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Abstract 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.

Abstract 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.

Abstract Background Previous research has shown an association between preoperative depressive symptoms and a poorer surgery outcome in lumbar spinal stenosis (LSS). It is not known whether depressive symptoms throughout the recovery period are relevant to the outcome of surgery in LSS. In this prospective clinical study the predictive value of preoperative and postoperative depressive symptoms with respect to the surgery outcome is reported. Methods 96 patients (mean age 62 years) with symptomatic lumbar spinal stenosis underwent decompressive surgery. They completed the same set of questionnaires preoperatively and 3 months, 6 months, 1 year and 2 years postoperatively. Depressive symptoms were assessed with the 21-item Beck Depression Inventory. Physical functioning and pain were assessed with the Oswestry Disability Index, the Stucki Questionnaire, self-reported walking ability and VAS rating. Logistic regression analyses were used to examine the predictive value of preoperative and postoperative depressive symptoms regarding the surgery outcome. A "good" outcome was defined in two ways: first, by gaining a 30% improvement in relation to the preoperative disability and pain, and second, by having a score at or below the median value for disability and pain on 2-year follow-up. Results Having elevated depressive symptoms particularly on 3-month follow-up was predictive of a poorer surgery outcome regarding pain and disability: when the outcome was defined as less than 30% improvement from the baseline, the OR's (with 95% confidence intervals) were 2.94 (1.06-8.12), Conclusions Preoperative and postoperative depressive symptoms may indicate those patients at greater risk of a poorer postoperative functional ability. For these patients, further clinical evaluation should be carried out, especially during postoperative stages.

Abstract Background Unemployment is a source of acute and long-term psychosocial stress. Acute and chronic psychosocial stress can induce pronounced changes in human immune responses. In this study we tested our hypothesis that stress-induced low-grade tissue inflammation is more prevalent among the unemployed. Methods We determined the inflammatory status of 225 general population subjects below the general retirement age (65 years in Finland). Those who had levels of both interleukin-6 (≥ 0.97 pg/mL) and high-sensitivity C-reactive protein (≥ 1.49 mg/L) above the median were assessed to have an elevated inflammatory status (n = 72). Results An elevated inflammatory status was more common among the unemployed than among other study participants (59% versus 30%, p = 0.011). In the final multivariate model, those who were unemployed had over five-fold greater odds for having an elevated inflammatory status (OR 5.20, 95% CI 1.55-17.43, p = 0.008). Conclusion This preliminary finding suggests that stress-induced low-grade inflammation might be a link between unemployment and ill health.

Abstract Background Leisure-time physical activity (LTPA) and cardiorespiratory fitness contribute to mental health. Hopelessness has been linked to impaired mental health, cardiovascular events and mortality. Previous studies have focused on physical exercise and depression. We examined the associations of LTPA and cardiorespiratory fitness with feelings of hopelessness. Methods In this cross-sectional study leisure-time physical activity, maximal oxygen uptake (VO2max), hopelessness and cardiovascular risk factors were assessed in a population-based cohort of 2428 men aged 42 – 60 years old at baseline. Results Men feeling more hopeless about their future and reaching goals were less physically active, less fit and had a higher prevalence of many cardiovascular risk factors than men with lower levels of hopelessness. In a logistic regression model adjusted for age, smoking, alcohol consumption, cardiovascular disease and socioeconomic status, men engaging in less than 60 min/week of moderate-to-vigorous LTPA were 37% (95% CI 11 – 67%) more likely to feel hopeless than those engaging in at least 2.5 h/wk of LTPA. After further adjusting for elevated depressive symptoms the association of LTPA and hopelessness remained significant. VO2max was also associated with hopelessness, but not after adjustment for depressive symptoms. Conclusion Moderate and vigorous LTPA and cardiorespiratory fitness were inversely associated with hopelessness in these middle-aged men. These findings suggest that physical inactivity and poor cardiorespiratory fitness is an important associate of hopelessness, a distinct element of low subjective well-being.

