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Depression Is the Leading Cause of Disability Around the World
Abstract
The proportion of the global population living with depression is estimated to be 322 million people—4.4% of the world’s population—according to a new report, “Depression and Other Common Mental Disorders: Global Health Estimates,” released by the World Health Organization. The report also includes data on anxiety disorders, which affect more than 260 million people—3.6% of the global population. The prevalence of these common mental disorders is increasing, particularly in low- and middle-income countries, with many people experiencing both depression and anxiety disorders simultaneously.
... Depression, often associated with anxiety, is a leading cause of disability around the world (Friedrich, 2017) (Friedrich, 2017) (Friedrich, 2017) (Friedrich, 2017), and the prevalence of these disorders has increased in the United States with the coronavirus pandemic, posing a growing public health concern (COVID-19 Mental Disorders Collaborators, 2021; Ettman et al., 2020a). In addition, there has been a significant impact from COVID-19-related lockdowns on lifestyle habits and mental health (Odone et al., 2020). ...
... Depression, often associated with anxiety, is a leading cause of disability around the world (Friedrich, 2017) (Friedrich, 2017) (Friedrich, 2017) (Friedrich, 2017), and the prevalence of these disorders has increased in the United States with the coronavirus pandemic, posing a growing public health concern (COVID-19 Mental Disorders Collaborators, 2021; Ettman et al., 2020a). In addition, there has been a significant impact from COVID-19-related lockdowns on lifestyle habits and mental health (Odone et al., 2020). ...
... Depression, often associated with anxiety, is a leading cause of disability around the world (Friedrich, 2017) (Friedrich, 2017) (Friedrich, 2017) (Friedrich, 2017), and the prevalence of these disorders has increased in the United States with the coronavirus pandemic, posing a growing public health concern (COVID-19 Mental Disorders Collaborators, 2021; Ettman et al., 2020a). In addition, there has been a significant impact from COVID-19-related lockdowns on lifestyle habits and mental health (Odone et al., 2020). ...
Although we have effective treatments for depression and anxiety, we lack mechanistic understanding or evidence-based strategies to tailor these treatments in the context of major comorbidities such as obesity. The current feasibility study uses functional neuroimaging and biospecimen data to determine if changes in inflammatory markers, fecal short-chain fatty acids, and neural circuit-based targets can predict depression and anxiety outcomes among participants with comorbid obesity. Blood and stool samples and functional magnetic resonance imaging data were obtained at baseline and 2 months, during the parent ENGAGE-2 trial. From 30 participants with both biospecimen and fMRI data, this subsample study explored the relationship among changes in inflammatory markers and fecal short-chain fatty acids and changes in neural targets, and their joint relationship with depression and anxiety symptoms. Bivariate and partial correlation, canonical correlation, and partial least squares analyses were conducted, with adjustments for age, sex, and treatment group. Initial correlation analyses revealed three inflammatory markers (IL-1RA, IL-6, and TNF-α) and five neural targets (in Negative Affect, Positive Affect, and Default Mode Circuits) with significantly associated changes at 2 months. Partial least squares analyses then showed that changes in IL-1RA and TNF-α and changes in three neural targets (in Negative Affect and Positive Affect Circuits) at 2 months were associated with changes in depression and anxiety symptoms at 6 months. This study sheds light on the plausibility of incorporation of inflammatory and gastrointestinal biomarkers with neural targets as predictors of depression and comorbid anxiety outcomes among patients with obesity.
... 9 Major depression, or depression alone, is estimated to be the primary cause of disability, ahead of cardiovascular diseases and cancer itself. 10 It is thus evident that the concomitance of depression and cancer is extremely disabling for patients. ...
... In advanced cancer, a higher threshold may be required, since anhedonia, a major component of the HADS, may be present at the end of life due to increasing physical illness and is not necessarily pathognomonic of a depressive illness in this population. 77 The PHQ-9, which scores each of the nine DSM criteria for major depression (0 ¼ not at all, 3 ¼ nearly every day), is a self-report instrument with established cut-off scores for mild (5)(6)(7)(8)(9), moderate (10)(11)(12)(13)(14), moderately severe (15)(16)(17)(18)(19) and severe depression (20)(21)(22)(23)(24)(25)(26)(27). 78 It has been validated in cancer populations 79 with a threshold score of 10 used to identify cases of clinical depression. ...
... Depression is one of the most common mental illnesses and the influence of depression on society is a serious concern for public health communities. American Psychiatric Association (APA) approximates that 6.9 percent of the population in the United States is currently affected [1], costing the United States $233 billion in 2016 [2]. The World Health Organization (WHO) estimates that depression affects around 322 million people, at a cost of approximately 2.5 trillion dollars worldwide in 2017 [3]. ...
... Depression characterized by a sad, empty, or irritated mood with somatic and cognitive changes can worsen the individuals' capacity to function, limiting performance in everyday duties and social life [5]. Depression is a leading cause of disability around the world [2] and depression can lead to suicide, one of the leading causes of death [6]. Moreover, it is estimated that around two-thirds of depression cases are undiagnosed. ...
Depression is a widespread mental health issue, affecting an estimated 3.8% of the global population. It is also one of the main contributors to disability worldwide. Recently it is becoming popular for individuals to use social media platforms (e.g., Reddit) to express their difficulties and health issues (e.g., depression) and seek support from other users in online communities. It opens great opportunities to automatically identify social media users with depression by parsing millions of posts for potential interventions. Deep learning methods have begun to dominate in the field of machine learning and natural language processing (NLP) because of their ease of use, efficient processing, and state-of-the-art results on many NLP tasks. In this work, we propose a hybrid deep learning model which combines a pretrained sentence BERT (SBERT) and convolutional neural network (CNN) to detect individuals with depression with their Reddit posts. The sentence BERT is used to learn the meaningful representation of semantic information in each post. CNN enables the further transformation of those embeddings and the temporal identification of behavioral patterns of users. We trained and evaluated the model performance to identify Reddit users with depression by utilizing the Self-reported Mental Health Diagnoses (SMHD) data. The hybrid deep learning model achieved an accuracy of 0.86 and an F1 score of 0.86 and outperformed the state-of-the-art documented result (F1 score of 0.79) by other machine learning models in the literature. The results show the feasibility of the hybrid model to identify individuals with depression. Although the hybrid model is validated to detect depression with Reddit posts, it can be easily tuned and applied to other text classification tasks and different clinical applications.
... Major depressive disorder (MDD) is a debilitating mental disorder that affects over 300 million people worldwide and a major contributor to the overall global burden of disease [1]. American Indians suffer a higher rate of depression compared to Caucasians and African-Americans [2,3]. ...
... Here we report findings from the first large-scale longitudinal lipidomic profiling of risk for depressive symptoms in 3721 fasting plasma samples from 1978 American Indians attending two clinical exams (~5. 5 year apart) in the Strong Heart Family Study. Our primary goals are to (1) identify individual lipid species associated with risk of depression beyond known clinical factors, and (2) examine whether longitudinal changes in plasma lipids are associated with changes in depressive symptoms and other psychosomatic traits. ...
Dyslipidemia has been associated with depression, but individual lipid species associated with depression remain largely unknown. The temporal relationship between lipid metabolism and the development of depression also remains to be determined. We studied 3721 fasting plasma samples from 1978 American Indians attending two exams (2001–2003, 2006–2009, mean ~5.5 years apart) in the Strong Heart Family Study. Plasma lipids were repeatedly measured by untargeted liquid chromatography-mass spectrometry (LC-MS). Depressive symptoms were assessed using the 20-item Center for Epidemiologic Studies for Depression (CES-D). Participants at risk for depression were defined as total CES-D score ≥16. Generalized estimating equation (GEE) was used to examine the associations of lipid species with incident or prevalent depression, adjusting for covariates. The associations between changes in lipids and changes in depressive symptoms were additionally adjusted for baseline lipids. We found that lower levels of sphingomyelins and glycerophospholipids and higher level of lysophospholipids were significantly associated with incident and/or prevalent depression. Changes in sphingomyelins, glycerophospholipids, acylcarnitines, fatty acids and triacylglycerols were associated with changes in depressive symptoms and other psychosomatic traits. We also identified differential lipid networks associated with risk of depression. The observed alterations in lipid metabolism may affect depression through increasing the activities of acid sphingomyelinase and phospholipase A2, disturbing neurotransmitters and membrane signaling, enhancing inflammation, oxidative stress, and lipid peroxidation, and/or affecting energy storage in lipid droplets or membrane formation. These findings illuminate the mechanisms through which dyslipidemia may contribute to depression and provide initial evidence for targeting lipid metabolism in developing preventive and therapeutic interventions for depression.
