Martin Maripuu

Short Telomeres in Depression and the General Population Are Associated with a Hypocortisolemic State

BACKGROUND The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in stress regulation, and leukocyte telomere length (TL) has been suggested to represent a cumulative measure of stress. Depression is intimately related with stress and frequently exhibits a dysregulated HPA axis. We aimed to study the relationships between TL and biological and psychological facets of stress in recurrent major depressive disorder and controls. METHODS Leukocyte TL was measured in 91 subjects with recurrent major depressive disorder and 451 control subjects. Stress was assessed from both a biological perspective, by assessing HPA axis function with a weight-adjusted very-low-dose dexamethasone suppression test (DST), and a psychological perspective, with self-report questionnaires. RESULTS TL was shorter among patients compared with control subjects (277 base pairs, p = .001). Overall, short TL was associated with a hypocortisolemic state (low post-DST cortisol and high percentage of cortisol reduction after the DST) among both patients and control subjects but more pronounced among patients. This state, which was overrepresented among patients, was characterized by high familial loading of affective disorders among patients (p = .001) and high C-reactive protein levels among control subjects (p = .040). TL was also inversely associated with stress measured with the Perceived Stress Questionnaire (r(s) = -.258, p = .003). CONCLUSIONS Short TL is associated with depression and hypocortisolism. Because hypocortisolism has been shown to develop from chronic stress exposure, our findings corroborate the concept of TL as a cumulative measure of stress and provide novel insights into the detrimental role of stress in depressive illness and the general population.

Relative Hypo-and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder : A Cross-Sectional Study

Background Depression in unipolar and bipolar disorders is associated with hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity. Also, unipolar disorder has recently been shown to exhibit HPA-axis hypoactivity. We studied for the first time how HPA-axis hypo- and hyperactivity relate to depression and disease burden in bipolar disorder. We were interested in studying hypocortisolism; characterized by increased HPA-axis negative feedback sensitivity and lower basal cortisol levels together with the opposite HPA-axis regulatory pattern of hypercortisolism. Methods This cross-sectional study includes 145 type 1 and 2 bipolar outpatients and 145 matched controls. A dexamethasone-suppression-test (DST) measures the negative feedback sensitivity and a weight-adjusted very-low-dose DST was employed, which is sensitive in identifying hypocortisolism and hypercortisolism. The 25th and 75th percentiles of control post-DST values were used as cut-offs identifying patients exhibiting relative hypo-, and hypercortisolism. Self-report questionnaires were employed: Beck-Depression-Inventory (BDI), Montgomery-Åsberg-Depression-Rating-Scale (MADRS-S), World-Health-Organization-Quality-of-Life-Assessment–100 and Global-Assessment-of-Functioning. Results Patients exhibiting relative hypocortisolism expectedly exhibited lowered basal cortisol levels (p = 0.046). Patients exhibiting relative hypercortisolism expectedly exhibited elevated basal levels (p<0.001). Patients exhibiting relative hypocortisolism showed 1.9–2.0 (BDI, p = 0.017, MADRS-S, p = 0.37) and 6.0 (p<0.001) times increased frequencies of depression and low overall life quality compared with patients exhibiting mid post-DST values (eucortisolism). Adjusted Odds Ratios (OR:s) for depression ranged from 3.8–4.1 (BDI, p = 0.006, MADRS-S, p = 0.011) and was 23.4 (p<0.001) for life quality. Patients exhibiting relative hypercortisolism showed 1.9–2.4 (BDI, p = 0.017, MADRS-S, p = 0.003) and 4.7 (p<0.001) times higher frequencies of depression and low overall life quality compared with patients exhibiting eucortisolism. Adjusted OR:s for depression ranged from 2.2–2.7 (BDI, p = 0.068, MADRS-S, p = 0.045) and was 6.3 (p = 0.008) for life quality. Limitations The cross-sectional design and lack of pre-established reference values of the DST employed. Conclusions Relative hypocortisolism and relative hypercortisolism were associated with depression and lower life quality, providing novel insights into the detrimental role of stress in bipolar disorder.

Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders.

