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The New England Journal of Medicine Jul 2021
Review
Topics: Adolescent; Antidepressive Agents; Depressive Disorder; Depressive Disorder, Major; Humans; Psychotherapy; Selective Serotonin Reuptake Inhibitors; Suicide
PubMed: 34320289
DOI: 10.1056/NEJMra2033475 -
Journal of Neural Transmission (Vienna,... Nov 2019Major depression is a leading contributor to the global burden of disease. This situation is mainly related to the chronicity and/or recurrence of the disorder, and to... (Review)
Review
Major depression is a leading contributor to the global burden of disease. This situation is mainly related to the chronicity and/or recurrence of the disorder, and to poor response to antidepressant therapy. Progress in this area requires valid animal models. Current models are based either on manipulating the environment to which rodents are exposed (during the developmental period or adulthood) or biological underpinnings (i.e. gene deletion or overexpression of candidate genes, targeted lesions of brain areas, optogenetic control of specific neuronal populations, etc.). These manipulations can alter specific behavioural and biological outcomes that can be related to different symptomatic and pathophysiological dimensions of major depression. However, animal models of major depression display substantial shortcomings that contribute to the lack of innovative pharmacological approaches in recent decades and which hamper our capabilities to investigate treatment-resistant depression. Here, we discuss the validity of these models, review putative models of treatment-resistant depression, major depression subtypes and recurrent depression. Furthermore, we identify future challenges regarding new paradigms such as those proposing dimensional rather than categorical approaches to depression.
Topics: Animals; Behavior, Animal; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Disease Models, Animal
PubMed: 31584111
DOI: 10.1007/s00702-019-02084-y -
Cells May 2021Major depressive disorder (MDD) is a heterogeneous disease affecting one out of five individuals and is the leading cause of disability worldwide. Presently, MDD is... (Review)
Review
Major depressive disorder (MDD) is a heterogeneous disease affecting one out of five individuals and is the leading cause of disability worldwide. Presently, MDD is considered a multifactorial disease with various causes such as genetic susceptibility, stress, and other pathological processes. Multiple studies allowed the formulation of several theories attempting to describe the development of MDD. However, none of these hypotheses are comprehensive because none of them can explain all cases, mechanisms, and symptoms of MDD. Nevertheless, all of these theories share some common pathways, which lead us to believe that these hypotheses depict several pieces of the same big puzzle. Therefore, in this review, we provide a brief description of these theories and their strengths and weaknesses in an attempt to highlight the common mechanisms and relationships of all major theories of depression and combine them together to present the current overall picture. The analysis of all hypotheses suggests that there is interdependence between all the brain structures and various substances involved in the pathogenesis of MDD, which could be not entirely universal, but can affect all of the brain regions, to one degree or another, depending on the triggering factor, which, in turn, could explain the different subtypes of MDD.
Topics: Animals; Depressive Disorder, Major; Humans
PubMed: 34064233
DOI: 10.3390/cells10061283 -
Zeitschrift Fur Kinder- Und... Nov 2019Depressive symptoms have long been associated with abnormalities in neural processing of reward. However, no review has yet consolidated evidence of such deficits in... (Review)
Review
Depressive symptoms have long been associated with abnormalities in neural processing of reward. However, no review has yet consolidated evidence of such deficits in adolescent depression, integrating findings across neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). The current review found consistent evidence of reduced striatal responses in anticipation and upon receipt of rewards, and blunted feedback-related negativity (FRN) potentials associated with depression in adolescence, consistent with the adult literature. Furthermore, while these occurred in currently depressed adolescents, they were also found to be predictive of the onset of depressive symptoms in longitudinal studies with community-based adolescent samples. This paper makes recommendations for future work to continue to elucidate this relationship, a greater understanding of which may lead to more targeted and efficacious treatments for depression in adolescence.
