Outi Poutanen

5-HTR1A, 5-HTR2A, 5-HTR6, TPH1 and TPH2 polymorphisms and major depression.

Genes that regulate the serotonin signalling system are potential targets for research in the aetiology of mood disorders and also in the treatment response of serotonin reuptake inhibitors. In this study, we evaluated the association of seven serotonin signal transduction-linked single nucleotide polymorphisms [HTR1A (rs6295), HTR2A (rs6313, rs6311 and rs7997012), HTR6 (rs1805054), TPH1 (rs1800532) and TPH2 (rs1386494)] with major depressive disorder and/or treatment outcome with serotonin reuptake inhibitors. Patients who met the criteria for major depressive disorder were treated for 6 weeks with fluoxetine, paroxetine or citalopram. The treatment response was evaluated with the Montgomery–Asberg Depression Rating Scale, and according to predefined response criteria, the patients were divided into responders, nonresponders, remitters and nonremitters. Altogether, 86 patients completed the entire study according to the study protocol. We had also a control population (N = 395) of healthy blood donors. None of the seven single nucleotide polymorphisms was associated with major depressive disorder or with treatment response in our study population of Finnish individuals.

Can onset and recovery in depression be predicted by temperament? A systematic review and meta-analysis

BACKGROUND Behavioural inhibition and more specifically harm avoidance temperament dimension (HA) has been found to be associated with depression. Temperament and Character Inventory (TCI) by Cloninger et al. is the most widely used instrument in the assessment of temperament. The aims of the present study were to explore 1) if current or future depressive symptoms in non-clinical adult sample can be explained by TCI temperament dimensions, and 2) if recovery from major depression (MDD) during the acute phase of treatment is predictable by TCI temperament dimensions. METHOD Literature search from eight databases. Systematic review and meta-analysis. RESULTS High HA was associated with current depressive symptoms in 11/12 studies and with depressive trait in 3/4 studies. In MDD studies, a consistent negative change in HA was found during treatment and this change was even more clearly associated with treatment response. LIMITATIONS The studies with general population samples were heterogeneous in methodology. Most of the intervention studies were of case-control design. CONCLUSIONS HA is indisputably associated with the risk and treatment response in depression.

Risk factors for depression in primary care. Findings of the TADEP project

BACKGROUND Depression is a common but poorly recognized disorder in primary care. Knowing risk factors related to depression can help doctors in diagnosing and treating depressive patients. METHODS A random sample of 1643 individuals, aged 18 to 64, attending community health centres in Central Finland, took part in an inquiry with an instrument (the DEPS) measuring their depressiveness. RESULTS Negative life events, poor physical health, poor marital or other interpersonal relationships, spouses poor health, poor socio-economic and work situation and problems with alcohol were the major variables explaining the variance of depressive symptoms both in regression and discriminant analyses. CONCLUSION In the primary care patients, negative life events, poor physical health, poor marital or other interpersonal relationships, spouses poor health, poor socio-economic and work situation and problems with alcohol indicate high risk for depression; they also often accumulate in the same patients. The connection between risk factors and depression is stronger in males than in females. LIMITATION The assessment of depression is based on the self-fulfilled scale and cannot, therefore, be directly generalized to clinical depression. Because of the cross-sectional study design, it is not possible to make any causal conclusion between risk factors and depression. CLINICAL RELEVANCE By paying attention to the most general risk factors of depression, general practitioners can become more sensitive in their recognition of depression.

Catechol-O-methyltransferase val108/158met genotype, major depressive disorder and response to selective serotonin reuptake inhibitors in major depressive disorder

The functional val108/158met polymorphism of the COMT gene (rs4680) was evaluated in major depressive disorder (MDD), and in the treatment response to antidepressants in MDD. We could not demonstrate any significant difference in the distribution of this COMT single-nucleotide polymorphism (SNP) in the treatment response to selective serotonin reuptake inhibitors or between patients with MDD and control subjects.