... There is widespread public health concern about depression, especially in developing countries [1]. It is expected that depression will contribute the most to the burden of disease by 2030 [2]. There are several diseases associated with depression, including suicide, obesity, hypertension and stroke, cardiovascular disease, and Alzheimer's disease [2][3][4]. ...
... It is expected that depression will contribute the most to the burden of disease by 2030 [2]. There are several diseases associated with depression, including suicide, obesity, hypertension and stroke, cardiovascular disease, and Alzheimer's disease [2][3][4]. The main known risk factors for depression are gender (most common in women), low education level, low income, smoking, nicotine dependence symptoms, alcohol consumption, body mass index (BMI), waist circumference, triglycerides, glucose, total cholesterol, blood urea nitrogen (BUN), genetic factors, etc. ...
Background
Depression is a psychiatric disorder with global public health concerns. Although a number of risk factors have been identified for depression, there is no clear relationship between biochemistry and depression. In this study, we assessed whether depressive disorders are significantly associated with biochemical indicators.
Methods
Our study included 17,561 adults (age ≥ 18 years) participating in the 2009-2018 National Health and Nutrition Examination Survey (NHANES). The relationship between depression and biochemical and obesity indicators was analyzed by logistic regression.
Results
As compared to the control group, men with depression showed significantly higher levels of gamma-glutamyl transferase, glucose, and triglycerides, and lower levels of albumin and total bilirubin. The depressed group had higher levels of alkaline phosphatase, bicarbonate, and sodium than the control group.
Conclusion
Several biochemical and anthropometric indices were associated with depression in this study. It would be interesting to further analyze their cause-effect relationship.
Limitations
This study is a cross-sectional study. The population is less restricted and does not exclude people with diabetes, pregnancy, etc., so it is less significant for a specific population. Dietary information was not included, as diet plays an important role in many indicators.
... The goal of this study was to investigate whether exposure to different types of racism is associated with poorer mental health, operationalized as depressive symptoms in this study. Considering that depression is the leading cause of disability, globally, linked to several chronic diseases, such as diabetes and cardiovascular disease, and Black Americans have been historically underserved by behavior healthcare, it is critical to gain a better understanding of how social factors such as perceptions of racism affect depressive symptoms among this population [13][14][15][16][17]. An innovation of this study is that it uses data exclusively comprised of college-educated Black Americans. ...
... In line with current research and clinical practice, patients who scored ≥10 were classified as meeting criteria for depression care [37,39]. We also examined severity of depressive symptoms using validated cut points for depression severity: moderate [PHQ score [10][11][12][13][14], moderate-severe [PHQ score [15][16][17][18][19] and severe [PHQ score > 19] [37,40] We also examined the PHQ as a continuous outcome given previous concerns about using thresholds and cut points to identify depressive symptoms in previous research [41,42]. ...
Evidence from previous research indicates that while socioeconomic status (SES) narrows Black-White health inequities, these inequities do not completely disappear, and in some cases, worsen. Why do Black-White health inequities persist, even when controlling for SES? It is critical to examine how perceptions of unfair treatment, especially those that are nuanced and subtle, affect the mental health of Black Americans with greater levels of SES. This study, using a new sample composed exclusively of college-educated Black Americans, investigated whether experiences related to racism were associated with poorer mental health. Qualtrics provided the sample from their nationwide panelists that met the research criteria. Inclusion criteria included the following: (1) self-identified as Black or African American; (2) at least 24 years old; (3) completed a 4-year college degree or higher. The findings from this study indicated that the effects of unfair treatment are significantly associated with poorer mental health. These findings highlight the insidious nature of contemporary racism as the everyday experiences of unfair treatment have a tremendous effect on depressive symptoms among this sample of college-educated Black Americans. Efforts to simply improve SES among historically marginalized groups will not bring about health equity. Findings from this study indicate that there are mental health costs associated with upward social mobility. It is likely that these costs, particularly the experience of everyday unfair treatment, likely diminish the social, economic and health returns on the human capital.
... Depression, one of the main causes of disability worldwide, is associated with a significant impairment of several areas of daily functioning and a poor quality of life, especially in older adults [1]. Furthermore, depression is the most common neuropsychiatric precursor of dementia in late life [2], which ultimately results in a continuously increasing healthcare service request and related economic costs and social burden [3]. ...
Background: Although the antidepressant potential of repetitive transcranial magnetic stimulation (rTMS), the pleiotropic effects in geriatric depression (GD) are poorly investigated. We tested rTMS on depression, cognitive performance, growth/neurotrophic factors, cerebral blood flow (CBF) to transcranial Doppler sonography (TCD), and motor-evoked potentials (MEPs) to TMS in GD. Methods: In this case series study, six drug-resistant subjects (median age 68.0 years) underwent MEPs at baseline and after 3 weeks of 10 Hz rTMS on the left dorsolateral prefrontal cortex. The percentage change of serum nerve growth factor, vascular endothelial growth factor, brain-derived growth factor, insulin-like growth factor-1, and angiogenin was obtained. Assessments were performed at baseline, and at the end of rTMS; psychocognitive tests were also repeated after 1, 3, and 6 months. Results: Chronic cerebrovascular disease was evident in five patients. No adverse/undesirable effect was reported. An improvement in mood was observed after rTMS but not at follow-up. Electrophysiological data to TMS remained unchanged, except for an increase in the right median MEP amplitude. TCD and neurotrophic/growth factors did not change. Conclusions: We were unable to detect a relevant impact of high-frequency rTMS on mood, cognition, cortical microcircuits, neurotrophic/growth factors, and CBF. Cerebrovascular disease and exposure to multiple pharmacological treatments might have contributed.
... Depressive disorders, including major depressive disorder and other forms of unipolar depression, affect over 350 million people worldwide, and are among the most prevalent of illnesses in all of medicine and making depression the leading cause of disability worldwide [29][30][31][32]. ...
Ketamine has emerged as a potential treatment for refractory depression. The clinical use of ketamine, however, has historically been confined to the field of anesthesiology. The majority of ketamine for affective disorder research has targeted psychiatrists. Expanded use of ketamine therapy will involve anesthesiologists, who possess a comprehensive understanding of its pharmacology. In this article, we provide a synthesis of past and current literature to provide a framework of the pharmacology, mechanisms, and clinical considerations for patient safety in the use of ketamine therapy for treatment-resistant depression. We caution support of indefinite administration of ketamine for depression due to lack of data on safety and efficacy with chronic use.
... The latest report of the global burden of disease has estimated that about 55 million individuals are affected by dementia, with growing trends up to 150 million cases estimated by 2050 (GBD 2019Dementia Forecasting Collaborators, 2022. Accompanying these estimates there is a prevalence of about 300 million people living with depression and >260 million people suffering from anxiety disorders worldwide (Friedrich, 2017). Albeit these conditions may be unrelated, there is evidence that sleep and depressive disorders may also represent prodromic symptoms of early onset cognitive impairment (Wennberg et al., 2017). ...
Healthy successful aging with preserved mental and cognitive health is expected to be one of the most important challenges of the growing old population globally. Studies investigating these multi-dimensional aspects of senescence are important to identify potential targets for early prevention. The aim of this study was to investigate the relation between adherence to the Mediterranean diet and mental and cognitive health, quality of life, and successful aging in middle-age and older adults living in Sicily, southern Italy. Data from a sample of 883 individuals was collected including information on food intake (through a 110-item food frequency questionnaire), sleep quality (through the Pittsburgh sleep quality index) depressive symptoms (through the Center for the Epidemiological Studies of Depression Short Form), quality of life (through the Manchester Short Assessment of Quality of Life), cognitive status (through the Short Portable Mental Status Questionnaire), and overall successful aging (through the Successful Aging Index). Multivariate logistic regression analyses were conducted to assess the association between adherence to the Mediterranean diet and the outcomes investigated. After adjustment for potential confounding factors, individuals in the highest quartile of adherence to the Mediterranean diet were less likely to have cognitive impairment (OR = 0.19, 95 % CI: 0.04, 0.86), depressive symptoms (OR = 0.19, 95 % CI: 0.08, 0.46) and more likely to have good quality of life (OR = 14.04, 95 % CI: 6.81, 28.93); significant results were also found for individuals in the third quartile of Mediterranean diet adherence and good sleep quality (OR = 1.65, 95 % CI: 1.03, 2.64). Moreover, individuals in the highest quartile of adherence were more likely to have a successful aging (OR = 1.65, 95 % CI: 1.01, 2.68). In conclusion, this study supports the hypothesis that adherence to the Mediterranean diet provides a positive trajectory toward a healthy successful aging, with major potential benefits toward mental and cognitive health.
