Åsa Westrin

Cytokine levels in the blood may distinguish suicide attempters from depressed patients.

Elevated plasma cytokines is a common finding in Major Depressive Disorder (MDD), although not consistent. It is currently not known whether the inflammatory changes are confined to any specific subgroup of depressive patients. We here analyzed three inflammatory markers in suicidal and non-suicidal depressed patients, as well as healthy controls. Plasma interleukin (IL)-2, IL-6 and tumor necrosis factor (TNF)-α were measured in 47 suicide attempters, 17 non-suicidal depressed patients and 16 healthy controls. Study participants were evaluated using the Comprehensive Psychopathological Rating Scale (CPRS) with subscales for anxiety and degree of depression, as well as the Suicide Assessment Scale (SUAS). We found increased levels of IL-6 and TNF-α as well as decreased IL-2 concentrations in suicide attempters compared to non-suicidal depressed patients and healthy controls. The results were adjusted for potential confounders of cytokine expression, such as age, sex, body mass index (BMI), degree of depression, anxiety, personality disturbance, abuse and type of medication. These results demonstrate for the first time that suicidal patients display a distinct peripheral blood cytokine profile compared to non-suicidal depressed patients. Thus, our study provides further support for a role of inflammation in the pathophysiology of suicidality.

Alterations of corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) plasma levels in mood disorder patients with a recent suicide attempt.

In order to receive a further understanding of stress-regulation in depressed suicide attempters, peptides that are supposed to be related to the stress system (the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system) were studied in plasma. When compared with healthy controls, cortisol was high (p<0.001) and corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) appeared to be low (p<0.001) in patients who had recently attempted suicide. Patients who had repeatedly attempted suicide had the lowest NPY. A correlation between NPY and cortisol (p<0.05) was found in suicidal patients with depression NOS, whereas beta-endorphins correlated with cortisol (p<0.01) in suicidal patients with major depressive disorder. A postdexamethasone decrease of NPY was noted in the controls but not in the patients. These results suggest stress system alterations in suicidal patients with mood disorders.

The acute response of plasma brain-derived neurotrophic factor as a result of exercise in major depressive disorder.

Brain-derived neurotrophic factor (BDNF) and other neurotrophins are believed to play an important role in affective disorders. In this study we investigated plasma-BDNF response during an incremental exercise test in 18 patients suffering from moderate major depressive disorder (MDD) and 18 controls. The patients were not treated with antidepressants or neuroleptics. Possible associations between plasma plasma-BDNF levels, dexamethasone suppression test cortisol levels and Montgomery-Asberg Depression Rating Scale (MADRS) scores were also tested. No difference in basal BDNF levels between patients and controls was found. BDNF increased significantly during exercise in both male and female patients as well as in male controls, with no significant differences between the groups. BDNF levels declined after exercise, but after 60 min of rest BDNF levels showed tendencies to increase again in male patients. No correlation between BDNF and cortisol or MADRS scores was found. We conclude that unmedicated patients with moderate depression and normal activity of the hypothalamic-pituitary-adrenal axis do not have a disturbed peripheral BDNF release during exercise. The BDNF increase 60 min after interruption of exercise in male patients might indicate up-regulated BDNF synthesis, but this needs to be further investigated in future studies.

Temperament traits in seasonal affective disorder, suicide attempters with non-seasonal major depression and healthy controls

BACKGROUND Very few studies have compared the temperament traits in matched suicidal and non-suicidal patients with major depression. METHODS We compared the temperament traits in two matched groups of patients with major depressive disorder (MDD), MDD with seasonal subtype (SAD) without any suicide attempt (n = 23) and MDD without seasonal variation who attempted suicide (non-SAD SA), and compared the patients to matched healthy controls by using the Karolinska Scales of Personality (KSP) and the Marke-Nyman Temperament (MNT) questionnaires. RESULTS Both the SAD and non-SAD SA groups showed significantly higher Somatic Anxiety, Muscular Tension, Psychasthenia, Irritability, Suspicion, and lower Socialization and Validity than the controls. The non-SAD SA group also showed significantly higher Psychic Anxiety, Detachment and Guilt as compared to controls. When the SAD and the non-SAD SA were compared, we found significantly higher Somatic Anxiety, Psychic Anxiety and Muscular Tension for the non-SAD SA group. CONCLUSIONS Both SAD and non-SAD SA patients display different temperament profiles compared to controls and in comparison with each other and the suicide attempters show especially high trait anxiety and hostility. CLINICAL RELEVANCE The results suggest that trait anxiety and hostility, but not impulsivity, are associated with suicidal behavior in major depression.