Abstract Background Psychiatric treatment of suicidal youths is often difficult and non-compliance in treatment is a significant problem. This prospective study compared characteristics and changes in cognitive functioning, self image and psychosocial functioning among 13 to 18 year-old adolescent psychiatric inpatients with suicide attempts (n = 16) and with no suicidality (n = 39) Methods The two-group pre-post test prospective study design included assessments by a psychiatrist, a psychologist and medical staff members as well as self-rated measures. DSM-III-R diagnoses were assigned using the SCID and thereafter transformed to DSM-IV diagnoses. Staff members assessed psychosocial functioning using the Global Assessment Scale (GAS). Cognitive performance was assessed using the Wechsler Adult Intelligence Scale, while the Offer Self-Image Questionnaire (OSIQ) was used to assess the subjects' self-image. ANCOVA with repeated measures was used to test changes from entry to discharge among the suicide attempters and non suicidal patients. Logistic regression modeling was used to assess variables associated with an improvement of 10 points or more in the GAS score. Results Among suicide attempter patients, psychosocial functioning, cognitive performance and both the psychological self and body-image improved during treatment and their treatment compliance and outcome were as good as that of the non-suicidal patients. Suicidal ideation and hopelessness declined, and psychosocial functioning improved. Changes in verbal cognitive performance were more pronounced among the suicide attempters. Having an improved body-image associated with a higher probability of improvement in psychosocial functioning while higher GAS score at entry was associated with lower probability of functional improvement in both patient groups. Conclusion These findings illustrate that a multimodal treatment program seems to improve psychosocial functioning and self-image among severely disordered suicidal adolescent inpatients. There were no changes in familial relationships, possibly indicating a need for more intensive family interventions when treating suicidal youths. Multimodal inpatient treatment including an individual therapeutic relationship seems recommendable for severely impaired psychiatric inpatients tailored to the suicidal adolescent's needs.

Abstract Background While physical health has improved considerably over recent decades in Finland, the disease burden of mental health, especially that of depression, has become increasingly demanding. However, we lack long-term data on the natural course of subjective well-being in the general population. The aim of this study was to investigate the long-term course of self-reported life satisfaction. Methods This was a 15-year prospective cohort study on a nationwide sample of adult Finnish twins (N = 9679), aged 18–45 and healthy at baseline, who responded to postal questionnaires in 1975, 1981 and 1990 including a 4-item life satisfaction scale (happiness/easiness/interest in life and feelings of loneliness). Life satisfaction score (range: 4–20) was classified into three categories: satisfied (4–6), intermediate (7–11) and dissatisfied group (12–20). The associations between life satisfaction scores during the follow-up were studied with linear/logistic regression. Results Moderate stability and only a slight effect of age or birth-cohort on mean life satisfaction score (LS) were detected. In 1990, 56% of all and 31% of the dissatisfied remained in the same LS category as at baseline. Only 5.9% of the study subjects changed from being satisfied to dissatisfied or vice versa. Correlations between continuous scores (1975, 1981 and 1990) were 0.3–0.4. Baseline dissatisfaction (compared to satisfaction) predicted dissatisfaction in 1981 (OR = 10.4; 95%CI 8.3–13.1) and 1990 (5.6; 4.6–6.8). Multiple adjustments decreased the risk only slightly. Conclusions Life satisfaction in adult Finns was moderately stable during 15 years. Among an identifiable group (i.e. the dissatisfied) life dissatisfaction may become persistent, which places them at a greater risk of adverse health outcomes.

Abstract Background Despite of an increasing body of research the associations between vitamin B12 and folate levels and the treatment outcome in depressive disorders are still unsolved. We therefore conducted this naturalistic prospective follow-up study. Our aim was to determine whether there were any associations between the vitamin B12 and folate level and the six-month treatment outcome in patients with major depressive disorder. Because vitamin B12 and folate deficiency may result in changes in haematological indices, including mean corpuscular volume, red blood cell count and hematocrit, we also examined whether these indices were associated with the treatment outcome. Methods Haematological indices, erythrocyte folate and serum vitamin B12 levels were determined in 115 outpatients with DSM-III-R major depressive disorder at baseline and serum vitamin B12 level again on six-month follow-up. The 17-item Hamilton Depression Rating Scale was also compiled, respectively. In the statistical analysis we used chi-squared test, Pearson's correlation coefficient, the Student's t-test, analysis of variance (ANOVA), and univariate and multivariate linear regression analysis. Results Higher vitamin B12 levels significantly associated with a better outcome. The association between the folate level and treatment outcome was weak and probably not independent. No relationship was found between haematological indices and the six-month outcome. Conclusion The vitamin B12 level and the probability of recovery from major depression may be positively associated. Nevertheless, further studies are suggested to confirm this finding.