... Depression and anxiety are the most common mental health conditions worldwide. 2 In addition to the involvement of our genetic heritage, psychological trauma, early brain lesions or neglect in childhood, and attachment disturbances can be at the origin of emotional disorders. 3 It is therefore interesting to note that the interplay between specific environmental challenges occurring during developmental periods seems to play an important role in the onset of emotional difficulties. ...
... Depression is highly prevalent across the entire lifespan worldwide and has become the leading cause of burden of disability globally (1). Depression is highly debilitating, causing reduced quality of life and severe functional disability, and because of its high rate of recurrence, depression is difficult to treat (2). ...
... Depression is characterized by prolonged sadness, loss of interest, difficulty to experience pleasure, and possibly leads to suicide in extreme cases (Friedrich, 2017). Globally, over 300 million people are suffering from this serious neurological disorder (World Health Organization, 2017). ...
IntroductionDepression is a serious psychiatric disorder characterized by prolonged sadness, loss of interest or pleasure. The dominant alpha peak activity in resting-state EEG is suggested to be an intrinsic neural marker for diagnosis of mental disorders.Methods
To investigate an association between alpha peak activity and depression severity, the present study recorded resting-state EEG (EGI 128 channels, off-line average reference, source reconstruction by a distributed inverse method with the sLORETA normalization, parcellation of 68 Desikan–Killiany regions) from 155 patients with depression (42 males, mean age 35 years) and acquired patients’ scores of Self-Rating Depression Scales. We measured both the alpha peak amplitude that is more related to synchronous neural discharging and the alpha peak frequency that is more associated with brain metabolism.ResultsThe results showed that over widely distributed brain regions, individual patients’ alpha peak amplitudes were negatively correlated with their depressive scores, and individual patients’ alpha peak frequencies were positively correlated with their depressive scores.DiscussionThese results reveal that alpha peak amplitude and frequency are associated with self-rating depressive score in different manners, and the finding suggests the potential of alpha peak activity in resting-state EEG acting as an important neural factor in evaluation of depression severity in supplement to diagnosis.
... Depression is one of the most widespread and enfeebling psychiatric disorders and one of the leading causes of disability and disease burden around the globe (World Health Organization, 2022;Mitchell, 2021;Jelinek et al., 2021;Friedrich, 2017;. Over 350 million individuals globally experience depression, with a rise of around 18% over the past decade (Wang, 2021;Arias-de la Torre et al., 2021;Ormel et al., 2022). ...
Background: Depression is the leading cause of disability worldwide. According to the United Nations health agency, it affects more than 300 million people around the world. Previous studies have suggested different psychological interventions to reduce the severity of depressive symptoms in developing countries. In Pakistan, there has been a lack of research to address this issue and introduce measures to overcome this gap. This double-blind, parallel randomized controlled trial aimed to evaluate the effect of Metacognitive Training for Depression (D-MCT) on the severity of depressive symptoms in comparison to treatment as usual (TAU). Methods: This was a parallel, two-arm, double-blind, feasibility, randomized controlled trial with a pre-post design. Sixty participants (experimental group, n = 30, and the control group, n = 30) were recruited from the departments of psychiatry at various hospitals across Rawalpindi and Islamabad from July to November 2022. The efficacy of D-MCT in reducing depressive symptoms, metacognition, mental health, and quality of life was investigated using a two-way factorial ANOVA. Results: The findings of this study showed that, in comparison to treatment as usual, D-MCT was more effective in reducing depressive symptom severity and maladaptive metacognitions in patients with depression. On the other hand, results also showed that D-MCT was significantly effective in enhancing quality of life and mental health in depression patients. Conclusions: D-MCT intervention has been introduced for the first time in Pakistan for patients with depression to improve depression treatment in Pakistan. This study would open up a new avenue for professionals to improve depression through this new intervention.
... Low back pain has been globally ranked the highest cause of disability and years lived with disability among various diseases [1]. Depression has similarly been documented as a leading cause of global health-related burden and disability [2]. ...
Low back pain and depression have been globally recognized as key public health problems and they are considered co-morbid conditions. This study explores both cross-sectional and longitudinal comorbid associations between back pain and major depression in the adult population in the United States. We used data from the Midlife in the United States survey (MIDUS), linking MIDUS II and III with a sample size of 2358. Logistic regression and Poisson regression models were used. The cross-sectional analysis showed significant associations between back pain and major depression. The longitudinal analysis indicated that back pain at baseline was prospectively associated with major depression at follow-up (PR 1.96, CI: 1.41, 2.74), controlling for health behavioral and demographic variables. Major depression at baseline was also prospectively associated with back pain at follow-up (PR 1.48, CI: 1.04, 2.13), controlling for a set of related confounders. These findings of a bidirectional comorbid association fill a gap in the current understanding of these comorbid conditions and could have clinical implications for the management and prevention of both depression and low back pain.
... As depression is the foremost cause of burden worldwide; the lack of enthusiasm, difficulty with life exposure, and daily life activities are badly affected, stimulating suicide in extreme cases (Friedrich, 2017). The risk factors of suicidality were found to be strongly associated with depressive disorder, mood disorders, hopelessness and stressful life events, etc. (Serafini et al., 2012;Turecki et al., 2019). ...
In recent decades, the primary intention of neuroscientists and psychiatrists been to evaluate the connectivity between brain regions and psychiatric disorders. The amygdala has central immersion in memory alliance, stress response, emotional perception, and automatic responses to emotional stimuli. This paper uses a meta-analysis approach to establish the relationship between structural resting state and functional amygdala connectivity with depression and suicide ideation with suicide behavior. In addition, this study explores the moderating effect of patients' demographic characteristics (gender and age) based on an effect meta-analysis of 30 studies. The results show that structural amygdala connectivity is positively related to the instability of depression, while for resting and task functional connectivity amygdala shows a significant negative connection with depression. Furthermore, the amygdala showed partial activation for non-suicide self-injuries and suicide ideation. From structural and functional magnetic imaging, the findings also support the moderating effect of the age of the participants on amygdala connectivity with psychiatric conditions. Generally, amygdala connectivity with psychiatric disorders was not significantly moderate with the role of gender, besides, this study enhances existing hypothetical review articles and further confirms the connectivity of the psychological condition with the amygdala region. It concludes that the amygdala plays a vital role in regulating and responding to emotions.
... Background Suicide is a public health concern and the leading case of disability worldwide [1]. According to the World Health Organization (WHO) latest estimates, 703 000 people die by suicide every year globally [2]. ...
Background
Despite widespread acknowledgment of the impact of stressful life events on suicide risk, the understanding of the psychological mechanisms underlying the relationship between stressful life events and suicide risk in major depressive disorder (MDD) remain unclear. This study aim to examine whether the distress tolerance mediates the relationship between the stressful life events and suicide risk in patients with MDD.
Methods
A cross-sectional study was carried out among 125 Chinese patients with MDD, mean age was 27.05 (SD=0.68) and 68.8% were females. The 17-item Hamilton Depression Rating scale (HAMD-17), the validated Chinese version of the Mini International Neuropsychiatric Interview (MINI) suicide module, Life Events Scale (LES) and Distress Tolerance Scale (DTS) were utilized to evaluate depressive symptoms, stressful life events, levels of distress tolerance, and suicide risk, respectively. Mediation analyses was used to test the mediation effect of distress tolerance on the relationship between stressful life events and suicide risk.
Results
The ratio of suicide risk in patients with MDD was 75.2%. Pearson correlation analysis showed that stressful life events were positively correlated with suicide risk(r=0.182, p<0.05). Stressful life events(r=-0.323, p<0.01) and suicide risk(r=-0.354, p<0.01) were negatively correlated with distress tolerance. Mediation analyses showed that the direct path from stressful life events to suicide risk was not significant (B= 0.012, 95% confidence interval (CI) [-0.017, 0.042]). Stressful life events affected suicide risk indirectly through distress tolerance (B= 0.018, 95% CI [0.007, 0.031]), and the mediating effect accounted for 60.0% of the total effect.
