Clinical and personal predictors of functioning in affective disorders: Exploratory results from baseline and 6-month follow-up of a randomised controlled trial.

Comprehensive knowledge of factors causing and sustaining functional impairment in patients with affective disorders is warranted. The aim is to investigate associations between clinical factors (such as affective symptoms) and personal factors (such as personality traits, coping strategies, and childhood trauma experiences) on functioning and improvement of functioning in patients with affective disorders. This exploratory study includes data from 103 patients with bipolar disorder and unipolar depressive disorder. Clinician-rated functioning was assessed at baseline using the Functioning Assessment Short Test (FAST), and performance-based functioning was assessed at baseline and 6-month follow-up using the Assessment of Motor and Process Skills (AMPS). Data on clinical and personal factors were collected at baseline. Personal factors were measured by the Eysenck Personality Inventory (EPQ), Coping Inventory for Stressful Situations (CISS) and Childhood Trauma Questionnaire (CTQ). Pearson correlations and multiple linear regression models were used to analyse the association of clinical and personal factors with baseline functioning (FAST) and to identify predictors of improvement in functioning (AMPS) from baseline to follow-up. At baseline, greater depressive symptom severity, the personality trait neuroticism, emotional coping, and childhood trauma all correlated with poorer functioning (higher FAST scores). In multiple linear regression models, depression severity, emotional coping and childhood trauma were significant predictors of poorer functioning. More childhood trauma was a predictor of less functional improvement measured by AMPS at 6-month follow-up. In conclusion, maladaptive coping styles and depressive symptoms contribute to functional impairment in patients with affective disorders, while childhood trauma has a negative impact on long-term functional outcomes.

Antidepressant continuation and adherence in pregnancy, and risk of antenatal hospitalization for unipolar major depressive and/or anxiety disorders.

BACKGROUND: Knowledge about the effectiveness of antidepressants in pregnancy is limited. We aimed to evaluate the association of antidepressant continuation in pregnancy and adherence with the risk of antenatal hospitalization for depression/anxiety. METHODS: In a population-based study based on the healthcare databases of the Lombardy region, Italy (2010-2020), we included 17,033 live-birth pregnancies within 16,091 women with antidepressant use before pregnancy. Antidepressant exposure was classified as continued in pregnancy versus discontinued proximal to pregnancy. Outcome measure was antenatal hospitalization for depression/anxiety. Propensity score matching analysis was performed to control for measured confounding. Stratification by pre-pregnancy antidepressant adherence based on the proportion of days covered (PDC) with antidepressants served to address confounding by disease severity. We applied 60 days lag-time for antidepressant exposure to minimize the risk of protopathic bias. RESULTS: There were 362 (2.1 %) antenatal hospitalizations for depression/anxiety. Among the matched pairs, the cumulative incidence was 3.5 (continued antidepressant) versus 2.1 (discontinued antidepressant) per 1000 person-months, yielding a hazard ratio (HR) of 1.76 (95 % confidence interval (CI): 1.34-2.33)). The HR declined to the null (1.02, 95 % CI: 0.62-1.69) in the stratified analysis of pregnancies with moderate-high adherence pre-pregnancy. Moderate-high adherence in pregnancy was associated with 85 % greater risk of the antenatal outcome, but the HR decreased with the 60 days lag-time (HR: 1.40, 95 % CI: 0.79-2.50). LIMITATIONS: Lack of information regarding antidepressant dosage. CONCLUSION: We found no difference in risk for antenatal hospitalization for depression/anxiety with antidepressant continuation or higher adherence in pregnancy, relative to discontinuation or lower adherence.

Combined physical activity training versus aerobic activity training in unipolar depressive disorder: a quasi-randomised evaluation study.

