Metabolomic profiles of 38 acylcarnitines in major depressive episodes before and after treatment.

BACKGROUND: Major depression is associated with changes in plasma L-carnitine and acetyl-L-carnitine. But its association with acylcarnitines remains unclear. The aim of this study was to assess metabolomic profiles of 38 acylcarnitines in patients with major depression before and after treatment compared to healthy controls (HCs). METHODS: Metabolomic profiles of 38 plasma short-, medium-, and long-chain acylcarnitines were performed by liquid chromatography-mass spectrometry in 893 HCs from the VARIETE cohort and 460 depressed patients from the METADAP cohort before and after 6 months of antidepressant treatment. RESULTS: As compared to HCs, depressed patients had lower levels of medium- and long-chain acylcarnitines. After 6 months of treatment, increased levels of medium- and long-chain acyl-carnitines were observed that no longer differed from those of controls. Accordingly, several medium- and long-chain acylcarnitines were negatively correlated with depression severity. CONCLUSIONS: These medium- and long-chain acylcarnitine dysregulations argue for mitochondrial dysfunction through fatty acid ß-oxidation impairment during major depression.

Anxious distress in people with major depressive episodes: a cross-sectional analysis of clinical correlates.

OBJECTIVE: Most people with major depressive episodes meet the criteria for the anxious distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feelings of tension, restlessness, difficulty concentrating, and fear that something awful may happen. This cross-sectional study was aimed at identifying clinical correlates of AD in people with unipolar or bipolar depression. METHODS: Inpatients with a current major depressive episode were included. Data on socio-demographic and clinical variables were collected. The SCID-5 was used to diagnose depressive episodes and relevant specifiers. The Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to assess the severity of depressive and manic (mixed) symptoms, respectively. Multiple logistic regression analyses were carried out to identify clinical correlates of AD. RESULTS: We included 206 people (mean age: 48.4 ± 18.6 yrs.; males: 38.8%) admitted for a major depressive episode (155 with major depressive disorder and 51 with bipolar disorder). Around two-thirds of the sample (N = 137; 66.5%) had AD. Multiple logistic regression models showed that AD was associated with mixed features, higher YMRS scores, psychotic features, and a diagnosis of major depressive disorder (p < 0.05). CONCLUSION: Despite some limitations, including the cross-sectional design and the inpatient setting, our study shows that AD is likely to be associated with mixed and psychotic features, as well as with unipolar depression. The identification of these clinical domains may help clinicians to better contextualize AD in the context of major depressive episodes.

Associations Between Forced Intercourse and Subsequent Depression Among Women in the U.S. General Population.

Forced intercourse is a high prevalence experience among US women, with high potential to produce subsequent major depressive episodes (MDE). However, the extent to which prior risk factors are associated with the timing of both sexual assault experiences and subsequent MDE onset is not known. The aim of this study was to document the associations between childhood depression, subsequent forced intercourse, and later MDE. We used retrospective information on childhood depression, forced intercourse, and MDE after forced intercourse from female respondents in the nationally representative 2017 US Panel Study of Income Dynamics-Transition to Adulthood Supplement (PSID-TAS, N = 1298, response rate: 87%). Multivariable logistic regression estimated these associations, controlling for age, race, poverty, religiosity, family history of depression, and adverse childhood experiences (such as parental physical abuse or parental violence). Women who experienced childhood depression (prevalence: 15%) had 2.57 times the odds of experiencing forced intercourse after depression onset, even after adjusting for these other risk factors. However, even though childhood depression is a powerful risk factor for later MDE, independent of that women who experienced forced intercourse had 2.28 times the odds of experiencing MDE after the occurrence of forced intercourse, adjusting for childhood depression and other risk factors. This study provided the first clear evidence for time-ordered associations between forced intercourse and subsequent MDE among women in the general population.

Mental Health Treatment Use, Perceived Treatment Need, and Reasons for Non-Use Among U.S. Adults with Serious Suicidal Thoughts During the COVID-19 Pandemic.

