Search

Background: Bipolar disorder may be associated with peripheral immune system dysfunction; however, results in individual studies are conflicting. Our aim was to systematically review evidence of peripheral cytokine alterations in bipolar disorder integrating findings from various affective states., Methods: We conducted a meta-analysis of studies comparing peripheral cytokine concentrations in patients with bipolar disorder with healthy control subjects. Results were reported according to the PRISMA statement., Results: Eighteen studies with a total of 761 bipolar disorder patients and 919 healthy controls were included. Overall, concentrations of soluble Interleukin (IL)-2 receptor (sIL-2R), tumor necrosis factor-α (TNF-α), soluble tumor necrosis factor receptor type 1 (sTNFR1) (p < 0.001 each), sIL-6R (p = 0.01) and IL-4 (p = 0.04) were significantly higher in bipolar patients compared with healthy controls. There were no significant differences between bipolar disorder patients and healthy control subjects for IL-1, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12, IL-1β, IL-1 receptor antagonist (IL-1RA), interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1) and sTNFR2., Conclusions: Employing a global approach, incorporating evidence across affective states, this meta-analysis found some support for peripheral inflammatory alterations in bipolar disorder. Results were limited by heterogeneity between studies, insufficient standardization and lacking control for confounders in individual studies. Further research exploring the role of the peripheral inflammatory system in relation to neuroinflammation is warranted., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk., Method: In a high-risk study, 234 healthy monozygotic and dizygotic twins with and without a co-twin history of affective disorder (high- and low-risk twins, respectively) were identified through nationwide registers and assessed at baseline using the Schedules for Clinical Assessment in Neuropsychiatry, the 17-item Hamilton Depression Rating Scale (HDRS), and the cognitive tests Trail Making Test Parts A and B, the Stroop test, and the Cambridge Cognitive Examination-Revised (CAMCOR). Participants were followed longitudinally at 6-month intervals for up to 9 years and finally reassessed with a personal interview to obtain information on whether they had developed psychiatric illness. The study was conducted between 2003 and 2012., Results: 36 participants (15.4%) developed psychiatric disorder, mainly affective and anxiety disorders (31 diagnoses) (ICD-10). Onset was predicted by decreased executive function as reflected by performance on the Trail Making Test A - B (hazard ratio [HR] = 1.02; 95% CI, 1.00-1.03) when adjusted for sex, age, years of education and HDRS score at baseline. Reduced global cognitive function as indicated by a lower CAMCOR score at baseline showed a trend toward an association with subsequent illness onset (P = .08). With regard to the 5 CAMCOR subscales, lower scores on attention (HR = 0.71; 95%, CI, 0.54-0.94) and language (HR = 0.76; 95% CI, 0.58-0.99) were significantly associated with subsequent illness onset., Conclusions: Among healthy individuals at heritable risk for affective disorder, discrete cognitive deficits, especially within executive function and attention, seem to predict subsequent onset of affective illness., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

Introduction: Electronic self-monitoring of affective symptoms using cell phones is suggested as a practical and inexpensive way to monitor illness activity and identify early signs of affective symptoms. It has never been tested in a randomised clinical trial whether electronic self-monitoring improves outcomes in bipolar disorder. We are conducting a trial testing the effect of using a Smartphone for self-monitoring in bipolar disorder., Methods: We developed the MONARCA application for Android-based Smartphones, allowing patients suffering from bipolar disorder to do daily self-monitoring-including an interactive feedback loop between patients and clinicians through a web-based interface. The effect of the application was tested in a parallel-group, single-blind randomised controlled trial so far including 78 patients suffering from bipolar disorder in the age group 18-60 years who were given the use of a Smartphone with the MONARCA application (intervention group) or to the use of a cell phone without the application (placebo group) during a 6-month study period. The study was carried out from September 2011. The outcomes were changes in affective symptoms (primary), social functioning, perceived stress, self-rated depressive and manic symptoms, quality of life, adherence to medication, stress and cognitive functioning (secondary and tertiary)., Analysis: Recruitment is ongoing., Ethics: Ethical permission has been obtained., Dissemination: Positive, neutral and negative findings of the study will be published., Registration Details: The trial is approved by the Regional Ethics Committee in The Capital Region of Denmark (H-2-2011-056) and The Danish Data Protection Agency (2013-41-1710). The trial is registered at ClinicalTrials.gov as NCT01446406.

