Inflammation, hippocampal volume, and cognition in schizophrenia: results from the Northern Finland Birth Cohort 1966.

Increased blood interleukin-6 (IL-6) levels are a replicated abnormality in schizophrenia, and may be associated with smaller hippocampal volumes and greater cognitive impairment. These findings have not been investigated in a population-based birth cohort. The general population Northern Finland Birth Cohort 1966 was followed until age 43. Subjects with schizophrenia were identified through the national Finnish Care Register. Blood IL-6 levels were measured in n = 82 subjects with schizophrenia and n = 5373 controls at age 31. Additionally, 31 patients with schizophrenia and 63 healthy controls underwent brain structural MRI at age 34, and cognitive testing at ages 34 and 43. Patients with schizophrenia had significantly higher median (interquartile range) blood IL-6 levels than controls (5.31, 0.85-17.20, versus 2.42, 0.54-9.36, p = 0.02) after controlling for potential confounding factors. In both schizophrenia and controls, higher blood IL-6 levels were predictors of smaller hippocampal volumes, but not cognitive performance at age 34. We found evidence for increased IL-6 levels in patients with midlife schizophrenia from a population-based birth cohort, and replicated associations between IL-6 levels and hippocampal volumes. Our results complement and extend the previous findings, providing additional evidence that IL-6 may play a role in the pathophysiology of schizophrenia and associated brain alterations.

Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns.

BACKGROUND: Inflammatory processes contribute to the pathophysiology of multiple chronic conditions. Genetic factors play a crucial role in modulating the inflammatory load, but the exact mechanisms are incompletely understood. OBJECTIVE: To assess genetic determinants of 16 circulating cytokines and cell adhesion molecules (inflammatory phenotypes) in Finns. METHODS: Genome-wide associations of the inflammatory phenotypes were studied in Northern Finland Birth Cohort 1966 (N=5284). A subsequent meta-analysis was completed for 10 phenotypes available in a previous genome-wide association study, adding up to 13 577 individuals in the study. Complementary association tests were performed to study the effect of the ABO blood types on soluble adhesion molecule levels. RESULTS: We identified seven novel and six previously reported genetic associations (p<3.1×10-9). Three loci were associated with soluble vascular cell adhesion molecule-1 (sVCAM-1) level, one of which was the ABO locus that has been previously associated with soluble E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) levels. Our findings suggest that the blood type B associates primarily with sVCAM-1 level, while the A1 subtype shows a robust effect on sE-selectin and sICAM-1 levels. The genotypes in the ABO locus associating with higher soluble adhesion molecule levels tend to associate with lower circulating cholesterol levels and lower cardiovascular disease risk. CONCLUSION: The present results extend the knowledge about genetic factors contributing to the inflammatory load. Our findings suggest that two distinct mechanisms contribute to the soluble adhesion molecule levels in the ABO locus and that elevated soluble adhesion molecule levels per se may not increase risk for cardiovascular disease.

Benzodiazepine Use Is Associated With Poorer Spinal Cord Stimulation Outcome in 373 Neuropathic Pain Patients.

OBJECTIVES: The aim of the study is to investigate whether benzodiazepine use differs between patients with favorable and unfavorable spinal cord stimulation (SCS) treatment outcome. We hypothesize that the patients with unfavorable SCS outcome would exhibit a higher level of benzodiazepine use. MATERIALS AND METHODS: Using a case-control study setting, we examined benzodiazepine use in SCS patients and in matched population controls as a potential risk factor poor SCS outcome. A total of 373 consecutive SCS patients treated in Kuopio University Hospital between 1997 and 2014 and their 1117 matched population controls were followed until patient death or the end of March 2016. RESULTS: Benzodiazepines were used during the 24-month period before or after SCS implantation by 42.3% of the SCS patients who had the device explanted, 39.5% who had an unsuccessful trial stimulation, 28.0% who still had the device at the end of the follow-up period, and 8.0% of the controls. Diazepam use before SCS increased the odds for explanting of SCS by 2.4-fold (95% Cl: 1.0-5.4). Starting clonazepam use after SCS was associated with a 5.2-fold (95% CI: 1.5-18.9) increase in the odds of unsuccessful trial stimulation. CONCLUSION: The benzodiazepine use in patients with poor SCS outcome illustrates the role of anxiety in SCS outcomes and the need for multidisciplinary treatment of pain.

