[Temperament and personality disorders as modifiers of depression]. / Temperamentti ja persoonallisuushäiriöt masennuksen muovaajina.

The connection of temperament with depression is manifested especially as an accentuated feature of avoidance of problems. Personality disorders lead to aberrant ways to make observations of oneself and other people, to control feelings and get along with other people. A personality disorder significantly worsens the prognosis of depression so that compared with mere depression, recovery is slower and recurrence more likely. We discuss the connection of adulthood temperament features, personality and personality disorders with depression.

TPH1 A218C polymorphism and temperament in major depression.

BACKGROUND: In major depression, one of the candidate genes possibly affecting the risk and severity of symptoms has been found to be tryptophan hydroxylase (TPH1). Variation in treatment response to antidepressive agents according to TPH1 genotype has also been found in several studies. However, the relationship between temperament and TPH1 genotype in major depression is poorly understood, as only one study has been published so far. There are no earlier studies on the interaction between temperament traits, antidepressive medication response and TPH1 genotype. This interaction was studied in 97 subjects with major depression treated for six weeks with selective serotonine reuptake inhibitors. METHODS: Temperament dimensions Harm Avoidance (HA), Novelty Seeking (NS), Reward Dependence (RD) and Persistence (P) scores at baseline (1) and endpoint (2) were rated with the Temperament and Character Inventory (TCI) and compared between TPH1 A218C genotypes. Multivariate analysis of co-variance (MANCOVA) was used to analyze the interaction between the TPH1 genotype, treatment response and the different temperament dimensions at baseline and endpoint. In the analysis model, treatment response was used as a covariate and TPH1 genotype as a factor. A post hoc analysis for an interaction between remission status and TPH1 A218C genotype at endpoint HA level was also performed. RESULTS: The number of TPH1 A-alleles was associated with increasing levels in NS1 and NS2 scores and decreasing levels in HA1 and HA2 scores between TPH1 A218C genotypes. In the MANCOVA model, TPH1 genotype and treatment response had an interactive effect on both HA1 and HA2 scores, and to a lesser degree on NS2 scores. Additionally, an interaction between remission status and TPH1 A218C genotype was found to be associated with endpoint HA score, with a more marked effect of the interaction between CC genotype and remission status compared to A-allele carriers. CONCLUSIONS: Our results suggest that in acute depression TPH1 A218C polymorphism and specifically the CC genotype together with the information on remission or treatment response differentiates between different temperament profiles and their changes.

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.

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.

Is 5-HTTLPR linked to the response of selective serotonin reuptake inhibitors in MDD?

The role of a functional polymorphism in the transcriptional control region of serotonin transporter gene (5-HTTLPR, SERTPR) has been studied intensively in major depression and in the response to selective serotonin inhibitors (SSRIs) in major depression. The findings have been contradictory, although majority of the studies indicate that the short allele is associated with poor response to SSRIs in major depression. In the present study, we evaluated the association of 5-HTTLPR with treatment response to SSRI medication in Finnish Caucasian MDD patients. A secondary purpose was to study the possible association of this particular polymorphism with major depressive disorder. The aim of the study was to replicate the previous findings in this area. Primary outcomes of the treatment were remission, defined by an exit score of seven or less, and response, defined by a reduction of at least 50% on the MADRS. We had also a control population of 375 healthy blood donors, as a secondary objective was to evaluate the possible association of this particular polymorphism with major depressive disorder. Twenty-nine of the 85 (34.1%) patients reached the remission and 58.8% achieved the predefined response criteria. The l/l genotype of 5-HTTLPR was presented in 51.7% of those patients who achieved remission vs. 25.0% in the non-remitters (P = 0.03). The result remained statistically significant after adjusting for age, gender, medication and MADRS points at the study entry. However, the small sample size limits the reliability of this result.

Temperament profiles, 5-HT2A genotype, and response to treatment with SSRIs in major depression.

Variation in antidepressive medication response according to 5-HT2A genotype has been reported in several studies. Temperament has been proposed to be one of the vulnerability factors in mood and anxiety disorders. We studied temperament profiles of 98 patients with major depression and explored the interaction between Temperament and Character Inventory (TCI) temperament dimensions, 5-HT2A genotype (SNPs rs6311, rs6313 and rs7997012) and treatment response. No interactive effects for TCI temperament dimensions and 5-HT2A genotypes on antidepressive treatment response were found.

