Research Topic

Mechanisms and Novel Therapeutic Strategies of Major Depressive Disorder, Memory Deficits, and Metabolic Homeostasis

About this Research Topic

Major Depressive Disorder (MDD) is a common neuropsychiatric disorder characterized by emotional and cognitive dysfunctions. Depression and memory deficits share common mechanisms in abnormalities in synaptic plasticity, neural circuits, gut-brain axis, and central and peripheral metabolic homeostasis. However, there is still a lack of understanding of the following questions that prevent the development of effective therapeutics for these disorders:

(i) Mechanisms underlying the interactions between depression and memory deficits. For example, studies showed that chronic unpredictable mild stress induces memory deficits, however, studies using other animal models like social defeat stress may not lead to impairment in memory. It is not clear what is the mechanism underlying the comorbidity of depression and memory deficits and this question needs to be further addressed.

(ii) Causal relationship between depression and memory disorders. Studies suggest that there are overlapping mechanisms underlying depression and memory deficits, however, it remains to be determined how these two neuropsychiatric disorders associated with each other and whether they contribute distinctly to the comorbidity.

(iii) The interaction of neurobiological changes and metabolic homeostasis contributing to the onset of neuropsychiatric disorders including depression, memory deficits, and their comorbidity. Chronic and severe metabolic diseases, including stroke, diabetes, hyperlipidemia, hypertension, and atherosclerosis are highly associated with depression and cognitive dysfunctions. Nevertheless, the crosstalk of neurobiological adaptations and metabolic dysregulations underlying these diseases is illusive.


In this Research Topic, we aim to advance the research by addressing the following questions:

1. What are the mechanisms of different types of memory deficits induced by different animal models of stress in the research of pathological basis and pharmacological interventions of depression?

2. What is the role of neural circuits such as the hippocampus-prefrontal cortex pathway and the hippocampus-hypothalamus pathway in the mechanisms of depression and memory deficits as well as their treatments?

3. What are the interactions among different types of cells in the brain (including neuron, astrocyte, microglia, and oligodendrocyte), and how do these interactions underlie the mechanisms of different pharmacological therapeutics of depression and memory deficits?

4. While emerging evidence has shown high comorbidity and overlapping mechanisms of neuropsychiatric disorders (depression and memory deficits) and metabolic diseases (atherosclerosis, obesity, diabetes, and stroke), there is an urgent need to develop novel and more efficient therapeutics for the treatment of comorbidity of these disorders. The combination of Chinese and western medicine may provide a new avenue for the endeavors to treat these diseases.


In summary, studies that examine the mechanisms of depression, memory deficits, metabolic diseases, and their comorbidities are welcome with the emphasis on the studies of the interaction between different brain regions and different cell types. Moreover, the exploration of safety and efficacy of novel therapeutic strategies for the treatment of these disorders by using a different type of medications such as Chinese medicine (such as formulas and crude extracts), antidepressants (such as fluoxetine and Citalopram), anti-dementia drugs (such as Memantine and Donepezil) are also welcome in this Research Topic. The combined use of the above treatments (for example, Chinese formula combined with donepezil against memory deficit, fluoxetine combined with memantine against depression) is welcome in this project if the study is novel. Specifically, we encourage new therapeutic strategies that combine two or more different medications to achieve better pharmacological effects.


Keywords: Depression, memory deficits, neural circuits, HPA axis, brain-gut axis, antidepressants, comorbidity, neuron, microglial, astrocyte, oligodendrocyte, stroke, diabetes, atherosclerosis, obesity


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Major Depressive Disorder (MDD) is a common neuropsychiatric disorder characterized by emotional and cognitive dysfunctions. Depression and memory deficits share common mechanisms in abnormalities in synaptic plasticity, neural circuits, gut-brain axis, and central and peripheral metabolic homeostasis. However, there is still a lack of understanding of the following questions that prevent the development of effective therapeutics for these disorders:

(i) Mechanisms underlying the interactions between depression and memory deficits. For example, studies showed that chronic unpredictable mild stress induces memory deficits, however, studies using other animal models like social defeat stress may not lead to impairment in memory. It is not clear what is the mechanism underlying the comorbidity of depression and memory deficits and this question needs to be further addressed.

(ii) Causal relationship between depression and memory disorders. Studies suggest that there are overlapping mechanisms underlying depression and memory deficits, however, it remains to be determined how these two neuropsychiatric disorders associated with each other and whether they contribute distinctly to the comorbidity.

(iii) The interaction of neurobiological changes and metabolic homeostasis contributing to the onset of neuropsychiatric disorders including depression, memory deficits, and their comorbidity. Chronic and severe metabolic diseases, including stroke, diabetes, hyperlipidemia, hypertension, and atherosclerosis are highly associated with depression and cognitive dysfunctions. Nevertheless, the crosstalk of neurobiological adaptations and metabolic dysregulations underlying these diseases is illusive.


In this Research Topic, we aim to advance the research by addressing the following questions:

1. What are the mechanisms of different types of memory deficits induced by different animal models of stress in the research of pathological basis and pharmacological interventions of depression?

2. What is the role of neural circuits such as the hippocampus-prefrontal cortex pathway and the hippocampus-hypothalamus pathway in the mechanisms of depression and memory deficits as well as their treatments?

3. What are the interactions among different types of cells in the brain (including neuron, astrocyte, microglia, and oligodendrocyte), and how do these interactions underlie the mechanisms of different pharmacological therapeutics of depression and memory deficits?

4. While emerging evidence has shown high comorbidity and overlapping mechanisms of neuropsychiatric disorders (depression and memory deficits) and metabolic diseases (atherosclerosis, obesity, diabetes, and stroke), there is an urgent need to develop novel and more efficient therapeutics for the treatment of comorbidity of these disorders. The combination of Chinese and western medicine may provide a new avenue for the endeavors to treat these diseases.


In summary, studies that examine the mechanisms of depression, memory deficits, metabolic diseases, and their comorbidities are welcome with the emphasis on the studies of the interaction between different brain regions and different cell types. Moreover, the exploration of safety and efficacy of novel therapeutic strategies for the treatment of these disorders by using a different type of medications such as Chinese medicine (such as formulas and crude extracts), antidepressants (such as fluoxetine and Citalopram), anti-dementia drugs (such as Memantine and Donepezil) are also welcome in this Research Topic. The combined use of the above treatments (for example, Chinese formula combined with donepezil against memory deficit, fluoxetine combined with memantine against depression) is welcome in this project if the study is novel. Specifically, we encourage new therapeutic strategies that combine two or more different medications to achieve better pharmacological effects.


Keywords: Depression, memory deficits, neural circuits, HPA axis, brain-gut axis, antidepressants, comorbidity, neuron, microglial, astrocyte, oligodendrocyte, stroke, diabetes, atherosclerosis, obesity


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

01 September 2021 Abstract
01 December 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

01 September 2021 Abstract
01 December 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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