Genetic risk scores associated with temperament clusters in Finnish depression patients.

OBJECTIVE: Cloninger's temperament dimensions have been studied widely in relation to genetics. In this study, we examined Cloninger's temperament dimensions grouped with cluster analyses and their association with single nucleotide polymorphisms (SNPs). This study included 212 genotyped Finnish patients from the Ostrobothnia Depression Study. METHODS: The temperament clusters were analysed at baseline and at six weeks from the beginning of the depression intervention study. We selected depression-related catecholamine and serotonin genes based on a literature search, and 59 SNPs from ten different genes were analysed. The associations of single SNPs with temperament clusters were studied. Using the selected genes, genetic risk score (GRS) analyses were conducted considering appropriate confounding factors. RESULTS: No single SNP had a significant association with the temperament clusters. Associations between GRSs and temperament clusters were observed in multivariate models that were significant after permutation analyses. Two SNPs from the DRD3 gene, two SNPs from the SLC6A2 gene, one SNP from the SLC6A4 gene, and one SNP from the HTR2A gene associated with the HHA/LRD/LP (high harm avoidance, low reward dependence, low persistence) cluster at baseline. Two SNPs from the HTR2A gene were associated with the HHA/LRD/LP cluster at six weeks. Two SNPs from the HTR2A gene and two SNPs from the COMT gene were associated with the HP (high persistence) cluster at six weeks. CONCLUSION: GRSs seem to associate with an individual's temperament profile, which can be observed in the clusters used. Further research needs to be conducted on these types of clusters and their clinical applicability.

Predictors of short-term response and the role of heavy alcohol use in treatment of depression.

BACKGROUND: Depression and alcohol use disorders frequently co-occur. However, research on psychosocial interventions for treating this dual pathology is limited. The Ostrobothnian Depression Study (ODS) aimed to increase the systematic use of evidence-based methods, particularly among patients with comorbid depression and substance use in a naturalistic setting. This is a secondary analysis of the ODS study. The aim of the present study was to explore the predictors of a response to treatment during the first six months of the ODS intervention with a specific focus on the role of comorbid heavy alcohol use. METHODS: The study sample (n = 242) comprised psychiatric specialist care patients with depression (Beck Depression Inventory score ≥ 17) at baseline. Patients with a baseline Alcohol Use Disorders Identification Test (AUDIT) score > 10 (n = 99) were assigned to the AUD (Alcohol Use Disorder) group in this study. The ODS intervention comprised behavioral activation (BA) for all and additional motivational interviewing (MI) for those in AUD group. The predictors of response to treatment (minimum of 50% reduction in depressive symptoms) during the first six months were analyzed with logistic regression models. RESULTS: In the total sample at six months (n = 150), predictors of response to treatment were more severe depression (OR 1.10, CI 1.02-1.18), larger amounts of alcohol consumed (OR = 1.16, CI 1.03-1.31) and antipsychotic medication "not in use" (OR = 0.17, CI 0.07-0.44). In the non-AUD group (n = 100), more severe depression (OR 1.12, CI 1.01-1.25) and antipsychotics "not in use" (OR 0.20, CI 0.06-0.67) also predicted a positive response. Among AUD group patients (n = 50), larger amounts of alcohol consumed (OR 1.54, CI 1.04-2.27) and antipsychotic medication "not in use" (OR 0.12, CI 0.02-0.60) predicted a response to the treatment intervention. CONCLUSIONS: The severity of symptoms and comorbid disorders were found to predict better treatment response, suggesting that the intervention was more effective in patients with severe symptoms. Patients with depression should be treated effectively regardless of having concomitant AUD. The results of this study suggest that BA combined with MI should be one of the treatment options for this dual pathology. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02520271 (11/08/2015).

Co-medication with disulfiram markedly increased serum clozapine levels: Two case reports.

