Tarja K. Melartin

Major depressive disorder and white matter abnormalities: A diffusion tensor imaging study with tract-based spatial statistics

BACKGROUND A few diffusion tensor imaging (DTI) studies have shown abnormalities in areas of white matter tracts involved in mood regulation in geriatric depressive patients, using a region-of-interest technique. A voxel-based morphometry DTI study of young depressive patients reported similar results. In this study, we explored the structure of the white matter of the whole brain with DTI in middle-aged major depressive disorder (MDD) patients, using novel tract-based spatial statistics. METHODS Sixteen MDD patients and 20 controls underwent DTI. An automated tract-based spatial method (TBSS) was used to analyze the scans. RESULTS Compared with controls, the MDD patients showed a trend for lower values of fractional anisotropy (FA) in the left sagittal stratum, and suggestive decreased FA in the right cingulate cortex and posterior body of corpus callosum. Regressing out the duration and severity of disorder in the model did not change the finding in the sagittal stratum, but dissipated the decrease of FA in latter regions. LIMITATIONS Possibly by reason of a relatively small study sample for a TBSS, the results are suggestive, and should be replicated in further studies. CONCLUSIONS A novel observer-independent DTI method showed decreased FA in the middle-aged MDD patients in white matter regions that have previously connected to the emotional regulation. Lower FA might imply underlying structural abnormalities that contribute to the dysfunction detected in the limbic-cortical network of depressive patients.

Incidence and Predictors of Suicide Attempts in DSM-IV Major Depressive Disorder: A Five-Year Prospective Study

OBJECTIVE Prospective long-term studies of risk factors for suicide attempts among patients with major depressive disorder have not investigated the course of illness and state at the time of the act. Therefore, the importance of state factors, particularly time spent in risk states, for overall risk remains unknown. METHOD In the Vantaa Depression Study, a longitudinal 5-year evaluation of psychiatric patients with major depressive disorder, prospective information on 249 patients (92.6%) was available. Time spent in depressive states and the timing of suicide attempts were investigated with life charts. RESULTS During the follow-up assessment period, there were 106 suicide attempts per 1,018 patient-years. The incidence rate per 1,000 patient-years during major depressive episodes was 21-fold (N=332 [95% confidence interval [CI]=258.6-419.2]), and it was fourfold during partial remission (N=62 [95% CI=34.6-92.4]) compared with full remission (N=16 [95% CI=11.2-40.2]). In the Cox proportional hazards model, suicide attempts were predicted by the months spent in a major depressive episode (hazard ratio=7.74 [95% CI=3.40-17.6]) or in partial remission (hazard ratio=4.20 [95% CI=1.71-10.3]), history of suicide attempts (hazard ratio=4.39 [95% CI=1.78-10.8]), age (hazard ratio=0.94 [95% CI=0.91-0.98]), lack of a partner (hazard ratio=2.33 [95% CI=0.97-5.56]), and low perceived social support (hazard ratio=3.57 [95% CI=1.09-11.1]). The adjusted population attributable fraction of the time spent depressed for suicide attempts was 78%. CONCLUSIONS Among patients with major depressive disorder, incidence of suicide attempts varies markedly depending on the level of depression, being highest during major depressive episodes. Although previous attempts and poor social support also indicate risk, the time spent depressed is likely the major factor determining overall long-term risk.

Depressive disorders in primary care: recurrent, chronic, and co-morbid

BACKGROUND Preceding longitudinal course and current somatic and psychiatric co-morbidity of depression have been little investigated in primary care. METHOD Consecutive patients (n = 1111) in primary care in the city of Vantaa, Finland, were screened for depression with the PRIME-MD, and positive cases interviewed by telephone. Cases with current depressive symptoms were diagnosed face-to-face with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P). A cohort of 137 patients with unipolar depressive disorders, comprising all patients with at least two depressive symptoms and clinically significant distress or disability, was recruited. The Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), medical records, rating scales, and a retrospective life-chart were used to obtain comprehensive cross-sectional and longitudinal information. RESULTS Current major depressive disorder (MDD) was the most prevalent depressive disorder (66%); it was usually mild to moderate but recurrent. A quarter of cases (23%) had MDD in partial remission or prodromal phase, and only 10% had true minor depression. Axis I co-morbidity was present in 59%, Axis II in 52%, and chronic Axis III disorders in 47%; only 12% had no co-morbidity. One third of patients presented with a psychological complaint, predicted by higher depression severity and younger age. CONCLUSION From a lifetime perspective, the majority of primary-care patients with depressive disorders suffer from recurrent MDD, although they are currently often in prodromal or residual phase. Psychiatric and somatic co-morbidity are highly prevalent. Treatment of depression in primary care should not rely on an assumption of short-lived, uncomplicated mild disorders.

