Association between inflammation and depression, especially in elderly patients, leads to conclusions about their shared influence on risk of cardiovascular disease and death. It might be found useful to predict those issues by monitoring inflammatory parameters, such as neutrophil/lymphocyte ratio (NLR). The aim of this study was to determine the NLR in elderly patients with unipolar depression compared with non-depressed elderly patients. NLR was measured in 684 Caucasian subjects (depressed: n = 465, non-depressed: n = 219), aged ≥ 60 (depressed: mean age 74.8 ± 7.8 years, non-depressed: mean age: 71.1 ± 5.7 years). There were two subgroups within depressed patients: first episode depression (n = 138, 29.6%) and recurrent depression (n = 328, 70.3%). NLR was calculated as ratio between absolute neutrophil count to absolute lymphocyte count. NLR was significantly higher in unmedicated patients with depression compared with healthy control (2.10 ± 2.13 vs. 2.01 ± 0.75, p = 0.004). It was higher in first episode depression compared with recurrent depression (2.11 ± 1.76 vs 1.64 ± 1.04, p < 0.05). There was a positive correlation with severity of symptoms. We found non-specific effect of treatment with antidepressants or antipsychotics on lower NLR. Increased NLR in patients with first episode of depression compared to recurrent depression and healthy control may have important clinical consequences. Severity of symptoms are positively correlated with NLR, which may indicate that with increasing severity of depression, the risk of cardiovascular events is also rising, which leads to higher mortality. In elderly patients with depression even a small reduction of such risk may translate into better prognosis and improve quality of live. The difference between first episode and recurrent depression in terms of inflammatory biomarkers requires further studies.

Obsessive-compulsive disorder (OCD) has been linked to reward dysfunctions, highlighting a possible role of anhedonia in OCD. Surprisingly, anhedonia in OCD has never been evaluated. Moreover, although nicotine typically has anti-anhedonic effects, anecdotal reports suggest low prevalence rates of smoking in OCD. To address these two phenomena, 113 individuals with OCD completed a battery of questionnaires assessing symptom severity, anhedonia, and smoking. 28.3% of the sample met criteria for clinically significant anhedonia, which correlated with Y-BOCS scores (r=0.44), even when controlling for depressive symptoms. 13.3% of the sample endorsed current smoking, a lower rate than seen in psychiatric disorders (40-90%) and the general adult population (19%). Results highlight high rates of anhedonia and yet reduced prevalence of smoking in OCD. In contrast to the known positive association between anhedonia and smoking, a negative association emerged. Future research is needed to address the unique interface between anhedonia and reward responsiveness in OCD. Potential clinical implications are discussed.

Recent findings have established a connection between inflammation and major depression and specifically the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression. This article reviews clinical and experimental studies examining the role of the HPA axis, HPA hyperactivity (resulting in increased cortisol levels), as well as the proinflammatory cytokines tumor necrosis factor, C-reactive protein, and the interleukins, in depressed patients. Similarly this paper will review data supporting increased cytokine levels in depression and specifically differential effects in treatment-resistant patients, as well as potentially distinguishing in particular depression subtypes. Understanding the role of the immune system and inflammation in patients with major depression is essential in order to develop efficacious treatments potentially targeting inflammation in relation to the depression in order to reduce patient symptomatology and comorbidities.

The heritability of some individual depressive symptoms has been well established. However, the causal genes related to individual depressive symptoms and genetic effects on the courses of individual depressive symptoms are still unclear. We examined these issues in 241 Korean patients who met the DSM-IV-TR criteria for major depression. Patients entered a 12-week clinical trial with antidepressants. A total of 1399 single-nucleotide polymorphisms (SNPs) of 79 candidate genes were assessed. The rs557762 and the TT haplotype in the 11th haplotype block of the GRIA3 gene were associated with feelings of guilt in females. The GGCCGGGC haplotype in the first haplotype block of TPH1 was significantly associated with middle insomnia. The ACAG haplotype in the 13th haplotype block of the GRIK2 gene was associated with somatic anxiety. Moreover, the effect of the rs557762 on guilt significantly varied across times. Our results indicate that there are associations between particular gene polymorphisms and some individual depressive symptoms. These results could contribute to understanding the biological mechanisms of depression.