Adverse childhood experiences and alexithymia in patients with major depressive disorder.

The purpose of the article: Adverse childhood experiences (ACEs) have been postulated to negatively affect the development of emotional regulation. However, little is known about specific associations between ACEs, depressive symptoms, and alexithymia or its components [i.e. difficulty in identifying feelings (DIF), difficulty in describing feelings to others (DDF) and externally-oriented thinking (EOT)] in patients with major depressive disorder (MDD). The aims of the present cross-sectional study were to (1) compare ACEs (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) between alexithymic and non-alexithymic patients with MDD; (2) explore whether specific ACEs, depressive symptoms or the interaction between sex and depressive symptoms predicted TAS-20 or its components.Materials and Methods: The study sample consisted of 186 psychiatric outpatients with MDD (aged 21-61 years, mean 33.87 years, SD 10.88) recruited from the Department of Psychiatry, Kuopio University Hospital between 2016-2019. Alexithymia and its components were assessed using the 20-item Toronto Alexithymia Scale (TAS-20). ACEs were assessed with the Trauma and Distress Scale (TADS).Results: Almost all patients with alexithymia and 80% of non-alexithymic patients reported that they had experienced emotional abuse or neglect, at least sometimes. Approximately 60% of MDD patients reported having experienced physical neglect and 30% described physical abuse. Emotional and physical abuse and neglect predicted DDF score.Conclusions: These findings suggest that among MDD patients, early experiences of emotional and physical abuse and neglect is associated with difficulties in describing feelings in adulthood.

Antipsychotic Use Among 1144 Patients After Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- At acute phase and neurointensive care, patients with aneurysmal subarachnoid hemorrhage (aSAH) may become agitated or delirious. We found no previous studies on psychotic disorders or antipsychotic drug (APD) use by long-term aSAH survivors. We defined the APD use and its risk factors among 12-month survivors of aSAH in an Eastern Finnish population-based cohort with long-term follow-up. Methods- We analyzed APD use in 1144 consecutive patients with aSAH alive at 12 months of the Kuopio intracranial aneurysm patient and family database and their age, sex, and birth municipality matched controls (3:1; n=3432) from 1995 to 2013 and median follow-up of 9 years. Using the Finish nationwide health registries, we obtained drug purchase and hospital discharge data. Results- In total, 140 (12%) of the 1144 patients started APD use first time after aSAH (index date), in contrast to 145 (4%) of the 3432 matched population controls. The cumulative rate of starting APD was 6% at 1 year and 9% at 5 years, in contrast to 1% and 2% in the controls, respectively. The rates at 1 and 5 years were only 1% and 2% in the 489 patients with a good condition (modified Rankin Scale score, 0 or 1 at 12 months; no shunt, intracerebral hemorrhage, or intraventricular hemorrhage). Instead, the highest rate of APD use, 23% at 5 years was among the 192 patients shunted for hydrocephalus after aSAH. Eighty-eight (63%) of the 140 aSAH patients with APD use had also concomitant antidepressant or antiepileptic drug use. Conclusions- The 12-month survivors of aSAH were significantly more likely to be started on APD after aSAH than their matched population controls. These patients often used antidepressant and antiepileptic drugs concomitantly. The use of APDs strongly correlated with signs of brain injury after aSAH, with low use if no signs of significant brain injury were present.

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression.

BACKGROUND AND AIM: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD). METHODS: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10 Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1 Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks. RESULTS: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression. CONCLUSIONS: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.

Comparison of early maladaptive schemas between borderline personality disorder and chronic depression.

