The Factors Influencing Depression Endpoints Research (FINDER) study: final results of Italian patients with depression

<p>Abstract</p> <p>Background</p> <p>Factors Influencing Depression Endpoints Research (FINDER) is a 6-month, prospective, observational study carried out in 12 European countries aimed at investigating health-related quality of life (HRQoL) in outpatients receiving treatment for a first or new depressive episode. The Italian HRQoL data at 6 months is described in this report, and the factors associated with HRQoL changes were determined.</p> <p>Methods</p> <p>Data were collected at baseline, 3 and 6 months of treatment. HRQoL was measured using components of the 36-item Short Form Health Survey (SF-36; mental component summary (MCS), physical component summary (PCS)) and the European Quality of Life-5 Dimensions (EQ-5D; visual analogue scale (VAS) and health status index (HSI)). The Hospital Anxiety and Depression Scale (HADS) was adopted to evaluate depressive symptoms, while somatic and painful physical symptoms were assessed by using the 28-item Somatic Symptom Inventory (SSI-28) and a VAS.</p> <p>Results</p> <p>Of the initial 513 patients, 472 completed the 3-month observation and 466 the 6-month observation. The SF-36 and EQ-5D mean (± SD) scores showed HRQoL improvements at 3 months and a further smaller improvement at 6 months, with the most positive effects for SF-36 MCS (baseline 22.0 ± 9.2, 3 months 34.6 ± 10.0; 6 months 39.3 ± 9.5) and EQ-5D HSI (baseline 0.4 ± 0.3; 3 months 0.7 ± 0.3; 6 months 0.7 ± 0.2). Depression and anxiety symptoms (HADS-D mean at baseline 13.3 ± 4.2; HADS-A mean at baseline 12.2 ± 3.9) consistently decreased during the first 3 months (8.7 ± 4.3; 7.5 ± 3.6) and showed a further positive change at 6 months (6.9 ± 4.3; 5.8 ± 3.4). Somatic and painful symptoms (SSI and VAS) significantly decreased, with the most positive changes in the SSI-28 somatic item (mean at baseline 2.4 ± 0.7; mean change at 3 months: -0.5; 95% CI -0.6 to -0.5; mean change at 6 months: -0.7; 95% CI -0.8 to -0.7); in 'interference of overall pain with daily activities' (mean at baseline 45.2 ± 30.7; mean change at 3 months -17.4; 95% CI -20.0 to -14.8; mean change at 6 months -24.4; 95% CI -27.3 to -21.6) and in 'having pain while awake' (mean at baseline 41.1 ± 29.0; mean change at 3 months -13.7; 95% CI -15.9 to -11.5; mean change at 6 months -20.2; 95% CI -22.8 to -17.5) domains. The results from linear regression analyses showed that the antidepressant switch within classes was consistently associated with a worsening in SF-36 MCS, EQ-5D VAS and HSI compared to non-switching treatment. Furthermore, between-group antidepressants (AD) switch was associated with a worse SF-36 MCS and EQ-5D HSI. MCS (<it>P </it>= 0.028), PCS (<it>P </it>= 0.036) and HSI (<it>P </it>= 0.002) were inversely related to the number of each previous additional depressive episode. PCS (<it>P </it>= 0.009) and HSI (<it>P </it>= 0.005) were also less improved in patients suffering from a chronic medical condition. Moreover, PCS (<it>P </it>= 0.044) and EQ-5D VAS (<it>P </it>< 0.0001) worsening was consistently associated with the presence of a psychiatric illness in the 24 months before baseline. For every additional point on the SSI-somatic score and on the overall pain VAS score at baseline, HSI score were on average 0.062 (<it>P </it>< 0.001) and 0.001 (<it>P </it>= 0.005) smaller, respectively.</p> <p>Conclusions</p> <p>After starting AD treatment, HRQoL improvements at 3 and 6 months were observed. However, several factors can negatively influence HRQoL, such as the presence of somatic and painful symptoms, the presence of any chronic medical condition or previous psychiatric illness.</p

Detecting depression in patients with coronary heart disease: a diagnostic evaluation of the PHQ-9 and HADS-D in Primary Care, findings from the UPBEAT-UK Study

People with coronary heart disease (CHD) are at heightened risk of depression, and this co-occurrence of conditions is associated with poorer outcomes including raised mortality. This study compares the diagnostic accuracy of two depression case finding instruments in CHD patients relative to a diagnostic standard, the revised Clinical Interview Schedule (CIS-R)

A systematic review of complex system interventions designed to increase recovery from depression in primary care

BACKGROUND: Primary care is being encouraged to implement multiprofessional, system level, chronic illness management approaches to depression. We undertook this study to identify and assess the quality of RCTs testing system level depression management interventions in primary care and to determine whether these interventions improve recovery. METHOD: Searches of Medline and Cochrane Controlled Register of Trials. 'System level' interventions included: multi-professional approach, enhanced inter-professional communication, scheduled patient follow-up, structured management plan. RESULTS: 11 trials met all inclusion criteria. 10 were undertaken in the USA. Most focussed on antidepressant compliance. Quality of reporting assessed using CONSORT criteria was poor. Eight trials reported an increase in the proportion of patients recovered in favour of the intervention group, yet did not account for attrition rates ranging from 5 to 50%. CONCLUSION: System level interventions implemented in the USA with patients willing to take anti-depressant medication leads to a modest increase in recovery from depression. The relevance of these interventions to countries with strong primary care systems requires testing in a randomised controlled trial