Analyzing the 2021 National Survey on Drug Use and Health data with generalized linear models, we examined: (1) COVID pandemic-related and other correlates of mental health treatment use and unmet perceived treatment need among U.S. adults who experienced serious suicidal thoughts (N = 3,177); and (2) correlates of self-reported reasons for not receiving treatment. We found that 61% used any mental health treatment, and 48% of users and 37% of nonusers reported perceived treatment need. Significant correlates of treatment use were demographic factors, insurance, major depressive disorder, and illicit drug use disorder. Significant correlates of perceived treatment need were age 18-34, some college education, and major depressive episode. Perceived negative effect of the COVID pandemic on mental health was a significant factor for both treatment use and perceived need. The most frequent reasons for not getting treatment were the cost of treatment or lack of insurance and stigma-related concerns.

Plasma and Platelet Brain-Derived Neurotrophic Factor (BDNF) Levels in Bipolar Disorder Patients with Post-Traumatic Stress Disorder (PTSD) or in a Major Depressive Episode Compared to Healthy Controls.

Post-traumatic stress disorder (PTSD) is a highly disabling mental disorder arising after traumatism exposure, often revealing critical and complex courses when comorbidity with bipolar disorder (BD) occurs. To search for PTSD or depression biomarkers that would help clinicians define BD presentations, this study aimed at preliminarily evaluating circulating brain-derived-neurotrophic factor (BDNF) levels in BD subjects with PTSD or experiencing a major depressive episode versus controls. Two bloodstream BDNF components were specifically investigated, the storage (intraplatelet) and the released (plasma) ones, both as adaptogenic/repair signals during neuroendocrine stress response dynamics. Bipolar patients with PTSD (n = 20) or in a major depressive episode (n = 20) were rigorously recruited together with unrelated healthy controls (n = 24) and subsequently examined by psychiatric questionnaires and blood samplings. Platelet-poor plasma (PPP) and intraplatelet (PLT) BDNF were measured by ELISA assays. The results showed markedly higher intraplatelet vs. plasma BDNF, confirming platelets' role in neurotrophin transport/storage. No between-group PPP-BDNF difference was reported, whereas PLT-BDNF was significantly reduced in depressed BD patients. PLT-BDNF negatively correlated with mood scores but not with PTSD items like PPP-BDNF, which instead displayed opposite correlation trends with depression and manic severity. Present findings highlight PLT-BDNF as more reliable at detecting depression than PTSD in BD, encouraging further study into BDNF variability contextually with immune-inflammatory parameters in wider cohorts of differentially symptomatic bipolar patients.

Serum claudin-5 levels among patients with unipolar and bipolar depression in relation to the pro-inflammatory cytokine tumor necrosis factor-alpha levels.

Accumulating evidence indicates that inflammation and neurovascular unit (NVU) dysfunction contribute to depression via disrupted blood-brain barrier (BBB) integrity. Claudin-5, an endothelial tight-junction protein expressed in the NVU and contributing to BBB integrity, has been implicated in psychiatric disorders, including major depressive disorder (MDD) and schizophrenia. In an animal model of depressive-like behavior, the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) was found to affect BBB permeability and claudin-5 expression of NVU endothelial cells. To the best of the authors' knowledge, this study is the first to assess the relationship between serum claudin-5 and TNF-α levels, during major depressive episodes (MDEs). Serum levels of claudin-5 and TNF-α of 40 patients diagnosed with current MDE [19 with MDD and 21 with bipolar disorder (BD)] and 28 matched healthy controls (HCs) were analyzed. Claudin-5 and TNF-α serum levels in the MDE group were significantly higher than in the HC one. Discrete analysis according to MDE type indicated significantly increased claudin-5 serum levels in BD but not in MDD patients, compared to HCs, even after controlling for confounders. In the MDE group, a significant positive correlation was found between claudin-5 and TNF-α serum levels. In complementary analysis, serum levels of the pro-inflammatory cytokine interleukin-6 were significantly higher among MDE patients compared to HCs, however, no significant correlation was found with claudin-5 levels. In conclusion, as indicated by preclinical studies, our clinical study suggests a possible specific interaction between the NVU/BBB marker claudin-5 and the inflammatory marker TNF-α in the pathogenesis of depression.