Conclusion
Distress tolerance completely played a mediating role between stressful life events and suicide risk. Further suicide prevention and intervention strategies should focus on increasing levels of distress tolerance in patients with MDD.
... Major depressive disorder (MDD) is a leading cause of disability worldwide [1]. The proportion of people living with depression is estimated to be 4.4% (322 million people) of the world's population [2]. Although depression can affect anyone at any point in their lives, it is more common in women than men [3]. ...
The pathophysiology of major depressive disorder (MDD) is diverse and multi-factorial, yet treatment strategies remain limited. While women are twice as likely to develop the disorder as men, many animal model studies of antidepressant response rely solely on male subjects. The endocannabinoid system has been linked to depression in clinical and pre-clinical studies. Cannabidiolic Acid-Methyl Ester (CBDA-ME, EPM-301) demonstrated anti-depressive-like effects in male rats. Here, we explored acute effects of CBDA-ME and some possible mediating mechanisms, using a depressive-like genetic animal model, the Wistar–Kyoto (WKY) rat. In Experiment 1, Female WKY rats underwent the Forced swim test (FST) following acute CBDA-ME oral ingestion (1/5/10 mg/kg). In Experiment 2, Male and female WKY rats underwent the FST after injection of CB1 (AM-251) and CB2 (AM-630) receptor antagonists 30 min before acute CBDA-ME ingestion (1 mg/kg, males; 5 mg/kg, females). Serum levels of Brain-Derived Neurotrophic Factor (BDNF), numerous endocannabinoids and hippocampal Fatty Acid Amide Hydrolase (FAAH) levels were assessed. Results indicate that females required higher doses of CBDA-ME (5 and 10 mg/kg) to induce an anti-depressive-like effect in the FST. AM-630 blocked the antidepressant-like effect in females, but not in males. The effect of CBDA-ME in females was accompanied by elevated serum BDNF and some endocannabinoids and low hippocampal expression of FAAH. This study shows a sexually diverse behavioral anti-depressive response to CBDA-ME and possible underlying mechanisms in females, supporting its potential use for treating MDD and related disorders.
... Mood disorder [major depressive disorder (MDD) and bipolar disorder (BD)] is a heterogeneous and complex psychiatric condition. It is a major public health issue, ranking as the leading cause of disability worldwide, and the burden of mood disorders continues to grow despite the availability of validated interventions (1). MDD and BD both exhibit similar severe depressive symptoms (major depression, MD) (2). ...
... Major depressive disorder (MDD) is a growing and debilitating condition affecting among 2 to 21% of people with an estimated lifetime prevalence, and representing the leading cause of disability worldwide [1,2]. Clinically, MDD is characterized by the cooccurrence of either depressed mood or anhedonia (core symptoms) with at least four somatic and non-somatic items with detrimental consequences for the individual (i.e., sleep alterations, appetite changes, pain, feeling of worthlessness, suicidal ideation, and so on) [3]. ...
Major depressive disorder (MDD) is a complex psychiatric disorder that, presented alone or with other comorbidities, requires different adjustments of antidepressant treatments. Some investiga-tions have demonstrated that psychoactive drugs, such as serotonin and norepinephrine reuptake inhibitors (SNRIs), can exert more effective and faster antidepressant effects than other common medications used, such as serotonin selective reuptake inhibitors (SSRIs), although these differ-ences are still controversial. During the last five years, the SNRI duloxetine has shown favorable results in clinical practice for the treatment of MDD, anxiety, and fibromyalgia. Through an online self-completed survey, in the present article, we collected information from 163 psychiatrists re-garding the use of duloxetine and its comparison with other psychiatric drugs, concerning psy-chiatrists’ knowledge and experience, as well as patients’ preferences, symptoms, and well-being. We discussed and contrasted physicians’ reports and the scientific literature, finding satisfactory concordances, and finally concluded that there is agreement regarding the use of duloxetine, not only due to its tolerability and effectiveness but also due to the wide variety of situations in which it can be used (e.g., somatic symptoms in fibromyalgia, diabetes) as it relieves neuropathic pain as well.
... Depression is a leading cause of disability and is a significant contributor to the overall global burden of disease [3,17]. Globally, more than 264 million people of all ages suffer from depression [49]. ...
Background
To date, evidence remained inconclusive explaining rural-urban and male-female differential in depression. Unlike other previous research on the association of several risk factors with depressive symptoms among the elderly, this study focussed on the socio-economic status-related inequality in the prevalence of depression among the elderly along with focussing urban-rural and male-female gradients of depression among the elderly.
Methods
This study used data from Longitudinal Ageing Study in India (LASI) Wave-I, 2017-18, survey. The outcome variable for this study was self-reported depression. Bivariate analysis was used to understand the prevalence by sociodemographic clusters. Fairlie decomposition analysis has been done to measures rural-urban inequalities for depression among older men and women.
Results
Results found that around 22 percent of urban elderly and 17 percent of rural elderly reported depression. A higher proportion of female elderly (22.6% vs. 18.4%) reported depression than male elderly. Almost one in every five elderly (20.6%) reported depression in India. The results found that a higher percentage of women in rural and urban areas reported depression than their male counterparts. While examining SES-related inequality in the prevalence of depression, education was a significant factor explaining the SES-related inequality in the prevalence of depression among female elderly and not in male elderly.
Conclusion
Given the large proportion of elderly reporting depression, this study highlights the need for improving health care services among the elderly. The increasing burden of depression in specific sub-populations also highlights the importance of understanding the broader consequences of depression among rural and female elderly.
Keywords
Depression; urban-rural differential; Gender differential; Decomposition analysis; India
... often occurring together with cardiovascular disease, diabetes, and autoimmune diseases (2,3). MDD imposes a significant emotional and socioeconomic burden, and The World Health Organization estimates that 322 million people around the world from depression, which is about 4.4% of the global population (4). ...
Objective
This study investigated the association between inflammatory cytokines and major depressive disorder.Methods
Plasma biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Statistical analysis of baseline biomarkers in the major depression disorder (MDD) group and healthy controls (HC) group, and differences in biomarkers before and after treatment. Spearman analysis was performed to correlate baseline and after treatment MDD biomarkers with the 17-item Hamilton Depression Rating Scale (HAMD-17) total scores. Receiver operator characteristic (ROC) curves were analyzed for the effect of biomarkers on MDD and HC classification and diagnosis.ResultsTumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were significantly higher in the MDD group than in the HC group, while high mobility group protein 1 (HMGB1) levels were significantly lower in the MDD group. The AUCs for HMGB1, TNF-α, and IL-6 were 0.375, 0.733, and 0.783, respectively, according to the ROC curves. MDD patients with brain-derived neurotrophic factor precursor (proBDNF) levels were positively correlated with total HAMD-17 scores. The levels of proBDNF levels were positively correlated with the total HAMD-17 score in male MDD patients, and brain-derived neurotrophic factor (BDNF) and interleukin 18 (IL-18) levels were negatively correlated with the total HAMD-17 score in female MDD patients.Conclusion
Inflammatory cytokines are associated with the severity of MDD, and TNF-α and IL-6 have the potential as objective biomarkers to aid in the diagnosis of MDD.
... Major depressive disorder (MDD) is a leading cause of disability worldwide and is increasing in prevalence (Friedrich, 2017). Unfortunately, little progress has been made in identifying biological indicators of treatment response, and much intervention is via trial-and-error. ...
Transcranial magnetic stimulation (TMS) can be useful for therapeutic purposes for a
variety of clinical conditions. Numerous studies have indicated the potential of this non-
invasive brain stimulation technique to recover brain function and to study physiological
mechanisms. Following this line, the articles contemplated in this Research Topic show
that this field of knowledge is rapidly expanding and considerable advances have been
made in the last few years. There are clinical protocols already approved for Depression
(and anxiety comorbid with major depressive disorder), Obsessive compulsive Disorder
(OCD), migraine headache with aura, and smoking cessation treatment but many
studies are concentrating their efforts on extending its application to other diseases,
e.g., as a treatment adjuvant. In this Research Topic we have the example of using
TMS for pain, post-stroke depression, or smoking cessation, but other diseases/injuries
of the central nervous system need attention (e.g., tinnitus or the surprising epilepsy).
Further, the potential of TMS in health is being explored, in particular regarding
memory enhancement or the mapping of motor control regions, which might also have
implications for several diseases.