This study aims to investigate whether: familial history of affective disorder, subclinical depressive symptoms and life events (LEs) are predictive of a later development of mood disorder (onset). In a high-risk study, 234 healthy monozygotic and dizygotic twins with and without a co-twin history of affective disorder (high and low risk twins, respectively) were identified through nationwide registers and assessed from 2002 to 2005. Participants were followed longitudinally at 6-months intervals for up to nine years and finally reassessed with a personal interview to obtain information on whether they had an onset. During the follow-up period (mean time 7.0 years), 36 participants (15.4%) developed onset. Onset was significantly associated with risk status (Hazard ratio (HR) = 1.38, 95% CI 1.08-1.76), female sex, HR = 2.70, 95% CI 1.19-6.97, age HR = 0.97, 95% CI 0.93-0.99), and also with baseline Hamilton 17 score (HR = 1.30, 95% CI 1.13-1.48), Becks Depression Inventory 21 (HR = 1.14, 95% CI, 1.05-1.24) and neuroticism (HR = 1.08, 95% 1.02-1.12). Finally, the experience of LEs lifetime before baseline predicted onset (HR = 1.20, 95% CI 1.01-1.46) and the experience of LEs during follow-up also predicted onset (HR = 1.06, 95% CI 1.01-1.11). These findings suggest that young individuals at familial risk of affective disorders are at enhanced risk of onset and at further risk when having female sex and more subclinical depressive symptoms at baseline. Further, they seem to experience more LEs and to be more vulnerable to these., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The duration of untreated illness has been considered a likely predictor of the course of psychotic disorders. However, there is only sparse data concerning the influence of treatment delay on the outcome of mood disorders. The present study aimed to assess the effect of prolonged untreated depression on the outcome of antidepressant treatment., Method: Patients aged 18-70 years with recent onset of the first lifetime depressive episode were systematically recruited by the Danish Psychiatric Central Research Register during a 2-year period. A total number of 399 individuals out of 1006 potential participants in the Register were interviewed, and 270 fulfilled the inclusion criteria. The validity of the diagnosis, duration of untreated illness, remission on first-line antidepressant treatment and a number of covariates, including psychiatric co-morbidity, personality disorders and traits, stressful life events prior to onset, and family history of psychiatric illness, were assessed by structured interviews., Results: The remission rate was significantly decreased among patients with six months or more of untreated depression as compared to patients who were treated with antidepressant medication earlier after onset (21.1% versus 33.7%, OR=0.5, 95% CI 0.3 to 0.9, p=0.03). The negative influence of a prolonged DUI on the outcome did not seem confounded by any of a wide range of demographic and clinical variables., Limitations: The outcome was evaluated retrospectively. The findings cannot be generalized to patients outside hospital settings., Conclusion: Initiation of antidepressant treatment more than six months after onset of first episode depression reduces the chance of obtaining remission. The results emphasize the importance of early recognition and treatment of patients suffering from depression., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according to affective state., Methods: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement., Results: Thirteen studies were included, comprising 556 bipolar disorder patients and 767 healthy controls, evaluating 15 different cytokines-, cytokine receptors- or cytokine antagonists. The levels of tumor necrosis factor-α (TNF-α), the soluble tumor necrosis factor receptor type 1 (sTNF-R1) and the soluble inlerleukin-2 receptor (sIL-2R) were elevated in manic patients compared with healthy control subjects (p<0.01 for each). Levels of sTNF-R1 and TNF-α were elevated in manic patients compared to euthymic patients (p=0.01 and p=0.04, respectively). sTNF-R1 levels were elevated in euthymic patients compared with healthy control subjects (p<0.01). There were no significant findings for other comparisons, including intra-individual alterations of cytokine levels., Limitations: Stratification according to mood state resulted in small study numbers for some cytokines. Findings were limited by heterogeneity, small sample sizes and a lack of control for confounding factors in individual studies., Conclusions: This meta-analysis found some support for immune dysregulation in bipolar disorder. Future research is warranted to elucidate the role of endogenous cytokine alterations in bipolar disorder. Clinical studies examining longitudinal changes within individuals are recommended., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The effect of selective serotonin reuptake inhibitors (SSRI) on healthy individuals remains unclear. We tested the hypothesis that escitalopram decreases perceived stress and salivary cortisol. The trial has a randomised, blinded, placebo-controlled, parallel-group design. After informed consent 80 healthy first-degree relatives to patients with depression were randomly allocated to receive daily tablets of escitalopram 10mg or placebo for 4 weeks. The area under the curve (AUC) for awakening and all day salivary cortisol was analysed in samples taken immediately after awakening and at 15-min intervals for the next hour, and at 12:00, 18:00 and 23:00. The salivary cortisol awakening response, all day salivary cortisol, and scale scores on sleep, pain, aggression, quality of life, and perceived stress assessed at entry were compared to values following 4 weeks of intervention. Statistically significant decreases were found in awakening salivary cortisol (P=0.04) and in all day salivary cortisol (P=0.02) in the escitalopram group compared with the placebo group. There were no statistically significant differences in perceived stress between the intervention groups. These findings from a randomised clinical trial suggest that a long-term escitalopram administration to healthy participants results in a decrease in the hypothalamic-pituitary-adrenal (HPA) activity measured by salivary cortisol compared with inert placebo. However, change in salivary cortisol was one out of multiple outcome measures. The results of the present trial do not refute salivary cortisol as a potential endophenotype for depression., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Abnormalities in psychomotor activity are a central and essential feature of affective disorder. Studies measuring differences in psychomotor activity between unipolar and bipolar disorder show divergent results and none have used a combined heart rate and movement monitor for measuring activity during free-living conditions., Objective: To compare objectively measured psychomotor activity in patients with unipolar and bipolar disorder in a remitted or mild/moderate depressive state. Further, both groups were compared to a healthy control group., Methods: A cross-sectional study of outpatients suffering from unipolar (n=20) and bipolar (n=18) disorder and healthy controls (n=31), aged 18-60 years. For three consecutive days a combined acceleration (m/s(2)) and heart rate (beats per minute) monitoring was used in conjunction with a step test to estimate activity energy expenditure (J/min/kg) as measures of psychomotor activity and physical fitness., Results: Overall score on Hamilton-17 items ranged between 0 and 22. Patients had higher sleeping heart rate (p<0.001), lower fitness (p=0.02), lower acceleration (p=0.004), and lower activity energy expenditure (p=0.004) compared to controls. Comparing unipolar and bipolar patients and adjusting for differences in Hamilton-17 revealed lower acceleration (p=0.01) and activity energy expenditure in bipolar patients (p=0.02); the difference was most prominent in the morning., Conclusions: Electronic monitoring of psychomotor activity may be a promising additional tool in the distinction between unipolar and bipolar affective disorder when patients present in a remitted or depressive state., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Cognitive dysfunction in unipolar disorder (UD) and bipolar disorder (BD) may persist into remission and affect psychosocial function. Executive and memory deficits during remission may be more pronounced in BD than UD. However, patients' subjective experience of cognitive difficulties is poorly understood, and it is unclear whether BD and UD patients experience different cognitive difficulties., Aims: To investigate whether there are differences in the quality and magnitude of subjective cognitive difficulties between UD and BD, and which factors influence the subjective cognitive difficulties in these patients., Methods: Patients with BD (n = 54) or UD (n = 45) were referred to the outpatient mood disorder clinic at Department of Psychiatry, Copenhagen University Hospital, following hospital discharge. Affective symptoms and patients' experience of cognitive symptoms were assessed at their initial consultation at the clinic., Results: Patients experienced mild to moderate cognitive impairment despite being in partial or full remission, but there were no differences in subjective difficulties between BD and UD. Subjective cognitive dysfunction was predicted by depression severity, anxiety and mania symptoms rather than by diagnosis, age, gender or alcohol misuse., Conclusion: The absence of difference in subjective cognitive difficulties between UD and BD contrasts with evidence of greater objective dysfunction in BD. This highlights a potential discord between subjective and objective measures of cognitive function. Subjective cognitive function was predicted by affective symptoms, perhaps suggesting that this reflects mood symptoms rather than objective deficits. This points to a clinical need for objective assessment of cognitive function in these patient groups.

