Linking atypical depression and insulin resistance-related disorders via low-grade chronic inflammation: Integrating the phenotypic, molecular and neuroanatomical dimensions

Insulin resistance (IR) and related disorders, such as T2DM, increase the risk of major depressive disorder (MDD) and vice versa. Current evidence indicates that psychological stress and overeating can induce chronic low-grade inflammation that can interfere with glutamate metabolism in MDD as well as insulin signaling, particularly in the atypical subtype. Here we first review the interactive role of inflammatory processes in the development of MDD, IR and related metabolic disorders. Next, we describe the role of the anterior cingulate cortex in the pathophysiology of MDD and IR-related disorders. Furthermore, we outline how specific clinical features of atypical depression, such as hyperphagia, are more associated with inflammation and IR-related disorders. Finally, we examine the regional specificity of the effects of inflammation on the brain that show an overlap with the functional and morphometric brain patterns activated in MDD and IR-related disorders

Role of inflammation in depression relapse

Abstract Major depressive disorder (MDD) is a leading cause of disability worldwide. After the first episode, patients with remitted MDD have a 60% chance of experiencing a second episode. Consideration of therapy continuation should be viewed in terms of the balance between the adverse effects of medication and the need to prevent a possible relapse. Relapse during the early stages of MDD could be prevented more efficiently by conducting individual risk assessments and providing justification for continuing therapy. Our previous work established the neuroimaging markers of relapse by comparing patients with recurrent major depressive disorder (rMDD) in depressive and remitted states. However, it is not known which of these markers are trait markers that present before initial relapse and, consequently, predict disease course. Here, we first describe how inflammation can be translated to subtype-specific clinical features and suggest how this could be used to facilitate clinical diagnosis and treatment. Next, we address the central and peripheral functional state of the immune system in patients with MDD. In addition, we emphasize the important link between the number of depressive episodes and rMDD and use neuroimaging to propose a model for the latter. Last, we address how inflammation can affect brain circuits, providing a possible mechanism for rMDD. Our review suggests a link between inflammatory processes and brain region/circuits in rMDD

Linking atypical depression and insulin resistance-related disorders via low-grade chronic inflammation: Integrating the phenotypic, molecular and neuroanatomical dimensions

Insulin resistance (IR) and related disorders, such as T2DM, increase the risk of major depressive disorder (MDD) and vice versa. Current evidence indicates that psychological stress and overeating can induce chronic low-grade inflammation that can interfere with glutamate metabolism in MDD as well as insulin signaling, particularly in the atypical subtype. Here we first review the interactive role of inflammatory processes in the development of MDD, IR and related metabolic disorders. Next, we describe the role of the anterior cingulate cortex in the pathophysiology of MDD and IR-related disorders. Furthermore, we outline how specific clinical features of atypical depression, such as hyperphagia, are more associated with inflammation and IR-related disorders. Finally, we examine the regional specificity of the effects of inflammation on the brain that show an overlap with the functional and morphometric brain patterns activated in MDD and IR-related disorders

Neural networks and the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation in depression

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