TMS is a non-invasive brain stimulation technique that can be used for modulating
brain activation or to study connectivity between brain regions. It has proven efficacy
against neurological and neuropsychiatric illnesses but the response to this stimulation
is still highly variable. Research works devoted to studying the response variability to
TMS, as well as large-scale studies demonstrating its efficacy in different sub-populations, are therefore of utmost importance. In this editorial, we summarize the main findings
and viewpoints detailed within each of the 12 contributing articles using TMS for health and/or disease applications
... Multiple studies have investigated the association between single diseases and disability [16][17][18] ; however, recent clinical guidelines have advocated the shifting of research and clinical practice from single diseases to multimorbidity. 19 20 Rather than merely counting the number of chronic diseases, an investigation of the impact of different combinations of chronic health diseases on health-related outcomes such as disability have been recommended. ...
Objective
This study aims to identify the unique multimorbidity combinations (MMCs) and their associations with the functional disability of Indian older adults. Moreover, the population attributable fractions (PAFs) were calculated to assess the potential impact of additional diseases in the nested groups on disability.
Design
A cross-sectional data were analysed in this study.
Setting and participants
The present study uses data from the first wave of the Longitudinal Ageing Study in India (2017–2018). The sample for the study consists of 27 753 aged 60 years and over.
Primary and secondary outcome measures
The primary outcome variable was functional disability, measured by the combined activities of daily living (ADL)-instrumental activities of daily living (IADL) index.
Results
Out of 197 uniquely identified MMCs, the combination of hypertension and high depressive symptoms (HDS) was the most prevalent (10.3%). Overall, all MMCs were associated with increased functional limitation. Specifically, the combination of hypertension, arthritis and HDS was associated with greater ADL-IADL disability than any other MMC. The addition of HDS in group 3 (hypertension and arthritis) (incidence rate ratios (IRR)=1.44; 95% CI 1.26 to 1.64) and the addition of arthritis in group 1 (hypertension, HDS) (IRR=1.48; 95% CI 1.28 to 1.71) and group 2 (hypertension, diabetes) (IRR=1.49; 95% CI 1.22 to 1.82) significantly increases the rates of ADL-IADL disability. The estimated PAFs of the group 1 (hypertension and HDS), group 3 (hypertension and arthritis) and group 4 (arthritis and HDS) for ADL-IADL disability were 22.5% (19.2–25.5), 21.6% (18.7–24.4) and 23.5% (20.6–26.3), respectively.
Conclusion
The findings from this study underscore the importance of addressing the morbidity combinations which are more disabling than the others in older adults. Understanding the somatic and psychological relevance of the morbidities in functional health is necessary and can help reduce disabilities among older adults.
... Our findings, overall, provide a critical context for prior research showing that chronic NCDs, notably CVDs, have become more prevalent among Indian older adults than in the general population, accounting for 28.1% of all deaths and 14.1% of all disability-adjusted life years (DALYs) [97]. Thus, while we focus on illnesses and physical disabilities, we must also be aware of mental health issues, particularly depression, which may become the leading cause of disability worldwide by 2030 [98]. The findings of our study must be interpreted within the context of several limitations. ...
... Due to the combined effect of prolonged life span and declining fertility rates, aging has become a global phenomenon and is expected to continue. In China, the world's most populous nation, the proportion of people aged 65 years is expected to triple, from 9.6 % in 2015 to 27.6 % in 2050 (Friedrich, 2017). Depression is a serious psychological problem and a public health concern among older adults (Allan et al., 2014), and an estimated 7 % of the world's older adults likely suffer from depression, accounting for 5.7 % of the total disabilities (Disability-Adjusted Life Years/DALYs) (WHO, 2017). ...
Background:
Depression harms older adults' physical health and quality of life, especially for those with disabilities. This study aims to investigate the epidemiological characteristics of depressive symptoms in older adults and influencing factors involving neuroticism in China.
Methods:
A multistage random sampling method was adopted to recruit older adults. The authors conducted a multiple mediating analysis to explore how overall family health and perceived social support affect the relationship between neuroticism and depressive symptoms in older adults.
Results:
A total of 1122 older adults were included in this study, and 529 individuals reported suffering from depressive symptoms (47.1 %). Mediation analysis results indicated that neuroticism had a direct predictive effect on depressive symptoms in older adults. Family health and perceived social support partly mediated the relationship between neuroticism and depressive symptoms in older adults. Moreover, depressive symptoms in older adults with high neuroticism was directly affected by decreasing family health and indirectly and cumulatively aggravated by the mediation of lower perceived social support.
Limitations:
The cross-sectional study design limits the conclusion about causation and directionality.
Conclusions:
Family health and perceived social support can prevent depressive symptoms in older adults with high neuroticism.
... Depression is a leading cause of morbidity and reduced quality of life globally (Friedrich, 2017). In the U.S., it is estimated that depression cost an estimated $326 billion annually in healthcare fees, absenteeism (days of missed work due), and presenteeism (lowered productivity while at work) in 2018 (Greenberg et al., 2021). ...
The COVID-19 pandemic has led to a worsening of mental health among U.S. adults. However, no review to date has synthesized the overall prevalence of population depressive symptoms in the U.S. over the COVID-19 pandemic. We aimed to document the population prevalence of depressive symptoms and psychological distress across time since the start of the COVID-19 pandemic, both to identify patterns that emerged in the literature and to assess the data sources, methods, sampling, and measurement used to examine population mental health during the pandemic. In a systematic review of the peer review literature, we identified 49 articles reporting 88 prevalence points of depressive symptoms and related constructs in nationally representative samples of U.S. adults from March 2020 to June 2021. First, we found that the average prevalence of poor mental health across studies was 12.9% for severe depression, 26.0% for at least moderate depression, and 36.0% for at least mild depression. Second, we found that women reported significantly higher prevalence of probable depression than men in 63% of studies that reported depression levels by gender and that results on statistically significant differences between racial and ethnic groups were mixed. Third, we found that the 49 articles published were based on 12 studies; the most common sources were the Household Pulse Survey (n = 15, 31%), the AmeriSpeak panel (n = 8, 16%), the Qualtrics panel (n = 8, 16%), and the Understanding America Study (n = 5, 10%). Prevalence estimates varied based on mental health screening instruments and cutoffs used. The most commonly used instruments were the Patient Health Questionnaire (PHQ) (n = 36, 73%) and the Kessler (n = 8, 16%) series. While the prevalence of population depression varied over time depending on the survey instruments, severity, and constructs reported, the overall prevalence of depression remained high from March 2020 through June 2021 across instruments and severity. Understanding the scope of population mental health can help policymakers and providers address and prepare to meet the ongoing and future mental health needs of U.S. adults in the post-COVID-19 context and beyond.
... 31,32 This is salient since depression is considered one of the leading causes of disability across the world, with even subclinical symptoms negatively impacting physical health, quality of life, and mental health. [33][34][35][36] It is also important to note that discrimination impacts help-seeking behaviors, including mistrust of the healthcare system. This has been found to be especially prevalent since COVID-19 among POC, thereby generating exceptional vulnerabilities to negative health outcomes. ...
Background
Discrimination is a pervasive societal issue that monumentally impacts people of color (POC). Many Black, Asian, and Hispanic/Latinx individuals report experiencing race-based discrimination in their lifetime. Discrimination has previously been linked to adverse health outcomes among POC, including stress, depressive, and posttraumatic stress disorder symptoms. These health disparities are posited to have become exacerbated by COVID-19 and the racial awakening of 2020. The current study examined the short- and long-term effects of discrimination on stress, depression, and oppression-based trauma among POC.
Methods
Participants were (n = 398) who identified as Black, Indigenous, Hispanic/Latinx, and Asian completed an online self-report survey assessing discrimination, depression, stress, and oppression-based trauma collected at 3 time points: (T1) beginning of the COVID-19 pandemic (May 2020), (T2) 6 weeks later during the racial awakening of 2020 (June 2020), (T3) one year later (June 2021).
Results
Significant positive paths were revealed from T1 discrimination to T2 depression, T2 stress, and T3 oppression-based trauma. The association between T1 discrimination and T3 oppression-based trauma was partially mediated by T2 depression, but not by stress; total and total indirect effects remained significant. The final model accounted for a significant proportion of the variance in T3 oppression-based trauma, T2 depression, and T2 stress.
Conclusion
Findings are consistent with prior research linking discriminatory experiences with mental health symptomatology and provide evidence that race-based discrimination poses harmful short-and long-term mental health consequences. Further research is necessary to better understand oppression-based trauma to improve the accuracy of clinical diagnosis and treatment of POC.