Medicare Benefits Schedule item numbers for transcranial magnetic stimulation (TMS): Questions arising.

OBJECTIVE: Four Medicare Benefits Schedule item numbers for Transcranial Magnetic Stimulation (TMS) treatment of unresponsive MDD were declared in Australia in 2021. They are accompanied by rules/conditions. The aim is to consider these rules/conditions in light of recent research and real-world experience. CONCLUSIONS: While evidence supports some listed rules/conditions, others lack clinical justification and deserve to be reconsidered. These include (a) ineligibility of patients who have previously received TMS, (b) a lifetime total limit of 50 treatments, (c) a second/final course being unavailable for 4 months following the completion of the first course, and (d) the second/final course being limited to 15 treatments.

Nitric Oxide Synthase activity in major depressive episodes before and after antidepressant treatment: Results of a large case-control treatment study.

BACKGROUND: Nitric oxide synthase (NOS) activity, an enzyme potentially involved in the major depressive episodes (MDE), could be indirectly measured by the L-Citrulline/L-Arginine ratio (L-Cit/L-Arg). The aim of this study was: (1) to compare the NOS activity of patients with a MDE to that of healthy controls (HC); (2) to assess its change after antidepressant treatment. METHODS: A total of 460 patients with a current MDE in a context of major depressive disorder (MDD) were compared to 895 HC for NOS activity (L-Cit/L-Arg plasma ratio). L-Arg and L-Cit plasma levels were measured using a MS-based liquid chromatography method. Depressed patients were assessed at baseline, and after 3 and 6 months of antidepressant treatment for depression severity and clinical response. RESULTS: Depressed patients had a lower NOS activity than HC at baseline [0.31 ± 0.09 v. 0.38 ± 0.12; 95% confidence interval (CI) -0.084 to -0.062, p < 0.0001]. Lower NOS activity at baseline predicted a higher response rate [odds ratio (OR) = 29.20; 95% CI 1.58-536.37; p = 0.023]. NOS activity in depressed patients increased significantly up to 0.34 ± 0.08 after antidepressant treatment (Est = 0.0034; 95% CI 0.0002-0.0067; p = 0.03). CONCLUSIONS: Depressed patients have a decreased NOS activity that improves after antidepressant treatment and predicts drug response. NOS activity may be a promising biomarker for MDE in a context of MDD.

Associations between water, sanitation, and depression among older people in Ghana: empirical evidence from WHO-SAGE Wave 2 survey.

BACKGROUND: While depression is the most frequent psychiatric disorder among the older adults, the use of water and sanitation has been associated with both physical and psychological adverse outcomes. We investigated the associations of water and sanitation with depressive symptoms among older adults in Ghana. METHODS: The study used data from 4,735 participants in the World Health Organization (WHO) Study on global AGEing and adult health (SAGE) Wave 2 of adults aged ≥50 years. Major depressive episode (MDE) was assessed using the World Mental Health Survey version of the Composite International Diagnostic Interview and we classified water and sanitation sources based on the Joint Monitoring Program. Multivariate logistic regressions evaluated the associations. RESULTS: Approximately 7.3% of respondents reported a MDE, 90% and 78% used improved water sources and sanitation facilities respectively, and 77% shared sanitation facilities. Individuals who used unimproved water sources and unimproved sanitation were 1.6 and 1.3 times more likely to report MDE respectively. Also, sex-based analysis showed that the effect of the use of unimproved water and sanitation on depression was much appreciable and more substantial among women compared to men. CONCLUSIONS: The findings suggest the importance of water and sanitation to the well-being of older people, particularly among women. Policies targeted at improving the mental health in old age should include water and sanitation.

An individualized treatment rule to optimize probability of remission by continuation, switching, or combining antidepressant medications after failing a first-line antidepressant in a two-stage randomized trial.

BACKGROUND: There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method. METHODS: Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects. RESULTS: Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1-30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining. CONCLUSIONS: An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results.

The relationship between depression with anxious distress DSM-5 specifier and mixed depression: a network analysis.