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.

Applicability of the DEPS Depression Scale: assessing format and individual items in subgroups of patients.

BACKGROUND: The role of questionnaires is important in improving the recognition of major depression. AIMS: Our aims were: 1) to compare the differences of structure between the Depression Scale (DEPS) and other instruments, and 2) to study whether the DEPS items function in the same way with patients grouped by gender, by age or by education, at the same time taking into account the level of depression. METHODS: The item topics of the DEPS and five other self-rating questionnaires (BDI-II, CES-D, HADS-D, PHQ-9, SCL-90-D), an interviewer rating scale (HAMD-17) and two diagnostic interviews for depression (ICD-10, DSM-IV) were listed in a table. The format of the questionnaires and the rating scale were compared. Differential item functioning (DIF) analysis using empirical material (n=1522) and logistic regression models was done to predict DEPS item responses across dichotomous categories for gender, age and education. RESULTS AND CONCLUSIONS: The DEPS scale items covered essential symptoms of depression. Of the instruments assessed, the DEPS seemed the most simple. DIF analyses with the DEPS scale revealed some socio-demographic variation in which symptoms were endorsed after matching for DEPS sum score. Clinically the DEPS has good applicability and accuracy for screening depression in working aged primary care patients.

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.

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

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.

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.

Stability of affect associated with autobiographical memories.

Childhood family atmosphere is a frequent topic in psychotherapy. Our aim was to assess the stability of affect associated with autobiographical memories. In a 7-year follow-up study of depression, 414 primary care patients and psychiatric outpatients both at baseline and at follow-up completed the self-inquiry Depression Scale (DEPS) and answered simple questions about the mental atmosphere in their childhood families. The prevalence and the distribution of changes in affect were calculated by cross-tabulation. Logistic regression analyses were used to assess associations between depressiveness and changes in affect. Nearly 50% of the sample had at least one change in the responses. Young age and male gender were significant predictors for changes. Depressiveness was associated with changes in miserable affect of the childhood home. Affect associated with autobiographical memories seems to change over a longer period. The association between depressiveness and changes in recollections is convoluted. The large number of changes of affects concerning autobiographical memories should be taken into account both in psychotherapy and in studies of life-long experiences. Future long follow-up studies with more specific multi-item measures on family atmosphere are needed.

Severe anorexia nervosa, co-occurring major depressive disorder and electroconvulsive therapy as maintenance treatment: a case report.

INTRODUCTION: It is difficult to treat patients who, in addition to having severe anorexia nervosa, also have severe symptoms of major depressive disorder and a tendency for impulsive acting out behaviour. Our case report considers the feasibility of maintenance electroconvulsive therapy in such complicated cases. CASE PRESENTATION: This is a case report of a woman with anorexia nervosa and co-morbid severe major depressive disorder who was treated with electroconvulsive therapy as a maintenance treatment. The maintenance electroconvulsive therapy was conducted without immediate complications. It had a positive effect on the patient's depressive symptoms and lability and her general wellbeing, although some cognitive deficits were observed. CONCLUSION: The maintenance electroconvulsive therapy seemed to support recovery in a case of refractory anorexia nervosa and a tendency for labile mood. The symptoms of co-occurring major depressive disorder were partly relieved and maintenance electroconvulsive therapy had some positive effect on weight gain.

The Depression Scale (DEPS) as a case finder for depression in various subgroups of primary care patients.