BACKGROUND: Alcohol use disorder (AUD) is a significant co-morbidity in patients with schizophrenia. Clozapine offers some benefits in treating patients with refractory schizophrenia and AUD, but co-medicating with disulfiram is also common. PROCEDURES: We report two cases where co-medicating with disulfiram led to a significant increase in clozapine serum levels. FINDINGS: Clozapine serum levels decreased to one-third in Patient 1 when disulfiram was discontinued and started to increase again when disulfiram was reintroduced. Patient 2 developed toxic serum levels of clozapine during disulfiram treatment combined with heavy coffee drinking and symptoms reminiscent of neuroleptic malignant syndrome. CONCLUSIONS: Clozapine and disulfiram are both metabolized by cytochrome P450 CYP1A2 and clinically relevant interaction through this shared pathway is possible.

The role of alcohol use and adiposity in serum levels of IL-1RA in depressed patients.

BACKGROUND: The role of Interleukin-1 Receptor antagonist (IL-1Ra), an innate antagonist to pro-inflammatory cytokine IL-1, has attracted increasing attention due to its potential pathogenic and therapeutic implications in depression. However, the role of alcohol and adiposity in modulating IL-1Ra cytokine pathway in depressed patients has remainned unknown. The aim of this study was to follow the changes in IL-1Ra serum levels in depressed patients with or without simultaneous alcohol use disorder (AUD) and different degrees of adiposity during 6 months of follow-up. MATERIALS AND METHODS: A total of 242 patients with depression were followed for 6 months. At baseline 99 patients had simultaneous AUD. Levels of serum IL-1Ra and common mediators of inflammation (IL-6, hs-CRP) were measured. Clinical assessments included Body Mass Index (BMI), Montgomery-Asberg Depression Rating Scale (MADRS) and Alcohol Use Disorders Identification Test (AUDIT) scores. RESULTS: Significant reductions in clinical symptoms and IL-1Ra were observed during 6-month follow-up. In hierarchical linear regression analysis, the effect of MADRS score, age, gender, and smoking had a combined effect of 2.4% in the model. The effect of AUDIT score increased the effect to 4.2% of variance (p = 0.08), whereas adding BMI increased the effect to 18.5% (p <  0.001). CONCLUSION: Adiposity may influence the IL-1Ra anti-inflammatory response in depressed patients, whereas the effect of alcohol consumption in these patients seems insignificant. These findings should be considered in studies on the role of IL-1Ra in depression. TRIAL REGISTRATION: Ostrobothnia Depression Study in ClinicalTrials.gov , Identifier NCT02520271 .

Glucagon-like peptide-1 serum levels are associated with weight gain in patients treated with clozapine.

Metabolic syndrome and related cardiovascular risk factors are well-known comorbidities among patients with schizophrenia. Biomarkers of these antipsychotic-associated metabolic adverse effects and antipsychotic-induced weight gain are needed. Glucagon-like peptide-1 (GLP-1) is involved in insulin secretion, regulation of satiety, inhibition of food intake, and inhibition of gastric emptying. GLP-1 also induces reduction in body weight. Visfatin/ NAMPT/ PBEF is an adipocytokine secreted by several cells and tissues. Increased plasma visfatin levels have been associated with overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases, low grade inflammation, and proinflammatory markers. Associations between antipsychotic-induced weight gain and serum visfatin and GLP-1 levels have been little studied in patients with schizophrenia. The aim of the present study was to test the possible role of serum GLP-1 and visfatin level alterations as markers of weight gain in association with metabolic and inflammatory markers in 190 patients (109 male, 81 female) with schizophrenia on clozapine treatment. High serum levels of GLP-1 correlated significantly with higher levels of visfatin, leptin, insulin, HOMA-IR, higher BMI, and weight change among men. Associations between serum visfatin levels and BMI or weight change were not found in the present patients. Serum GLP-1 level seems to be a marker of metabolic risk factors among men with schizophrenia on clozapine treatment. Female patients may be more sensitive to suppressive effects of clozapine on GLP-1 secretion. Patients on clozapine would benefit from GLP-1 agonists as preventive treatment.

Impact of Comorbid Alcohol Use Disorder on Health-Related Quality of Life Among Patients With Depressive Symptoms.