Objective: Alterations in gene expression in bipolar disorder have been found in numerous studies. It is unclear whether such alterations are related to specific mood states. As a biphasic disorder, mood state-related alterations in gene expression have the potential to point to markers of disease activity, and trait-related alterations might indicate vulnerability pathways. This review therefore evaluated the evidence for whether gene expression in bipolar disorder is state or trait related., Methods: A systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline for reporting systematic reviews, based on comprehensive database searches for studies on gene expression in patients with bipolar disorder in specific mood states, was conducted. We searched Medline, Embase, PsycINFO, and The Cochrane Library, supplemented by manually searching reference lists from retrieved publications., Results: A total of 17 studies were included, comprising 565 patients and 418 control individuals. Six studies evaluated intraindividual alterations in gene expression across mood states. Two of five studies found evidence of intraindividual alterations in gene expression between a depressed state and a euthymic state. No studies evaluated intraindividual differences in gene expression between a manic state and a euthymic state, while only one case study evaluated differences between a manic state and a depressed state, finding altered expression in seven genes. No study investigated intraindividual variations in gene expression between a euthymic state and multiple states of various polarities (depressive, manic, hypomanic). Intraindividual alterations in expression of the same genes were not investigated across studies. Only one gene (the brain-derived neurotrophic factor gene; BDNF) was investigated across multiple studies, showing no alteration between bipolar disorder patients and control individuals., Conclusions: There is evidence of some genes exhibiting state-related alterations in expression in bipolar disorder; however, this finding is limited by the lack of replication across studies. Further prospective studies are warranted, measuring gene expression in various affective phases, allowing for assessment of intraindividual differences., (© 2012 John Wiley and Sons A/S.)

Bipolar disorder is a great challenge to patients, relatives and clinicians, and there is a need for development of new methods to identify prodromal symptoms of affective episodes in order to provide efficient preventive medical and behavioural intervention. Clinical trials prove that electronic monitoring is a feasible, valid and acceptable method. Hence it is recommended, that controlled trials on the effect of electronic monitoring on patients' course of illness, level of function and quality of life are conducted.

Background: Patients with affective disorders experience cognitive dysfunction in addition to their affective symptoms. The relationship between subjectively experienced and objectively measured cognitive function is controversial with several studies reporting no correlation between subjective and objective deficits., Aims: To investigate whether there is a correlation between subjectively reported and objectively measured cognitive function in patients with affective disorders, and whether subjective complaints predict objectively measured dysfunction., Methods: The study included 45 participants; 15 with bipolar disorder (BD), 15 with unipolar disorder (UD) and 15 healthy individuals. Participants' subjectively experienced cognitive function and objective cognitive function were assessed with the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) and the Screen for Cognitive Impairment in Psychiatry (SCIP), respectively. Patients were rated for affective symptoms with Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS)., Results: Patients demonstrated subjective and objective cognitive dysfunction relative to controls (P-values ≤ 0.01) but there were no differences between patient groups (P > 0.1). We found no correlation between subjectively experienced and objectively measured cognitive dysfunction in BD (P = 0.7), and a non-significant trend towards a correlation in UD (P = 0.06), which disappeared when controlling for gender (P = 0.1)., Conclusion: Our results suggest that it is not necessarily patients who have cognitive complaints that are most impaired. If confirmed in a larger sample, our findings suggest that neuropsychological assessment is warranted to elucidate the potential role of cognitive dysfunction in patients' everyday lives and to inform treatment strategies targeting these difficulties.

Background: Patients with affective disorder have higher mortality not only because of their affective illness but also because of a higher risk of death from physical illness especially cardiovascular diseases., Aim: To investigate the prevalence in a naturalistic cohort of patient treated at a Mood Disorder Clinic., Methods: Patients were evaluated for the presence of metabolic syndrome (MeS) according to modified NCEP ATP III criteria., Results: Of the 143 patients eligible for participation, 100 patients participated in the study (32% male, mean age 43.6 ± 14.2); the prevalence of MeS was 26%. Higher age and high body mass index (BMI) were significantly associated with MeS. No association between present medication and MeS was seen., Conclusion: More than a quarter of affectively ill patients had MeS, which emphasizes the importance of integrated somatic and psychiatric care in order to reduce this group of patients' risk profile concerning cardiovascular diseases and diabetes. Clinically, it seems reasonable to prioritize overweight and obese patients for further examination.

Background: The Minor Melancholia Mood Checklist (MMCL-32) was developed to identify sub-threshold states of major depression. The MMCL-32 can be considered as the counterpole to the Hypomanic Check List (HCL-32)., Methods: Principal component analysis (PCA) without rotation was used to identify a bidirectorial principal component. To evaluate the clinical validity of the bidirectorial factors, with reference to brief recurrent depression, the Bech-Rafaelsen Melancholia Scale was used., Results: We included 59 patients with bipolar I disorder (SCID criteria) and 57 patients with unipolar depression (more than one major depressive episode without hypomanic or manic episodes). They were all outpatients, but had recently been discharged from inpatient treatment. The PCA identified two contrasting factors: 17 items with negative loadings (psychasthenic depression factor) and 15 items with positive loadings (cognitive depression factor). When PCA was applied exclusively to the bipolar patients, 5 items within the cognitive factor were identified. When applied exclusively to the unipolar patients, 5 items within the psychasthenic factor were identified. The non-remitted bipolar patients scored higher on the cognitive factor (P=0.01) than the remitted. On the psychasthenic factor (P=0.06), the non-remitted unipolar patients scored higher than the remitted patients., Conclusion: The MMCL-32 was found psychometrically valid in measuring sub-threshold states of major depression with rather specific factors for bipolar and unipolar depression. Focusing on these factors could be a clinical aid to distinguish patients at risk of developing a bipolar course., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Current pharmacological treatments for depression have a significant treatment-onset-response delay, an insufficient efficacy for many patients and fail to reverse cognitive dysfunction. Erythropoietin (EPO) has neuroprotective and neurotrophic actions and improves cognitive function in animal models of acute and chronic neurodegenerative conditions and in patients with cognitive decline., Methods: We systematically reviewed the published findings from animal and human studies exploring the potential of EPO to treat depression-related cognitive dysfunction and depression., Results: We identified five animal studies (two in male rats, two in male mice and one in male rats and mice) and seven human proof-of-concept studies (five in healthy volunteers and two in depressed patients) that investigated the above. All of the reviewed animal studies but one and all human studies demonstrated beneficial effects of EPO on hippocampus-dependent memory and antidepressant-like effects. These effects appear to be mediated through direct neurobiological actions of EPO rather than upregulation of red cell mass., Conclusions: The reviewed studies demonstrate beneficial effects of EPO on hippocampus-dependent memory function and on depression-relevant behavior, thus highlighting EPO as a candidate agent for future management of cognitive dysfunction and mood symptoms in depression. Larger-scale clinical trials of EPO as a treatment for mood and neurocognitive symptoms in patients with mood disorder are therefore warranted.