Borderline personality disorder (BPD) and chronic depression (CD) are common and challenging mental disorders. Maladaptive cognitive schemas have been proposed to increase vulnerability to both disorders. In order to elucidate the role of maladaptive cognitive schemas in BPD and CD, this study compared psychiatric outpatients with BPD (N = 30) and CD (N = 30) in terms of early maladaptive schemas (EMSs). The groups were compared using the Young Schema Questionnaire short form-extended (YSQ-S2-extended) and the 15D health status questionnaire. BPD patients showed higher endorsement on the majority of EMSs, poorer social functioning, and greater concurrent distress than CD patients. However, after controlling for concurrent effects of psychological distress, the groups did not differ in 14 out of the 18 EMSs. These findings point to significant similarities in maladaptive beliefs between the 2 disorders and do not support broad, specific patterns of EMSs associated with either disorder. The results highlight the need for further study of the role of maladaptive schemas in the development and treatment of chronic mental disorders.

The Association Between Musculoskeletal Pain and Circulating Ornithine: A Population-Based Study.

Objective: Based on several previous clinical studies, we hypothesized that ornithine levels are different among subjects with persistent musculoskeletal pain compared with other subjects in the population. Design: The study sample consisted of 221 adults with nonpersistent pain, 76 with persistent pain, and 61 with no pain. Concentrations of glutamic acid, ornithine, citrulline, arginine, proline, and spermidine were analyzed using a mass spectrometer. Setting: Lapinlahti municipality in Finland. Results: For the subjects with no pain, nonpersistent pain, and persistent pain, the ornithine concentrations for men were 85.3 µmol/L (SD = 28.9 µmol/L), 98.9 µmol/L (SD = 37.8 µmol/L), and 102.1 µmol/L (SD = 37.1 µmol/L; P = 0.033), respectively. The corresponding concentrations for women were 82.8 µmol/L (SD = 25.2 µmol/L), 83.7 µmol/L (SD = 27.8 µmol/L), and 103.2 µmol/L (SD = 34.9 µmol/L; P = 0.0031). There were no significant differences between the pain groups for any of the other investigated amino acids. Relative sex-specific ornithine concentration adjusted for age, glomerular filtration rate, smoking, body mass index, physical activity, and depressive symptoms was associated with pain ( P = 0.025), the ornithine level being higher in the persistent pain group than in the no pain ( P = 0.006) and nonpersistent pain ( P = 0.032) groups. Conclusion: Ornithine levels are elevated in general population subjects with persistent pain.

Dietary patterns are associated with the prevalence of alexithymia.

Recent evidence supports the association between healthy dietary patterns and a reduced risk of depression. The objective was: (1) to examine the associations between dietary patterns and alexithymic features; and (2) investigate whether these possible associations are explained by depressive symptoms in a cross-sectional study among the Finnish general population aged 25-65 years. The study population was a part of the population-based Kuopio Depression Study (KUDEP) conducted in central-eastern Finland (n = 1747). Dietary data were collected using a food frequency questionnaire and dietary patterns from 22 predefined food groups, which were extracted by factor analysis. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20) and depression using the 21-item Beck Depression Inventory (BDI-21). Altogether, 173 of the study subjects (9.9%) were alexithymic. Three dietary patterns were identified: "prudent," "Western" and "traditional." Lower scores for a healthy prudent dietary pattern and higher scores for an unhealthy Western dietary pattern were associated with an increased likelihood of belonging to the alexithymic group among subjects with elevated depressive symptoms. Among subjects without depressive symptoms, alexithymia was associated with lower scores in the prudent dietary pattern, but also with higher scores in the traditional dietary pattern. General population subjects with alexithymic features may have unhealthier dietary patterns than non-alexithymic subjects.

Antidepressant Use After Aneurysmal Subarachnoid Hemorrhage: A Population-Based Case-Control Study.

