Outi Mantere

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.

The Mood Disorder Questionnaire improves recognition of bipolar disorder in psychiatric care

BackgroundWe investigated our translation of The Mood Disorder Questionnaire (MDQ) as a screening instrument for bipolar disorder in a psychiatric setting in Finland.MethodsIn a pilot study for the Jorvi Bipolar Study (JoBS), 109 consecutive non-schizophrenic psychiatric out- and inpatients in Espoo, Finland, were screened for bipolar disorder using the Finnish translation of the MDQ, and 38 of them diagnostically interviewed with the SCID.ResultsForty subjects (37%) were positive in the MDQ screen. In the SCID interview, twenty patients were found to suffer from bipolar disorder, of whom seven (70%) of ten patients with bipolar I but only two (20%) of ten with bipolar II disorder had been previously clinically correctly diagnosed. The translated MDQ was found internally consistent (alpha 0.79) and a feasible screening tool.ConclusionsBipolar disorder, particularly type II, remains commonly unrecognized in psychiatric settings. The Mood Disorder Questionnaire is a feasible screen for bipolar disorder, which could well be integrated into psychiatric routine practice.

Differences in incidence of suicide attempts during phases of bipolar I and II disorders.

BACKGROUND Differences in the incidence of suicide attempts during various phases of bipolar disorder (BD), or the relative importance of static versus time-varying risk factors for overall risk for suicide attempts, are unknown. METHODS We investigated the incidence of suicide attempts in different phases of BD as a part of the Jorvi Bipolar Study (JoBS), a naturalistic, prospective, 18-month study representing psychiatric in- and outpatients with DSM-IV BD in three Finnish cities. Life charts were used to classify time spent in follow-up in the different phases of illness among the 81 BD I and 95 BD II patients. RESULTS Compared to the other phases of the illness, the incidence of suicide attempts was 37-fold higher [95% confidence interval (CI) for relative risk (RR): 11.8-120.3] during combined mixed and depressive mixed states, and 18-fold higher (95% CI: 6.5-50.8) during major depressive phases. In Coxs proportional hazards regression models, combined mixed (mixed or depressive mixed) or major depressive phases and prior suicide attempts independently predicted suicide attempts. No other factor significantly modified the risks related to these time-varying risk factors; their population-attributable fraction was 86%. CONCLUSIONS The incidence of suicide attempts varies remarkably between illness phases, with mixed and depressive phases involving the highest risk by time. Time spent in high-risk illness phases is likely the major determinant of overall risk for suicide attempts among BD patients. Studies of suicidal behavior should investigate the role of both static and time-varying risk factors in overall risk; clinically, management of mixed and depressive phases may be crucial in reducing risk.

Differences in outcome of DSM-IV bipolar I and II disorders.

OBJECTIVES To investigate whether the course of bipolar disorder (BD) type II is more depressive than that of BD I, and, if so, to explore the underlying factors that cause this difference. METHODS In a prospective, naturalistic study of 191 secondary care psychiatric in- and outpatients diagnosed in an acute phase of BD I or II, 160 patients (85.1%) were followed for 18 months. Using a life chart, the exact timing of symptom states in follow-up was examined. Differences between BD I (n = 75) and II (n = 85) in duration of index phase and episode, time to full remission and recurrence, and time in any mood episode were investigated. RESULTS Patients with BD II spent a higher proportion of time ill (47.5% versus 37.7%; p = 0.02) and in depressive symptom states (58.0% versus 41.7%; p = 0.003) than BD I patients. This was a result of the higher proportion (61.7% versus 48.6%; p = 0.03) and mean number (1.69 versus 1.11; p = 0.006) of depressive illness phases in BD II, rather than of differences in the duration of depressive phases. Type of index phase strongly predicted the outcome. In linear regression models, both BD II and type of index phase predicted more time spent in depressive symptom states. CONCLUSIONS In medium-term follow-up, BD II patients spend about 40% more time in depressive symptom states than BD I patients because a higher proportion of BD II patients have depressive phases and the frequency of these is higher. Differences in type of index phase may markedly confound differences in outcome between BD I and II.

P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts

We investigated the effect of nine candidate genes on risk for mood disorders, hypothesizing that predisposing gene variants not only elevate the risk for mood disorders but also result in clinically significant differences in the clinical course of mood disorders. We genotyped 178 DSM‐IV bipolar I and II and 272 major depressive disorder patients from three independent clinical cohorts carefully diagnosed with semistructured interviews and prospectively followed up with life charts for a median of 60 (range 6–83) months. Healthy control subjects (n = 1322) were obtained from the population‐based national Health 2000 Study. We analyzed 62 genotyped variants within the selected genes (BDNF, NTRK2, SLC6A4, TPH2, P2RX7, DAOA, COMT, DISC1, and MAOA) against the presence of mood disorder, and in post‐hoc analyses, specifically against bipolar disorder or major depressive disorder. Estimates for time ill were based on life charts. The P2RX7 gene variants rs208294 and rs2230912 significantly elevated the risk for a familial mood disorder (OR = 1.35, P = 0.0013, permuted P = 0.06, and OR = 1.44, P = 0.0031, permuted P = 0.17, respectively). The results were consistent in all three cohorts. The same risk alleles predicted more time ill in all cohorts (OR 1.3, 95% CI 1.1–1.6, P = 0.0069 and OR 1.7, 95% CI 1.3–2.3, P = 0.0002 with rs208294 and rs2230912, respectively), so that homozygous carriers spent 12 and 24% more time ill. P2RX7 and its risk alleles predisposed to mood disorders consistently in three independent clinical cohorts. The same risk alleles resulted in clinically significant differences in outcome of patients with major depressive and bipolar disorder.