Background and Aim: In psychiatric clinical practice, comorbidity of depression and alcohol use disorder (AUD) is common. Both disorders have a negative impact on health-related quality of life (HRQoL) in general population. However, research on the impact of comorbid AUD on HRQoL among clinically depressed patients is limited. The purpose of this study was to explore the impact of a psychosocial treatment intervention on HRQoL for depressive patients in specialized psychiatric care with a special focus on the impact of AUD on HRQoL. Material and Methods: Subjects were 242 patients of the Ostrobothnia Depression Study (ClinicalTrials.gov Identifier NCT02520271). Patients referred to specialized psychiatric care who scored at least 17 points on the Beck Depression Inventory at baseline and who had no psychotic disorders were included in the ODS. The treatment intervention in ODS comprised behavioral activation for all but began with motivational interviewing for those with AUD. HRQoL was assessed regularly during 24-month follow-up by the 15D instrument. In the present study, HRQoL of ODS patients with or without AUD was compared and the factors explaining 15D score analyzed with a linear mixed model. In order to specify the impact of clinical depression on HRQoL during the early phase of treatment intervention, a general population sample of the Finnish Health 2011 Survey was used as an additional reference group. Results: HRQoL improved among all ODS study sample patients regardless of comorbid AUD during the first year of follow-up. During 12-24 months of follow-up the difference between groups was seen as HRQoL continued to improve only among the non-AUD patients. A combination of male gender, anxiety disorder, and AUD was associated with the poorest HRQoL in this sample. In combined sample analyses with the reference group, clinical depression had an impact on HRQoL in short-term follow-up regardless of the treatment intervention. Conclusions: This study suggests that, in terms of improvement in HRQoL, the heterogenous group of depressive patients in specialized psychiatric care can be successfully treated with behavioral activation in combination with motivational interviewing for those with AUD. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02520271. Ostrobothnia Depression Study (ODS). A Naturalistic Follow-up Study on Depression and Related Substance Use Disorders. (2015). Available online at: https://clinicaltrials.gov/ct2/show/NCT02520271.

Electroconvulsive therapy increases temporarily plasma vascular endothelial growth factor in patients with major depressive disorder.

OBJECTIVES: Vascular endothelial growth factor (VEGF) has been related to the etiology of major depressive disorder (MDD). The findings involving the effects of electroconvulsive therapy (ECT) on the VEGF levels have been conflicting. The aim was to examine the possible changes in the VEGF levels and their associations with clinical outcome in patients with MDD during ECT. METHODS: The study comprised 30 patients suffering from MDD. Their plasma VEGF levels were measured at baseline and 2 and 4 hr after the first, fifth, and last ECT session. The severity of depression was quantified by the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: The VEGF levels increased between the 2-hr and 4-hr measurements during the first (p = .003) and the fifth (p = .017) sessions. The baseline VEGF levels between individual ECT sessions remained unchanged during the ECT series. No correlations were found between the increased VEGF levels and the clinical outcome. CONCLUSIONS: Electroconvulsive therapy increased the VEGF levels repeatedly at the same time point in two different ECT sessions. These increases had no association with the response to ECT. Consequently, VEGF may act as a mediator in the mechanism of action of ECT.

A Survey of Electroconvulsive Therapy in Finland.