BACKGROUND AND PURPOSE: To elucidate the predictors of antidepressant use after subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) in a population-based cohort with matched controls. METHODS: The Kuopio sIA database includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland, with 3 matched controls for each patient. The use of all prescribed medicines has been fused from the Finnish national registry of prescribed medicines. In the present study, 2 or more purchases of antidepressant medication indicated antidepressant use. The risk factors of the antidepressant use were analyzed in 940 patients alive 12 months after sIA-SAH, and the classification tree analysis was used to create a predicting model for antidepressant use after sIA-SAH. RESULTS: The 940 12-month survivors of sIA-SAH had significantly more antidepressant use (odds ratio, 2.6; 95% confidence interval, 2.2-3.1) than their 2676 matched controls (29% versus 14%). Classification tree analysis, based on independent risk factors, was used for the best prediction model of antidepressant use after sIA-SAH. Modified Rankin Scale until 12 months was the most potent predictor, followed by condition (Hunt and Hess Scale) and age on admission for sIA-SAH. CONCLUSIONS: The sIA-SAH survivors use significantly more often antidepressants, indicative of depression, than their matched population controls. Even with a seemingly good recovery (modified Rankin Scale score, 0) at 12 months after sIA-SAH, there is a significant risk of depression requiring antidepressant medication.

Reduced serum adiponectin levels in alexithymia.

OBJECTIVES: Clinical studies have demonstrated that circulating cytokine profiles may differ between alexithymic and non-alexithymic subjects. We examined whether the levels of adiponectin (µg/ml) and resistin (ng/ml) are independently related to alexithymic features in a population-based sample. METHODS: In 2005, clinical data including laboratory assessments were obtained from a sub-sample (n = 308) of the Kuopio Depression Study general population study including subjects aged 25-64 years. Based on the Toronto Alexithymia Scale score in 1998, 1999, 2001 and 2005, a group of subjects with high alexithymic features (n = 85) was formed and compared with non-alexithymic controls (n = 206). RESULTS: Serum adiponectin levels were significantly lower in subjects with alexithymic features than in non-alexithymic control subjects. No difference was found in resistin levels. Similarly, in a logistic regression model adjusted for age, gender and body mass index (BMI), lowered levels of adiponectin, but not resistin, were associated with an increased likelihood of belonging to the group with alexithymic features. Further adjustments for cardiovascular risk factors (i.e. smoking, BMI, metabolic syndrome, alcohol use, and coronary heart disease), depressive symptoms (Hamilton Depression Rating Scale with 17 items) and the use of antidepressants in addition to age and gender did not change these patterns. CONCLUSIONS: Our findings suggest that a disturbed anti-inflammatory balance may characterize alexithymia. In addition, our results widen the concept of alexithymia and highlight the role of immune system alterations and stress in alexithymic individuals.

Biological and other health related correlates of long-term life dissatisfaction burden.

BACKGROUND: Mental health is interconnected with somatic health and can manifest itself in biological processes. Life dissatisfaction is an indicator of subjective well-being, but information on its biological correlates is scarce. The aim of this study was to investigate the biological correlates along with other health-related factors of long-term life dissatisfaction in a population-based sample. METHODS: As part of the Kuopio Depression Study, health questionnaires were sent to a randomly selected population-based sample in 1998, 1999, and 2001. In 2005, among a clinically studied sub-sample (n = 305), the 7-year long-term life dissatisfaction burden was assessed by summing life satisfaction scores from previous health questionnaires. Several sociodemographic, health, health behavior, and biological factors were investigated in respect to their associations to categorized (low and high) and continuous (linear regression) life satisfaction burden score (higher values indicating dissatisfaction). RESULTS: In the final linear regression model long-term life dissatisfaction burden was significantly associated with poor social support (B = 0.138; p < 0.001), marital status (i.e. living alone) (B = 0.049; p = 0.019), current smoking (B = 0.087; p < 0.001), poor sleep (B = 0.052; p = 0.001), use of statins (B = -0.052; p = 0.002) and lower serum adiponectin level (B = -0.001; p = 0.039) whereas association of metabolic syndrome was marginally nonsignificant (B = 0.029; p = 0.055). CONCLUSION: Long-term life dissatisfaction is associated with adverse health, health behavioral, and social factors, as well as with a decreased anti-inflammatory buffer capacity, all indicating close relationships between subjective well-being and somatic morbidity.