OBJECTIVE: The positive effect of sport and exercise interventions on the treatment of unipolar depressive disorder (UDD) is well documented with respect to aerobic exercise. However, few studies have determined the effectiveness of other types of interventions (e.g., weight training, body and mind oriented, qigong or progressive muscle relaxation). Additionally, the effectiveness of specific combined sport and exercise approaches has rarely been investigated. Therefore, recommendations for the use of sport and exercise therapy to treat UDD have been developed. METHODS: This quasi-randomised study used a pretest/posttest design to compare the effectiveness of two different interventions (aerobic activity training vs. combined physical activity training) on psychiatric outcome parameters in a day clinic psychiatric setting. A total of 62 participants were quasi-randomised to one of the two conditions. Affective, cognitive, psychosocial and neuropsychological changes were assessed by a battery of questionnaires before (t1) and after (t2) treatment. Accelerometers were used to assess energy consumption. RESULTS: The results show that both training interventions have similar effects on the treatment of UDD. CONCLUSION: These findings highlight the effectiveness of different physical activities in the treatment of UDD and provide further information for good clinical practice.

Biological mechanisms and possible primary prevention of depression.

Individuals with unipolar depressive disorder (UDD) are having an increased risk of death and development of dementia in later life. It is widely expected that in a near future UDD would be the leading cause of death; therefore, a primary inexpensive prevention of UDD will be of a great importance to the society. Several studies provide evidences supporting the positive effect of Mediterranean diet on a reduced risk for development of depression.

Comparison of cognitive impairments with lipid profiles and inflammatory biomarkers in unipolar and bipolar depression.

Cognitive impairments is one of important accompanied symptom in Unipolar depressive disorder (UD) and bipolar disorder (BD) that was hard to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. In this study, we could highlight the difference of cognitive ability in UD and BD by testing lipid profiles and inflammatory biomarkers in major depressive episodes (MDE). 207 subjects (96 unipolar and 111 bipolar depressed patients) were included in this study. We applied Montreal Cognitive Assessment (MoCA) to test cognitive ability. The 24-item Hamilton Depression Rating Scale was used for assessment at the beginning of treatment. A series of clinical variables and lipid profiles were collected from clinic record. We detected pro-inflammatory biomarkers Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), C-reaction protein (CRP) levels and brain-derived neurotrophic factor (BDNF) by enzyme linked immunosorbent assay. From the results, cognitive impairments were more popular in BD than UD, most obviously in severe cognitive impairments (MoCA score<23). And UD showed better cognitive ability than BD in MoCA, particularly in language domain. Compared lipid profiles like total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and lipoprotein α (Lpα), we found that ApoB was higher in BD than UD that maybe a risk factor in cognition. There was no obviously difference in TC, TG, HDL-C, LDL-C, ApoA1, or Lpα. Also, we found CRP level in BD was higher than UD, and showed no significant difference in IL-1ß and IL-6 levels. Furthermore, BDNF level which was neurotrophic biomarker for cognition and mood was significantly declined in BD compared with UD. Correlation analysis showed that ApoB and CRP was negative closed associated with MoCA scores. And BDNF level was positive related with cognitive ability in MDE patients. From our results mentioned that quantitative lipid profiles and inflammatory biomarkers analysis might help to objectively identify between these disorders and up our understanding of their pathophysiology. And ApoB, CRP and BDNF could be as potential peripheral candidates in cognitive evaluation to distinguish UD and BD.

Mood and Activity Measured Using Smartphones in Unipolar Depressive Disorder.