Introduction: The serotonergic neurotransmitter system is closely linked to depression and personality traits. It is not known if selective serotonin reuptake inhibitors (SSRI) have an effect on neuroticism that is independent of their effect on depression. Healthy individuals with a genetic liability for depression represent a group of particular interest when investigating if intervention with SSRIs affects personality. The present trial is the first to test the hypothesis that escitalopram may reduce neuroticism in healthy first-degree relatives of patients with major depressive disorder (MD)., Methods: The trial used a randomized, blinded, placebo-controlled parallel-group design. We examined the effect of four weeks escitalopram 10 mg daily versus matching placebo on personality in 80 people who had a biological parent or sibling with a history of MD. The outcome measure on personality traits was change in self-reported neuroticism scores on the Revised Neuroticism-Extroversion-Openness-Personality Inventory (NEO-PI-R) and the Eysenck Personality Inventory (EPQ) from entry until end of four weeks of intervention., Results: When compared with placebo, escitalopram did not significantly affect self-reported NEO-PI-R and EPQ neuroticism and extroversion, EPQ psychoticism, NEO-PI-R openness, or NEO-PI-R conscientiousness (p all above 0.05). However, escitalopram increased NEO-PI-R agreeableness scores significantly compared with placebo (mean; SD) (2.38; 8.09) versus (-1.32; 7.94), p = 0.046), but not following correction for multiplicity. A trend was shown for increased conscientiousness (p = 0.07). There was no significant effect on subclinical depressive symptoms (p = 0.6)., Conclusion: In healthy first-degree relatives of patients with MD, there is no effect of escitalopram on neuroticism, but it is possible that escitalopram may increase the personality traits of agreeableness and conscientiousness., Trial Registration: Clinicaltrials.gov NCT00386841.

Background: Depression is accompanied by an inflammatory reaction and activation of cell mediated immunity (CMI) and stressors may induce the cytokine network in humans. The proinflammatory cytokine interleukin-18 (IL-18) is less investigated in depression but highly relevant since it is produced by activated macrophages and expressed in the brain., Methods: The distribution of six polymorphisms in IL10, IL18 and NF was compared between patients with a single episode of depression either preceded by a stressful life event (n=182), or occurring without a prior stressful life event (n=106) and a group of healthy control individuals (n=335)., Results: The major C allele of the IL18 rs187238 and the major G allele of rs1946518 had a significantly higher prevalence among the patients with a stressful life event prior to onset of disease than both patients without a stressful life event and compared with the healthy controls individuals. None of the examined IL10 or NF alleles were differently distributed among these groups., Limitations: Data are nominally significant and not resistant to correction for multiple testing., Conclusion: The major C allele of the IL18 rs187238 and the major G allele rs1946518 have previously been associated with higher expression of IL-18 mRNA. Our data suggest that this genetic trend towards higher IL-18 production may increase the susceptibility to depression in response to stressful life events., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The effect of selective serotonin receptor inhibitors (SSRIs) on healthy individuals remains unclear. The aim of the trial was to evaluate the effect of the SSRI escitalopram on cognitive function in healthy first-degree relatives of patients with major depressive disorder (FDRs). A total of 80 FDRs were randomized to escitalopram (10 mg/day) (n = 41) versus placebo (n = 39) for 4 weeks. Neuropsychological tests and ratings of mood were applied at entry (T0) and at 4 weeks (T4). The main outcome measure was calculated as the change (T4-T0) in a general cognition score, which was the standardized mean of 13 test measures. Mean change in the general cognition score was not significantly increased with escitalopram compared with placebo (p = 0.37) or for any of the specific tests. In univariate analyses no statistically significant correlations were found between change in the general cognitive score and the variables age, sex, Hamilton depression score 17 items, Danish Adult Reading Test-45, and plasma escitalopram levels, respectively. These results suggest that treatment with escitalopram does not improve or impair cognitive function in FDRs. Improvement in cognitive function following treatment of depressed patients with SSRIs seems to be related to the effects on depressive symptoms rather than to a direct effect of the SSRI.

Background: The Hypomania Checklist (HCL-32) was developed to identify subthreshold bipolarity in patients with major depression. An HCL-32 version with fewer items has been suggested., Methods: Principal component analysis (PCA) without rotation was used to identify active/elevated mood versus risk-taking/irritable behaviour in the HCL-32. Using the Bech-Rafaelsen Mania Scale as index of clinical validity a shorter version was developed. Item response theory analysis was used to evaluate whether the total score of the HCL-32 was sufficient to measure subthreshold bipolarity. The short 13-item Mood Disorder Questionnaire (MDQ) was used for comparison., Results: In accordance with the SCID-II criteria, we included 59 bipolar I and 63 unipolar (depressed) outpatients who had recently been discharged from inpatient treatment. In the HCL-32, PCA identified the two contrasting factors: active/elevated mood versus risk-taking/irritable behaviour. The clinical validation analysis focussed on 20 HCL items as the most acceptable (HCL-20). Item response analysis accepted that the total scores of the HCL-32/HCL-20 were a sufficient statistic, as was the total score of the MDQ. Among the unipolar (depressed) patients not responding to their antidepressive medication, subtreshold bipolarity was identified in 55% of patients using the HCL-20, 36% using the HCL-32, but only 18% using the MDQ., Limitations: Only outpatients recently discharged from inpatient treatment were studied. A further limitation is that 9.5% of the unipolar patients had only suffered from one episode, which, however had led to hospitalisation., Conclusion: The HCL-20 was found to identify subthreshold bipolarity in up to 55% of inpatients with major depressive disorder not responding to antidepressive medication., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Depression is considered resistant when two treatment attempts with antidepressants from different classes fail to produce significant clinical improvement. In cases of treatment-resistant depression, it is recommended to reevaluate the diagnosis, clarify comorbidity, substance abuse and lack of compliance. Regarding treatment, evidence is sparse, but switching to a different antidepressant, and combination or augmentation with another agent, admission and treatment with ECT are the options. The choice of treatment must be based on the characteristics of the depression, the severity of treatment resistance and side effects.