TPH1 218A/C polymorphism is associated with major depressive disorder and its treatment response

The association between the tryptophan hydroxylase 1 (TPH1) 218A/C polymorphism and (1) severity of major depressive disorder (MDD) and (2) response to treatment was studied. There were three study populations, the first consisting of 119 treatment-resistant MDD inpatients treated with electro-convulsive therapy (ECT), and the second of 98 MDD open care patients treated with selective serotonin reuptake inhibitors (SSRI). In addition, there was a control population of 395 healthy blood donors. The first aim of the study was to compare the genotypes of the patient with those of the healthy controls and between patient populations. The second aim was to compare the genotypes of MDD patients achieving remission with basic SSRI treatment (MADRS<8) with the genotypes of non-responders to ECT (defined as MADRS>15). TPH1 218A/C polymorphism was associated with the risk of MDD. CC genotype was significantly more common in patients (including both ECT and SSRI treated patients) than in controls (38.2% and 26.8% respectively; p=0.008), and its frequency was significantly higher in more severe forms of depression, i.e. in ECT treated patients compared with SSRI treated patients (42.0% and 33.7%, p=0.026). CC genotype was also associated with lower probability of achieving remission. It was significantly more frequent among ECT non-responders than among SSRI remitters (53.1% and 23.3%, p=0.049). In this Finnish population TPH1 218A/C polymorphism was associated with the risk of MDD and treatment response; CC genotype was associated with the increased risk of MDD and lower probability of responding treatment. Further studies with larger samples will be required to confirm the results.

Temperament profiles, major depression, and response to treatment with SSRIs in psychiatric outpatients

OBJECTIVE The Temperament and Character Inventory (TCI) is commonly used in adult populations. Our aim was to explore: (1) if there are specific differences in temperament dimensions related to depression in comparison with general population, (2) if the treatment response during the acute phase of major depressive disorder (MDD) is predictable by TCI temperament dimensions. METHOD Temperament profiles in 98 MDD patients were compared with a Finnish community sample. The patients were treated with serotonin selective reuptake inhibitors (SSRIs) for 6 weeks and their temperament profiles were assessed at baseline and endpoint. The harm avoidance (HA) and depression scores at baseline and endpoint were modelled with path analysis. For path modelling, we tested the relationships between different temperament dimensions and depression symptoms and other clinical variables with Mancova model. RESULTS The HA scores were significantly higher in patients both at baseline and endpoint compared to the Northern Finland 1966 Birth Cohort (NFBC). The patients, and especially males, had slightly higher reward dependency (RD) scores. HA at endpoint explained moderately the Montgomery Åsberg Depression Rating Scale (MADRS) endpoint score. HA endpoint score was strongly explained by HA baseline score. CONCLUSIONS HA is associated with risk of and treatment response to depression.

Seven-year outcome of depression in primary and psychiatric outpatient care: results of the TADEP (Tampere Depression) II Study.

The objective of this article was to determine a 7-year naturalistic progression of depression as well as a number of potential prognostic factors among Finnish primary care and psychiatric care patients. Depression-screened patients from primary care and psychiatric care, aged 18–64, were interviewed in 1991–92 with the Present State Examination (PSE) as the diagnostic instrument. The patients were re-contacted in 1998–99, and their depression at final assessment (FinalA) and during the follow-up period (F-up) was assessed by telephone interview using the Composite International Diagnostic Interview—Short Form (CIDI-SF). 250 primary care (58.1%) and 170 (40.2%) psychiatric care patients were successfully followed. Of the primary care patients with severe depression at baseline, 42.4% had had depression during F-up and 21.2% had depression at FinalA. For the patients with mild depression at baseline, the corresponding figures were nearly the same, but for the patients with depressive symptoms clearly lower. Of the psychiatric care patients with severe depression at baseline, 61.0% had had depression during F-up and 26.2% had depression at FinalA. As with primary care patients, the corresponding figures were nearly the same for mild depression at baseline but clearly lower for depressive symptoms. Experienced lifetime mood elevation was associated with having depression during F-up in both primary care and psychiatric care patients. High Depression Scale (DEPS) score at baseline was associated with having depression at FinalA in primary care patients, but in psychiatric care patients, it was the high Hamilton Rating Scale for depression (HAM-D) and drinking problems. Severe depression and mild depression are predictive for subsequent depression at both levels of care. The long-term prognosis for depression is better in primary care. DEPS and HAM-D are useful, prognostic instruments.