... Major depression disorder (MDD) is the leading cause of disability around the world (Friedrich, 2017). Although there are many pharmacological options available, one third to half of patients are resistant to antidepressants (Rush et al., 2006;Souery et al., 2007). ...
Background:
In 2008, the U.S. FDA approved rTMS as a treatment against medication-resistant depression. However, real-world rTMS outcomes remain understudied. This study investigates how rTMS for depression is delivered in routine clinical practice in France, and measures its effectiveness as well as its moderators.
Methods:
Five centers provided retrospective data on patients who were treated with rTMS for treatment-resistant depression from January 2015 to December 2020. Patients were assessed twice using a hetero-questionnaire, with baseline and immediate post-treatment assessments. We conducted univariate analyses to study which factors were significantly associated with rTMS effectiveness. We then included age, gender, and significant factors in a multivariate model.
Results:
We collected data from 435 patients with a mean age of 51.27 (14.91): 66 % were female, and 26 % suffered from bipolar depression. Stimulation was delivered using four different stimulation parameters: 1 Hz (7 % of the individuals), 10 Hz (43 %), 20 Hz (12 %), and 50 Hz (intermittent Theta Burst Stimulation, iTBS) (38 %). The mean improvement of depressive symptoms was 33 % (p < 0.001, effect-size: 0.79). Response and remission rates were of 31 % and 22.8 %, respectively. In the multivariate analysis, improvement in depressive symptoms was associated with higher baseline symptoms.
Conclusion:
This is one of the largest studies that investigates, with careful clinician-rated scales by trained psychiatrists, the effect of rTMS in naturalistic settings. Repetitive TMS appears to be effective in routine clinical practice, although its efficacy could be improved by analyzing predictors of response, as well as personalized targeting of specific brain areas.
... Common mental health problems such as depression and the anxiety disorders are predictive of disability [1,2], impaired quality of life [3], and considerable societal costs [4,5]. In many healthcare systems, primary care has a responsibility to treat patients with mild to moderate mental health problems, while maintaining high quality care and short waiting times [6]. ...
Background
In many health care systems, primary care is tasked with offering psychological treatment for common mental disorders. Resources are often limited, which complicates widespread dissemination of traditional psychological treatments. Stepped care models where the less resource-intensive interventions are delivered first, can be employed, but often do not eliminate the need for a thorough diagnostic assessment, which can be time-consuming, has the potential to bottleneck patient intake, and can add to waiting times. Novel low-threshold formats are needed to improve access to mental health care in the primary care setting.
Methods
This was a single-group prospective cohort study (N = 91). We assessed the feasibility of a video-delivered course as a first-line intervention for patients seeking help for mental health problems at a primary care center. The course had a transdiagnostic approach, suitable for both depression and anxiety disorders, and was based on cognitive behavioral techniques. Patients in need of psychosocial assessment, which usually entailed a four- to six-week wait, were referred by physicians or triage nurses. Study participants could start within a week, without the need for conventional diagnostic assessment, and were informed that they would be offered assessment after the course if needed. Key feasibility outcomes included participant satisfaction, attendance rates, the proportion of participants in need of additional clinical intervention after the course, and the rate of clinically significant improvement in anxiety and depression symptoms.
Results
Participants scored a mean of 21.8 (SD = 4.0, 9–32, n = 86) on the Client Satisfaction Questionnaire-8; just below our target of 22. The mean attendance rate was 5.0/6 lectures (SD = 1.6, range: 0–6, n = 91). Forty-six percent (37/81) reported experiencing no need of further clinical intervention after the course. The rate of clinically significant improvement was 59% (27/46) for anxiety and 48% (22/46) for depression. No serious adverse event was reported.
Conclusions
Delivering a low-threshold online video-delivered mental health course in primary care appears to be feasible. Adjustments to further improve patient satisfaction are warranted, such as offering the choice of participating online or face-to-face.
Trial Registration
(ClinicalTrials.gov NCT04522713) August 21, 2020.
Objective:
To evaluate the effect of psychotherapies on ego defense mechanisms and the reduction of depressive symptoms in a 12-month follow-up period.
Methods:
This longitudinal and quasi-experimental study nested within a randomized clinical trial included a clinical sample of adults (18-60 years) diagnosed with major depressive disorder using the Mini-International Neuropsychiatric Interview. Two models of psychotherapy were used: Supportive Expressive Dynamic Psychotherapy (SEDP) and Cognitive Behavioral Therapy (CBT). Defense Style Questionnaire 40 was used to analyze defense mechanisms and the Beck Depression Inventory was used to measure the depressive symptoms.
Results:
The total sample comprised 195 patients (113 SEDP and 82 CBT), with the mean age was 35.63 (11.44) years. After adjustments, increased mature defenses was significantly associated with reduced depressive symptoms at all follow-up times (p < 0.001) and the decrease in immature defenses was significantly associated with the reduction of depressive symptoms at all follow-up times (p < 0.001). While neurotic defenses were not associated with a reduction in depressive symptoms at any time of follow-up (p > 0.05).
Conclusion:
Both models of psychotherapy were effective in increasing mature defenses and decreasing immature ones, as well as decreasing depressive symptoms at all evaluation times. With this, it is understood that a greater understanding of these interactions will allow a more adequate diagnostic and prognostic evaluation and the design of useful strategies that adapt to the patient's reality.
Background:
Relevant studies have shown that gut microbiome plays an important role in the occurrence, development and treatment of major depressive disorder (MDD). Many studies have also shown that, selective serotonin reuptake inhibitors (SSRIs) antidepressants can improve the symptoms of depression by changing the distribution of gut microbiome, Here we investigated whether a distinct gut microbiome was associated with Major depressive disorder (MDD), and how it was modulated by SSRIs antidepressants.
Method:
In this study, we analyzed the gut microbiome composition of 62 patients with first-episode MDD and 41 matched healthy controls, before SSRIs antidepressants treatment, using 16S rRNA gene sequencing. MDD patients characterized as treatment-resistant (TR) or responders (R) to antidepressants by score reduction rate were ≥50 % after SSRIs antidepressants treatment for eight weeks.
Results:
LDA effect size (LEfSe) analysis found that there were 50 different bacterial groups among the three groups, of which 19 genera were mainly at the genus level. The relative abundance of 12 genera increased in the HCs group, 5 genera in the R group increased in relative abundance, and 2 genera in the TR group increased in relative abundance. The correlation analysis of 19 bacterial genera and the score reduction rate showed that Blautia, Bifidobacterium and Coprococcus with higher relative abundance in the treatment effective group were related to the efficacy of SSRIs antidepressants.
Conclusions:
Patients with MDD have a distinct gut microbiome that changes after SSRIs antidepressants treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients with MDD.
Major depressive disorder is a leading cause of disability worldwide; therefore, effective treatment options are crucial. However, due to the highly heterogeneous nature of depression, a comprehensive understanding of the disease is lacking and treatment options are limited. Whilst the pathology of depression is complex, neuroendocrine–immune interactions have consistently been linked to the disease. Hypothalamic–pituitary–adrenal (HPA) axis dysfunction has been identified as one of the main contributing factors, impacting 50–80% of patients with depression. The ‘glucocorticoid resistance model’ provided the first explanations of this dysfunction, suggesting reduced function of the glucocorticoid receptor; thus, glucocorticoid resistance, seen in some MDD patients, allows pro-inflammatory pathways to evade normal feedback inhibition by glucocorticoids. However, recent research has suggested alternative mechanisms, which identify cortisol as a pro-inflammatory mediator of stress reactions. Additional research into glucocorticoid dysfunction in MDD has also found single nucleotide polymorphisms in FKBP5, a key regulator of glucocorticoid receptor function, to play a role in HPA axis dysfunction and thus confer risk of depression. These effects are mediated by gene–environment interactions, specifically adverse early-life events. Whilst the underlying epigenetic mechanisms are not fully understood, increased FKBP5 mRNA expression and altered FKBP5 methylation are thought to play a role in impaired HPA axis function. An increased understanding of the interactions involving FKBP5 may in turn increase understanding of the pathophysiology of depression. This will allow identification of high-risk individuals who have past adverse early-life experiences. In turn, this may also impact the course of future antidepressant treatment and development.
Background:
While implicit distraction could ameliorate negative feelings in patients with major depressive disorders (MDD), it remains unclear whether patients could benefit from explicit, voluntary distraction. Meanwhile, though the dorsolateral prefrontal cortex (DLPFC) is established as a crucial brain region involved in attentional control, the causal relationship between the DLPFC and voluntary distraction is unexplored in patients.