OBJECTIVES: The purpose of this study was to explore the use of electroconvulsive therapy (ECT) in Finland in 2013. This included the rate of use, patient ages, sex, number of treatments, patient diagnoses, regional distribution, and availability of ECT. METHODS: A structured electronic questionnaire was used to collect data regarding the use of ECT from 21 Finnish hospital districts' 29 psychiatric ECT units. Data for comparison were collected from scientific publications concerning the use of ECT in Sweden, Norway, Denmark, and Estonia. RESULTS: Of 29 psychiatric ECT units, 25 (86%) responded. Electroconvulsive therapy was available in all except 1 hospital district, which used the services of another hospital district. Electroconvulsive therapy was administered to 1023 patients in total. The mean number of treatments per patient was 9.7. Twenty-three persons per 100,000 inhabitants received ECT. The ECT rate between hospital districts varied from 7.5 to 53.0 per 100,000 inhabitants. The mean number and median were 24.9 and 21.7 per 100,000 inhabitants, respectively. Maintenance therapy was administered to 27.1% of patients. Most (75%) of the ECT units indicated the capability to administer ECT to all patients who required it. The most common indications for ECT were major depression (38.4%), psychotic depression (30.9%), and bipolar disorder with depressive episodes (14.2%). CONCLUSIONS: Electroconvulsive therapy was available in every hospital district in Finland. In Finland, ECT was administered at approximately the same level as in Norway, Denmark, and Estonia (24, 32, and 28 per 100,000 inhabitants, respectively), but less than in Sweden (41 per 100,000 inhabitants).

Implementing physical exercise and music interventions for patients suffering from dementia on an acute psychogeriatric inpatient ward.

Background: Increasing attention is focusing on psychosocial interventions for treating patients with dementia. Aims: This observational intervention study investigated the impact of physical exercise and music interventions among patients with dementia on an acute psychogeriatric ward. Materials and methods: The data were collected during February 2009-December 2010 (n = 89; treatment as usual) and during April 2011-March 2013 (n = 86; treatment as usual with physical exercise, e.g. balance, flexibility, strength training, and music interventions, e.g. singing, listening to music and playing instruments). The primary outcome measure was the Neuropsychiatric Inventory and the secondary outcome measures were the Alzheimer's Disease Cooperative Study-Activities of Daily Living, the Barthel Index, and the Mini-Mental State Examination. Results: In both groups, neuropsychiatric symptoms (NPS) decreased (p < .001) but daily functioning deteriorated (p < .001). No significant between-group differences for either outcome variable were found. Based on linear mixed models, fewer exercise sessions associated with more severe symptoms (p = .030), and the time variable (admission/discharge) with a decline in the level of NPS (p < .001). Moreover, female gender (p = .026) and more exercise sessions (p = .039) associated with an increased level of functioning (p = .031) and the time variable (admission/discharge) with a drop in the level of functioning during hospitalization (p < .001). Conclusion: Although no differences were found between the study groups, analysis within the intervention group suggest that physical exercise may have some positive effects for both NPS and the level of functioning in some patients with dementia while no positive effects regarding music interventions were found.

Assessment of alcohol consumption in depression follow-up using self-reports and blood measures including inflammatory biomarkers.

AIMS: Alcohol consumption has been suggested a major role in the pathogenesis and prognosis of depression. However, reliable identification of hazardous drinking continues to be problematic. We compared the accuracy of different biomarkers and self-reports of alcohol consumption in the follow-up study of depression. METHODS: Data from 202 patients with major depressive disorder were obtained through self-reports, AUDIT and AUDIT-C questionnaires and biomarker analyses. The clinical assessments and measurements of biomarkers (GT, CDT, GT-CDT-combination, MCV, ALT, AST, hs-CRP, IL-6) were performed at baseline and after six months of treatment. Based on self-reported alcohol intake at baseline the patients were classified to three subgroups. RESULTS: About 27.2% of patients were categorized to high-risk drinkers, 26.3% low-risk drinkers and 46.5% abstainers. High-risk drinkers showed significantly higher mean values of GT, CDT, GT-CDT-combination and IL-6 than abstainers, diagnostic accuracy being highest with the combined marker of GT-CDT. The accuracy of AUDIT and AUDIT-C to detect high-risk drinking was also significant. During follow-up, the differences observed in the biomarkers at baseline disappeared together with recovery from depression. CONCLUSIONS: Our data suggest the combined use of GT-CDT and AUDIT questionnaires to improve the identification of drinking of patients with depression. This approach could be useful for improving treatment adherence and outcome in depressed patients.

Status of inflammation and alcohol use in a 6-month follow-up study of patients with major depressive disorder.

