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.

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.

Temperament and character profiles associated with depression and treatment response in patients with or without comorbid substance abuse.

There is limited knowledge on the relationship between temperament and character profiles and substance abuse comorbidity in depressed patients. We recruited 127 depressed patients without alcohol use problems (non-AUP) and 89 depressed patients with alcohol use problems (AUP). We assessed all patients using the Temperament and Character Inventory (TCI-R) at baseline and after 6 weeks of treatment. Using univariate general linear models (GLMs), we analyzed differences in TCI-R between AUP and non-AUP. GLMs were also used in analyzing the associations between TCI-R changes and antidepressive treatment responses measured with changes in Montgomery Åsberg Depression Rating Scale score (ΔMADRS). Alcohol use explained independently significant proportions of the variation in Novelty Seeking, Self-Directedness, and Persistence. Reward Dependence score change explained 14.1% of the ΔMADRS in AUP, but was non-significant in non-AUP. Character score changes in Self-Directedness and Self-Transcendence explained together 14.1% of ΔMADRS in non-AUP, whereas they were all non-significant in AUP. AUP compared with non-AUP patients had lower Self-Directedness and Persistence and higher Novelty Seeking scores. Detected changes in Reward Dependence and lower Self-Directedness in AUP patients could be reflective of different biological mechanisms associated with depressive symptomatology in alcohol abuse. Changes in character are associated with acute treatment response in non-AUP.

A cluster model of temperament as an indicator of antidepressant response and symptom severity in major depression.

OBJECTIVE: Not enough is known about which patients suffering from major depressive disorder benefit from antidepressant drug treatment. Individual temperament is relatively stable over a person's lifespan and is thought to be largely biologically predefined. We assessed how temperament profiles are related to depression and predict the efficacy of antidepressant treatment. METHODS: We recruited one hundred Finnish outpatients (aged 19 to 72) suffering from major depressive disorder, of whom 86 completed the 6-week study. We assessed their temperament features with the Temperament and Character Inventory and used cluster analysis to determine the patient's temperament profile. We also categorized the patients according to the vegetative symptoms of major depressive disorder. RESULTS: There was an association between skewed temperament profile and severity of major depressive disorder, but the temperament profiles alone did not predict antidepressant treatment response. Those with higher baseline vegetative symptoms score had modest treatment response. Our model with baseline Montgomery Åsberg Depression Rating Scale (MADRS) vegetative symptoms, age and temperament clusters as explanatory variables explained 20% of the variance in the endpoint MADRS scores. CONCLUSION: The temperament clusters were associated both with severity of depression and antidepressive treatment response of depression. The effect of the temperament profile alone was modest but, combined with vegetative symptoms of depression, their explanatory power was more marked suggesting that there could be an association of these two in the biological basis of MDD.