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. [ABSTRACT FROM AUTHOR]

Aims: Aberrant dopamine transmission in extrastriatal brain regions has been repeatedly illustrated among patients with schizophrenia. Differences between typical and second-generation antipsychotics in dopamine D2 receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D2/3 receptor apparent binding potential (BPapp) and occupancy in midbrain and temporal cortex among clozapine-, olanzapine- and haloperidol-treated schizophrenia patients. Methods: Dopamine D2/3 binding was studied on single-photon emission computed tomography ligand [123I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug-naïve patients and seven healthy controls. Results: Statistically significant differences in midbrain dopamine D2/3 receptor BPapp ( P = 0.015) and occupancy ( P = 0.016) were observed between the clozapine, olanzapine and haloperidol groups. The lowest occupancy was found in clozapine-treated patients (5%), followed by olanzapine-treated patients (28%), compared to haloperidol-treated patients (40%). No significant differences were observed in the temporal poles. Occupancy changed substantially depending on the comparison group used (either drug-naïve vs healthy controls) in the examined brain areas ( P = 0.001), showing an overestimation with all antipsychotics when the healthy control group was used. Conclusion: Both typical and second-generation antipsychotics occupy cortical dopamine D2/3 receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D2/3 occupancy between classical antipsychotics and second-generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Leisure-time physical activity (LTPA) and cardiorespiratory fitness contribute to mental health. Hopelessness has been linked to impaired mental health, cardiovascular events and mortality. Previous studies have focused on physical exercise and depression. We examined the associations of LTPA and cardiorespiratory fitness with feelings of hopelessness. Methods: In this cross-sectional study leisure-time physical activity, maximal oxygen uptake (VO2max), hopelessness and cardiovascular risk factors were assessed in a population-based cohort of 2428 men aged 42 - 60 years old at baseline. Results: Men feeling more hopeless about their future and reaching goals were less physically active, less fit and had a higher prevalence of many cardiovascular risk factors than men with lower levels of hopelessness. In a logistic regression model adjusted for age, smoking, alcohol consumption, cardiovascular disease and socioeconomic status, men engaging in less than 60 min/ week of moderate-to-vigorous LTPA were 37% (95% CI 11 - 67%) more likely to feel hopeless than those engaging in at least 2.5 h/wk of LTPA. After further adjusting for elevated depressive symptoms the association of LTPA and hopelessness remained significant. VO2max was also associated with hopelessness, but not after adjustment for depressive symptoms. Conclusion: Moderate and vigorous LTPA and cardiorespiratory fitness were inversely associated with hopelessness in these middle-aged men. These findings suggest that physical inactivity and poor cardiorespiratory fitness is an important associate of hopelessness, a distinct element of low subjective well-being. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the dopamine function of the temporal cortex in major depressive disorder using [123I]epidepride to image D2/3 receptor binding sites. Ten major depressives and 10 healthy controls were selected from a general population sample for single-photon emission computed tomography imaging. Among the major depressives there was a strong bilateral correlation between the scores on the 21-item Hamilton Depression Rating Scale and D2/3 receptor binding. Dopaminergic abnormalities may be present in the temporal cortices of major depressives. [ABSTRACT FROM AUTHOR]

Background: Despite of an increasing body of research the associations between vitamin B12 and folate levels and the treatment outcome in depressive disorders are still unsolved. We therefore conducted this naturalistic prospective follow-up study. Our aim was to determine whether there were any associations between the vitamin B12 and folate level and the six-month treatment outcome in patients with major depressive disorder. Because vitamin B12 and folate deficiency may result in changes in haematological indices, including mean corpuscular volume, red blood cell count and hematocrit, we also examined whether these indices were associated with the treatment outcome. Methods: Haematological indices, erythrocyte folate and serum vitamin B12 levels were determined in 115 outpatients with DSM-III-R major depressive disorder at baseline and serum vitamin B12 level again on six-month follow-up. The 17-item Hamilton Depression Rating Scale was also compiled, respectively. In the statistical analysis we used chi-squared test, Pearson's correlation coefficient, the Student's t-test, analysis of variance (ANOVA), and univariate and multivariate linear regression analysis. Results: Higher vitamin B12 levels significantly associated with a better outcome. The association between the folate level and treatment outcome was weak and probably not independent. No relationship was found between haematological indices and the six-month outcome. Conclusion: The vitamin B12 level and the probability of recovery from major depression may be positively associated. Nevertheless, further studies are suggested to confirm this finding. [ABSTRACT FROM AUTHOR]