Introduction: The mechanisms by which selective serotonin re-uptake inhibitors (SSRI) act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. The aim of the AGENDA trial was to investigate whether long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first-degree relatives to patients with major depressive disorder (MDD)., Methods: Eighty healthy first-degree relatives to patients with MDD were randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUC(total)) for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention., Results: Change in CorAUC(total) showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in CorAUC(total), rho = -0.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUC(total)., Conclusion: The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first-degree relatives to patients with MDD. Increasing levels of escitalopram tended to decrease the HPA-response in the DEX-CRH test and this effect increased with age., Trial Registration: ClinicalTrials.gov NCT00386841.

Background: It is unclear, whether age-of-onset identifies subgroups of depression., Aim: To assess the clinical presentation of depression with onset in the early adult age (18-30 years) as compared to depression with later onset (31-70 years)., Method: A total number of 301 patients with first episode depression were systematically recruited. Characteristics including psychiatric co-morbidity, personality disorders and traits, stressful life events prior to onset, family history, and treatment outcome were assessed by structured interviews and compared by chi-square tests for categorical data, t-tests for continuous parametric data and Mann-Whitney U-test for continuous nonparametric data. Logistic and multiple regression analyses were used to adjust the analyses for potentially confounding variables., Results: Patients with early onset of depression were characterised by a higher prevalence of co-morbid personality disorders, higher levels of neuroticism, and a lower prevalence of stressful life events preceding onset compared to patients with later age-of-onset. There were no differences in severity of the depressive episode, treatment outcome or family loading of psychiatric illness., Conclusion: Early adult onset of depression is associated with co-morbid personality deviances, whereas late onset is associated with environmental risk factors.

Background: Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission., Methods/design: The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission are recruited and randomised to receive weekly infusions of Epo (Eprex; 40,000 IU) or saline (NaCl 0.9%) for 8 weeks. Randomisation is stratified for age and gender. The primary outcome parameters for the two studies are: depression severity measured with the Hamilton Depression Rating Scale 17 items (HDRS-17) 1 in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT) 23. With inclusion of 40 patients in each study we obtain 86% power to detect clinically relevant differences between intervention and placebo groups on these primary outcomes., Trial Registration: The trial is approved by the Local Ethics Committee: H-C-2008-092, Danish Medicines Agency: 2612-4020, EudraCT: 2008-04857-14, Danish Data Agency: 2008-41-2711 and ClinicalTrials.gov: NCT 00916552.

The pathophysiology of depression has been associated to dysregulation of the hypothalamic-pituitary-adrenal axis and the use of salivary cortisol measures is increasingly being incorporated into research. The aim of the present study was to investigate whether salivary cortisol differs for patients with depression and control persons. We did a systematic review with sequential meta-analysis and meta-regression according to the PRISMA Statement based on comprehensive database searches for studies of depressed patients compared to control persons in whom salivary cortisol was measured. Twenty case-control studies, including 1354 patients with depression and 1052 control persons were identified. In a random-effects meta-analysis salivary cortisol was increased for depressed patients as compared to control persons on average 2.58 nmol/l (95% C.I.: 0.95-4.21) p=0.002 in the morning and on average 0.27 nmol/l (95% C.I.: 0.03-0.51) p=0.03 in the evening. In a fixed-effects model the mean difference was 0.58 nmol/l (95% C.I.). Study sequential cumulative meta-analyses suggested random error for the finding of this rather small difference between groups. The reference intervals for morning salivary cortisol in depressed patients (0-29 nmol/l) and control persons (1-23 nmol/l) showed substantial overlap suggesting lack of discriminative capacity. These results should be interpreted with caution as the heterogeneity for the morning analysis was large and a funnel plot, suggested presence of bias. Further, in meta-regression analyses higher intra-assay coefficients of variation in cortisol kits (p=0.07) and mean age (p=0.08) were associated with a higher mean difference of morning salivary cortisol between depressed and controls, while gender and depression severity were not. Based on the available studies there is not firm evidence for a difference of salivary cortisol in depressed patients and control persons and salivary cortisol is unable to discriminate between persons with and without depression., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: It has never been investigated whether first depression differs in patients who have experienced bereavement compared to patients who have not., Method: Patients discharged with a diagnosis of a single depressive episode from a psychiatric in- or outpatient hospital setting were consecutively sampled from the Danish Psychiatric Central Research Register. Patients participated in an extensive interview including the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and the Interview of Recent Life Events (IRLE)., Results: Among 301 patients with a first depression, 26 patients (4.7%) had experienced death of a first degree relative (parent, sibling, child) or a near friend, 163 patients (54.2%) had experienced other moderate to severe stressful life events and 112 patients had not experienced stressful life events in a 6 months period prior to the onset of depression. Patients who had experienced bereavement did not differ from patients with other stressful life events or from patients without stressful life events in socio-demographic variables or in the phenomenology of the depression, psychiatric comorbidity, family history or response to antidepressant treatment., Conclusion: Bereavement-related first episode depression does not differ from other kinds of first depression.

