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

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.

Using animal models for the studies of schizophrenia and depression: The value of translational models for treatment and prevention

“…Adverse environmental factors, genetic background, and their interaction are the main risk factors for depression ( Cross-Disorder Group of the Psychiatric Genomics Consortium, 2013 ; Richter-Levin and Xu, 2018 ; Silva et al, 2021 ). Animal models for depression often involve stress exposure and evaluate anhedonia, helplessness, motivation, and despair behaviors, as behavioral features; some examples are the chronic mild stress (CMS) model, learned helplessness (LH), and maternal separation ( Schmidt et al, 2011 ; Czéh et al, 2016 ; Maier and Seligman, 2016 ; Antoniuk et al, 2019 ; Kaufling, 2019 ; Su and Si, 2022 ).…”

“…Although each single animal model certainly cannot recapitulate all the aspects of complex human disorders, they can bring unique and often unexpected insights that are the building blocks for novel therapies. Also, the clinical behavioral and neurobiological circuit dysfunction differ on the individual level ( Otte et al, 2016 ; Su and Si, 2022 ), which reflects that even human conditions are not homogeneous. Therefore, regarding protocols used to understand some aspects of behavioral and neurobiological features of depression and schizophrenia, stress seems to be a mutual variable in both rodent models and the human condition.…”

Characteristics of implicit schemas in patients with major depressive disorder

“… 1 Low mood and diminished interest are the main symptoms of MDD. 2 As an important treatment focus for MDD, many psychotherapy theories emphasise the importance of implicit self-schema and other-schema, 3–5 which refer to the information and organisation mode about oneself or others. 6 For example, Beck, the founder of cognitive therapy pointed out that patients with MDD had negative perceptions of self, others and the world (ie, core beliefs) that are automatic and unconscious.…”

“…Major depressive disorder (MDD) is a common mood disorder with a high incidence and high disease burden 1. Low mood and diminished interest are the main symptoms of MDD 2. As an important treatment focus for MDD, many psychotherapy theories emphasise the importance of implicit self-schema and other-schema,3–5 which refer to the information and organisation mode about oneself or others 6.…”

Decoding psychosis: from national genome project to national brain project

“…Anhedonia in depression is an example of this. 46 Because few biological markers have been proven clinically valid for psychoses after many years of exploration, focusing on core symptoms offers the alternative approach. The notion of identifying the core feature of a disease is also advocated in the new International Classification of Diseases-11 (ICD-11) guidelines.…”