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      Progress and challenges in research of the mechanisms of anhedonia in major depressive disorder

      review-article
      1 , 2 , 3 , 4 , 1 , 2 , 3 , 4 ,
      General Psychiatry
      BMJ Publishing Group
      depressive disorder, major

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          Abstract

          There is an increasing heavy disease burden of major depressive disorder (MDD) globally. Both high diagnostic heterogeneity and complicated pathological mechanisms of MDD pose significant challenges. There is much evidence to support anhedonia as a core feature of MDD. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, anhedonia is further emphasised as a key item in the diagnosis of major depression with melancholic features. Anhedonia is a multifaceted symptom that includes deficits in various aspects of reward processing, such as anticipatory anhedonia, consummatory anhedonia, and decision-making anhedonia. Anhedonia is expected to become an important clinicopathological sign for predicting the treatment outcome of MDD and assisting clinical decision making. However, the precise neurobiological mechanisms of anhedonia in MDD are not clearly understood. In this paper, we reviewed (1) the current understanding of the link between anhedonia and MDD; (2) the biological basis of the pathological mechanism of anhedonia in MDD; and (3) challenges in research on the pathological mechanisms of anhedonia in MDD. A more in-depth understanding of anhedonia associated with MDD will improve the diagnosis, prediction, and treatment of patients with MDD in the future.

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          The role of inflammation in depression: from evolutionary imperative to modern treatment target.

          Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.
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            Depression

            Major depression is a common illness that severely limits psychosocial functioning and diminishes quality of life. In 2008, WHO ranked major depression as the third cause of burden of disease worldwide and projected that the disease will rank first by 2030.1 In practice, its detection, diagnosis, and management often pose challenges for clinicians because of its various presentations, unpredictable course and prognosis, and variable response to treatment.
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              Major depressive disorder.

              Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. The aetiology of MDD is multifactorial and its heritability is estimated to be approximately 35%. In addition, environmental factors, such as sexual, physical or emotional abuse during childhood, are strongly associated with the risk of developing MDD. No established mechanism can explain all aspects of the disease. However, MDD is associated with alterations in regional brain volumes, particularly the hippocampus, and with functional changes in brain circuits, such as the cognitive control network and the affective-salience network. Furthermore, disturbances in the main neurobiological stress-responsive systems, including the hypothalamic-pituitary-adrenal axis and the immune system, occur in MDD. Management primarily comprises psychotherapy and pharmacological treatment. For treatment-resistant patients who have not responded to several augmentation or combination treatment attempts, electroconvulsive therapy is the treatment with the best empirical evidence. In this Primer, we provide an overview of the current evidence of MDD, including its epidemiology, aetiology, pathophysiology, diagnosis and treatment.
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                Author and article information

                Journal
                Gen Psychiatr
                Gen Psychiatr
                gpsych
                gpsych
                General Psychiatry
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2517-729X
                2022
                24 February 2022
                : 35
                : 1
                : e100724
                Affiliations
                [1 ]departmentDepartment of Clinical Psychopharmacology , Peking University Sixth Hospital , Beijing, People's Republic of China
                [2 ]departmentDepartment of Clinical Psychopharmacology , Peking University Institute of Mental Health , Beijing, People's Republic of China
                [3 ]NHC Key Laboratory of Mental Health (Peking University) , Beijing, People's Republic of China
                [4 ]National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) , Beijing, People's Republic of China
                Author notes
                [Correspondence to ] Professor Tianmei Si; si.tian-mei@ 123456163.com
                Author information
                http://orcid.org/0000-0001-9823-2720
                Article
                gpsych-2021-100724
                10.1136/gpsych-2021-100724
                8883269
                35309242
                527ab8bf-87c4-4958-a452-db82e08b307d
                © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 28 November 2021
                : 11 February 2022
                Funding
                Funded by: National Key Technology R&D Program;
                Award ID: 2015BAI13B01
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81630031
                Categories
                Review
                1506
                Custom metadata
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                depressive disorder, major
                depressive disorder, major

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