Multiple barriers against successful care provision for depressed patients in general internal medicine in a Japanese rural hospital: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>A general internist has an important role in primary care, especially for the elderly in rural areas of Japan. Although effective intervention models for depressed patients in general practice and primary care settings have been developed in the US and UK medical systems, there is little information regarding even the recognition rate and prescription rate of psychotropic medication by general internists in Japan. The present study surveyed these data cross-sectionally in a general internal medicine outpatient clinic of a Japanese rural hospital.</p> <p>Methods</p> <p>Patients were consecutively recruited and evaluated for major depressive disorder or any mood disorder using the Patient Health Questionnaire (PHQ). Physicians who were blinded to the results of the PHQ were asked to diagnose whether the patients had any mental disorders, and if so, whether they had mood disorders or not. Data regarding prescription of psychotropic medicines were collected from medical records.</p> <p>Results</p> <p>Among 312 patients, 27 (8.7%) and 52 (16.7%) were identified with major depressive disorder and any mood disorder using the PHQ, respectively. Among those with major depressive disorder, 21 (77.8%) were recognized by physicians as having a mental disorder, but only three (11.1%) were diagnosed as having a mood disorder.</p> <p>Only two patients with major depressive disorder (7.4%) had been prescribed antidepressants. Even among those (n = 15) whom physicians diagnosed with a mood disorder irrespective of the PHQ results, only four (26.7%) were prescribed an antidepressant.</p> <p>Conclusions</p> <p>Despite a high prevalence of depression, physicians did not often recognize depression in patients. In addition, most patients who were diagnosed by physicians as having a mood disorder were not prescribed antidepressants. Multiple barriers to providing appropriate care for depressed patients exist, such as recognizing depression, prescribing appropriate medications, and appropriately referring patients to mental health specialists.</p

Altered cardiac autonomic nervous function in depression

Background:Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia.Methods:Individuals (n&thinsp;=&thinsp;53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score &ge;20 and a Zung Self-Rating Depression Scale score&thinsp;&gt;&thinsp;53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals&thinsp;&gt;&thinsp;50 ms different from preceding interval (pNN50). Pearson&rsquo;s correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)).Results:The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P&lt;.05). The mean value of the LF in the depression group was higher than the in control group (P&lt;.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P&lt;.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P&lt;.05), particularly supraventricular arrhythmias.Conclusions:Our findings suggest that depression is accompanied by dysfunction of the cardiac autonomic nervous system, and further, that depression severity is linked to severity of this dysfunction. Individuals with depression appear to be susceptible to premature atrial and/or ventricular disease

The development and psychometric properties of a measure of clinicians’ attitudes to depression: the revised Depression Attitude Questionnaire (R-DAQ)

Background: Depression is a common mental disorder associated with substantial disability. It is inadequately recognised and managed, and clinicians’ attitudes to this condition and its treatment may play a part in this. Most research in this area has used the Depression Attitude Questionnaire (DAQ), but analyses have shown this measure to exhibit problems in psychometric properties and suitability for the health professionals and settings where depression recognition may occur. Methods: We revised the DAQ using a pooled review of findings from studies using this measure, together with a Delphi study which sought the opinions of a panel of relevant experts based in the UK, USA, Australia, and European countries (n = 24) using 3 rounds of questioning to consider attitude dimensions, content, and item wording. After item generation, revision and consensus (agreement >70%) using the Delphi panel, the revised DAQ (R-DAQ) was tested with 1193 health care providers to determine its psychometric properties. Finally the test-retest reliability of the R-DAQ was examined with 38 participants. Results: The 22-item R-DAQ scale showed good internal consistency: Cronbach’s alpha coefficient was 0.84; and satisfactory test-retest reliability: intraclass correlation coefficient was 0.62 (95% C.I. 0.37 to 0.78). Exploratory factor analysis favoured a three-factor structure (professional confidence, therapeutic optimism/pessimism, and a generalist perspective), which accounted for 45.3% of the variance. Conclusions: The R-DAQ provides a revised tool for examining clinicians’ views and understanding of depression. It addresses important weaknesses in the original measure whilst retaining items and dimensions that appeared valid. This revised scale is likely to be useful in examining attitudes across the health professional workforce and beyond the confines of the UK, and may be valuable for the purpose of evaluating training that aims to address clinicians’ attitudes to depression. It incorporates key dimensions of attitudes with a modest number of items making it applicable to use in busy clinical settings

Early reduction in painful physical symptoms is associated with improvements in long-term depression outcomes in patients treated with duloxetine