Topics: Adolescent; Depression; Depressive Disorder; Electroencephalography; Humans; Magnetic Resonance Imaging; Neuroimaging; Reward
PubMed: 30957688
DOI: 10.1024/1422-4917/a000663 -
The Lancet. Psychiatry Sep 2021A rate-limiting step in the prevention and early intervention of depressive disorders in young people is our insufficient understanding of causal mechanisms. One... (Review)
Review
A rate-limiting step in the prevention and early intervention of depressive disorders in young people is our insufficient understanding of causal mechanisms. One plausible pathophysiological pathway is disturbance in the 24 h sleep-wake cycle and the underlying circadian system. Abnormalities in circadian rhythms are well documented in adults with various depressive disorders and have been linked to core clinical features, including unstable mood, daytime fatigue, non-restorative sleep, reduced motor activity, somatic symptoms, and appetite and weight change. In this Review, we summarise four areas of research: basic circadian biology and animal models of circadian disturbances; developmental changes in circadian rhythms during adolescence and implications for the emergence of adolescent-onset depressive syndromes; community and clinical studies linking 24 h sleep-wake cycle disturbances and depressive disorders; and clinical trials of circadian-based treatments. We present recommendations based on a highly personalised, early intervention model for circadian-linked depression in young people.
Topics: Animals; Circadian Rhythm; Depressive Disorder; Humans; Sleep Wake Disorders
PubMed: 34419186
DOI: 10.1016/S2215-0366(21)00034-1 -
Annual Review of Psychology Jan 2020Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to available treatments. Chronic or early-life stress is... (Review)
Review
Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to available treatments. Chronic or early-life stress is one of the key risk factors for depression. In addition, a growing body of data implicates chronic inflammation as a major player in depression pathogenesis. More recently, the gut microbiota has emerged as an important regulator of brain and behavior and also has been linked to depression. However, how this holy trinity of risk factors interact to maintain physiological homeostasis in the brain and body is not fully understood. In this review, we integrate the available data from animal and human studies on these three factors in the etiology and progression of depression. We also focus on the processes by which this microbiota-immune-stress matrix may influence centrally mediated events and on possible therapeutic interventions to correct imbalances in this triune.
Topics: Animals; Depressive Disorder; Gastrointestinal Microbiome; Humans; Inflammation; Stress, Psychological
PubMed: 31567042
DOI: 10.1146/annurev-psych-122216-011613 -
Journal of Neuroinflammation Feb 2020Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder (MDD).... (Review)
Review
Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder (MDD). It has been postulated that acupuncture may achieve its treatment effects on MDD through suppression of vagal nerve inflammatory responses. Our previous research established that taVNS significantly increases amygdala-dorsolateral prefrontal cortex connectivity, which is associated with a reduction in depression severity. However, the relationship between taVNS and the central/peripheral functional state of the immune system, as well as changes in brain neural circuits, have not as yet been elucidated. In the present paper, we outline the anatomic foundation of taVNS and emphasize that it significantly modulates the activity and connectivity of a wide range of neural networks, including the default mode network, executive network, and networks involved in emotional and reward circuits. In addition, we present the inflammatory mechanism of MDD and describe how taVNS inhibits central and peripheral inflammation, which is possibly related to the effectiveness of taVNS in reducing depression severity. Our review suggests a link between the suppression of inflammation and changes in brain regions/circuits post taVNS.
Topics: Brain; Depressive Disorder; Humans; Nerve Net; Vagus Nerve Stimulation
PubMed: 32050990
DOI: 10.1186/s12974-020-01732-5 -
Clinical Nutrition (Edinburgh, Scotland) Oct 2019There is a large body of evidence which supports the role of inflammation in the pathophysiology of mental health disorders, including depression. Dietary patterns have... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
There is a large body of evidence which supports the role of inflammation in the pathophysiology of mental health disorders, including depression. Dietary patterns have been shown to modulate the inflammatory state, thus highlighting their potential as a therapeutic tool in disorders with an inflammatory basis. Here we conduct a systematic review and meta-analysis of current literature addressing whether there is a link between the inflammatory potential of a diet and risk of depression or depressive symptoms.