Background: Smartphones comprise a promising tool for symptom monitoring in patients with unipolar depressive disorder (UD) collected as either patient-reportings or possibly as automatically generated smartphone data. However, only limited research has been conducted in clinical populations. We investigated the association between smartphone-collected monitoring data and validated psychiatric ratings and questionnaires in a well-characterized clinical sample of patients diagnosed with UD. Methods: Smartphone data, clinical ratings, and questionnaires from patients with UD were collected 6 months following discharge from psychiatric hospitalization as part of a randomized controlled study. Smartphone data were collected daily, and clinical ratings (i.e., Hamilton Depression Rating Scale 17-item) were conducted three times during the study. We investigated associations between (1) smartphone-based patient-reported mood and activity and clinical ratings and questionnaires; (2) automatically generated smartphone data resembling physical activity, social activity, and phone usage and clinical ratings; and (3) automatically generated smartphone data and same-day smartphone-based patient-reported mood and activity. Results: A total of 74 patients provided 11,368 days of smartphone data, 196 ratings, and 147 questionnaires. We found that: (1) patient-reported mood and activity were associated with clinical ratings and questionnaires (p < 0.001), so that higher symptom scores were associated with lower patient-reported mood and activity, (2) Out of 30 investigated associations on automatically generated data and clinical ratings of depression, only four showed statistical significance. Further, lower psychosocial functioning was associated with fewer daily steps (p = 0.036) and increased number of incoming (p = 0.032), outgoing (p = 0.015) and missed calls (p = 0.007), and longer phone calls (p = 0.012); (3) Out of 20 investigated associations between automatically generated data and daily patient-reported mood and activity, 12 showed statistical significance. For example, lower patient-reported activity was associated with fewer daily steps, shorter distance traveled, increased incoming and missed calls, and increased screen-time. Conclusion: Smartphone-based self-monitoring is feasible and associated with clinical ratings in UD. Some automatically generated data on behavior may reflect clinical features and psychosocial functioning, but these should be more clearly identified in future studies, potentially combining patient-reported and smartphone-generated data.

The effect of smartphone-based monitoring and treatment on the rate and duration of psychiatric readmission in patients with unipolar depressive disorder: The RADMIS randomized controlled trial.

BACKGROUND: Patients with unipolar depressive disorder are frequently hospitalized, and the period following discharge is a high-risk-period. Smartphone-based treatments are receiving increasing attention among researchers, clinicians, and patients. We aimed to investigate whether a smartphone-based monitoring and treatment system reduces the rate and duration of readmissions, more than standard treatment, in patients with unipolar depressive disorder following hospitalization. METHODS: We conducted a pragmatic, investigator-blinded, randomized controlled trial. The intervention group received a smartphone-based monitoring and treatment system in addition to standard treatment. The system allowed patients to self-monitor symptoms and access psycho-educative information and cognitive modules. The patients were allocated a study-nurse who, based on the monitoring data, guided and supported them. The control group received standard treatment. The trial lasted six months, with outcome assessments at 0, 3, and 6 months. RESULTS: We included 120 patients with unipolar depressive disorder (ICD-10). Intention-to-treat analyses showed no statistically significant differences in time to readmission (Log-Rank p=0.9) or duration of readmissions (B=-16.41,95%CI:-47.32;25.5,p=0.3) (Primary outcomes). There were no differences in clinically rated depressive symptoms (p=0.6) or functioning (p=0.1) (secondary outcomes). The intervention group had higher levels of recovery (B=7,29, 95%CI:0.82;13,75,p=0.028) and a tendency towards higher quality of life (p=0.07), wellbeing (p=0,09) satisfaction with treatment (p=0.05) and behavioral activation (p=0.08) compared with the control group (tertiary outcomes). LIMITATIONS: Patients and study-nurses were unblinded to allocation. CONCLUSIONS: We found no effect of the intervention on primary or secondary outcomes. In tertiary outcomes, patients in the intervention group reported higher levels of recovery compared to the control group.

Exploring the clinical outcome of Mindfulness-Based Cognitive Therapy for bipolar and unipolar depressive patients in routine clinical practice: a pilot study.

BACKGROUND: Mindfulness Based Cognitive Therapy (MBCT) has been adopted as an evidence-based treatment for unipolar depressive disorder (UDD). Although MBCT has not been included in the treatment guidelines for bipolar disorder (BD), MBCT is regularly being offered to patients with BD in routine clinical practice. In this pilot study we used routine outcome monitoring (ROM) data to explore whether there are indications that patients with BD might benefit less from MBCT than patients with UDD in terms of feasibility and effectiveness. METHODS: The study population consisted of patients with BD (n = 30) or UDD (n = 501) who received MBCT at the Radboudumc Centre for Mindfulness in Nijmegen, the Netherlands. Patients completed self-report measures of depressive symptom severity, worry, well-being, mindfulness skills and self-compassion pre- and post MBCT as part of the ROM. RESULTS: There were significant less patients with BD who decided to start MBCT after intake than patients with UDD. No differences in dropout between groups were found. Results showed significant moderate to large improvements in both groups after MBCT, while no differences between groups were found, on all outcome measures. CONCLUSIONS: This study demonstrates that there are no indications that MBCT, when delivered in heterogeneous patient groups in routine clinical practice, is less beneficial for patients with BD than patients with UDD in terms of feasibility and effectiveness. This lends support to conduct an adequately powered RCT to examine the (cost-)effectiveness of MBCT in BD as the next step before implementing MBCT on a larger scale in patients with BD.