Unipolar depression is moderately heritable. It is unclear whether structural brain changes associated with unipolar depression are present in healthy persons at risk of the disorder. Here we investigated whether a genetic predisposition to unipolar depression is associated with structural brain changes. A priori, hippocampal volume reductions were hypothesized. Using a high-risk study design, magnetic resonance imaging brain scans were obtained from 59 healthy high-risk subjects having a co-twin with unipolar depression, and 53 healthy low-risk subjects without a first-degree family history of major psychiatric disorder. High-risk twins had smaller hippocampal volumes than low-risk twins (p<0.04). The finding was most pronounced in DZ twins. Groups did not differ on global brain tissue volumes or regional tissue volumes assessed in exploratory voxel-wise whole cerebrum analyses. In conclusion, hippocampal volume reduction may index a predisposition to develop depression and thus may be predictive of future onset of the disorder. Further studies are needed to elucidate the role of (shared) environmental and genetic factors., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Genetic polymorphisms seem to influence the response on antidepressant treatment and moderate the impact of stress on depression. The present study aimed to assess, whether allelic variants and stressful life events interact on the clinical outcome of depression. In a sample of 290 systematically recruited patients diagnosed with a single depressive episode according to ICD-10, we assessed the outcome of antidepressant treatment and the presence of stressful life events in a 6-month period preceding onset of depression by means of structured interviews. Further, we genotyped nine polymorphisms in the genes encoding the serotonin transporter, brain derived neurotrophic factor, catechol-O-methyltransferase, angiotensin converting enzyme, tryptophan hydroxylase, and the serotonin receptors 1A, 2A, and 2C. We found no evidence that the effects of the genetic polymorphisms on treatment outcome were dependent on stressful life events experienced by the individual prior to onset of depression., (2009 Elsevier B.V. and ECNP. All rights reserved.)

Life stress is a robust risk factor for later development of mood disorders, particularly for individuals at familial risk. Likewise, scoring high on the personality trait neuroticism is associated with an increased risk for mood disorders. Neuroticism partly reflects stress vulnerability and is positively correlated to frontolimbic serotonin 2A (5-HT(2A)) receptor binding. Here, we investigate whether neuroticism interacts with familial risk in relation to frontolimbic 5-HT(2A) receptor binding. Twenty-one healthy twins with a co-twin history of mood disorder and 16 healthy twins without a co-twin history of mood disorder were included. They answered self-report personality questionnaires and underwent [(18)F]altanserin positron emission tomography. We found a significant interaction between neuroticism and familial risk in predicting the frontolimbic 5-HT(2A) receptor binding (p=0.026) in an analysis adjusting for age and body mass index. Within the high-risk group only, neuroticism and frontolimbic 5-HT(2A) receptor binding was positively associated (p=0.0037). In conclusion, our data indicate that familial risk and neuroticism interact in their relation to frontolimbic 5-HT(2A) receptor binding. These findings point at a plausible neurobiological link between genetic and personality risk factors and vulnerability to developing mood disorders. It contributes to our understanding of why some people at high risk develop mood disorders while others do not. We speculate that an increased stress reactivity in individuals at high familial risk for mood disorders might enhance the effect of neuroticism in shaping the impact of potential environmental stress and thereby influence serotonergic neurotransmission.

Background: Variations in the serotonin transporter gene (5-HTTLPR) and stressful life events are associated with affective disorders., Aim: To investigate whether the distribution of the alleles of the 5-HTTLPR is associated with a genetic predisposition to affective disorder and whether these variations interact with life events in relation to depressive symptoms, neuroticism and salivary cortisol., Method: In a high-risk population study, healthy monozygotic and dizygotic twins with (high-risk twins) and without (low-risk twins) a co-twin history of affective disorder were identified through nationwide registers., Results: When comparing the 81 individuals homozygote for the long allele with the 125 individuals hetero- and homozygote for the short allele no associations between the allele distribution and a genetic predisposition were found. The presence of the short allele of the 5-HTTLPR and the experience of SLE was associated with a higher neuroticism score, but not with depressive symptoms nor awakening or evening salivary cortisol., Conclusion: A combination of variants in 5-HTTLPR and environmental stress seems to increase neuroticism in healthy individuals., (Copyright 2009 Elsevier Inc. All rights reserved.)

Coping styles may influence the perceived life stress experienced by an individual and, therefore, also be critical in the development of affective disorders. This study examined whether familial risk of affective disorder is associated with the use of maladaptive coping styles, in healthy individuals. One hundred twelve high-risk and 78 low-risk individuals were identified through nation-wide registers and invited to participate in an extensive psychiatric evaluation including the Coping Inventory for Stressful Situations. The high-risk individuals used more Emotion-oriented (p = 0.001) and Avoidance coping (p = 0.04) than individuals not at risk. Adjusted for gender, age, years of education, and recent stressful life events the high-risk individuals used more emotion-oriented coping (p = 0.03). In conclusion, maladaptive coping style may represent a trait marker for mood disorder improving maladaptive coping styles may be a target for selective prevention focusing on subgroups at high risk of developing an affective disorder.

Background: It has never been investigated whether comorbid personality disorder or neuroticism predicts a poor treatment outcome in first episode depression., Methods: Medically treated patients discharged with a diagnosis of a single depressive episode from a psychiatric in- or outpatient hospital setting were consecutively sampled from the Danish Psychiatric Central Research Register. The patients participated in an extensive interview including the Schedules for Clinical Assessment in Neuropsychiatry, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders and a detailed assessment of medical treatment history using standardised procedures (Treatment Response to Antidepressants Questionnaire, TRAQ). Remission was defined as a score of < or =7 on the Hamilton Depression Rating Scale, 17 items, and a score of > or =4 on the TRAQ following (1) a first adequate trial of antidepressant treatment, and (2) 2 trials of antidepressant treatment. Further personality traits were assessed by means of the Eysenck Personality Questionnaire., Results: Among a total of 301 patients with a single depressive episode, 31.9% fulfilled diagnostic criteria for at least 1 personality disorder of any kind. Comorbid personality disorder was associated with a 2.2-times (95% CI: 1.1-4.2) increased risk of non-remission following the first antidepressant trial, whereas no effect was found following the second antidepressant trial (OR: 1.6; 95% CI: 0.8-3.4). A high level of neuroticism was associated with non-remission in first as well as second trials., Conclusion: Comorbid personality disorder and high levels of neuroticism in first episode depression predict an increased risk of non-remission from depression., (2010 S. Karger AG, Basel.)