Depression and major weight gain: a 6-year prospective follow-up of outpatients.

BACKGROUND: Depression and weight change are linked, but there is a paucity of studies on their association during clinical treatment. The present study investigated how risk factors for a weight gain of at least 10% (major weight gain) and mental health modify their mutual association during a 6-year prospective follow-up of depressed outpatients. METHOD: The study sample consisted of 121 depressed treatment-seeking outpatients with a mean age of 44.9 years. A 6-year follow-up started in January 1996. At baseline and on follow-up after 2 and 6 years, psychiatric diagnoses were obtained using the Structured Clinical Interview for DSM-III-R (SCID-I), while cluster C personality disorders (PD) were assessed on 6-month follow-up (SCID-II). Depression was also assessed with the Hamilton Rating Scale for Depression (HAM-D) and general psychopathology with the Symptom Checklist-90 (SCL-90) at baseline and at the end of the 6-year follow-up. Weight changes were based on measurements at baseline and at the end of the follow-up. Logistic regression was used to study the factors associated with major weight gain (≥ 10%). RESULTS: Altogether, 16% of the study sample experienced major weight gain during the 6-year follow-up. Adverse childhood/adolescent experiences as a self-perceived cause of depression (OR 3.72, 95% CI 1.06-13.1, p=0.040), higher scores in the HAM-D (OR 1.11, 95% CI 1.02-1.22, p=0.019) and the SCL-90 subscale of anxiety (OR 2.22, 95% CI 1.11-4.42, p=0.023) at baseline, and cluster C PD at 6 months (OR 3.16, 95% CI 1.11-8.97, p=0.031) were separately associated with major weight gain after adjusting for age, gender, and baseline body mass index (BMI). CONCLUSION: The severity of depressive and anxiety symptoms and linking adverse childhood with depression at the beginning of treatment, as well as cluster C PD at 6 months, were predictors of major weight gain.

The role of mental health, personality disorders and childhood adversities in relation to life satisfaction in a sample of general population.

BACKGROUND: Mental health disorders are one of the leading causes of the disease burden globally. AIM: The aim of this population-based study was to investigate the relationship between life satisfaction and mental health by taking into account its less studied areas, such as personality disorders and childhood adversities. METHODS: The sample of this cross-sectional study was derived from a population-based Kuopio Depression Study performed in Eastern Finland. Health questionnaires were mailed in 1998, 1999, 2001 and 2005 including questions on several clinical factors. Questions on childhood home were asked in 1999. The inclusion criteria for the final study sample in 2005 were based on previously repeatedly (1998, 1999, 2001) reported life satisfaction, depression or alexithymic features (with/without). Psychiatric diagnoses of major depressive disorder and personality disorder were confirmed by structured clinical interview I and II for DSM-IV in 2005. Logistic regression analyses were performed to assess the studied relationships. RESULTS: In general, the broad spectrum of poor mental health indicators was associated with concurrent life dissatisfaction. After multiple adjustments, major depressive disorder (MDD), hopelessness and mental distress remained independent correlates of life dissatisfaction, while personality disorder or self-reported childhood adversities lost their significance when these other factors were included in the model. CONCLUSIONS: Mental health is closely interwoven with life satisfaction. Even if personality disorder and childhood adversities were significant correlates of life dissatisfaction, adverse concurrent mental symptoms and features and MDD were its strongest correlates.

Elevated levels of serum IL-5 are associated with an increased likelihood of major depressive disorder.