Aberrant Neural Activity in Patients With Bipolar Depressive Disorder Distinguishing to the Unipolar Depressive Disorder: A Resting-State Functional Magnetic Resonance Imaging Study.

This study aims to explore the intrinsic patterns of spontaneous activity of bipolar depression (BD) patients by analyzing the fractional amplitude of low frequency fluctuation (fALFF) that help differentiate BD from unipolar depressive disorder(UD). Twenty eight patients with BD, 47 patients with UD and 29 healthy controls were enrolled to receive the resting-state functional magnetic resonance imaging (rs-fMRI) scans. The group differences of fALFF values were calculated among three groups. In addition, the correlations between the clinical variables and mfALFF values were estimated. The brain regions with activation discrepancies among three groups are located in precuneus, the left middle temporal gyrus (MTG) and left inferior parietal lobe (IPL) and lingual gyrus. Compared with HC group, BD group shows decreased fALFF in precuneus, the left IPL and increased fALFF in lingual gyrus remarkably; UD group shows significantly decreased fALFF in precuneus, the left MTG and the left IPL. On the contrast of patients with UD, patients with BD have significantly increased fALFF value in the left precuneus, the left MGT and lingual gyrus. Furthermore, a negative correlation is found between the mfALFF values in precuneus and the scores of cognitive impairment factor in the UD group. The similar pattern of intrinsic activity in PCC suggests depressive state-dependent change. The aberrant patterns of intrinsic activity in precuneus, the IPL and lingual gyrus might be provide quantitative nodes that help to conduct further study for better distinguishing between BD and UD.

Clinical and demographic predictors of response to rTMS treatment in unipolar and bipolar depressive disorders.

OBJECTIVE: Previous studies investigated predictors of repetitive transcranial magnetic stimulation (rTMS) response in depressive disorders but there is still limited knowledge about clinical predictors. Moreover, predictors of rTMS response in bipolar depression (BDD) are less studied than unipolar depression (UDD). METHODS: We performed a binary logistic regression analysis in 248 patients with depressive disorders (unipolar N=102, bipolar N=146) who received 20 sessions of DLPFC rTMS (High-frequency rTMS, low-frequency rTMS, bilateral rTMS) to investigate significant clinical and demographic predictors of rTMS response. We also investigated effects of depression type, response (yes, no) and time on reducing somatic and cognitive-affective symptoms of patients. RESULTS: Depression type (unipolar vs. bipolar) did not have a significant effect on rTMS response. 45% of all patients, 51.5% of UDD patients and 41% of BDD patients, responded to rTMS treatment. Age was the only significant demographic predictor of treatment response in all patients. Cognitive-affective symptoms, compared to somatic symptoms were significant predictors for treatment response to rTMS. Common and unique clinical predictor for UDD and BDD were identified. CONCLUSIONS: Younger patients and those with cognitive-affective rather than somatic symptoms benefit more from DLPFC rTMS treatment. rTMS is effective in UDD and BDD patients. Patients should be selected based on clinical and demographic profile. SIGNIFICANCE: Findings are based on the largest thus far reported sample of patients with depressive disorders that received DLPFC rTMS.

Depression severity and concentration difficulties are independently associated with HRQOL in patients with unipolar depressive disorders.