INTRODUCTION: Epidemiological, clinical, and treatment response characteristics of major depression with anxious distress (ADS) are quite similar to those of mixed depression, but no study investigated the symptom interplay of these conditions. OBJECTIVE: To analyze the correlations among symptom criteria for major depression with ADS and for mixed depression using a network analysis. METHODS: Two hundred and forty-one outpatients with major depression were consecutively recruited. DSM-5 criteria for major depression with ADS or with mixed features (MF) and Koukopoulos' criteria for mixed depression (MXD) were assessed using a structured clinical interview. RESULTS: A total of 58.9% of patients met DSM-5 criteria for major depression with ADS, 48.5% for MXD, and 2.5% for major depression with MF, so that the symptoms of this specifier were excluded from the network analysis. The most frequent symptoms were difficulty concentrating due to worries (57.7%), feeling keyed up or on edge (51%) (major depression with ADS), and psychic agitation or inner tension (51%) (MXD). Psychic agitation or inner tension had a central position in the network and bridged MXD to major depression with ADS through feeling keyed up or on edge. CONCLUSIONS: Criteria for major depression with ADS and for MXD are partially overlapping, with psychic agitation or inner tension and feeling keyed up or on edge that feature in both conditions and are difficult to distinguish in clinical practice. The clarification of the relationship between these two psychopathological conditions could bring important implications for diagnosis, prognosis, and treatment of depressive episodes.

Patient and physician perspectives of a smartphone application for depression: a qualitative study.

BACKGROUND: Despite an increasing number of smartphone apps, such therapeutic tools have not yet consistently demonstrated their efficacy and many suffer from low retention rates. To ensure the development of efficient apps associated with high adherence, we aimed to identify, through a user-centred design approach, patient and physician expectations of a hypothetical app dedicated to depression. METHODS: We conducted semi-structured interviews with physicians (psychiatrists and general practitioners) and patients who had experienced a major depressive episode during the last 12 months using the focus group method. The interviews were audio recorded, transcribed and analysed using qualitative content analysis to define codes, categories and emergent themes. RESULTS: A total of 26 physicians and 24 patients were included in the study. The focus groups showed balanced sex and age distributions. Most participants owned a smartphone (83.3% of patients, 96.1% of physicians) and were app users (79.2% of patients and 96.1% of physicians). The qualitative content analysis revealed 3 main themes: content, operating characteristics and barriers to the use of the app. Expected content included the data collected by the app, aiming to provide information about the patient, data provided by the app, gathering psychoeducation elements, therapeutic tools and functionalities to help with the management of daily life and features expected for this tool. The "operating characteristics" theme gathered aims considered for the app, its potential target users, considered modalities of use and considerations around its accessibility and security of use. Finally, barriers to the use of the app included concerns about potential app users, its accessibility, safety, side-effects, utility and functioning. All themes and categories were the same for patients and physicians. CONCLUSIONS: Physician and patient expectations of a hypothetical smartphone app dedicated to depression are high and confirmed the important role it could play in depression care. The key points expected by the users for such a tool are an easy and intuitive use and a personalised content. They are also waiting for an app that gives information about depression, offers a self-monitoring functionality and helps them in case of emergency.

Social norms and the association between intimate partner violence and depression in rural Bangladesh-a multilevel analysis.

BACKGROUND: Intimate partner violence (IPV) is highly prevalent globally and associated with adverse mental health outcomes among women. In IPV-endemic contexts like Bangladesh, previous research has found no association between low levels of IPV and depression. Although IPV and attitudes justifying IPV against women are highly prevalent in this context, nothing is known about how related contextual norms affect associations between individual-level IPV exposure and depression. The present study examines if village-level IPV norms, characterized using village-level (Level 2) prevalence of a) IPV-justifying attitudes (injunctive norms) and b) physical IPV (descriptive norms), modifies the individual-level (Level 1) associations between the severity of recent IPV and major depressive episode (MDE) among women in rural Bangladesh. METHODS: Data were drawn from a nationally-representative sample consisting of 3290 women from 77 villages. Multilevel models tested cross-level interactions between village-level IPV norms and recently experienced individual-level IPV on the association with past 30-day MDE. RESULTS: The prevalence of IPV was 44.4% (range: 9.6-76.2% across villages) and attitudes justifying IPV ranged from 1.6% to 49.8% across villages. The prevalence of MDE was 16.8%. The risk of MDE at low levels of IPV severity (versus none) was greater in villages with the least tolerant attitudes toward IPV compared to villages where IPV was more normative, e.g., interaction RR = 1.42 (95% CI: 0.64, 3.15) for low physical IPV frequency and injunctive norms. CONCLUSIONS: The association between IPV and depression may be modified by contextual-level IPV norms, whereby it is exacerbated in low-normative contexts.