BACKGROUND: Inflammatory mediators in both the peripheral circulation and central nervous system (CNS) are dysregulated in major depressive disorder (MDD). Nevertheless, relatively little is known about the role of the T-helper (Th)-2 effector cytokines interleukin (IL)-5 and IL-13 in MDD. METHODS: We examined the serum levels of these cytokines and a Th-1 comparison cytokine, interferon (IFN)-γ, in 116 individuals (MDD, n = 58; controls, n = 58). RESULTS: In our basic multivariate model controlling for the effects of potential confounders on the associations between MDD and the examined cytokines, each 1-unit increase in the serum IL-5 level increased the likelihood of belonging to the MDD group by 76% (OR 1.76, 95% CI 1.03-2.99, p = 0.04; model covariates: age, gender, marital status, daily smoking and alcohol use). The likelihood further increased in models additionally controlling for the effects of the use of antidepressants and NSAIDS, and a diagnosis of asthma. No such associations were detected with regard to IL-13 (OR 1.08, 95% CI 0.96-1.22, p = 0.22) or IFN-γ (OR 1.02, 95% CI 0.99-1.05, p = 0.23). CONCLUSIONS: Elevated levels of IL-5, which uses the neural plasticity-related RAS GTPase-extracellular signal-regulated kinase (Ras-ERK) pathway to mediate its actions in the central nervous system (CNS), could be one of the factors underlying the depression-related changes in CNS plasticity.

Low-grade inflammation and depressive symptoms as predictors of abdominal obesity.

AIM: Abundant evidence suggests that depression is a risk factor for cardiovascular disease and metabolic syndrome. Systemic low-grade inflammation and evolving abdominal obesity are hypothesised to be underlying mechanisms explaining the relationship. To test this hypothesis we examined the association of depressive symptoms and inflammation in developing abdominal obesity. METHODS: The subjects were 726 non-diabetic men, 42-60 of age at baseline, participating in the Kuopio Ischemic Heart Disease Risk Factor Study. The follow-up data was collected 11 years after the baseline. Low-grade inflammation was defined as serum C-reactive protein ≥2 mg/l and depressive symptoms were assessed by the Human Population Laboratory Depression Scale. Incident abdominal obesity was defined as waist girth >102 cm. RESULTS: Men with low-grade inflammation and depressive symptoms were more likely (OR 4.28, 95% CI 1.93-12.01) to develop abdominal obesity during the 11-year follow-up than in men not having either of these conditions, adjusting for age, smoking, alcohol consumption, prevalent cardiovascular disease, physical activity and socioeconomic status. These men were also more likely (OR 3.94, 95% CI 1.38-11.26) to develop metabolic syndrome. CONCLUSIONS: The presence of systemic low-grade inflammation together with depressive symptoms seems to detect men at a particularly high risk of developing abdominal obesity over a long period of time.

[Glucocorticoids and aetiopathogenesis of depression]. / Glukokortikoidien yhteys masennuksen syntyyn ja oirekuvaan.

Current research interest is increasingly directed towards the role of glucocorticoid actions and inflammation. A failure in the stress system regulation appears to largely characterize depression. New research data have substantially diversified the theoretical concept of association between overactivity of HPA-axis and depression. The glucocorticoid effects are regulated by glucocorticoid reseptor gene polymorphisms, and glucocorticoid resistance is often associated with depression. Moreover, immune system disturbances affect the development of depression, and an altered balance of pro- and anti-inflammatory cytokines is also observable. Treatment methods that follow the new developments of the glucocorticoid theory are being developed.

Alexithymia and tissue inflammation.

BACKGROUND: Altered immune responses are seen in depression, and recent data suggest that similar changes could also be observable in alexithymia. We examined whether the inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 are independently related to alexithymia or its factors in a population-based sample. METHODS: This study formed a clinical part of the Kuopio Depression (KUDEP) general population study focusing on the mental health of a general population of adults aged 25-64 years (n = 308). Alexithymia was measured using the Toronto Alexithymia Scale (TAS-20), and depressive symptoms were assessed using the Beck Depression Inventory (BDI-21). RESULTS: The levels of IL-6 (in picograms per milliliter) and hs-CRP (in milligrams per liter) were significantly higher in alexithymic than in nonalexithymic subjects (IL-6 effect size, ES: 0.50; hs-CRP ES: 0.27). The BDI scores, hs-CRP and IL-6 explained 33.5% of the variation in TAS scores in the whole study population. According to logistic regression analysis, hs-CRP but not IL-6 increased the likelihood of belonging to the alexithymic group. This observation remained unaltered after additional adjustments for chronic inflammation-related disorders, the use of inflammation-modulating medications and depressive symptoms. CONCLUSIONS: Our findings suggest that the association between hs-CRP and alexithymia resembles that observed in depressed patients. It is, however, independent of depressive symptoms. These findings widen our view on the stress-alexithymia concept.