INTRODUCTION: The studies on the relationship between alcohol consumption, the status of inflammation, and depression have produced conflicting results. In this study, we followed patients with major depressive disorders by monitoring biomarkers of inflammation together with biomarkers of heavy alcohol use. METHOD: The levels of IL-6 (interleukin-6), IL-8 (interleukin-8), hs-CRP (high sensitivity C-reactive protein), YKL-40 (also known as Chitinase-3-like protein 1 or CHI3L1), and biomarkers of alcohol consumption and liver status (GT, CDT, ALT, alkaline phosphatase) were measured at baseline and after 6 months of psychiatric treatment from 242 patients suffering from current major depressive disorder (MDD) with (n = 99) or without (n = 143) alcohol use disorder (AUD). RESULTS: At baseline, the patients with MDD + AUD showed higher levels of inflammatory biomarkers IL-6 (p < 0.001), hs-CRP (p < 0.01), YKL-40 (p < 0.05), and biomarkers of alcohol consumption, than the corresponding group of non-AUD patients. These differences disappeared during follow-up and recovery from depression. The level of IL-8 decreased significantly in both AUD (p < 0.05) and non-AUD (p < 0.05) patients. During follow-up, the biomarkers of alcohol consumption, GT and CDT, in AUD patients were found to decrease in parallel with serum YKL-40 levels. CONCLUSIONS: Alcohol consumption appears to modulate the status of inflammation in depressive patients. A more systematic use of biomarkers of inflammation together with biomarkers of alcohol consumption and liver status may prove to be of value in a more comprehensive assessment and treatment of patients with depression.

The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression.

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants for the treatment of major depressive disorder (MDD). However, treatment response during an initial therapeutic trial is often poor and is difficult to predict. Heterogeneity of response to SSRIs in depressed patients is partly driven by co-occurring somatic disorders such as coronary artery disease (CAD) and obesity. CAD and obesity may also be associated with metabolic side effects of SSRIs. In this study, we assessed the association of CAD and obesity with treatment response to SSRIs in patients with MDD using a polygenic score (PGS) approach. Additionally, we performed cross-trait meta-analyses to pinpoint genetic variants underpinnings the relationship of CAD and obesity with SSRIs treatment response. First, PGSs were calculated at different p value thresholds (PT) for obesity and CAD. Next, binary logistic regression was applied to evaluate the association of the PGSs to SSRIs treatment response in a discovery sample (ISPC, N = 865), and in a replication cohort (STAR*D, N = 1,878). Finally, a cross-trait GWAS meta-analysis was performed by combining summary statistics. We show that the PGSs for CAD and obesity were inversely associated with SSRIs treatment response. At the most significant thresholds, the PGS for CAD and body mass index accounted 1.3%, and 0.8% of the observed variability in treatment response to SSRIs, respectively. In the cross-trait meta-analyses, we identified (1) 14 genetic loci (including NEGR1, CADM2, PMAIP1, PARK2) that are associated with both obesity and SSRIs treatment response; (2) five genetic loci (LINC01412, PHACTR1, CDKN2B, ATXN2, KCNE2) with effects on CAD and SSRIs treatment response. Our findings implicate that the genetic variants of CAD and obesity are linked to SSRIs treatment response in MDD. A better SSRIs treatment response might be achieved through a stratified allocation of treatment for MDD patients with a genetic risk for obesity or CAD.

Outcome of neuropsychiatric symptoms and daily functioning of patients with dementia treated on an acute psychogeriatric ward.