Mood disorders are common mental illnesses. Among the factors associated with major depression are exposures to infectious diseases including hepatitis C, influenza, varicella-zoster, and herpes viruses. In this study, we sought to evaluate further associations between viral exposure and depression. From the US Center for Disease Control's National Health and Nutrition Examination Survey, we obtained data about depression status, antidepressant use, exposure to hepatitis A, hepatitis B, herpes simplex virus type 1, herpes simplex virus type 2, human immunodeficiency virus, and cytomegalovirus, and sociodemographic variables and evaluated associations between depression and viral exposure in adjusted multivariable models. Herpes simplex virus type 2 was associated with an increased risk of depression, whereas hepatitis A, hepatitis B, and herpes simplex virus type 1 were not. Higher cytomegalovirus antibody levels were associated with depression in subjects seropositive for cytomegalovirus. In conclusion, exposure to herpes simplex virus type 2 and possibly cytomegalovirus are associated with depression in an adult US sample.

This study analyzes the performance of the Center for Epidemiologic Studies Depression Scale (CES-D) to screen for major depressive disorder (MDD) in adults. We divided adults into three groups such as community-indwelling adults, patients with chronic diseases, and psychiatric patients. Electronic searches were performed on the MEDLINE, EMBASE, CINAHL, and PsycINFO database using the following keywords: depression, depressive disorder, major, and CES-D scale. The Quality Assessment of Diagnostic Accuracy Studies-2 was applied to assess the risk of bias in diagnostic studies. We reviewed 33 studies, including 18,271 adults that met the selection criteria. In meta-analysis, the pooled sensitivity was 0.86 on community-indwelling adults, 0.85 on patients with chronic diseases and 0.85 on psychiatric patients. The pooled specificity was 0.74, 0.84, and 0.88, respectively, and the summary receiver-operating characteristic curves were 0.88, 0.91, and 0.93, respectively. The RE correlation was a negative value (-0.394) only in patients with chronic diseases, showing no heterogeneity between studies. The CES-D, which has shown high diagnostic accuracy in adults, can be recommended for use as a first-stage screener for MDD. As a result, the early application of the CES-D can lead to disease prevention in adults at risk for depression.

Recent studies provided inconsistent evidence for the association between epilepsy and risk of depression.

Cyberbullying is a category of bullying that occurs in the digital realm/medium of electronic text. In this study, we used meta-analysis to explore the relation between cyberbullying victimization and depression. We investigated 57 empirical studies from 17 countries (74 effect sizes and 105, 440 participants). The results showed that there was a significant positive relation between cyberbullying victimization and depression (r = .291, 95% CI = [.246, .335]). Moreover, we found that gender, age and publication year significantly moderated the relation between cyberbullying victimization and depression.

Depression is a highly prevalent risk factor for both the onset of cardiovascular disease (CVD) and the mortality of CVD patients, and people suffering from CVD are more likely to develop depression than healthy individuals. The aim of this review is to summarize recent findings regarding the underlying relationship between CVD and depression. Literature search and review were conducted using PubMed, Google Scholar, Wanfang Med Online, and Baidu Scholar databases. CVD and depression are intimately related and researchers from around the world have proposed and validated various mechanisms that may potentially explain the comorbidity of CVD and depression. Recent studies have suggested that depression and CVD may manifest as two distinct clinical conditions in two different organs, the brain and the heart, respectively, but may also be linked by shared mechanisms. Of these, inflammation involving the immune system is thought to be a common mechanism of depression and heart disease, with specific inflammatory cytokines or pathways being potential targets for the prevention and treatment of the concurrent diseases. Therefore, inflammation may play an important role in bridging the link between depression and CVD, a finding that can have important clinical implications for the prevention and early intervention of these conditions.

Epidemiological studies have demonstrated that depression may be a risk factor for Alzheimer's disease (AD); however, the biological mechanisms of the transition from depression to AD are still not clear. Changes of amyloid β protein (Aβ) metabolism and increased glucocorticoid (GC) levels have been found in both depression and AD. Moreover, several studies in animal models have demonstrated that GC administration changes Aβ metabolism. To reveal whether GC affects amyloid metabolism in patients with depression, we evaluated serum levels of Aβ40, Aβ42 and cortisol at admission in 187 inpatients with major depressive disorder (MDD) and 224 healthy comparisons. Additionally, we re-evaluated the serum levels of Aβs in 27 patients with MDD 1 year later. The results of multiple regression analyses revealed that serum cortisol and Aβ levels are not correlated at the time of admission. However, serum cortisol levels at admission correlated with serum Aβ42 levels and Aβ40/Aβ42 ratio 1 year later. These findings suggest that increased cortisol in patients with MDD may influence the metabolism of Aβ over prolonged periods of time.