BACKGROUND Cardiovascular disease (CVD) is one of the main causes of excess deaths in affective disorders. Affective disorders are associated with increased frequencies of CVD risk-factors such as obesity, dyslipidemia, and metabolic syndrome. Stress-induced chronic cortisol excess has been suggested to promote obesity and metabolic syndrome. Chronic stress with frequent or persisting hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity may, over time, lead to a state of low HPA-axis activity, also denoted hypocortisolism. A low-dose weight-adjusted dexamethasone-suppression-test (DST) is considered to be a sensitive measure of hypocortisolism. METHODS 245 patients with recurrent depression or bipolar disorder and 258 controls participated in a low-dose DST and were also examined with regard to metabolic status. RESULTS Patients with hypocortisolism (low post-DST cortisol) compared with patients without hypocortisolism (normal or high post-DST cortisol) exhibited increased odds ratios (OR) for obesity (OR=4.0), overweight (OR=4.0), large waist (OR=2.7), high LDL (OR=4.2), low HDL (OR=2.4), high LDL/HDL ratio (OR=3.3), high TC/HDL ratio (OR=3.4) and metabolic syndrome (OR=2.0). A similar pattern but less pronounced was also found in the control sample. LIMITATIONS The cross sectional study design and absence of analyses addressing lifestyle factors. CONCLUSIONS Our findings suggest that a substantial portion of the metabolic disorders and cardiovascular risk factors seen in recurrent affective disorders are found among individuals exhibiting hypocortisolism. This might indicate that long-term stress is a central contributor to metabolic abnormalities and CVD mortality in recurrent affective disorders.

Association between gastrointestinal symptoms and affectivity in patients with bipolar disorder

AIM To study if anxiety, depression and experience of stress are associated with gastrointestinal (GI) symptoms in patients with bipolar disorder. METHODS A total of 136 patients with bipolar disorder (mean age 49.9 years; 61% women) and 136 controls from the general population (mean age 51.0 years; 60% women) were included in the study. GI symptoms were assessed with The Gastrointestinal Symptom Rating Scale-irritable bowel syndrome (GSRS-IBS), level of anxiety and depression with The Hospital Anxiety and Depression Scale (HADS) and stress-proneness with Perceived Stress Questionnaire. Over a ten year period, all visits in primary care were retrospectively recorded in order to identify functional GI disorders. RESULTS In subjects with low total HADS-score, there were no significant differences in GI-symptoms between patients and controls (GSRS-IBS 7.0 vs 6.5, P = 0.513). In the patients with bipolar disorder there were significant correlations between all GSRS and HADS subscores for all symptom clusters except for “constipation” and “reflux”. Factors associated to GI symptoms in the patient group were female sex (adjusted OR = 2.37, 95%CI: 1.07-5.24) and high HADS-Depression score (adjusted OR = 3.64, 95%CI: 1.07-12.4). These patients had also significantly more visits for IBS than patients with low HADS-Depression scores (29% vs 8%, P = 0.008). However, there was no significant differences in consulting behaviour for functional GI disorders between patients and controls (25% vs 17%, P = 0.108). CONCLUSION Female patients and patients with high HADS depression score reported significantly more GI symptoms, whereas patients with low HADS scores did not differ from control subjects.

Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders

Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders

The Association between Affectivity, Perceived Stress and Pain in Patients with Bipolar Disorder

Objective: Patients with bipolar disorder commonly experience recurrent/chronic pain, usually associated with worsening of the psychic state. The primary aim of the study was to evaluate the association to state anxiety, depression, perceived stress and concurrent pain. A secondary aim was to determine the locations and characteristics of pain. Method: A cross-sectional study was conducted on 87 bipolar type 1 and 50 bipolar type 2 patients (mean age 50.4 years; 63% women). HADS-A and HADS-D was used to determine the levels of anxiety and depression, the Perceived Stress Questionnaire (PSQ) was used to measure the perception of stress, and experience of pain was determined using a validated pain questionnaire including the duration, characteristics and location of pain. Results: Eighty-six patients (63%) reported pain, and all but 5 of these had chronic pain (≥ 3 months). Patients with pain scored significantly higher on anxiety, depression and perceived stress, and significantly lower on well being than patients with no pain. In a logistic regression using different pain locations as the dependent variables and age, gender, HADS-D, HADS-A and PSQ index score as covariates, female gender was found to be significantly associated with abdominal pain (adjusted OR 4.59; CI: 1.09-19.2), thoracic spine pain (adjusted OR 4.32; CI: 1.37-14.3), shoulder pain (adjusted OR 3.39; CI: 1.17-4.39) and ≥3 pain locations (adjusted OR 2.55; CI: 1.06-6.13. In both males and females the experience of stress was significantly associated with the presence of any pain (adjusted OR 5.56; CI: 1.61-19.2), hip pain (adjusted OR 5.52; CI 1.41-21.7) and neck pain (adjusted OR 3.37; CI: 1.10-10.3). Finally, depressive mood is significantly associated with abdominal pain (adjusted OR 12.1; CI: 2.18-67.9) and knee pain (adjusted OR 5.90; CI:1.47-23.6). Conclusions: In patients with bipolar disorder the experience of stress and depressive mood, but not level of anxiety, is strongly related to pain.