BACKGROUND: Dementia is associated with progressive deterioration in multiple cognitive domains, functional impairment and neuropsychiatric symptoms (NPS). AIMS: The aim of this study was to explore the factors associated with the outcome of NPS and daily functioning in patients with dementia during acute psychogeriatric hospitalization. MATERIALS AND METHOD: The data (n = 175) were collected between 2009 and 2013 in naturalistic settings on one acute psychogeriatric ward at one university hospital in Finland. Behavioural symptoms were assessed using the Neuropsychiatric Inventory (NPI) and activities of daily living using the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). RESULTS: During the hospital stay (45 days ±30.4) NPI total score decreased from 33.9 to 18.2 (p < .001). Daily functioning score decreased from 31.7 to 20.9 (p < .001). The number of patients taking antipsychotics (96-130, p = .004) and anxiolytics (54-102, p < .001) increased from admission to discharge. Overall mean dosage (mg/day) of antipsychotics (from 40.2 to 72.0 in chlorpromazine equivalents, p < .00) and anxiolytics (from 3.43 to 7.47 in diazepam equivalents, p < .001) also increased. Higher antipsychotic dosage at discharge was a significant predictor for large NPI score change (p = .002) indicating better symptom reduction. Neither higher antipsychotic dosage or anxiolytic dosage at discharge were significant predictors for ADL score change. CONCLUSIONS: Neuropsychiatric symptoms improved while deterioration was found in daily functioning from admission to discharge. Higher antipsychotic dosage at discharge was a predictor for larger NPI score change indicating better symptom reduction. Preventing threatening ADL decline during hospital stay is especially important.

Successful Curriculum Change in Health Management and Leadership Studies for the Specialist Training Programs in Medicine in Finland.

In Finland, the specialization programs in Medicine and Dentistry can be undertaken at all five university medical faculties in 50 specialization programs and in five programs for Dentistry. The specialist training requires 5 or 6 years (300-360 ECTS credits) of medical practice including 9 months of service in primary health care centers, theoretical substance specific education, management studies, and passing a national written exam. The renovation of the national curriculum for the specialization programs was implemented, first in 2008 and officially in August 2009, when theoretical multi-professional social, health management and leadership studies (10-30 ECTS credits) were added to the curriculum. According to European Credit Transfer and Accumulation System (ECTS), 1 ECTS credit (henceforth, simply "ECTS") means 27-30 h of academic work National guidelines for the multi-professional leadership training include the basics of organizational management and leadership, the social and healthcare system, human resources (HR) management, leadership interaction and organizational communication, healthcare economy, legislation (HR) and data management. Each medical faculty has implemented management studies autonomously but according to national guidelines. This paper will describe how the compulsory management studies (10 ECTS) have been executed at the Universities of Tampere and Turku. In Tampere, the 10 ECTS management studies follow a flexible design of six academic modules. Versatile modern teaching methods such as technology-assisted and student orientated learning are used. Advanced supplementary management studies (20 ECTS) are also available. In Turku, the 10 ECTS studies consist of academic lectures, portfolio and project work. Attendees select contact studies (4-6 ECTS) from yearly available 20 ECTS and proceed at their own pace. Portfolio and project comprise 2-5 ECTS each. The renovation of medical specializing physicians' management and leadership education has been a successful reform. It has been observed that positive attitudes and interest toward management overall are increasing among younger doctors. In addition, management and leadership education will presumably facilitate medical doctors' work as managers also. Continuous development of medical doctors' management and leadership education for physicians and dentists is needed while the changing and complex healthcare environment requires both professional and leadership expertise.

Reversible psychiatric adverse effects related to deep brain stimulation of the anterior thalamus in patients with refractory epilepsy.

OBJECTIVE: Anterior nucleus of thalamus (ANT) deep brain stimulation (DBS) is becoming a more common treatment for drug-resistant epilepsy. Epilepsy and depression display a bidirectional association. Anterior nucleus of thalamus has connections to anterior cingulate cortex and orbitomedial prefrontal cortex, hence, a possible role in emotional and executive functions, and thus, ANT DBS might exert psychiatric adverse effects. Our aim was to evaluate previous and current psychiatric symptoms in patients with epilepsy undergoing ANT DBS surgery and assess the predictability of psychiatric adverse effects. Programming-related psychiatric adverse effects are also reported. METHOD: Twenty-two patients with ANT DBS for retractable epilepsy were examined, and a psychiatric evaluation of depressive and other psychiatric symptoms was performed with Montgomery and Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Symptom Checklist prior to surgery, concentrating on former and current psychiatric symptoms and medications. The follow-up visit was one year after surgery. RESULTS: At the group level, no changes on mood were observed during ANT DBS treatment. Two patients with former histories of depression experienced sudden depressive symptoms related to DBS programming settings; these were quickly alleviated after changing the stimulation parameters. In addition, two patients with no previous histories of psychosis gradually developed clear paranoid and anxiety symptoms that also relieved slowly after changing the programming settings. CONCLUSION: The majority of our ANT DBS patients did not experience psychiatric adverse effects. Certain DBS parameters might predispose to sudden depressive or slowly manifesting paranoid symptoms that are reversible via programming changes.