Previous studies suggest that insulin-sensitizing agents could play a significant role in the treatment of major depression, particularly depression in patients with documented insulin resistance or those who are resistant to standard psychopharmacological approaches. This study aimed to assess the effects on depressive symptoms with adjuvant treatment with the PPARγ-agonist pioglitazone. Patients (N=37) with non-psychotic, non-remitting depression receiving standard psychiatric regimens for depression were randomized across an insulin sensitivity spectrum in a 12-week double blind, randomized controlled trial of pioglitazone or placebo. Improvement in depression was associated with improvement in glucose metabolism but only in patients with insulin resistance. An age effect was also shown in that response to pioglitazone was more beneficial in younger aged patients. Study findings suggest differential improvement in depression severity according to both glucose metabolic status and level of depression at baseline. A greater understanding of the reciprocal links between depression and IR may lead to a dramatic shift in the way in which depression is conceptualized and treated, with a greater focus on treating and/or preventing metabolic dysfunction.

No abstract available

We conducted an epigenome-wide association study of Major Depressive Disorder (MDD) in brain-derived DNA using two analytic approaches. DNA methylation data (GSE41826) was used in differential methylation (DM) analyses controlling for age, sex, suicide status, and post-mortem interval; and in weighted gene co-methylation network analyses (WGCNA) in probes mapping to transcription start sites. No probes in the DM analysis survived FDR correction. Nominally significant DM probes were enriched in synaptic function-related genes. WGCNA revealed one module correlated with MDD, enriched in genes associated with mitochondrial function. DM and WGCNA both showed enrichment of genes involved in transcription and DNA binding.

Childhood exposure to parental threatening behaviors places adolescents at greater risk for depression. However, the association between parental threatening behaviors and depressive symptoms among trauma-exposed inpatient youth, and potential factors that exacerbate the harmful effects of such parenting, have remained unexplored. One factor that may contribute to depression is low emotional clarity, which is characterized by difficulties recognizing and understanding one's emotions. The current investigation examined the interactive effects of childhood exposure to maternal threatening behaviors and emotional clarity deficits in relation to depressive symptoms among inpatient psychiatric youth who had been exposed to a potentially traumatic event (i.e., exposure to actual or threatened death, serious injury, or sexual violence). Participants (N = 50, Mage = 15.1 years, SD = 0.51, range 12-17) completed measures of emotion dysregulation, childhood exposure to maternal threatening behavior, and depressive symptoms. A significant interaction was found between exposure to maternal threatening behaviors and deficits in emotional clarity in relation to depressive symptom severity. Greater exposure to maternal threatening behaviors was related to more severe depressive symptoms, yet only among children with greater deficits in emotional clarity. Findings underscore the need for interventions that target emotional clarity among trauma-exposed youth who have experienced parental threats.

Depression remains a great societal burden and a major treatment challenge. Most antidepressant medications target serotonergic raphé nuclei. Acute tryptophan depletion (ATD) modulates serotonin function. To better understand the raphé's role in mood networks, we studied raphé functional connectivity in depression. Fifteen depressed patients were treated with sertraline for 12 weeks and scanned during ATD and sham conditions. Based on our previous findings in a separate cohort, resting state MRI functional connectivity between raphé and other depression-related regions (ROIs) was analyzed in narrow frequency bands. ATD decreased raphé functional connectivity with the bilateral thalamus within 0.025-0.05 Hz, and also decreased raphé functional connectivity with the right pregenual anterior cingulate cortex within 0.05-0.1 Hz. Using the control broadband filter 0.01-0.1 Hz, no significant differences in raphé-ROI functional connectivity were observed. Post-hoc analysis by remission status suggested increased raphé functional connectivity with left pregenual anterior cingulate cortex in remitters (n=10) and decreased raphé functional connectivity with left thalamus in non-remitters (n=5), both within 0.025-0.05 Hz. Reducing serotonin function appears to alter coordination of these mood-related networks in specific, low frequency ranges. For examination of effects of reduced serotonin function on mood-related networks, specific low frequency BOLD fMRI signals can identify regions implicated in neural circuitry and may enable clinically-relevant interpretation of functional connectivity measures. The biological significance of these low frequency signals detected in the raphé merits further study.