Characteristics of somatic symptoms among Chinese patients diagnosed with major depressive episode.

PURPOSE: This study aimed to describe the clinical features of somatic symptoms among Chinese patients diagnosed with major depressive episode (MDE). METHODS: A total of 213 inpatients with MDE from two mental health hospitals were recruited and investigated using the Somatic Symptom Inventory (SSI), Hamilton rating scale for depression, Hamilton rating scale for anxiety, and a demographic questionnaire. RESULTS: The participants included 142 patients with unipolar depression and 71 patients with bipolar depression. The mean SSI score of all participants was 49.30 (SD = 14.80). "Feeling fatigued, weak, or tired all over" was found to be the most common somatic symptom (61.0% reported moderate levels or above), followed by "feeling of being not in as good physical health as most of your friends" (56.3%), and "feeling weak in parts of the body" (49.3%). "Headache" and "soreness in muscles" were common painful symptoms. Both patients with unipolar and bipolar depression had similar somatic symptoms, including painful and non-painful ones. The somatic symptoms of all participants were closely correlated with the severity of depression and anxiety (P < 0.01). Patients with anxiety, older age, low education, and negative life events in the last year had more somatic symptoms. CONCLUSIONS: Inpatients with MDE of somatic symptoms are common, which were significantly correlated with the severity of depression and anxiety. Further efforts should focus on early recognition and integrated care model management of patients based on their characteristics to improve their quality of life and treatment outcomes.

Perception of Unmet Need after Seeking Treatment for a Past Year Major Depressive Episode: Results from the 2018 National Survey of Drug Use and Health.

Depression, a leading cause of disability and mortality world-wide that one in five U.S. adults are estimated to experience in their lifetime, presents special complications in treatment. While it is well-recognized that there are several barriers to even obtaining treatment for depression, once an individual obtains treatment they may not receive the type of care that they need. In order to examine common factors of those who experienced an unmet treatment need for depression despite seeking mental health treatment, we examined data from the 2018 National Survey of Drug Use and Health (NSDUH). We cross-sectionally compared two groups of individuals who both met criteria for a past year Major Depressive Episode (MDE) and sought mental health treatment, however one group reported an unmet treatment need and the other did not. Results indicate a variety of personal identity and social factors associated with perceiving an unmet treatment need, including age, race/ethnicity, sexual attraction, marital status, poverty level, health insurance, substance misuse, global health, and role impairment. This study contributes to the literature by providing further support for disparities in depression treatment at the consumer, provider, and systemic levels that have downstream effects for health equity policy and public health promotion.

Lack of association between unipolar or bipolar depression and serum aquaporin-4 autoantibodies.