Long term life dissatisfaction and subsequent major depressive disorder and poor mental health.

BACKGROUND: Poor mental health, especially due to depression, is one of the main public health problems. Early indicators of poor mental health in general population are needed. This study examined the relationship between long-term life dissatisfaction and subsequent mental health, including major depressive disorder. METHOD: Health questionnaires were sent to a randomly selected population-based sample in 1998 and repeated in 1999 and 2001. In 2005, a clinically studied sub-sample (n = 330) was composed of subjects with (n = 161) or without (n = 169) repeatedly reported adverse mental symptoms at all three previous data collection times. Clinical symptom assessments were performed with several psychometric scales: life satisfaction (LS), depression (HDRS, BDI), hopelessness (HS), mental distress (GHQ), dissociative experiences (DES), and alexithymia (TAS). The long-term life dissatisfaction burden was calculated by summing these life satisfaction scores in 1998, 1999, 2001 and dividing the sum into tertiles. Psychiatric diagnoses were confirmed by SCID-I for DSM-IV in 2005. Logistic regression analyses were performed to assess the studied relationship. RESULTS: The previous life dissatisfaction burden associated with adverse socio-demographic, life style and clinical factors. In adjusted logistic regression analyses, it was independently and strongly associated with subsequent major depressive disorder in 2005, even when the concurrent LS score in 2005 was included in the model. Excluding those with reported major depressive disorder in 1999 did not alter this finding. LIMITATIONS: MDD in 1999 was based on self-reports and not on structured interview and LS data in 2001-2005 was not available. CONCLUSIONS: The life satisfaction burden is significantly related to major depressive disorder and poor mental health, both in cross-sectional and longitudinal settings.

Sedentary lifestyle and emergence of hopelessness in middle-aged men.

BACKGROUND: A sedentary lifestyle and psychosocial factors such as hopelessness and depression increase cardiovascular risk. Cross-sectional evidence suggests positive effects of physical exercise on psychological well being, but the time order of the relationship between physical activity and hopelessness has not been addressed. DESIGN: Population-based prospective cohort study with 630 middle-aged men participating in the 4-year follow-up and 509 men in the 11-year follow-up. METHODS: We investigated the association of leisure-time physical activity (LTPA) with the development of hopelessness during the follow-up. LTPA and hopelessness were quantified with questionnaires. RESULTS: In cross-sectional analyses, LTPA was inversely associated with hopelessness, independently of depression. Among men who did not have feelings of hopelessness at baseline, those who reported engaging in at least 2.5 h/week of moderate-to-vigorous physical activity had a lower risk (odds ratio 0.65, 95% confidence interval: 0.39-1.09, P for the trend=0.047) to feel hopeless than sedentary men 4 years later after adjustment for age, smoking, alcohol consumption, cardiovascular disease and socioeconomic status. Furthermore, this relationship was not explained by body mass index or maximal oxygen uptake. Adjustment for depressive symptoms slightly weakened the association (odds ratio 0.66, 95% confidence interval: 0.39-1.11, P for the trend=0.060). After 11 years, men who reported being physically active at baseline were still less likely to feel hopeless, after adjusting for age. However, after further adjustment for other confounding factors the association was no longer significant. CONCLUSION: Moderate-to-vigorous physical activity seems to prevent development of hopelessness in middle-aged men. This protective effect may diminish over time.