A considerable body of literature has reported on emotion perception deficits and the relevance of these impairments in persons with depression and bipolar disorder. Fifty-one studies published between 1981-February 2009 were examined regarding emotion perception abilities between patient and control groups, and potential methodological, demographic and clinical moderators. Studies were identified through a computerized literature search of the MEDLINE, PsychINFO, and PubMed databases. The Meta-analysis Of Observational Studies in Epidemiology (MOOSE) standard (Stroup et al., 2000) was followed in the extraction of relevant studies and data. Data on emotion perception, methodology, demographic and clinical characteristics were compiled and analyzed using Comprehensive Meta-Analysis version 2.0 (Biostat, 2005). The meta-analysis revealed a moderate deficit in emotion perception in both bipolar disorder and major depressive disorder, irrespective of task type, diagnosis, age of onset/duration of illness, sex, and hospitalization status. Several factors that moderated the observed impairment include self-reported depression, age at time of testing, and years of education. Emotion perception impairment in bipolar disorder and major depressive disorder represents a moderate and stable deficit that appears to be moderated by a limited number of demographic and clinical factors.

Repetitive transcranial magnetic stimulation (rTMS) has been used to treat postpartum depression (PPD), but its effectiveness is still uncertain. To evaluate the effect of rTMS on depression symptoms and recognition function in patients with PPD, we systematically searched CNKI, WanFang, VIP, EMbase, PubMed, CENTRAL, Web of Science, Physiotherapy Evidence Database from inception to June 2019 for randomized controlled trials (RCT) in English or Chinese concerning PPD in women treated with rTMS. Reference lists were also searched. RCT were included if they compared rTMS with no intervention or sham in patients with PPD. Related data was extracted and risk of bias was assessed by two investigators independently. Of 81 identified studies, 14 met our inclusion criteria (n=884 participants). Compared with control group, rTMS treatment yielded a reduction in Hamilton Depression Rating Scale score and Edinburgh Postnatal Depression Scale score, and improved the cognitive function of patients with PPD. Current evidence of RCT showed that rTMS could improve depression symptoms and cognitive function in patients with PPD.

The aim of this study was to explore outcome to antidepressants profile in melancholic unipolar depression. We conducted a systematic review of electronic databases and meta-analysis of randomized and nonrandomized trials comparing: 1) outcome to antidepressants and placebo between melancholic and non-melancholic depression; 2) outcome to different antidepressant classes in melancholic depression. Two outcomes were considered: clinical remission and response. Significant lower odds of remission to antidepressants in melancholic than in non-melancholic depressions were found. Although no significant differences were observed in the response to antidepressants between both subtypes of depression, those with melancholic features had lower odds of response to placebo. Finally, treatment of melancholic depression with serotonin reuptake inhibitors was associated with lower odds of remission compared with tricyclic antidepressants, and similar outcome compared with venlafaxine. Melancholia seems to show a differential pattern of outcome to antidepressants, which could be clinically valuable for a better implementation of personalized medicine of depression. Due to several limitations, further research is needed to support these preliminary findings.

Late-life depression remains an underdiagnosed clinical entity, mainly because the presence of cognitive impairment in the elderly leads clinicians to suspect dementia rather than depression. Our objective was to analyze the cognitive abilities of elderly depressed patients using the Montreal Cognitive Assessment (MoCA) in relation to the presence or absence of suicidal ideation. The MoCA, Beck Scale of Suicidal Ideation, Hamilton Anxiety Scale, and Hamilton Depression Scale were administered to 72 patients with a recent history of late life depression: 43 with suicidal ideation and 29 non-suicidal controls. The results show that suicidal patients demonstrated significantly worse performance on the MoCA total score and the delayed recall subtest in comparison to non-suicidal controls. In addition, after adjusting for age and depression, poorer performance on the MoCA total score correlated to the presence of suicidal ideation. We found that the MoCA total score is able to predict the presence of suicidal ideation in depressed elderly patients in a fair-to-good manner. As late-life depression is already established as a potential prodrome of dementia, longitudinal follow-up may determine whether depressed individuals with suicidal ideation are at higher risk of converting to dementia.

To systematically examine the effectiveness, tolerability, and safety of brexanolone infusion in treating postpartum depression (PPD).