The influence of adversity and perceived social support on the outcome of major depressive disorder in subjects with different levels of depressive symptoms.

BACKGROUND Adverse life events and social support may influence the outcome of major depressive disorder (MDD). We hypothesized that outcome would depend on the level of depressive symptoms present at the outset, with those in partial remission being particularly vulnerable. METHOD In the Vantaa Depression Study (VDS), patients with DSM-IV MDD were interviewed at baseline, and at 6 and 18 months. Life events were investigated with the Interview for Recent Life Events (IRLE) and social support with the Interview Measure of Social Relationships (IMSR) and the Perceived Social Support Scale - Revised (PSSS-R). The patients were divided into three subgroups at 6 months, those in full remission (n = 68), partial remission (n = 75) or major depressive episode (MDE) (n = 50). The influence of social support and negative life events during the next 12 months on the level of depressive symptoms, measured by the Hamilton Rating Scale for Depression (HAMD), was investigated at endpoint. RESULTS The severity of life events and perceived social support influenced the outcome of depression overall, even after adjusting for baseline level of depression and neuroticism. In the full remission subgroup, both severity of life events and subjective social support significantly predicted outcome. However, in the partial remission group, only the severity of events, and in the MDE group, the level of social support were significant predictors. CONCLUSIONS Adverse life events and/or poor perceived social support influence the medium-term outcome of all psychiatric patients with MDD. These factors appear to have the strongest predictive value in the subgroup of patients currently in full remission.

Functional and work disability in major depressive disorder

We examined factors related to social and occupational disability, social adjustment, and work disability among patients with major depressive disorder (MDD), the dominant mental disorder causing functional and work disability. The Vantaa Depression Study comprises a cohort of 269 psychiatric inpatients and outpatients with MDD in the city of Vantaa, Finland. Axis I and II diagnoses were assessed via semistructured WHO Schedules for Clinical Assessment in Neuropsychiatry Version 2.0 and Structured Clinical Interview for DSM-III-R personality disorders interviews. Global disability, social and work adjustment, and being at work or on sick leave were assessed. The most important factors associated with level of social, functional, and work disability were severity and recurrence of depression, but older age and current Axis I and II comorbidity also significantly contributed. Of those employed, almost half (43%) were on sick leave. The most pervasive factors explaining level of functional and work disability among patients with MDD were severity and recurrence of depression. However, older age and comorbidity also contributed.

Course and outcome of depressive disorders in primary care: a prospective 18-month study.

BACKGROUND Depressive disorders are known to often be chronic and recurrent both in the general population and in psychiatric settings. However, despite its importance for public health and services, the outcome of depression in primary care is not well known. METHOD In The Vantaa Primary Care Depression Study (PC-VDS), 1111 consecutive primary-care patients were screened for depression with the Prime-MD screen, and 137 diagnosed with DSM-IV depressive disorders by interviewing with the Structured Clinical Interview for DSM-IV (SCID)-I/P and SCID-II. This cohort was prospectively followed-up at 3, 6 and 18 months. Altogether 123 patients (90%) completed the 18-month follow-up, including 79 with major depressive disorder (MDD) and 44 with subsyndromal disorders. Duration of the index episode and the timing of relapses/recurrences were examined using a life-chart. RESULTS Of the patients with MDD, only a quarter [25% (20/79)] achieved and remained in full remission, while another quarter [25% (20/79)] persisted in major depressive episode for 18 months. The remaining 49% (39/79) suffered from residual symptoms or recurrences. In Cox regression models, time to remission and recurrences were robustly predicted by severity of depression, and less consistently by co-morbid substance-use disorder, chronic medical illness or cluster C personality disorder. Of the subsyndromal patients, 25% (11/44) proceeded to MDD. CONCLUSIONS This prospective medium-term study verified the high rate of recurrences and chronicity of depression also in primary care. Severity of depressive symptoms and co-morbidity are important predictors of outcome. Development of chronic disease management for depression is warranted in primary care.