<p>Abstract</p> <p>Background</p> <p>To investigate the association of the change of painful physical symptoms (PPS) after 4 weeks, with the 6-month treatment outcomes of depressive symptoms in patients treated with duloxetine in clinical practice.</p> <p>Methods</p> <p>Multicenter, prospective, 6-month, non-interventional study in adult outpatients with a depressive episode and starting treatment with duloxetine. Depression severity was assessed by the clinician (Inventory for Depressive Symptomatology [IDS-C]) and patient (Kurz-Skala Stimmung/Aktivierung [KUSTA]). Somatic symptoms and PPS were assessed using the patient-rated Somatic Symptom Inventory (SSI) and visual analog scales (VAS) for pain items. Association of change in PPS with outcomes of depressive symptoms was analyzed based on mean KUSTA scores (mean of items mood, activity, tension/relaxation, sleep) and achievement of a 50% reduction in the total IDS-C score after 6 months using linear and logistic regression models, respectively.</p> <p>Results</p> <p>Of the 4,517 patients enrolled (mean age: 52.2 years, 71.8% female), 3,320 patients (73.5%) completed the study. 80% of the patients had moderate to severe overall pain (VAS > 30 mm) at baseline. A 50% VAS overall pain reduction after 4 weeks was associated with a 13.32 points higher mean KUSTA score after 6 months, and a 50% pain reduction after 2 weeks with a 6.33 points improvement. No unexpected safety signals were detected in this naturalistic study.</p> <p>Conclusion</p> <p>Pain reduction after 2 and 4 weeks can be used to estimate outcomes of long-term treatment with duloxetine. PPS associated with depression have a potential role in predicting remission of depressive symptoms in clinical practice.</p

Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target

Prioritization of genes driving congenital phenotypes of patients with de novo genomic structural variants

Background:Genomic structural variants (SVs) can affect many genes and regulatory elements. Therefore, the molecular mechanisms driving the phenotypes of patients carrying de novo SVs are frequently unknown. Methods:We applied a combination of systematic experimental and bioinformatic methods to improve the molecular diagnosis of 39 patients with multiple congenital abnormalities and/or intellectual disability harboring apparent de novo SVs, most with an inconclusive diagnosis after regular genetic testing. Results: In 7 of these cases (18%), whole-genome sequencing analysis revealed disease-relevant complexities of the SVs missed in routine microarray-based analyses. We developed a computational tool to predict the effects on genes directly affected by SVs and on genes indirectly affected likely due to the changes in chromatin organization and impact on regulatory mechanisms. By combining these functional predictions with extensive phenotype information, candidate driver genes were identified in 16/39 (41%) patients. In 8 cases, evidence was found for the involvement of multiple candidate drivers contributing to different parts of the phenotypes. Subsequently, we applied this computational method to two cohorts containing a total of 379 patients with previously detected and classified de novo SVs and identified candidate driver genes in 189 cases (50%), including 40 cases whose SVs were previously not classified as pathogenic. Pathogenic position effects were predicted in 28% of all studied cases with balanced SVs and in 11% of the cases with copy number variants. Conclusions:These results demonstrate an integrated computational and experimental approach to predict driver genes based on analyses of WGS data with phenotype association and chromatin organization datasets. These analyses nominate new pathogenic loci and have strong potential to improve the molecular diagnosis of patients with de novo SVs

WELLFOCUS PPT – modified positive psychotherapy to improve well-being in psychosis: study protocol for a pilot randomised controlled trial

BACKGROUND: The promotion of well-being is an important goal of recovery oriented mental health services. No structured, evidence-based intervention exists that aims to increase the well-being in people with severe mental illness such as psychosis. Positive psychotherapy (PPT) is a promising intervention for this goal. Standard PPT was adapted for use with people with psychosis in the UK following the Medical Research Council framework for developing and testing complex interventions, resulting in the WELLFOCUS Model describing the intended impact of WELLFOCUS PPT. This study aims to test the WELLFOCUS Model, by piloting the intervention, trial processes, and evaluation strategy. METHODS/DESIGN: This study is a non-blinded pragmatic pilot RCT comparing WELLFOCUS PPT provided as an 11-session group therapy in addition to treatment as usual to treatment as usual alone. Inclusion criteria are adults (aged 18–65 years) with a main diagnosis of psychosis who use mental health services. A target sample of 80 service users with psychosis are recruited from mental health services across the South London and Maudsley NHS Foundation Trust. Participants are randomised in blocks to the intervention and control group. WELLFOCUS PPT is provided to groups by specifically trained and supervised local therapists and members of the research team. Assessments are conducted before randomisation and after the group intervention. The primary outcome measure is well-being assessed by the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes include good feelings, symptom relief, connectedness, hope, self-worth, empowerment, and meaning. Process evaluation using data collected during the group intervention, post-intervention individual interviews and focus groups with participants, and interviews with trial therapists will complement quantitative outcome data. DISCUSSION: This study will provide data on the feasibility of the intervention and identify necessary adaptations. It will allow optimisation of trial processes and inform the evaluation strategy, including sample size calculation, for a future definitive RCT. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04199273 – WELLFOCUS study: an intervention to improve well-being in people with psychosis, Date registered: 27 March 2013, first participant randomised on 26 April 2013