Methods:
Combing explicit distraction and transcranial magnetic stimulation (TMS), this study investigated whether TMS-activated DLPFC facilitates voluntary distraction in MDD patients. Eighty patients diagnosed with current MDD underwent either active (n = 40) or sham (n = 40) TMS sessions, followed by receiving negative social feedback from other patients, during which they were requied to use distraction strategy to down-regulate their painful feelings. Electroencephalogram was recorded during the task.
Results:
Both the subjective emotional rating and the amplitude of late positive potential showed that depressed patients successfully down-regulate their negative emotions via voluntary distraction, and the TMS-activated left DLPFC produced a larger benefit of emotion regulation compared to the sham TMS group. Results also revealed that while emotion regulation effect was negatively associated with depressive symptoms in the sham TMS group, this correlation was largely diminished when patients' left DLPFC was activated by TMS during the voluntary distraction.
Conclusions:
These findings demonstrated that distraction is valuable for emotion regulation in MDD patients and they could be beneficial in voluntary distraction by activating their left DLPFC using neural modulation techniques. This study has valuable implications for clinical treatement of emotional dysregulation in MDD patients.
Background:
Chronic unpredictable mild stress (CUMS) can induce depressive behaviours and alter the composition of the gut microbiome. Although modulating gut microbiota can improve depression-like behaviour in rats, the mechanism of action is unclear. Additionally, gut microbiota can affect brain function through the neuroendocrine pathway. This pathway may function by regulating the secretion of neurotransmitters such as tryptophan (TRP). Metabolites of TRP, such as 5-hydroxytryptamine (5-HT) and kynurenine (KYN), are related to the pathophysiological process of depression. Indoleamine-2, 3-dioxygenase-1 (IDO1) and Tryptophan hydroxylase 2 (TPH2) are the key rate-limiting enzymes in TRP metabolism and play an important role in KYN and 5-HT metabolism.
Methods:
Rats were subjected to four weeks of CUMS and given rifaximin150 mg/kg by oral gavage daily. After modelling, we investigated the rat's behaviours, composition of the faecal microbiome, neurotransmitter metabolism and key metabolic enzymes of the TRP pathway in the hippocampus (HIP).
Results:
Rifaximin administration improved depressive behaviour in rats, corrected intestinal microbiota disorders and HIP TRP metabolism and regulated the expression of IDO1 and TPH2 in the HIP.
Conclusions:
Rifaximin improves depression-like behaviour in CUMS rats by influencing the gut microbiota and tryptophan metabolism.
Anhedonia, a lack of pleasure in things an individual once enjoyed, and rumination, the process of perseverative and repetitive attention to specific thoughts, are hallmark features of depression. Though these both contribute to the same debilitating disorder, they have often been studied independently and through different theoretical lenses (e.g., biological vs. cognitive). Cognitive theories and research on rumination have largely focused on understanding negative affect in depression with much less focus on the etiology and maintenance of anhedonia. In this paper, we argue that by examining the relation between cognitive constructs and deficits in positive affect, we may better understand anhedonia in depression thereby improving prevention and intervention efforts. We review the extant literature on cognitive deficits in depression and discuss how these dysfunctions may not only lead to sustained negative affect but, importantly, interfere with an ability to attend to social and environmental cues that could restore positive affect. Specifically, we discuss how rumination is associated to deficits in working memory and propose that these deficits in working memory may contribute to anhedonia in depression. We further argue that analytical approaches such as computational modeling are needed to study these questions and, finally, discuss implications for treatment.
The majority of children with maltreatment histories do not go on to develop depression in their adolescent and adult years. These individuals are often identified as being "resilient", but this characterization may conceal difficulties that individuals with maltreatment histories might face in their interpersonal relationships, substance use, physical health, and/or socioeconomic outcomes in their later lives. This study examined how adolescents with maltreatment histories who exhibit low levels of depression function in other domains during their adult years. Longitudinal trajectories of depression (across ages 13-32) in individuals with (n = 3,809) and without (n = 8,249) maltreatment histories were modeled in the National Longitudinal Study of Adolescent to Adult Health. The same "Low," "increasing," and "declining" depression trajectories in both individuals with and without maltreatment histories were identified. Youths with maltreatment histories in the "low" depression trajectory reported lower romantic relationship satisfaction, more exposure to intimate partner and sexual violence, more alcohol abuse/dependency, and poorer general physical health compared to individuals without maltreatment histories in the same "low" depression trajectory in adulthood. Findings add further caution against labeling individuals as "resilient" based on a just single domain of functioning (low depression), as childhood maltreatment has harmful effects on a broad spectrum of functional domains.
In this study, the effects of antidepressants on large-scale brain networks and the neural basis of individual differences in response were explored. A total of 41 patients with major depressive disorder (MDD) and 42 matched healthy controls (HCs) were scanned by resting-state functional magnetic resonance imaging separately at baseline and after a 12-week follow-up. The patients with MDD received escitalopram for 12 weeks. After treatment, patients were classified into those with MDD in remission [MDDr, endpoint 17-item Hamilton Depression Rating Scale (HAMD) total score ≤7] and those in nonremission (MDDnr). The human Brainnetome Atlas was used to define large-scale networks and compute within- and between-network resting-state functional connectivity (rsFC). Results showed the decreased subcortical network (SCN)-ventral attention network (VAN) connectivity at baseline increased in patients with MDD after 12-week treatment, and it was comparable with that of HCs. This change was only observed in patients with MDDr. However, the decreased within-network rsFC in SCN and default mode network (DMN) persisted in all patients with MDD, including those with MDDr and MDDnr, after treatment. The strength of SCN-VAN connectivity at baseline was significantly negatively correlated with the reduction rate of HAMD score in all patients with MDD. Thus, SCN-VAN connectivity may be an antidepressant target associated with depressive state changes and a predictor of treatment response to serotonin reuptake inhibitors. The within-network rsFC in SCN and DMN may reflect a trait-like abnormality in MDD. These findings provide further insights into the mechanism of antidepressants and their individual differences in response. The trial name is "Appropriate technology study of MDD diagnosis and treatment based on objective indicators and measurement" (URL: http://www.chictr.org.cn/showproj.aspx?proj=21377; registration number: ChiCTR-OOC-17012566).
Inflammatory depression is closely related to neuroinflammation. However, current anti-inflammatory drugs have low permeability to cross blood–brain barrier with difficulties reaching the central nervous system to provide therapeutic effectiveness. To overcome this limitation, the nano-based drug delivery technology was used to synthesize melanin-like polydopamine nanoparticles (PDA NPs) (~ 250 nm) which can cross the blood–brain barrier. Importantly, PDA NPs with abundant phenolic hydroxyl groups function as excellent free radical scavengers to attenuate cell damage caused by reactive oxygen species or acute inflammation. In vitro experiments revealed that PDA NPs exhibited excellent antioxidative properties. Next, we aimed to investigate the therapeutic effect of PDA NPs on inflammatory depression through intraperitoneal injection to the lipopolysaccharide-induced inflammatory depression model in mice. PDA NPs significantly reversed the depression-like behavior. PDA NPs was also found to reduce the peripheral and central inflammation induced by LPS, showing that alleviated splenomegaly, reduced serum inflammatory cytokines, inhibited microglial activation and restored synaptic loss. Various experiments also showed that PDA NPs had good biocompatibility both in vivo and in vitro. Our work suggested that PDA NPs may be biocompatible nano-drugs in treating inflammatory depression but their clinical application requires further study.
Graphical Abstract
Well-established animal models of depression have described a proximal relationship between stress and central nervous system (CNS) inflammation - a relationship mirrored in the peripheral inflammatory biomarkers of individuals with depression. Evidence also suggests that stress-induced proinflammatory states can contribute to the neurobiology of treatment-resistant depression. Interestingly, ketamine, a rapid-acting antidepressant, can partially exert its therapeutic effects via anti-inflammatory actions on the hypothalamic-pituitary-adrenal (HPA) axis, the kynurenine pathway or by cytokine suppression. Further investigations into the relationship between ketamine, inflammation and stress could provide insight into ketamine's unique therapeutic mechanisms and stimulate efforts to develop rapid-acting, anti-inflammatory-based antidepressants.
Background: The association between obesity and depression has been frequently reported. However, it still remains unclear which anthropometric indicators for obesity could be the best measure to explain its linkage with depressive symptoms.