Background: Studies on gender differences in depression have usually included a mixture of patients with first-episode, chronic and recurrent depression. Consequently, the results might be confounded by the history of depression among participants. The present study evaluated gender differences in sociodemographic, clinical and treatment variables among patients suffering exclusively from single-episode depression., Method: Systematic recruitment of 301 participants via the Danish Psychiatric Central Research Register and assessment by means of questionnaires and interviews regarding psychiatric diagnoses, personality traits and disorders, stressful life events, family history, and treatment response., Results: Female patients showed a higher level of neuroticism and more residual anxiety symptoms after treatment of the depression. There were no gender differences in severity of depression, psychiatric co-morbidity (including personality disorders), stressful life events prior to onset, family loading of psychiatric disorders, or treatment outcome., Conclusion: The results provide evidence for a higher level of anxiety and neuroticism among females with a recent onset of depression, whereas other clinical characteristics of first-episode depression were equivalent between male and female patients. Only patients with contact to a psychiatric hospital were included; thus, the results cannot be generalized to patients in primary care., (2010 S. Karger AG, Basel.)

Background: A polymorphism in the serotonin transporter (5-HTT) gene seems to moderate the influence of stressful life events on depression. However, the results from previous studies of gene-environment interactions in depression are inconsistent and might be confounded by the history of depression among participants., Method: We applied a case-only design, including 290 ethnically homogeneous patients suffering exclusively from first episode depression. Psychiatric mo-morbidity, personality traits and disorders and stressful life events in a six months period preceding onset of depression were evaluated by means of interviews and questionnaires. Additionally, we genotyped nine polymorphisms in the genes encoding the serotonin transporter, brain derived neurotrophic factor, catechol-O-methyltransferase, angiotensin converting enzyme, tryptophane hydroxylase, and the serotonin receptors 1A, 2A, and 2C., Results: The low activity variants of the 5-HTT-linked polymorphic region in the serotonin transporter gene and the Met-allele of a single nucleotide polymorphism (Val66Met) in the gene encoding brain derived neurotrophic factor were independently associated with the presence of stressful life events prior to onset of depression, also when corrected for the effect of age, gender, marital status, personality disorder, neuroticism, and severity of depressive symptoms at the time of interview., Conclusion: Polymorphisms in the genes encoding the serotonin transporter and the brain derived neurotrophic factor interact with recent stressful life events on depression among patients with no history of previous depressive episodes.

Background: Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated with a familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol., Method: In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified through nationwide registers., Results: Familiar predisposition to unipolar and bipolar disorder was not associated with any specific genotype pattern of the BDNF Val66Met polymorphism, not in this sample of 124 val/val, 58 val/met and 8 met/met individuals. However, the combination of having a high familiar risk of affective disorder and the met allele was associated with a higher whole blood BDNF (p=0.02) and a higher evening cortisol level (p=0.01), but not with awakening cortisol., Conclusion: Individuals at high risk of affective disorders and who are carriers of the met allele of the Val66Met polymorphism may present with an enhanced stress response. The presence of a specific genotype alone may not enhance the risk of developing an affective episode. Rather, the altered stress response may be expressed only in combination with other risk variants through interactions with the environment.

Background: It is unclear whether medical treatment outcome in first episode depression differ for patients with and without stressful life events prior to onset of depression., Methods: Patients discharged with a diagnosis of a single depressive episode from a psychiatric in- or outpatient hospital setting were consecutively sampled from the Danish Psychiatric Central Research Register. Patients participated in an extensive interview including the schedules for clinical assessment in neuropsychiatry (SCAN), the Structured Clinical Interview for DSM-IV axis II personality disorders (SCID-II) and the interview of recent life events (IRLE). Medical treatment history was assessed in detail using standardised procedures (TRAQ). Remission was defined as a score or= 4 on TRAQ following (1) first trial of antidepressant treatment (2) two adequate trials of antidepressant treatment., Results: A total of 399 patients participated in the interview and among these 301 patients obtained a SCAN diagnosis of a single depressive episode. A total of 62.8% of the 301 patients experienced at least one moderate to severe stressful life event in a 6 months period prior to symptom onset. The presence of a stressful life event or the number of stressful life events did not predict remission from first or second antidepressant drug trial-nor when adjusted for differences in age, gender or prevalence of co-morbid personality disorders., Conclusions: Medical treatment outcome in first episode depression does not depend on the prevalence of moderate to severe stressful life events prior to symptom onset.

Mood disorders are elicited through a combination of genetic and environmental stress factors, and treatment with selective serotonin reuptake inhibitors ameliorates depressive symptoms. Changes in the serotonin transporter (SERT) binding may therefore occur in depressive patients and in subjects at risk for developing depression. The aim of this study was to explore whether abnormalities in SERT might be present in healthy individuals with familial predisposition to mood disorder. Nine individuals at high familial risk (mean age 32.2+/-4.2 years) and 11 individuals at low risk (mean age 32.4+/-5.0 years) for developing mood disorder were included. The subjects were healthy twins with or without a co-twin history of mood disorder identified by linking information from the Danish Twin Register and the Danish Psychiatric Central Register. Regional in vivo brain serotonin transporter binding was measured with [(11)C]DASB PET. The volumes of interest included the orbitofrontal cortex, the dorsolateral prefrontal cortex, the ventrolateral prefrontal cortex, anterior cingulate, caudate, putamen, thalamus, and midbrain. We found that individuals at high familial risk for mood disorders had a 35% reduction in SERT binding in dorsolateral prefrontal cortex (p=0.014, Bonferroni corrected) and on a trend basis a 15% reduction in anterior cingulate (p=0.018, un-corrected). The depression and symptom scores of the high and the low risk individuals were not significantly different. In conclusion, our data suggest that a low SERT binding in dorsolateral prefrontal cortex represents a trait marker for mood disorders.

