The Relationship Between Smoking and Suicidal Behavior in Psychiatric Patients with Major Depressive Disorder.

Smoking is frequently associated with suicidal behavior, but also with confounding other risk factors. We investigated whether smoking independently predicts suicidal ideation, attempts (SAs), or modifies risk of SAs during major depressive episodes (MDEs). In the Vantaa Depression Study (VDS), a 5-year prospective study of psychiatric patients (N = 269) with major depressive disorder (MDD), we investigated the association of suicidal ideation and smoking, and smoking as an independent risk factor for SAs in 2-level analyses of risk during MDEs. Smoking was not significantly associated with suicidal ideation, nor SAs after controlling for confounding factors, and no evidence of a significant effect during MDEs was found. Smoking was neither significantly associated with suicidal ideation, nor predicted suicide attempts.

Differences in incidence of suicide attempts between bipolar I and II disorders and major depressive disorder.

OBJECTIVES: Whether risk of suicide attempts (SAs) differs between patients with bipolar disorder (BD) and patients with major depressive disorder (MDD) is unclear. We investigated whether cumulative risk differences are due to dissimilarities in time spent in high-risk states, incidence per unit time in high-risk states, or both. METHODS: Incidence rates for SAs during various illness phases, based on prospective life charts, were compared between patients from the Jorvi Bipolar Study (n = 176; 18 months) and the Vantaa Depression Study (n = 249; five years). Risk factors and their interactions with diagnosis were investigated with Cox proportional hazards models. RESULTS: By 18 months, 19.9% of patients with BD versus 9.5% of patients with MDD had attempted suicide. However, patients with BD spent 4.6% of the time in mixed episodes, and more time in major depressive episodes (MDEs) (35% versus 21%, respectively) and in subthreshold depression (39% versus 31%, respectively) than those with MDD. Compared with full remission, the combined incidence rates of SAs were 5-, 25-, and 65-fold in subthreshold depression, MDEs, and BD mixed states, respectively. Between cohorts, incidence of attempts was not different during comparable symptom states. In Cox models, hazard was elevated during MDEs and subthreshold depression, and among patients with preceding SAs, female patients, those with poor social support, and those aged < 40 years, but was unrelated to BD diagnosis. CONCLUSIONS: The observed higher cumulative incidence of SAs among patients with BD than among those with MDD is mostly due to patients with BD spending more time in high-risk illness phases, not to differences in incidence during these phases, or to bipolarity itself. BD mixed phases contribute to differences involving very high incidence, but short duration. Diminishing the time spent in high-risk phases is crucial for prevention.

Depression and smoking: a 5-year prospective study of patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) and smoking are major public health problems and epidemiologically strongly associated. However, the relationship between smoking and depression and whether this is influenced by common confounding factors remain unclear, in part due to limited longitudinal data on covariation. METHODS: In the Vantaa Depression Study, psychiatric out- and inpatients with DSM-IV MDD and aged 20-59 years at were followed from baseline to 6 months, 18 months, and 5 years. We investigated course of depression, smoking, and comorbid alcohol-use disorders among the 214 patients (79.6% of 269) participating at least three time points; differences between smoking versus nonsmoking patients, and covariation of MDD, smoking, and alcohol-use disorders. RESULTS: Overall, 31.3% of the patients smoked regularly, 41.1% intermittently, and 27.6% never. Smokers were younger, had more alcohol-use disorders and Cluster B and C personality disorder symptoms, a higher frequency of lifetime suicide attempts, higher neuroticism, smaller social networks, and lower perceived social support than never smokers. Smoking and depression had limited longitudinal covariation. Depression, smoking, and alcohol-use disorders all exhibited strong autoregressive tendencies. CONCLUSIONS: Among adult psychiatric MDD patients, smoking is strongly associated with substance-use and personality disorders, which may confound research on the impact of smoking. Rather than depression or smoking covarying or predicting each other, depression, smoking, and alcohol-use disorders each have strong autoregressive tendencies. These findings are more consistent with common factors causing their association than either of the conditions strongly predisposing to the other.

A 5-year prospective study of predictors for disability pension among patients with major depressive disorder.