Effect of electroconvulsive therapy on brain-derived neurotrophic factor levels in patients with major depressive disorder.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been associated with depression and its treatment response. The aim of the present study was to explore the effect of electroconvulsive therapy (ECT) on serum and plasma BDNF levels and change of Montgomery-Asberg Depression Rating Scale (MADRS) and their associations in patients with major depressive disorder (MDD). METHODS: The study included thirty patients suffering from MDD. Their serum and plasma BDNF levels were examined before ECT (baseline) and after the first, fifth, and last ECT session. The severity of the depression and the response to ECT were measured with MADRS. RESULTS: Electroconvulsive therapy caused no significant changes in serum BDNF levels. Plasma BDNF levels decreased during the fifth ECT session between the baseline and the 2-hr samples (p = 0.019). No associations were found between serum or plasma BDNF levels and remission. The correlations between plasma and serum BDNF levels in each measurement varied between 0.187 and 0.636. CONCLUSIONS: Neither serum nor plasma BDNF levels were systematically associated with the clinical remission. However, the plasma BDNF levels somewhat varied during the ECT series. Therefore, the predictive value of BDNF for effects of ECT appears to be at least modest.

Behavioral activation versus treatment as usual in naturalistic sample of psychiatric patients with depressive symptoms: a benchmark controlled trial.

BACKGROUND: More systematic use of evidence-based brief therapies is needed in the treatment of depression within psychiatric care. The aim of this study was to explore the impact of behavioral activation therapy (BA) for patients with depressive symptoms in a routine clinical setting of secondary psychiatric care. METHODS: The BA-treated intervention group (n = 242) comprised patients with depressive symptoms (Beck Depression Inventory (BDI) score ≥ 17 at baseline). The control group (n = 205) patients received treatment as usual in the same catchment area. The groups were matched at baseline using BDI and Alcohol Use Disorders Identification Test scores and inpatient/outpatient status. The groups were compared at 6-, 12- and 24-month follow-up points on functional outcome (Global Assessment of Functioning scale), service use, dropout and deaths. The Montgomery-Åsberg Depression Rating Scale was used to assess depressive symptoms in the intervention group. RESULTS: The estimated difference in GAF score between intervention and control group patients was significant at 12- and 24-months follow-up points in favor of intervention group (GAF score difference 4.85 points, p = 0.006 and 5.71 points, p = 0.005, respectively; estimate for patient group 2.26, p = 0.036). The rates of dropout, mortality and service use were similar between the groups. Among the intervention group patients, the estimated improvement in MADRS score compared to baseline was statistically significant throughout the follow-up (p < 0.001 at all follow-up points). CONCLUSIONS: The systematic use of BA among secondary psychiatric care depressive patients provides encouraging results despite the patients had various comorbid non-psychotic disorders. TRIAL REGISTRATION: ClinicalTrials.gov , Identifier NCT02520271, Release Date: 06/27/2015, retrospectively registered.

Temperament clusters associate with anxiety disorder comorbidity in depression.