Life events, social support, and onset of major depressive episode in Finnish patients

We investigated differences in life events and social support between subgroups of depressed patients and the distribution of life events in phases preceding or during depression. In the Vantaa Depression Study, 269 psychiatric patients with DSM-IV major depressive disorder were diagnosed with Schedule for Clinical Assessment in Neuropsychiatry, Version 2.0, and Structured Clinical Interview for DSM-III-R personality disorders (SCID-II). Life events during the 12 months preceding the interview were investigated with the Interview for Recent Life Events, and social support with the Interview Measure of Social Relationships and the Perceived Social Support Scale—Revised. Nearly all patients (91%) reported life events, on average 4.1 per preceding year. No major differences between sociodemographic or clinical subgroups were found; the frequency of events was somewhat greater among the younger subjects, whereas those with comorbid alcoholism or personality disorders perceived less social support. Although events were distributed evenly between the time preceding depression, the prodromal phase, and the index major depressive episode, two thirds of the patients attributed their depression to some event. Despite clinical and sociodemographic heterogeneity, patients with major depressive disorder are fairly homogeneous in terms of life events during the preceding year. Events do not cluster in any particular phase of the progression to an episode.

Co-morbidity and stability of melancholic features in DSM-IV major depressive disorder

BACKGROUND The descriptive validity of the melancholic features specifier of the DSM-IV major depressive disorder (MDD) is uncertain. Little is known about its relationship to psychiatric co-morbidity, stability across episodes, or strength in predicting course of illness. METHOD The Vantaa Depression Study (VDS) is a prospective, naturalistic cohort study of 269 patients with a new episode of DSM-IV MDD who were interviewed with SCAN and SCID-II between 1 February 1997 and 31 May 1998, and again at 6 and 18 months. Ninety-seven (36%) MDD patients met DSM-IV criteria for the melancholic features specifier, and were contrasted with 172 (64 %) subjects with a non-melancholic MDD. The duration of the index episode was examined using a life chart. RESULTS We found no difference in rates of any current co-morbid Axis I or II disorders between melancholic and non-melancholic depressed patients. Of those who had melancholic features at the index episode and subsequent episodes during the 18-month follow-up, only 22 % (5/23) presented melancholic features during the latter. The non-melancholic subtype switched to melancholic in 25 % (8/32) of cases. Differences in the course of melancholic and non-melancholic depression were very minor. CONCLUSIONS The descriptive validity of the DSM-IV melancholic features specifier may be questionable in MDD. There appear to be no major differences in current co-morbidity, or course of depression between melancholic and non-melancholic patients. The consistency of DSM-IV melancholic features across episodes appears weak.

Determinants of functional disability and social adjustment in major depressive disorder: a prospective study.

We examined prospectively factors influencing social and occupational disability and social adjustment among patients with major depressive disorder. The Vantaa Depression Study comprises a cohort of psychiatric inpatients and outpatients with major depressive disorder in the city of Vantaa, Finland. We prospectively interviewed 193 of 269 (72%) patients both 6 and 18 months after baseline. Axis I and II diagnoses were assessed via semistructured WHO Schedules for Clinical Assessment in Neuropsychiatry 2.0 and SCID-II interviews. Global disability and social and work adjustment were assessed. Patients’ functional disability and social adjustment were alleviated concurrently with recovery from depression during the follow-up. The current level of functioning and social adjustment of a patient with depression was predicted by severity of depression, recurrence before baseline and during follow-up, lack of full remission, and time spent depressed. Comorbid psychiatric disorders, personality traits (neuroticism), and perceived social support had significant influence.

Five-year outcome of major depressive disorder in primary health care

BACKGROUND Primary health care provides treatment for most patients with depression. Despite their importance for organizing services, long-term course of depression and risk factors for poor outcome in primary care are not well known. METHOD In the Vantaa Primary Care Depression Study, a stratified random sample of 1119 patients representing primary care patients in a Finnish city was screened for depression with the Primary Care Evaluation of Mental Disorders. SCID-I/P and SCID-II interviews were used to diagnose Axis I and II disorders. The 137 patients with DSM-IV depressive disorder were prospectively followed up at 3, 6, 18 and 60 months. Altogether, 82% of patients completed the 5-year follow-up, including 102 patients with a research diagnosis of major depressive disorder (MDD) at baseline. Duration of the index episode, recurrences, time spent in major depressive episodes (MDEs) and partial or full remission were examined with a life-chart. RESULTS Of the MDD patients, 70% reached full remission, in a median time of 20 months. One-third had at least one recurrence. The patients spent 34% of the follow-up time in MDEs, 24% in partial remission and 42% in full remission. Baseline severity of depression and substance use co-morbidity predicted time spent in MDEs. CONCLUSIONS This prospective, naturalistic, long-term study of a representative cohort of primary care patients with depression indicated slow or incomplete recovery and a commonly recurrent course, which need to be taken into account when developing primary care services. Severity of depressive symptoms and substance use co-morbidity should be systematically evaluated in planning treatment.