OBJECTIVE: There is a scarcity of prospective long-term studies on work disability caused by depression. We investigated predictors for disability pension among psychiatric patients with MDD. METHOD: The Vantaa Depression Study followed up prospectively 269 psychiatric in- and out-patients with DSM-IV MDD for 5 years with a life chart, including 230 (91.3%) patients belonging to labour force. Information on disability pensions was obtained from interviews, patient records and registers. RESULTS: Within 5 years, 20% of the patients belonging to labour force at baseline were granted a disability pension. In multivariate analyses, the significant baseline predictors for granted disability pension were age ≥50 years (HR = 3.91, P < 0.001), subjective inability to work (HR = 2.14, P = 0.008) and introversion (HR = 1.08, P = 0.049). When follow-up variables were included, the predictors were age more than 50 (OR = 6.25, P < 0.001), proportion of time spent depressed (OR = 14.6, P < 0.001), number of comorbid somatic disorders (OR = 1.47, P = 0.013) and lack of vocational education (OR = 2.38, P = 0.032). CONCLUSION: Of psychiatric patients with depression, one-fifth were granted a disability pension within 5 years. Future disability pension can be predicted by baseline older age, personality factors, functional disability, lack of vocational education and comorbid somatic disorders. Longitudinally, accumulation of time spent depressed appears decisive for pensioning.

Family history of psychiatric disorders and the outcome of psychiatric patients with DSM-IV major depressive disorder.

BACKGROUND: Major Depressive Disorder (MDD) is often comorbid with other heritable disorders. The correlates of a family history (FH) of mood disorders but not of comorbid disorders among MDD patients have been investigated. Since bipolar disorder (BD) is highly heritable, latent BD may bias findings. METHODS: The Vantaa Depression Study included 269 psychiatric out- and in-patients with DSM-IV MDD, diagnosed with semistructured interviews and followed-up for 5 years with a life-chart. The FH of mood, psychotic disorders, and alcoholism among first-degree relatives of 183 patients was investigated. RESULTS: Three fourths (74.9%) of patients reported a FH of some major mental disorder; 60.7% of mood disorder, 36.6% alcoholism, and 10.9% psychotic disorder. In multivariate regression models, a FH of mood disorder was associated with high neuroticism (OR 1.08 [1.02-1.15], p=0.014); a FH of alcoholism with alcohol dependence, number of cluster B personality disorder symptoms, and dysthymia (OR 2.27 [1.01-5.08], p=0.047; OR=1.11 [1.01-1.23], p=0.030; and OR 4.35 [1.51-12.5], p=0.007), and a FH of psychotic disorder with more time spent with depressive symptoms (OR 1.03 [1.00-1.05], p=0.043). However, after excluding those who later switched to BD, several of the associations abated or lost significance. LIMITATIONS: Family history was ascertained only by an interview of the proband. CONCLUSIONS: The majority of MDD patients have a positive FH besides mood also of other disorders. A mood disorder FH may correlate with higher neuroticism, alcoholism FH with alcoholism or personality disorders. FH studies of MDD should take into account the impact of patients switching to BD.

Treatment attitudes and adherence of psychiatric patients with major depressive disorder: a five-year prospective study.

BACKGROUND: The prevalence, long-term temporal consistency and factors influencing negative attitudes and poor treatment adherence among psychiatric patients with major depressive disorder (MDD) are not well known. METHODS: In the Vantaa Depression Study (VDS), a prospective 5-year study of psychiatric patients with DSM-IV MDD, 238 (88.5%) patients' attitudes towards and adherence to both antidepressants and psychotherapeutic treatments at baseline, 6 months, 18 months and 5 years was investigated. RESULTS: Throughout the follow-up, most patients reported positive attitudes towards pharmacotherapy and psychosocial treatments, and good adherence. While attitudes became more critical over time, adherence to psychosocial treatment improved, but remained unchanged for pharmacotherapy. Employment predicted positive attitude (OR=1.97, 95% CI 1.01-3.83, P=0.046), and larger social network good adherence (OR=1.11, 95% CI 1.00-1.23, P=0.042) to pharmacotherapy at the last follow-up. Cluster B personality disorder symptoms predicted negative attitude (OR=0.82, 95% CI 0.70-0.96, P=0.012) and poor adherence (OR=0.83, 95% CI 0.72-0.95, P=0.007), but cluster C symptoms positive attitude (OR=1.30, 95% CI 1.09-1.54, P=0.003), and living alone good adherence (OR=3.13, 95% CI 1.10-9.09, P=0.032) to psychosocial treatment. LIMITATIONS: Patients may exaggerate their adherence to treatments. Attrition from follow-up may occur due to undetected negative change in treatment attitude or adherence. CONCLUSIONS: Among psychiatric MDD patients in long-term follow-up, treatment attitudes and adherence to pharmaco- and psychotherapy were and remained mostly positive. They were significantly predicted by personality features and social support. Attention to adherence of those with cluster B personality disorders, or poor social support, may be needed.

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.

Maintenance pharmacotherapy for recurrent major depressive disorder: 5-year follow-up study.