BACKGROUND: Individual temperament is associated with psychiatric morbidity and could explain differences in psychiatric comorbidities. We investigated the association of temperament profile clusters with anxiety disorder comorbidity in patients with depression. METHODS: We assessed the temperament of 204 specialized care-treated depressed patients with the Temperament and Character Inventory (TCI-R) and their diagnoses with the Mini International Neuropsychiatric Interview. Two-step cluster analysis was used for defining patients' temperament profiles and logistic regression analysis was used for predicting different anxiety disorders for various temperament profiles. RESULTS: Four temperament clusters were found: 1) Novelty seekers with highest Novelty Seeking scores (n = 56),2) Persistent with highest Persistence scores (n = 36), 3) Reserved with lowest Novelty Seeking scores (n = 66) and 4) Wearied with highest Harm avoidance, lowest Reward Dependence and lowest Persistence scores (n = 58). After adjusting for clinical variables, panic disorder and/or agoraphobia were predicted by Novelty seekers' temperament profile with odds ratio [OR] = 3.5 (95% confidence interval [CI] = 1.8 - 6.9, p < 0.001), social anxiety disorder was predicted by Wearied temperament profile with OR = 3.4 (95% CI = 1.6 - 7.5, p = 0.002), and generalized anxiety disorder was predicted by Reserved temperament profile with OR = 2.6 (95% CI = 1.2 - 5.3, p = 0.01). LIMITATIONS: The patients' temperament profiles were assessed while displaying depressive symptoms, which may have affected results. CONCLUSIONS: Temperament clusters with unique dimensional profiles were specifically associated with different anxiety disorders in this study. These results suggest that TCI-R could offer a valuable dimensional method for predicting the risk of anxiety disorders in diverse depressed patients.

Temperament and character profiles are associated with depression outcome in psychiatric secondary care patients with harmful drinking.

BACKGROUND: Temperament and character profiles have been associated with depression outcome and alcohol abuse comorbidity in depressed patients. How harmful alcohol use modifies the effects of temperament and character on depression outcome is not well known. Knowledge of these associations could provide a method for enhancing more individualized treatment strategies for these patients. METHODS: We screened 242 depressed patients with at least moderate level of depressive symptoms. The Alcohol Use Disorders Identification Test (AUDIT) was used for identifying patients with marked alcohol use problems (AUP, AUDIT≥11). After 6 weeks of antidepressive treatment 173 patients were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Temperament and Character Inventory (TCI-R). Outcome of depression (MADRS scores across three follow-up points at 6 weeks, 6 months and 24 months) was predicted with AUP, gender, and AUP x Gender and AUP x Time interactions together with temperament and character dimension scores in a linear mixed effects model. RESULTS: Poorer outcome of depression (MADRS scores at 6 weeks, 6 months and 24 months) was predicted by AUP × Time interaction (p = 0.0002) together with low Reward Dependence (p = 0.003). Gender and all other temperament and character traits were non-significant predictors of the depression outcome in the mixed effects model. CONCLUSIONS: Possibly due to the modifying effect of alcohol use problems, high Reward Dependence was associated with better depression treatment outcome at 6 months. Harm Avoidance and Self-Directedness did not predict depression outcome when alcohol use problems were controlled.

Low tumor necrosis factor-α levels predict symptom reduction during electroconvulsive therapy in major depressive disorder.

Objective: Changes in the tumor necrosis factor-α (TNFα) have been associated with major depressive disorder (MDD). Findings concerning the effects of electroconvulsive therapy (ECT) on the TNFα level have been contradictory. The aim was to examine the immediate and long-term changes in the TNFα level and their associations with symptom reduction in patients with MDD during ECT. Method: The study included 30 patients with MDD. Their TNFα levels were measured at baseline and 2 and 4 hr after the first, fifth and last ECT session. Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale (MADRS). Results: The TNFα level decreased from baseline to the 2- and 4-hr measurements. There was a correlation between the first ECT session TNFα levels and the relative symptom reduction according to the MADRS score after the ECT series. Both the first (baseline) ECT and 4-hr TNFα levels were lower in responders than in nonresponders. Conclusion: ECT consistently induced a decrease in the TNFα level after each studied session. A low TNFα level at the first ECT appeared to predict a symptom reduction. These findings suggest that TNFα might have a role in the pathogenesis in MDD and in the mechanism of action of ECT.