Advances in functional MRI research in bipolar disorder:from the perspective of mood states

Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder.However,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well understood.This reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood states.We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood state.We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects.Finally,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.

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

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.

Nuclear receptors modulate inflammasomes in the pathophysiology and treatment of major depressive disorder

Major depressive disorder(MDD)is highly prevalent and is a significant cause of mortality and morbidity worldwide.Currently,conventional pharmacological treatments for MDD produce temporary remission in<50%of patients;therefore,there is an urgent need for a wider spectrum of novel antidepressants to target newly discovered underlying disease mechanisms.Accumulated evidence has shown that immune inflammation,particularly inflammasome activity,plays an important role in the pathophysiology of MDD.In this review,we summarize the evidence on nuclear receptors(NRs),such as glucocorticoid receptor,mineralocorticoid receptor,estrogen receptor,aryl hydrocarbon receptor,and peroxisome proliferator-activated receptor,in modulating the inflammasome activity and depression-associated behaviors.This review provides evidence from an endocrine perspective to understand the role of activated NRs in the pathophysiology of MDD,and to provide insight for the discovery of antidepressants with novel mechanisms for this devastating disorder.