Practice guidelines endorse maintenance antidepressant treatment for recurrent major depressive disorder. In the Vantaa Depression Study, we followed 218 psychiatric patients with major depressive disorder for up to 5 years with a life-chart. Of these patients, 86 (39.4%) had more than three lifetime episodes and an indication for maintenance pharmacotherapy. However, of these, only 57% received treatment and only for 16% of the time indicated. Good adherence to pharmacotherapy in the acute phase independently predicted maintenance treatment. The tertiary preventive impact of maintenance treatment may remain limited, as many patients with major depressive disorder either do not receive it, or receive it for too short a period.

Predictors for switch from unipolar major depressive disorder to bipolar disorder type I or II: a 5-year prospective study.

OBJECTIVE: In this naturalistic study, we investigated the rate, time course, and predictors of a diagnostic switch from unipolar major depressive disorder (MDD) to bipolar disorder type I or II during a 5-year follow-up. METHOD: The Vantaa Depression Study included at baseline 269 psychiatric outpatients (82.9%) and inpatients (17.1%) with DSM-IV MDD, diagnosed using structured and semi-structured interviews and followed up at 6 months, 18 months, and 5 years between February 1, 1997 and April 30, 2004. Information on 248 MDD patients (92.2%) was available for analyses of the risk of diagnostic switch. Cox proportional hazards models were used. RESULTS: Twenty-two subjects (8.9%) with previous unipolar MDD switched to bipolar disorder type II and 7 (2.8%) to type I. Median time for switch to bipolar type I was significantly shorter than to type II. In Cox proportional hazards analyses, severity of MDD (hazard ratio [HR] = 1.08, 95% CI = 1.00 to 1.15, p = .036), obsessive-compulsive disorder (OCD) (HR = 5.00, 95% CI = 2.04 to 12.5, p < .001), social phobia (HR = 2.33, 95% CI = 1.00 to 5.26, p = .050), and large number of cluster B personality disorder symptoms (HR = 1.10, 95% CI = 1.02 to 1.20, p = .022) predicted switch. CONCLUSION: Among outpatients with MDD in secondary level psychiatric settings, diagnostic switch to bipolar disorder usually refers to type II rather than type I. The few switching to bipolar type I do so relatively early. Predictors for diagnostic switch include not only features of mood disorder, such as severity, but may also include some features of psychiatric comorbidity, such as concurrent social phobia, OCD, and symptoms of cluster B personality disorders.

Long-term outcome of major depressive disorder in psychiatric patients is variable.

OBJECTIVE: The prevailing view of outcome of major depressive disorder (MDD), based on mostly inpatient cohorts sampled from tertiary centers, emphasizes chronicity and frequent recurrences. We investigated the long-term outcome of a regionally representative psychiatric MDD cohort comprising mainly outpatients. METHOD: The Vantaa Depression Study included 163 patients with DSM-IV MDD (71.5% of those eligible) diagnosed using structured and semistructured interviews and followed up at 6 months, 18 months, and 5 years with a life chart between February 1, 1997, and April 30, 2004. The effects of comorbid disorders and other predictors on outcome were comprehensively investigated. RESULTS: Over the 5-year follow-up, 98.8% of patients achieved a symptom state below major depressive episode (MDE) criteria, and 88.4% reached full remission, with the median time to full remission being 11.0 months. Nearly one third (29.3%) had no recurrences, whereas 30.0% experienced 1, 12.9% experienced 2, and 27.9% experienced 3 or more recurrences. Preceding dysthymic disorder (p = .028), cluster C personality disorder (p = .041), and longer MDE duration prior to entry (p = .011) were the most significant predictors of longer time in achieving full remission. Severity of MDD and comorbidity, especially social phobia, predicted probability of, shorter time to, and number of recurrences. CONCLUSION: Previous literature on mostly inpatient MDD may have, by generalizing from patients with the most severe psychopathology, overemphasized chronicity of MDD. The long-term outcome of MDD in psychiatric care is variable, with about one tenth of patients having poor, one third having intermediate, and one half having favorable outcomes. In addition to known predictors, cluster C personality disorders and social phobia warrant further attention as predictors of MDD outcome among outpatients.

Expression of the cytomegalovirus genome in kidney allografts during active and latent infection.

Cytomegalovirus (CMV) infection is suggested to be a risk factor for chronic rejection. Here we investigated whether CMV can persist in renal allografts, and in which structures the viral genome is found during an acute infection and a latent period after an active infection. CMV infection was diagnosed in 72/157 patients by CMV antigenemia tests and by viral cultures. CMV antigens were demonstrated in 38 available biopsies by immunohistochemistry, and CMV genome by DNA hybridization in situ. Standard histology was also performed. CMV antigens were detected in 7/15 biopsies obtained during acute infection, in three with acute rejection, and chronic changes in the other biopsies. CMV genome was located in inflammatory cells, in tubuli and in the capillary endothelium. During a latent period without a positive finding in blood or urine, CMV antigens were still found in 6/31 biopsies. CMV DNA was found in inflammatory cells, tubular and glomerular structures and in the endothelium of the arterioles. During the latent period with persistent CMV in the graft, in most cases (10/12) mild to moderate chronic changes were recorded.