PURPOSE: Cognitive impairment is a core feature of major depressive disorder (MDD), and dysfunctions in this area strongly contribute to MDD-associated disability. Whether cognitive impairment has an independent clinical course and a unique impact on HRQOL is still debated. We sought to characterize the relationship between depression severity and HRQOL, evaluating the burden of concentration difficulties on HRQOL. METHODS: Six hundred ninety-two patients with unipolar depressive disorders recruited in 19 Italian centers answered a self-administered survey (SF-12 questionnaire, socio-demographic information). A psychiatrist completed a standardized data collection form encompassing a depression severity scale (MADRS) and clinical information. RESULTS: There was a strong graded association between the severity of depressive symptoms and both the physical (ω 2 = 0.13; p < 0.01) and mental (ω 2 = 0.34; p < 0.01) SF-12 domains. Additionally, we observed a strong association between concentration difficulties and all HRQOL outcomes independent of other symptoms of depression and robust to adjustment for possible confounders. CONCLUSIONS: Our data corroborate previous findings suggesting that cognitive impairment is a feature of unipolar depressive disorders partially independent of the severity of other symptoms, and may represent a specific target of therapy with a strong impact on patients' functioning and quality of life.

Personalized cognitive training in unipolar and bipolar disorder: a study of cognitive functioning.

Patients with unipolar depressive disorder and in the depressive phase of bipolar disorder often manifest psychological distress and cognitive deficits, notably in executive control. We used computerized cognitive training in an attempt to reduce psychological affliction, improve everyday coping, and cognitive function. We asked one group of patients (intervention group) to engage in cognitive training three times a week, for 20 min each time, for eight consecutive weeks. A second group of patients (control group) received standard care only. Before the onset of training we administered to all patients self-report questionnaires of mood, mental and psychological health, and everyday coping. We also assessed executive control using a broad computerized neurocognitive battery of tests which yielded, among others, scores in Working Memory, Shifting, Inhibition, Visuomotor Vigilance, Divided Attention, Memory Span, and a Global Executive Function score. All questionnaires and tests were re-administered to the patients who adhered to the study at the end of training. When we compared the groups (between-group comparisons) on the amount of change that had taken place from baseline to post-training, we found significantly reduced depression level for the intervention group. This group also displayed significant improvements in Shifting, Divided Attention, and in the Global executive control score. Further exploration of the data showed that the cognitive improvement did not predict the improvements in mood. Single-group data (within-group comparisons) show that patients in the intervention group were reporting fewer cognitive failures, fewer dysexecutive incidents, and less difficulty in everyday coping. This group had also improved significantly on the six executive control tests and on the Global executive control score. By contrast, the control group improved only on the reports of cognitive failure and on working memory.

Implication of the Global Burden of Disease Caused by Psychiatric Disorders in the Viewpoint of Mental Health Professionals / 신경정신의학

OBJECTIVES: The aim of this study was to investigate how mental health professionals in Korea evaluate the burden of disease caused by psychiatric disorders and to propose future directions of the public mental health policies. METHODS: A questionnaire was mailed to 240 mental health professionals, who were composed of psychiatrists from mental hospitals and staffs who are nurses, clinical psychologists and social workers working in the community mental health centers in June, 2004. Two hundred twenty four out of two hundred forty subjects (93.3%), which were composed of 104 psychiatrists and 120 staffs, completed the questionnaire. The questionnaire included 6-item questions about the burden of disease in Korea. RESULTS: Mental health professionals reported that the five diseases with the biggest burden were malignant neoplasms, traffic accidents, schizophrenia, alcohol use disorders and cerebrovascular diseases, consecutively. The burden of alcohol use disorders, cerebrovascular diseases, traffic accidents, unipolar depressive disorder and malignant neoplasms are expected to increase over the next several years. The proportions of psychiatric disorders among all the diseases in terms of burden of disease and medical costs were estimated as 18.4% (+/-12.8) and 12.0% (+/-11.7) respectively. CONCLUSION: This study showed that many of Korean mental health professionals have under-estimated burden of psychiatric disorders, especially, unipolar depressive disorder. It would be necessary to emphasize the importance of unipolar depressive disorder in applying educational and public programs for the mental health professionals, as well as for the general population.