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

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.

Gender differences in bipolar disorder type I and II

Objective:  We investigated gender differences in bipolar disorder (BD) type I and II in a representative cohort of secondary care psychiatric in‐ and out‐patients.

Inflammation theories in psychotic disorders: a critical review.

Recent research suggests that inflammation and immunity may have a role in the etiology of psychotic disorders. There is evidence of proinflammatory activation of the innate immune system and an activation of the T-cells of the adaptive immune system in both schizophrenia and bipolar disorder. Studies of antipsychotic-naïve patients with first-episode psychosis have found that inflammation is present already at this stage. Some of these abnormalities resolve after the initiation of treatment, suggesting that they are state markers of acute psychosis, but other abnormalities persist. There is also evidence for prenatal infections being involved in the etiology of schizophrenia. Several hypotheses link inflammation and immunity with psychotic disorders. In this review, we focus on hypotheses related to prenatal development, disturbed regulation of neurogenesis, microglial activation, autoimmunity and microbial environment, and consider the potential confounding effects related to stress, childhood adversities, lifestyle and medical comorbidity as well as some methodological limitations. We also review the current evidence for the effectiveness of anti-inflammatory medication in the treatment of psychotic disorders.

A prospective latent analyses study of psychiatric comorbidity of DSM-IV bipolar I and II disorders

OBJECTIVE To test two hypotheses of psychiatric comorbidity in bipolar disorder (BD): (i) comorbid disorders are independent of BD course, or (ii) comorbid disorders associate with mood. METHODS In the Jorvi Bipolar Study (JoBS), 191 secondary-care outpatients and inpatients with DSM-IV bipolar I disorder (BD-I) or bipolar II disorder (BD-II) were evaluated with the Structured Clinical Interview for DSM-IV Disorders, with psychotic screen, plus symptom scales, at intake and at 6 and 18 months. Three evaluations of comorbidity were available for 144 subjects (65 BD-I, 79 BD-II; 76.6% of 188 living patients). Structural equation modeling (SEM) was used to examine correlations between mood symptoms and comorbidity. A latent change model (LCM) was used to examine intraindividual changes across time in depressive and anxiety symptoms. Current mood was modeled in terms of current illness phase, Beck Depression Inventory (BDI), Young Mania Rating Scale, and Hamilton Depression Rating Scale; comorbidity in terms of categorical DSM-IV anxiety disorder diagnosis, Beck Anxiety Inventory (BAI) score, and DSM-IV-based scales of substance use and eating disorders. RESULTS In the SEM, depression and anxiety exhibited strong cross-sectional and autoregressive correlation; high levels of depression were associated with high concurrent anxiety, both persisting over time. Substance use disorders covaried with manic symptoms (r = 0.16-0.20, p < 0.05), and eating disorders with depressive symptoms (r = 0.15-0.32, p < 0.05). In the LCM, longitudinal intraindividual improvements in BDI were associated with similar BAI improvement (r = 0.42, p < 0.001). CONCLUSIONS Depression and anxiety covary strongly cross-sectionally and longitudinally in BD. Substance use disorders are moderately associated with manic symptoms, and eating disorders with depressive mood.

Temperament and character traits predict future burden of depression

BACKGROUND Personality traits are associated with depressive symptoms and psychiatric disorders. Evidence for their value in predicting accumulation of future dysphoric episodes or clinical depression in long-term follow-up is limited, however. METHODS Within a 15-year longitudinal study of a general-population cohort (N=751), depressive symptoms were measured at four time points using Beck׳s Depression Inventory. In addition, 93 primary care patients with DSM-IV depressive disorders and 151 with bipolar disorder, diagnosed with SCID-I/P interviews, were followed for five and 1.5 years with life-chart methodology, respectively. Generalized linear regression models were used to predict future number of dysphoric episodes and total duration of major depressive episodes. Baseline personality was measured by the Temperament and Character Inventory (TCI). RESULTS In the general-population sample, one s.d. lower Self-directedness predicted 7.6-fold number of future dysphoric episodes; for comparison, one s.d. higher baseline depressive symptoms increased the episode rate 4.5-fold. High Harm-avoidance and low Cooperativeness also implied elevated dysphoria rates. Generally, personality traits were poor predictors of depression for specific time points, and in clinical populations. Low Persistence predicted 7.5% of the variance in the future accumulated depression in bipolar patients, however. LIMITATIONS Degree of recall bias in life charts, limitations of statistical power in the clinical samples, and 21-79% sample attrition (corrective imputations were performed). CONCLUSION TCI predicts future burden of dysphoric episodes in the general population, but is a weak predictor of depression outcome in heterogeneous clinical samples. Measures of personality appear more useful in detecting risk for depression than in clinical prediction.