Sequential analysis of adhesion molecules and their ligands in rat renal allografts during the development of chronic rejection.

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are important in endothelial cell-leukocyte interactions. In this sequential study, the expression of ICAM-1 and VCAM-1 and their ligands LFA-1 and VLA-4 as well as major histocompatibility complex class II antigens (MHC class II), and interleukin-2-receptor (IL-2R) were investigated during the development of chronic renal allograft rejection in a rat model. The time-related expression of adhesion molecules and their ligands in the graft was correlated to the chronic allograft damage index (CADI). In association with an initial short immune activation, there was a significant ICAM-1 and VCAM-1 induction in the vascular endothelium and the tubular epithelium. In the interstitium, there was infiltration of lymphocytes expressing ligand molecules VLA-4 and LFA-1, as well as activation markers MHC class II and IL-2R. Thereafter, the expression declined together with the increase of CADI-values. In end-stage chronic rejection, there was practically no expression of ICAM-1 and VCAM-1. In the interstitium, there were only few ligand-expressing leukocytes. In conclusion, adhesion molecules and their ligands are involved in the induction phase of the process but no longer in the later stages of chronic rejection.

Rat cytomegalovirus infection in kidney allograft recipients is associated with increased expression of intracellular adhesion molecule-1 vascular adhesion molecule-1, and their ligands leukocyte function antigen-1 and very late antigen-4 in the graft.

BACKGROUND: Cytomegalovirus (CMV) infection is suggested to be a risk factor for chronic rejection. We have recently shown that rat CMV (RCMV) increases the inflammatory response and accelerates chronic rejection in a model of rat kidney allograft. In this study, the early inflammatory response and time-related expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and their ligands, leukocyte function antigen-1 (LFA-1) and very late antigen-4 (VLA-4), in the grafts were investigated in RCMV-infected rats and compared to noninfected rats developing chronic rejection. METHODS: Transplantations were performed in a rat strain combination of DA (RT1a)->BN (RT1n) receiving triple drug immunosuppression. One group of rats was infected with RCMV, and the other was left uninfected. The grafts were harvested at different time points after transplantation. The adhesion molecules, their ligands and activation markers, MHC class II antigens and interleukin-2-receptors (IL-2-R), were demonstrated by monoclonal antibodies and immunoperoxidase staining from frozen sections of the grafts. Graft histology was evaluated according to the Banff criteria. RESULTS: RCMV caused a significant, prolonged increase of VCAM-1 and ICAM-1 expression in the vascular endothelium compared to the noninfected grafts. Also, the number of cells expressing activation markers, LFA-1 and VLA-4 was significantly enhanced in these animals. Significantly enhanced histological changes of chronic rejection were seen in the RCMV-infected group. CONCLUSIONS: Prolonged, increased expression of ICAM-1 and VCAM-1, and increased numbers of inflammatory cells expressing their ligands in the CMV infected grafts, were associated with accelerated chronic allograft nephropathy.

Time-related effects of cytomegalovirus infection on the development of chronic renal allograft rejection in a rat model.

Cytomegalovirus (CMV) infection is a risk factor for chronic allograft rejection. The histological findings of chronic renal allograft rejection include inflammation, vascular intimal thickening, glomerulosclerosis, tubular atrophy and fibrosis. We have developed a rat model of renal transplantation in which transplants, after an early inflammatory episode, end up with chronic rejection within 60 days. During the early phase of the process in this model, CMV increased and prolonged the inflammatory response, the expression of adhesion molecules, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and their ligands, lymphocyte function antigen-1 and very late antigen-4 in the graft. Simultaneously, the production of various growth factors, such as transforming growth factor beta, platelet-derived growth factor and connective tissue growth factor was upregulated, which induce smooth muscle cell proliferation in the vascular wall and collagen synthesis by fibroblasts. Chronic rejection developed within 20 days in CMV-infected grafts. In summary, CMV infection accelerated and enhanced the early immune response, the induction of growth factors and collagen synthesis, and the development of chronic rejection in renal allografts.

Maternal antihypertensive therapy with beta-blockers associated with poor outcome in very-low birthweight infants.

The progress of 36 very-low birthweight (less than or equal to 1500 g) infants born to mothers with pregnancy-induced hypertonia or pre-eclampsia was studied. During the first year of life, 7 out of 19 infants died when the mothers' antihypertensive regimen included beta-blockers. Four of the deaths occurred within 15 days. There were no deaths in 16 infants whose mothers were treated with other antihypertensive treatment (P = 0.006). These results suggest that maternal beta-blocker therapy may have adverse effects on the very-low birthweight infants.