Methods: This is a cross-sectional analytical study. Secondary data was analyzed using information from the Demographic and Health Survey of Peru (ENDES in Spanish). Data from the years 2018 to 2021 were reviewed. The outcome of interest was the presence of depressive symptoms, assessed with the Patient Health Questionnaire-9 (PHQ-9). The exposure variable was the presence of obesity, which was evaluated by body mass index (BMI) and abdominal circumference. Crude and adjusted odds ratios (cOR and aOR) were calculated using logistic regression. Both prevalence and association measures were presented with 95% confidence intervals (95% CI).
Results: A total of 141,134 subjects were included in the study. Depression was present in 2.51% (95% CI 2.38–2.65). Obesity according to BMI was present in 25.42% (95% CI 24.97–25.88), while abdominal obesity was shown in 41.67% (95% CI 41.19–42.15). In the multivariate analysis, a statistically significant association was found in regard to symptoms of depression in patients with abdominal obesity (aOR: 1.13; 95% CI 1.03–1.24), while no association was found with obesity according to BMI.
Conclusions: Abdominal circumference could be a better anthropometric measure than BMI to evaluate the association between obesity and depressive symptoms in the Peruvian population.
Background:
A bidirectional relationship between chronic pain (CP) and mental disorders has been reported, and coffee was believed to be associated with both. However, the association of coffee in this bidirectional relationship remains unclear. We aim to analyze the association of coffee consumption on the relationship of CP with depression and anxiety.
Methods:
A total of 376,813 participants from UK Biobank were included. We collected data on anxiety, depression and CP from objects of our study population. The association of coffee consumption on the relationship of CP with depression and anxiety was assessed through logistic/linear regression models. Moreover, seemingly unrelated estimation test (SUEST) was used to compare whether the coefficients differed in two different groups.
Results:
We observed significant associations of coffee consumption in the interaction of CP with depression and anxiety, such as the association of multisite chronic pain (MCP) on self-reported depression (βcoffee = 0.421, βnon-coffee = 0.488, PSUEST = 0.001), and the association of MCP on generalized anxiety disorder-7 (GAD-7) scores (βcoffee = 0.561, βnon-coffee = 0.678, PSUEST = 0.004) were significantly different between coffee drinking and non-coffee drinking groups. Furthermore, in analysis stratified by gender, we found headache (βmale = 0.392, βfemale = 0.214, PSUEST = 0.022) and hip pain (βmale = 0.480, βfemale = 0.191, PSUEST = 0.021) had significant associations with self-reported depression between males and females groups in coffee drinkers.
Conclusions:
Our results suggested that coffee consumption has a significant association on the relationship of CP with depression and anxiety.
The large-scale disruptions to physical activity during the coronavirus pandemic have been found to be a leading predictor of common mental disorders. In addition, regular physical exercise has been found to alleviate anxiety, sadness and depression during the pandemic. These findings, together with numerous studies published before the pandemic on the effects of physical activity on mental health, should be considered in the provision of mental health care following the pandemic. Cross-sectional research has revealed that all types of exercise and sport are associated with a reduced mental health burden. Therefore, the effectiveness of exercise and sport participation in sustainable mental health care as well as the causal relationship between exercise, psychosocial health and common mental disorders merit further investigation. Physical activity and sport, with their global accessibility, significant and clinically meaningful efficacy as well as virtual absence of adverse effects, offer a promising option for the promotion of mental health, including the prevention and treatment of common mental disorders. Physical exercise and sport are likely to become valuable public mental health resources in the future.
Cumulative evidence shows that gut microbiome can influence brain function and behavior via the inflammatory processes. However, the role of interaction between gut dysbiosis and C-reactive protein (CRP) in the development of anxiety and depression remains to be elucidated. In this study, a total of 3,321 independent SNP loci associated with gut microbiome were driven from genome-wide association study (GWAS). Using individual level genotype data from UK Biobank, we then calculated the polygenetic risk scoring (PRS) of 114 gut microbiome related traits. Moreover, regression analysis was conducted to evaluate the possible effect of interaction between gut microbiome and CRP on the risks of Patient Health Questionnaire-9 (PHQ-9) (N = 113693) and Generalized Anxiety Disorder-7 (GAD-7) (N = 114219). At last, 11 candidate CRP× gut microbiome interacting were detected for PHQ-9 score, such as F_Ruminococcaceae (β=-0.009, P =2.2 × 10 ⁻³ ), G_Akkermansia (β=-0.008, P =7.60 × 10 ⁻³ ), F_Acidaminococcaceae (β=0.008, P =1.22 × 10 ⁻² ), G_Holdemanella (β=-0.007, P =1.39 × 10 ⁻² ) and O_Lactobacillales (β=0.006， P =1.79 × 10 ⁻² ). 16 candidate CRP ×gut microbiome interacting were detected for GAD-7 score, such as O_Bacteroidales (β=0.010, P =4.00 × 10 ⁻⁴ ), O_Selenomonadales (β=-0.010, P =1.20 × 10 ⁻³ ), O_Clostridiales (β=0.009, P =2.70 × 10 ⁻³ ) and G_Holdemanella (β= -0.008, P =4.20 × 10 ⁻³ ). Our results support the significant effect of interaction between CRP and gut microbiome on the risks of anxiety and depression, and identified several candidate gut microbiome for them.
Objectives:
Mild traumatic brain injury (mTBI) is a signature injury of military conflicts and is prevalent in veterans with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Although therapeutic transcranial magnetic stimulation (TMS) can reduce symptoms of depression and PTSD, whether traumatic brain injury (TBI) affects TMS responsiveness is not yet known. We hypothesized mTBI would be associated with higher pretreatment symptom burden and poorer TMS response.
Materials and methods:
We investigated a registry of veterans (N = 770) who received TMS for depression across the US Veterans Affairs system. Of these, 665 (86.4%) had data on TBI and lifetime number of head injuries while 658 had complete data related to depression outcomes. Depression symptoms were assessed using the nine-item Patient Health Questionnaire and PTSD symptoms using the PTSD Checklist for DSM-5. Linear mixed effects models and t-tests evaluated whether head injuries predicted symptom severity before treatment, and how TBI status affected clinical TMS outcomes.
Results:
Of the 658 veterans included, 337 (50.7%) reported previous mTBI, with a mean of three head injuries (range 1-20). TBI status did not predict depressive symptom severity or TMS-associated changes in depression (all p's > 0.1). TBI status was associated with a modest attenuation of TMS-associated improvement in PTSD (in patients with PTSD Checklist for DSM-5 scores > 33). There was no correlation between the number of head injuries and TMS response (p > 0.1).
Conclusions:
Contrary to our hypothesis, presence of mTBI did not meaningfully change TMS outcomes. Veterans with mTBI had greater PTSD symptoms, yet neither TBI status nor cumulative head injuries reduced TMS effectiveness. Limitations include those inherent to retrospective registry studies and self-reporting. Although these findings are contrary to our hypotheses, they support the safety and effectiveness of TMS for MDD and PTSD in patients who have comorbid mTBI.
Background:
Differentiating bipolar depression (BD) from unipolar depression (UD) is a major clinical challenge. Identifying the potential classifying biomarkers between these two diseases is vital to optimize personalized management of depressed individuals.
Methods:
Here, we aimed to integrate neuroimaging and clinical data with machine learning method to classify BD and UD at the individual level. Data were collected from 31 healthy controls (HC group) and 80 depressive patients with an average follow-up period of 7.51 years. Of these patients, 32 got diagnosis conversion from major depressive disorder (MDD) to BD (BD group) and 48 remain persistent diagnosis of MDD (MDD group). Using graph theory and functional connectivity (FC) analysis, we investigated the differences in reward circuit properties among three groups. Then we applied a support vector machine and leave-one-out cross-validation methods to classify BD and UD patients based on neuroimaging and clinical data.
Results:
Compared with MDD and HC, BD showed decreased degree centrality of right mediodorsal thalamus (MD) and nodal efficiency (NE) of left ventral pallidum. Compared with BD and HC, MDD showed decreased NE of right MD and increased FC between right MD and bilateral dorsolateral prefrontal cortex and left ventromedial prefrontal cortex. Notably, the classifier obtained high classification accuracies (87.50 %) distinguishing BD and UD patients based on reward circuit properties and clinical features.
Limitations:
The classifying model requires out-of-sample replication analysis.
Conclusion:
The reward circuit dysfunction can not only provide additional information to assist clinical differential diagnosis, but also in turn informed treatment decision of depressive patients.
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