Aquaporin-4 (AQP4), an astrocyte water channel protein, is the target antigen of serum immunoglobulin G (IgG) autoantibody in neuromyelitis optica spectrum disorders (NMOsd), a group of inflammatory, demyelinating diseases of the central nervous system. Recently, a reduction in blood vessels coverage by AQP4-immunoreactive astrocytes was demonstrated in depressed patients, indicating a role for AQP4 in mood disorders. Moreover, a possible association between depression and serum AQP4-IgG was suggested in a case report of a treatment resistant depression (TRD) patient diagnosed with NMOsd with positive serum AQP4 autoantibodies. We investigated, for the first time, the presence of serum AQP4-IgG in patients with unipolar and bipolar depression and healthy controls (HCs). In this multicenter study, 25 major depressive disorder (MDD) and 25 bipolar disorder (BD) patients, during an acute major depressive episode (MDE), and 30 matched HCs were screened for the presence of serum AQP4-IgG, using a cell-based assay. The MDE patients underwent a repeated AQP4-IgG assessment at a 3-month follow-up visit. The MDE group (N = 50) had illness duration of 12.7 years (SD = 10.5), 12% of them were psychotropic medication-free and 26% were defined as TRD. All MDE patients and HCs, including three BD patients who experienced a manic switch, were seronegative for AQP4-IgG at baseline and follow-up assessments. In conclusion, contrary to our hypothesis, AQP4 autoantibodies were not detected in serum of unipolar and bipolar depressed patients. However, AQP4 may still play a role in the pathogenesis of mood disorders through different mechanisms of action such as altered brain AQP4 expression.

Validation of the Russian version of neurological disorders depression inventory for epilepsy (NDDI-E).

OBJECTIVE: To translate and validate the English version of the Neurologic Depression Disorders Inventory in Epilepsy (NDDI-E) into the Russian language as an instrument for rapid detection of major depressive episodes (MDE) for patients with epilepsy (PWE) from Russian Federation. METHODS: One hundred and 75 consecutive PWE were included in the study. All patients were assessed with Mini-International Neuropsychiatric Interview (MINI 6.0.0), Hospital Anxiety and Depression Scale (HADS) and the Russian version of NDDI-E. Chi-square, Fisher's exact and Mann-Whitney tests were used to compare PWE with and without MDE. We analyzed internal structural validity, external validity, and receiver operator characteristics. RESULTS: None of the participants had any difficulties in understanding the questions of NDDI-E. The internal consistency of the inventory was satisfactory (Cronbach's ά = 0.856). Correlation between the NDDI-E and the HADS scores was moderate (r = 0.64, P < 0.001), indicating acceptable external validity. NDDI showed good capacity to detect MDE, with area under the curve of 0.919 (95% CI = 0.868-0.955; standard error: 0.019; P < 0.001). An optimal cut-off point with the highest Yuden's index (J = 0.699) was  > 12. At this point NDDI-E showed sensitivity of 88.16% (95% CI = 78.7%-94.4%), specificity of 81.82% (95% CI = 72.8%-88.9%), positive predictive value of 59.3% (95% CI = 48.8%-69.0%), negative predictive value of 95.8% (95% CI = 92.5%-97.7%). CONCLUSION: Russian version of NDDI-E is an affordable and fast screening tool with a good combination of sensitivity and specificity.

The relationship between depression risk perception and self-help behaviours in high risk Canadians: a cross-sectional study.

BACKGROUND: Self-help may reduce the risk of depression, and risk perception of depression may influence initiating self-help. It is unknown how risk perception is associated with self-help behaviours. The objectives of this study are to (1) describe the self-help strategies used by high-risk Canadians in relation to the accuracy of perceived depression risk, by sex, and (2) identify demographic and clinical factors associated with self-help behaviours. METHODS: Baseline data from a randomized controlled trial including 358 men and 356 women at high-risk of developing depression were used. Following methods used in cancer research, risk perception accuracy was determined by comparing the participant's self-perceived and objective risk of developing depression and classifying as accurate, over-estimation and under-estimation based on a ± 10% threshold. The participant's objective depression risk was assessed using sex-specific multivariable risk predictive algorithms. Frequency of using 14 self-help strategies was assessed. One-way ANOVA testing was used to detect if differences in risk perception accuracy groups existed, stratified by sex. Linear regression was used to investigate the clinical and demographic factors associated with self-help behaviours, also stratified. RESULTS: Compared to accurate-estimators, male over-estimators were less likely to "leave the house daily," and "participate in activities they enjoy." Male under-estimators were also less likely to "participate in activities they enjoy." Both male 'inaccurate' perception groups were more likely to 'create lists of strategies which have worked for feelings of depression in the past and use them'. There were no significant differences between self-help behaviours and risk perception accuracy in women. Regression modeling showed negative relationships between self-rated health and self-help scores, irrespective of sex. In women, self-help score was positively associated with age and educational attainment, and negatively associated with perceived risk. In men, a positive relationship with unemployment was also seen. CONCLUSIONS: Sex differences exist in the factors associated with self-help. Risk perception accuracy, work status, and self-rated health is associated with self-help behaviours in high-risk men. In women, factors related to self-help included age, education, self-rated health status, and perceived risk. More research is needed to replicate findings. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov (NCT02943876) as of 10/21/16.