Long-term and preventative treatment for seasonal affective disorder

Recurrent major depressive disorder with regular seasonal patterns, commonly known as seasonal affective disorder (SAD), has evoked substantial research in the last two decades. It is now recognised that SAD is a common condition with prevalence rates between 0.4% and 2.9% of the general population, and that patients with SAD experience significant morbidity and impairment in psychosocial function.There is good evidence that bright light therapy and antidepressant medications are effective for the short-term treatment of SAD; however, given that SAD is characterised by recurrent major depressive episodes, long-term and maintenance treatment must be considered. Unfortunately, there are few studies of longer term (>8 weeks) and maintenance (preventative) treatments for SAD. The weight of evidence suggests that light therapy usually needs to be continued daily throughout the winter season because of rapid relapse when light is stopped too early in the treatment period. However, some studies support the use of antidepressants to continue the response from a brief (1–2 weeks) course of light therapy early in the depressive episode, as soon as the first symptoms emerge in autumn. Only small studies have examined preventative treatment (before onset of symptoms) with light therapy, all of which have methodological limitations. The best evidence for preventative treatment in SAD comes from antidepressant studies. Three large, randomised, placebo-controlled studies have shown that preventative treatment with bupropion XL reduces the recurrence rate of depressive episodes in patients with SAD.Given the limitations in the evidence base and the inconsistent recurrence rate of winter depressive episodes, clinical recommendations for long-term and preventative treatment must individualise treatment choices and weigh potential benefits against possible adverse effects.

Correlations between plasma-neuropeptides and temperament dimensions differ between suicidal patients and healthy controls.

BACKGROUND Decreased plasma levels of plasma-neuropeptide Y (NPY) and plasma-corticotropin releasing hormone (CRH), and increased levels of plasma delta-sleep inducing peptide (DSIP) in suicide attempters with mood disorders have previously been observed. This study was performed in order to further understand the clinical relevance of these findings. METHODS Examination of correlates between temperament dimensions (Karolinska Scales of Personality (KSP), the Eysenck Personality Questionnaire together with the IVE- impulsiveness scale (EPQI), and the Marke-Nyman Temperament (MNT)) and NPY, CRH and DSIP and serum-cortisol in the dexamethasone suppression test (DST) in 38 suicidal patients and matched controls. RESULTS NPY correlated significantly and positively with psychasthenia, irritability, and stability and significantly and negatively with validity in patients, but significantly and negatively with muscular tension, psychasthenia, verbal aggression and irritability in controls. DSIP correlated significantly and positively with impulsiveness (EPQI) in controls. CRH correlated negatively with lie in controls. Cortisol correlated significantly and positively with validity, extraversion and verbal aggression and significantly and negatively with inhibition of aggression in controls. CONCLUSION NPY may be related to stress tolerance. DSIP seems to be associated with impulsivity/antisocial traits. LIMITATIONS Non-suicidal patients were not included in the examination. CLINICAL RELEVANCE The state of depression or stress seems to influence the correlations studied.

Exercise-induced release of cytokines in patients with major depressive disorder.

