders (n=1633), pure depressive disorders (n=1794), and pure somatoform disorders (n=479). Personality pathology was measured with the Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF). RESULTS: The pure depressive disorder group, in comparison to the other two disorder groups, exhibited the worst psychopathological and functional health image and most personality pathology. In the pure anxiety disorder group, the highest mean was found for the personality trait Anxiousness; and in the pure depressive disorder group for the traits Identity problems, Affective lability, Anxiousness, and Restricted expression. LIMITATIONS: The cross-sectional nature of the study limits the conclusions that can be drawn. CONCLUSIONS: The assessment of comorbid personality pathology in depressive-, anxiety-, somatoform disorders is clinically relevant, whether a patient has a personality disorder or not. This way, treatment could partly be focused on specific personality traits that may be counterproductive for treatment outcome, especially in depressive disorders.

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

BACKGROUND: Dyslipidemia 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. METHODS: Within 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 ß was determined and considered significant when %Δ>10. RESULTS: The 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. CONCLUSIONS: Increased 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.

Adulthood trauma and HPA-axis functioning in healthy subjects and PTSD patients: a meta-analysis.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA)-axis dysregulation has inconsistently been associated with posttraumatic stress disorder (PTSD). Yet, trauma exposure rather than PTSD may be responsible for HPA-axis dysregulation. In two meta-analyses, we assessed the association of adulthood trauma exposure and HPA-axis functioning in healthy subjects with and without PTSD. METHOD: A literature search in Pubmed and PsychInfo, using keywords and MeSH terms such as cortisol, emotional trauma, and PTSD, was performed. Only studies that included mentally healthy trauma-exposed (TE) individuals as well as non-exposed (NE) healthy individuals and/or PTSD patients (PTSD) were selected. This resulted in 1511 studies of which ultimately, 37 studies (21 TE versus NE and 34 TE versus PTSD, N=2468) were included. Methodological quality of all studies was assessed according to specific quality criteria. Pooled effect sizes (Hedges's g) on cortisol levels were compared. For all analyses, random effect models were used. RESULTS: Cortisol levels were neither significantly different between TE versus NE subjects (-0.029; 95%CI: -0.145; 0.088) nor between TE subjects versus PTSD patients (0.175; 95%CI: -0.012; -0.362). Subgroup analyses showed an increased cortisol suppression after the low dose dexamethasone suppression test (DST) in TE versus NE subjects (-0.509; 95%CI: -0.871; -0.148). This meta-analysis was limited by the fact that lifetime psychiatric illness and childhood trauma were not an exclusion criterion in all 37 studies. CONCLUSION: Neither adulthood trauma exposure nor PTSD were associated with differences in HPA-axis functioning, although adulthood trauma may augment cortisol suppression after the DST. More evidence on other dynamic tests of HPA-axis functioning in PTSD and adulthood trauma exposure is needed.