Lower plasma vascular endothelial growth factor A in major depressive disorder not normalized after antidepressant treatment: A case control study.

OBJECTIVE: Vascular endothelial growth factor A is a growth factor with pro-angiogenic and neurotrophic properties. Anti-vascular endothelial growth factor A treatments, used to treat cancers and opthalmic diseases, are known to induce depressive symptoms. Thus, we hypothesized that vascular endothelial growth factor A plasma levels are low in patients experiencing a major depressive episode in the context of major depressive disorder, which consequently increase after antidepressant treatment. The aim of this study was to compare plasma vascular endothelial growth factor A levels in patients with major depressive episode-major depressive disorder before and after antidepressant treatment. METHODS: Vascular endothelial growth factor A fasting plasma levels of 469 major depressive episode-major depressive disorder patients were compared with healthy controls. Depressed patients were assessed for remission after 3 and 6 months of antidepressant treatment. Bivariate and multivariate analyses adjusted for sex, age, body mass index and tobacco use were performed. RESULTS: As compared to healthy controls, major depressive episode patients had lower vascular endothelial growth factor A, 66.0 (38.3) pg/mL (standard deviation) vs 83.2 (49.2) pg/mL, p < 0.0001. Plasma vascular endothelial growth factor A levels did not change after antidepressant treatment, even in remitters, and remained lower than those of healthy controls, 64.9 (39.3) pg/mL vs 83.2 (49.2) pg/mL, p < 0.0001. CONCLUSION: Depressed patients with major depressive disorder have lower plasma vascular endothelial growth factor A levels than healthy controls during their major depressive episode and after remission following antidepressant treatment. New strategies targeting enhancement of plasma vascular endothelial growth factor A could be promising for the prevention and treatment of major depressive disorder.

Norwegian reference data on the Fatigue Questionnaire and the Patient Health Questionnaire-9 and their interrelationship.

BACKGROUND: Population-based reference data on frequently used questionnaires are important for comparative purposes. Due to changes in health and lifestyles, such data should be updated every other decade. The objectives of this study were to establish Norwegian population-based reference data on the Fatigue Questionnaire (FQ) and the Patient Health Questionnaire-9 (PHQ-9) on depression, to compare the FQ-scores with our previous reference data from 1996, and to explore the relationship between the scores on these two instruments. METHODS: In 2015, a representative sample of 6,012 Norwegians aged 18-80 years was mailed a questionnaire including the FQ and the PHQ-9, and 36% responded. Complete FQ-scores were delivered by 2,041 subjects, and complete PHQ-9 scores by 2,086 subjects. The scores are displayed according to sex and 10-year age groups. RESULTS: Few 2015 mean scores of mental, physical, and total fatigue differed significantly from those of 1996, and the same was found for the prevalence rates of chronic fatigue. The exception was a significantly lower prevalence in 2015 of mean fatigue scores and prevalence of chronic fatigue in females ≥ 60 years. The prevalence of major depressive episode (MDE) based on the PHQ-9 sum score cut-off ≥ 10 was 5.9% for males and 9.8% for females, and 2.5% and 3.8% using a DSM-based algorithm with at least five endorsed criteria including either anhedonia or depressed mood. The correlation between the FQ and the PHQ-9 was 0.59, implying 36% shared variance. CONCLUSIONS: This study showed considerable interrelationship between the FQ and the PHQ-9 constructs. The reference data show that scores on the FQ have only improved significantly in persons aged 60 or more years between 1996 and 2015. Our prevalence findings of MDE based on the PHQ-9 are in accordance with the findings from other countries. The FQ and the PHQ-9 should be used together in epidemiological and clinical studies.