METHODS
A systematic literature search was performed to identify studies that reported an association between the inflammatory potential of the diet and risk of depressive symptoms or diagnosis of depression. Random effect models were used to meta-analyse effect sizes. Quality assessment, publication bias, sensitivity and subgroup analyses were also performed.
RESULTS
Eleven studies, with a total of 101,950 participants at baseline (age range: 16-72 years old), were eligible for review. A significant association between a pro-inflammatory diet and increased risk of depression diagnosis or symptoms was evident, relative to those on an anti-inflammatory diet (OR: 1.40, 95% confidence intervals: 1.21-1.62, P < 0.001). No publication bias was detected; however, some study heterogeneity was evident (I = 63%, P < 0.001). Subgroup analyses suggested the main source of study heterogeneity was the study design (cross-sectional or longitudinal) and the effect measure used (odds ratio, hazard ratio or relative risk).
CONCLUSION
These results provide an association between pro-inflammatory diet and risk of depression. Thus, adopting an anti-inflammatory diet may be an effective intervention or preventative means of reducing depression risk and symptoms.
Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Depressive Disorder; Diet; Female; Humans; Inflammation; Male; Middle Aged; Young Adult
PubMed: 30502975
DOI: 10.1016/j.clnu.2018.11.007 -
Journal of American College Health : J... Jan 2020This study examined differences in substance use, depression, and academic functioning among ADHD and non-ADHD college students. Included 1,748 students (ages 18-25;... (Comparative Study)
Comparative Study
This study examined differences in substance use, depression, and academic functioning among ADHD and non-ADHD college students. Included 1,748 students (ages 18-25; women 68.4%; Caucasian 71.3%) with and without history of ADHD. We assessed the relationship of ADHD to substance use variables, controlling for depressive symptoms and examined relationships with GPA. ADHD students were more likely to have engaged in frequent alcohol use, binge drinking, regular marijuana use and to have used other drugs in the last year. They reported higher depression symptoms than non-ADHD students, although substance abuse risk remained high even when controlling for depressive symptoms. ADHD students had lower overall GPA than those without ADHD. However, this difference was no longer significant when controlling for depression and marijuana use. College campuses should consider programing aimed at identifying ADHD students at risk for developing substance abuse problems and emotional difficulties.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Depressive Disorder; Educational Status; Female; Humans; Male; Southeastern United States; Students; Substance-Related Disorders; Universities; Young Adult
PubMed: 30257141
DOI: 10.1080/07448481.2018.1515754 -
Australasian Psychiatry : Bulletin of... Jun 2020An incorrect false positive diagnosis of melancholia can lead to inappropriate treatment and illness prolongation. This paper therefore seeks to introduce the concept of... (Review)
Review
OBJECTIVE
An incorrect false positive diagnosis of melancholia can lead to inappropriate treatment and illness prolongation. This paper therefore seeks to introduce the concept of 'pseudo-melancholia' to capture such instances and provide clinical examples of contributing at-risk scenarios.
METHODS
The author draws on clinical experience to provide exemplars of circumstances most risking a false positive diagnosis of melancholia.
RESULTS
Pseudo-melancholia can result from invalid measures of melancholia and from several functional and organic conditions presenting with suggested melancholic features.
CONCLUSIONS
Recognising high-risk pseudo-melancholia scenarios has the potential to advance a change in diagnostic formulation, provide a more diagnosis-specific intervention and so avert a secondary diagnosis of 'treatment resistant depression'.
Topics: Depressive Disorder; Depressive Disorder, Treatment-Resistant; Diagnosis, Differential; Diagnostic Errors; Humans
PubMed: 32157900
DOI: 10.1177/1039856220908167