BACKGROUND Patients with major depressive disorder (MDD) may display elevated plasma levels of pro-inflammatory substances. Although the underlying mechanisms are unknown, inflammation has been proposed to play a direct role in the generation of depressive symptoms. Skeletal muscle is a potent producer of cytokines, and physical exercise has been suggested to alleviate symptoms of depression. In this study we therefore addressed the question of whether MDD patients display altered levels of pro-, anti-inflammatory and regulatory factors in the blood in response to acute exercise. METHODS Eighteen MDD patients and 18 healthy controls performed a maximal-workload exercise challenge. Blood samples were taken before the test, at sub-maximal and maximal workload, as well as 30 and 60 min after testing. The plasma levels of SAA, TNF-alpha, S-VCAM, S-ICAM, CRP, IFN-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 and IL-13 were assayed using multiplex sandwich ELISA. RESULTS Exercise-induced significant changes in the plasma levels of inflammatory substances in both MDD patients and controls. IL-8, IL-6 and TNF-alpha increased, and IL-4 decreased during the challenge in both groups. In addition, IFN-gamma decreased in the controls. There was a significant difference in IL-6 reactivity between the groups at the sub-max timepoint. LIMITATIONS Group sizes are comparably limited. CONCLUSION Exercise induces changes in the blood levels of cytokines in unmedicated MDD patients. Whether these changes affect symptoms of depression should be evaluated in long-term studies of the anti-depressive effects of exercise.

The dexamethasone suppression test and CSF-5-HIAA in relation to suicidality and depression in suicide attempters.

This study tested suicidality in relation to cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and the dexamethasone suppression test. Patients with nonsuppression of cortisol had the highest scores of the Suicide Assessment Scale (SUAS) and the Montgomery Asberg Depression Rating Scale (MADRS), respectively (P < 0.05; P < 0.01). The results persisted when analysed for covariance with CSF-5-HIAA. We have previously noted an elevated suicide risk in suicide attempters with high SUAS-scores, why a large part of nonsuppressors may be at high risk for future suicide.

Growth hormone, prolactin and cortisol response to exercise in patients with depression

BACKGROUND A blunted growth hormone and prolactin response to pharmacological stress test have previously been found in depressed patients, as well as an increased cortisol response to psychosocial stress. This study investigated these hormones in response to acute exercise using an incremental bicycle test. METHOD A cross-sectional comparison of cortisol, growth hormone, and prolactin in depressed (n=137) and healthy (n=44) subjects during rest and in response to an incremental bicycle test. Secondly, we tested the depressed patients again after a 4-month randomized naturalistic exercise intervention. RESULTS Resting plasma levels of growth hormone (GH), cortisol, or prolactin (PRL) did not differ between depressed and healthy subjects (all p-values>.12). In response to an incremental bicycle test the GH (p=.02) and cortisol (p=.05) response in depressed was different compared to healthy controls. The effect of acute exercise stress on PRL (p=.56) did not differ between depressed and healthy subjects. Apart from a decrease in GH response in the strength-training group (p=.03) the pragmatic exercise intervention did not affect resting hormonal levels, or the response to acute exercise. CONCLUSIONS Patients with mild to moderate depression had a different growth hormone and cortisol response to acute exercise stress compared to healthy controls. Strength training was able to reduce the growth hormone response to acute exercise stress in this patient population. Studies with more rigorous inclusion criteria and higher exercise frequencies are needed to evaluate and confirm the possible effect of exercise in depressed subjects.

CSF testosterone in 43 male suicide attempters.

Several studies have shown a relationship between high testosterone and violent aggressive behaviour. The general aim of this study was to gain knowledge of the importance of testosterone in suicide attempters. Testosterone in cerebrospinal fluid (CSF) was analysed in men with a recent suicide attempt, diagnostically subdivided into groups according to DSM-III-R axis I and II diagnosis and mode of suicidal behaviour. In general, our patients had lower CSF testosterone levels than aggressive violent patients in other studies. Patients with depression NOS or dysthymia showed higher CSF testosterone levels than the rest. Significant positive correlation between testosterone and irritability or a negative correlation with social desirability was found in diagnostic subgroup of patients, specifically axis II, cluster B personality disorders. The results suggest that suicide attempts may be mediated by different biological variables than aggression.