Objective: To validate the ICD-10 diagnosis of a single depressive episode as used in daily clinical psychiatric practice and as recorded in the Danish Psychiatric Central Research Register., Methods: Patients discharged with a diagnosis of a single depressive episode were consecutively sampled from the register and diagnosed according to an interview using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN)., Results: A total of 75.4% of 399 patients with a register diagnosis of a single depressive episode also got this diagnosis according to the SCAN interview (82.8% for severe type of a single depression, 76.0% for moderate type of a single depression and 65.2% for mild type of a single depression)., Conclusion: The ICD-10 diagnosis of a single depressive episode can be used in daily clinical practice with sufficient precision. The validity of the diagnosis is highest for severe and moderate type of depression and decreases for mild depression.

Dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a biological endophenotype for affective disorders. In the present study the hypothesis that a high genetic liability to affective disorder is associated with higher cortisol levels was tested in a cross-sectional high-risk study. Healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Awakening and evening salivary cortisol levels were compared between the 190 High- and Low-Risk twins. The 109 High-Risk twins had significantly higher evening cortisol levels than the 81 Low-Risk MZ twins, also after adjustment for age, sex, and the level of subclinical depressive symptoms. No significant difference was found in awakening cortisol levels between High-Risk and Low-Risk twins. In conclusion, a high genetic liability to affective disorder was associated with a higher evening cortisol level, but not with awakening cortisol level. Future prospective family, high-risk and twin studies are needed to decide whether abnormalities in the HPA axis can be identified as an endophenotype of affective disorder.

Background: Depression has been associated with decreased blood BDNF concentrations; but it is unclear if low blood BDNF levels are a state or a trait marker of depression., Methods: We investigated blood BDNF concentrations in a twin population including both subjects highly predisposed and protected against affective disorder. Whole blood assessed for BDNF concentrations and correlated to risk status, neuroticism, and number of stressful life events., Results: Between the groups, we found no significant difference in whole blood BDNF levels. Women at high-risk for depression who had experienced three or more recent stressful events (n=26) had decreased whole blood BDNF levels compared to high-risk women with two or less recent stressful events (n=35), 21.6+/-7.0 vs. 18.5+/-4.1 ng/ml, respectively, (p<0.05). No such association was found in low-risk women or in men. In men, however, low neuroticism scores and two or less recent stressful events were associated with decreased whole blood BDNF levels (n=50, p<0.05)., Limitations: The cross-sectional design limits the possibility of drawing firm conclusions on causatility of the findings., Conclusion: The genetic risk of developing depression does not translate directly into whole blood BDNF levels. In females who are genetically disposed for depression and subjected to recent stressful life events whole blood BDNF levels are lower.

Although numerous studies have dealt with changes in blood brain-derived neurotrophic factor (BDNF), methodological issues about BDNF measurements have only been incompletely resolved. We validated BDNF ELISA with respect to accuracy, reproducibility and the effect of storage and repeated freezing cycles on BDNF concentrations. Additionally, the effect of demographic characteristics in healthy subjects on BDNF was verified. Whole blood and serum was collected from 206 healthy subjects and a subgroup was genotyped for BDNF Val66Met polymorphism. The effect of age, gender, BDNF genotype and thrombocyte count on whole blood BDNF was assessed. The BDNF ELISA measurement was accurate, 91.6+/-3.0%, and showed high reproducibility, whereas inter-assay and intra-subject variations were modest, 8.4+/-5.2% and 17.5+/-14.1%, respectively. Storage of whole blood samples at 4 degrees C significantly decreased BDNF concentration, while repeated freezing cycles and storage at -20 degrees C was without any effect. Storage at -20 degrees C of serum, but not whole blood, was associated with a significant decrease in BDNF concentration. Women had significantly higher whole blood BDNF concentrations than men (18.6+/-1.3 ng/ml versus 16.5+/-1.4 ng/ml), and showed a right-skewed BDNF concentration distribution. No association between whole blood BDNF concentrations and thrombocyte count, age, or BDNF genotype was found. In conclusion, the BDNF ELISA assay determines whole blood BDNF accurately and with high reproducibility. Female gender is associated with higher whole blood BDNF concentrations whereas age, thrombocyte count and BDNF Val66Met polymorphism were un-associated.

Objective: To examine whether a high genetic liability to develop affective disorder is associated with specific personality traits., Method: A cross-sectional, high-risk, case-control study. Through nation-wide registers, healthy monozygotic (MZ) and dizygotic (DZ) twins with (high-risk twins) and without (the control group/low-risk twins) a co-twin history of affective disorder were identified. Personality traits were compared for a total of 211 high-risk and low-risk twins., Results: In univariate analyses, the high-risk twins had a higher level of neuroticism than the control twins (P = 0.03). In multivariate analyses, a high genetic liability to affective disorder was not significantly associated with neuroticism but correlated to sex, minor psychopathology and recent life events., Conclusion: A high genetic liability to affective disorder showed an association with neuroticism, but the association interacts with other predictors of affective disorder such as female gender, minor psychopathology and recent adversity.

There is consensus that genetic factors are the most important risk factor for both bipolar and unipolar disorders. Concerning other risk factors there seems to be complex interactions between biological, psychological and sociological factors. For bipolar disorder, suggestive findings have been provided concerning pregnancy and stressful life events and female gender and stressful life events are the most reliable factors for unipolar disorder. Clinical and research recommendations are given in order to create strategies for the prevention of affective disorders.

Background: The disability and hardship associated with affective disorder is shared by the family members of affective patients and might affect the family member's quality of life., Method: In a cross-sectional, high-risk, case-control study, monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. The aim of the present study was to investigate the hypothesis that a genetic liability to affective disorder is associated with a lower perception of quality of life., Results: Univariate analyses showed that quality of life in all domains was impaired for the 121 High-Risk twins compared to the 84 Low-Risk twins. In multiple regression analyses, the differences remained significant after adjustment for sex, age, marital status and years of education. Adjusted for the effect of subclinical anxiety and depressive symptoms, the differences were significant on the domain environment and total WHOQoL-BREF and marginally significant on the domain physical health and overall quality of life., Limitations: It is not possible from the cross-sectional analyses to distinguish between subsyndromal state and trait scores., Conclusions: Perceived health related quality of life might share common familial vulnerability with affective disorders. Having a co-twin with affective disorder seem to have a negative influence on quality of life of the healthy co-twin and this influence might be due to the genetic liability to affective disorder. These findings need to be replicated in future family studies.