The validity of the Depression Scale (DEPS) to assess the severity of depression in primary care patients

BACKGROUND There is a need for a simple depression questionnaire also capable of assessing the severity of depression. The Depression Scale (DEPS), has been a very popular self-rating depression questionnaire in Finland for >15 years. OBJECTIVE Our aim was to examine whether the DEPS has the ability to differentiate clearly defined levels of depression in primary care patients. METHODS Primary care patients aged 18-64 years completed a postal questionnaire including the DEPS. All screen-positive subjects and every 10th screen-negative subject were invited for interview using the Present State Examination (PSE) as the gold standard. Complete DEPS score was available for 410 patients. Descriptive statistics of the DEPS in the six diagnostic PSE classes were computed. Four of the PSE classes were selected for further analyses of depression severity. Receiver Operating Characteristic curves, sensitivity, specificity, ideal cut-off points and area under the curve were calculated. The ability of the DEPS to differentiate levels of functioning was also evaluated. RESULTS The DEPS identified three groups of patients: those with no psychiatric symptoms, those with some depressive symptoms and those with clinical depression. The margins between the levels were thin: the ideal cut-off point for clinical depression was 11/12 and for any level of depression 9/10. The DEPS was also able to differentiate three levels of functioning. CONCLUSIONS The DEPS has some ability to identify severity of depression in primary care patients. Further research with larger unscreened material is called for.

Gender differences in the symptoms of major depression and in the level of social functioning in public primary care patients.

Abstract Background: There are no great differences in the symptom profiles of depression between the genders in observer rating scales, but women self-report more symptoms. Objective: To compare gender differences in symptom profiles of clinical depression in primary care with a short self-report depression scale and an observer-rated scale for social functioning. Methods: A sample of 436 primary care patients aged 18–64 years were screened using the Depression Scale (DEPS) and interviewed using the Present State Examination (PSE). Level of social functioning was also assessed. Sum scores and single items of DEPS were compared between men and women in the groups of both depressive and non-depressive patients, and the interactions between gender and depression were analysed. Results: Depressive men scored poorer on both instruments. Feeling that everything is an effort and feeling worthless were typical for depressive men. Feeling blue was more typical for non-depressive women than for non-depressive men. Conclusion: In this sample of primary care patients, there were differences in the symptom profiles of depression between men and women. Depressive men more commonly had serious symptoms than depressive women. Clinically, male depression deserves more attention. The psychosocial profile of public primary care patients in Finland warrants further research.

No support for a role for BDNF gene polymorphisms rs11030101 and rs61888800 in major depressive disorder or antidepressant response in patients of Finnish origin.

Brain-derived neurotrophic factor (BDNF) is suggested to play a role in the aetiology of major depression and in the antidepressant response in patients with major depression. Several BDNF gene polymorphisms have been investigated in the above-mentioned context. The aim of the present study was to examine the role of two BDNF gene polymorphisms (rs11030101 and rs61888800) in relation to the response to selective serotonin reuptake inhibitor medication in 106 patients of Finnish origin suffering from major depression. The secondary objective was to evaluate the association of these two BDNF polymorphisms in major depression, as we also had a control population of 386 healthy individuals. We did not find any significant differences in the distribution of these two BDNF gene polymorphisms in our patient population in relation to remission or response to treatment with selective serotonin reuptake inhibitor. Also, there were no significant differences between the patients and the controls.