PURPOSE: The quick and simple Depression Scale (DEPS) has been a popular self-rating depression scale in Finland for nearly 15 years. The purpose was to assess the validity of the DEPS in various subgroups of patients. MATERIALS AND METHODS: Primary care patients, aged 18-64, completed a postal questionnaire including the DEPS. Of the 1643 patients all screen-positive subjects and every 10th screen-negative subject were invited for interview (the Present State Examination, PSE). Complete DEPS scores were available for 410 patients. They were grouped by gender, age, marital status, perceived physical health, basic education and the Michigan Alcoholism Screening Test (MAST) score. Separately for each subgroup, receiver operating characteristic (ROC) curve analyses were done, sensitivity, specificity, area under the curve (AUC), predictive values and likelihood ratios were calculated, and Cronbach's alpha was estimated. RESULTS: The DEPS was valid in general, but best for patients with basic education longer than 9 years. DISCUSSION: The key statistical figures for the DEPS were comparable to the figures for other short self-rating scales. CONCLUSION: The DEPS is a valid case finder for primary care patients in the age group 18-64 years, and especially suitable for more highly educated patients. Future studies comparing the DEPS with other simple depression rating scales are needed.

Predicting lifetime mood elevation in primary care patients and psychiatric patients.

Unipolar depression is undoubtedly the most common affective disorder, but recently the role of bipolar disorders has become more and more significant. The aim of the study was to improve the detection of mood elevations by careful anamnestic assessment, especially family history and psychosocial functional skills. A sample, screened for depression, of 430 primary care patients and 423 psychiatric patients aged 18-64 were interviewed in 1991-1992 using the Present State Examination. Anamnestic information was obtained by questionnaire and interview. Participants were re-contacted in 1998-1999. Experienced lifetime mood elevation was assessed in the follow-up study using the main criteria of the ICD-10 in a telephone interview by three research psychiatrists. Patient's smoking, suicidality in the Hamilton Depression Scale (HAM-D), problems in making contact with the opposite sex when a teenager, and mental problems in either of the parents when the patient was < or = 15 years were associated with experienced lifetime mood elevation. Quick and easy questions about smoking and difficulties in making contact with the opposite sex may improve the detection of mood elevation.

The performance of diagnostic measures of depression in alexithymic and nonalexithymic subjects.

OBJECTIVE: The objective of this study was to examine how the outcomes of a structured diagnostic interview for depression are related to the results of a self-report scale in alexithymic and nonalexithymic groups. MATERIALS AND METHODS: Subjects (N=389) recruited from primary care and psychiatric care completed the Depression Scale (DEPS) and the 20-item Toronto Alexithymia Scale. Major depression was diagnosed using the Composite International Diagnostic Interview-Short-Form by telephone. RESULTS: In the group without major depression, the DEPS scores of the alexithymic subjects were significantly higher than those of the nonalexithymic subjects. In the group with major depression, the ideal cutoff points of the DEPS, assessed by receiver operating characteristic analyses, were essentially higher for the alexithymic patients. CONCLUSIONS: Alexithymic subjects without major depression may be rated as depressive if the only criterion is the score on a self-report scale. Furthermore, alexithymic patients may require higher cutoff points in a self-report depression scale.

Alexithymia and life satisfaction in primary healthcare patients.

The relationship between life satisfaction and alexithymia was studied in a sample of 229 patients as a part of a naturalistic follow-up study of depression in Finnish primary health care. The measures were the abbreviated Life Satisfaction Scale and the 20-item Toronto Alexithymia Scale. Depression was assessed by telephone with the short form of the Composite International Diagnostic Interview. Of all subjects, 19.2% were alexithymic, and 9.2% were depressed. Alexithymia was negatively associated with life satisfaction even when depression and other confounding factors were controlled for. Alexithymia is a risk factor for life dissatisfaction in primary-care patients.

The Depression Scale as a screening instrument for a subsequent depressive episode in primary healthcare patients.

BACKGROUND: There are numerous instruments for screening for depression. A feasible screen is good at both recognising and predicting depression. AIMS: To study the ability of the Depression Scale and its items to recognise and predict a depressive episode. METHOD: A sample of patients attending primary care was examined in 1991-992 and again 7 years later. The accuracy of the Depression Scale at baseline and at follow-up was tested against the Short Form of the Composite International Diagnostic Interview (CIDI-SF) diagnosis of depression at follow-up. The sensitivity and specificity of the Depression Scale and its items were assessed. RESULTS: Both baseline and follow-up Depression Scale scores were consistent with the CIDI-SF diagnoses. It was possible to find single items efficient at both recognising and predicting depression. CONCLUSIONS: The Depression Scale is a useful screening instrument for depression, with both diagnostic and predictive validity.