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.
Previous neuroimaging studies have revealed abnormal functional connectivity of brain networks in patients with major depressive disorder (MDD), but findings have been inconsistent. A recent big‐data ...study found abnormal intrinsic functional connectivity within the default mode network in patients with recurrent MDD but not in first‐episode drug‐naïve patients with MDD. This study also provided evidence for reduced default mode network functional connectivity in medicated MDD patients, raising the question of whether previously observed abnormalities may be attributable to antidepressant effects. The present study (ClinicalTrials.gov identifier: NCT03294525) aimed to disentangle the effects of antidepressant treatment from the pathophysiology of MDD and test the medication normalization hypothesis. Forty‐one first‐episode drug‐naïve MDD patients were administrated antidepressant medication (escitalopram or duloxetine) for 8 weeks, with resting‐state functional connectivity compared between posttreatment and baseline. To assess the replicability of the big‐data finding, we also conducted a cross‐sectional comparison of resting‐state functional connectivity between the MDD patients and 92 matched healthy controls. Both Network‐Based Statistic analyses and large‐scale network analyses revealed intrinsic functional connectivity decreases in extensive brain networks after treatment, indicating considerable antidepressant effects. Neither Network‐Based Statistic analyses nor large‐scale network analyses detected significant functional connectivity differences between treatment‐naïve patients and healthy controls. In short, antidepressant effects are widespread across most brain networks and need to be accounted for when considering functional connectivity abnormalities in MDD.
The present study aimed to disentangle the effects of antidepressant treatment from the pathophysiology of MDD and test the medication normalization hypothesis. Both Network‐Based Statistic analyses and large‐scale network analyses revealed intrinsic functional connectivity decreases in extensive brain networks after treatment, while no significant functional connectivity differences were found between treatment‐naïve patients and healthy controls. These results indicate that antidepressant effects are widespread across most brain networks and need to be accounted for when considering functional connectivity abnormalities in MDD.
Over the last decade, researchers have found abnormal expression of transient receptor potential (TRP) channels. In particular, members of the thermally sensitive subclass (thermo-TRPs) are involved ...in many disease processes. Moreover, they have a vital role in the occurrence and development of gastric cancer (GC). Accordingly, thermo-TRPs constitute a major pharmacological target, and the elucidation of the mechanisms underlying their response to physiological stimuli or drugs is key for notable advances in GC treatment. Therefore, this paper summarizes the existing literature about thermo-TRP protein expression changes that are linked to the incidence and progression of GC. The review also discusses the implication of such association to pathology and cell physiology and identifies potential thermo-TRP protein targets for diagnosis and treatment of GC.
Abnormalities in large-scale, structural and functional brain connectivity have been increasingly reported in patients with major depressive disorder (MDD). However, MDD-related alterations in ...functional interaction between the cerebral hemispheres are still not well understood. Resting state fMRI, which reveals spontaneous neural fluctuations in blood oxygen level dependent signals, provides a means to detect interhemispheric functional coherence. We examined the resting state functional connectivity (RSFC) between the two hemispheres and its relationships with clinical characteristics in MDD patients using a recently proposed measurement named "voxel-mirrored homotopic connectivity (VMHC)".
We compared the interhemispheric RSFC, computed using the VMHC approach, of seventeen first-episode drug-naive patients with MDD and seventeen healthy controls. Compared to the controls, MDD patients showed significant VMHC decreases in the medial orbitofrontal gyrus, parahippocampal gyrus, fusiform gyrus, and occipital regions including the middle occipital gyrus and cuneus. In MDD patients, a negative correlation was found between VMHC of the fusiform gyrus and illness duration. Moreover, there were several regions whose VMHC showed significant negative correlations with the severity of cognitive disturbance, including the prefrontal regions, such as middle and inferior frontal gyri, and two regions in the cereballar crus.
These findings suggest that the functional coordination between homotopic brain regions is impaired in MDD patients, thereby providing new evidence supporting the interhemispheric connectivity deficits of MDD. The significant correlations between the VMHC and clinical characteristics in MDD patients suggest potential clinical implication of VMHC measures for MDD. Interhemispheric RSFC may serve as a useful screening method for evaluating MDD where neural connectivity is implicated in the pathophysiology.
Exploring the neural basis related to different mood states is a critical issue for understanding the pathophysiology underlying mood switching in bipolar disorder (BD), but research has been scarce ...and inconsistent.
Resting-state functional magnetic resonance imaging data were acquired from 162 patients with BD: 33 (hypo)manic, 64 euthymic, and 65 depressive, and 80 healthy controls (HCs). The differences of large-scale brain network functional connectivity (FC) between the four groups were compared and correlated with clinical characteristics. To validate the generalizability of our findings, we recruited a small longitudinal independent sample of BD patients (n = 11). In addition, we examined topological nodal properties across four groups as exploratory analysis.
A specific strengthened pattern of network FC, predominantly involving the default mode network (DMN), was observed in (hypo)manic patients when compared with HCs and bipolar patients in other mood states. Longitudinal observation revealed an increase in several network FCs in patients during (hypo)manic episode. Both samples evidenced an increase in the FC between the DMN and ventral attention network, and between the DMN and limbic network (LN) related to (hypo)mania. The altered network connections were correlated with mania severity and positive affect. Bipolar depressive patients exhibited decreased FC within the LN compared with HCs. The exploratory analysis also revealed an increase in degree in (hypo)manic patients.
Our findings identify a distributed pattern of large-scale network disturbances in the unique context of (hypo)mania and thus provide new evidence for our understanding of the neural mechanism of BD.
Individuals with major depressive disorder (MDD) have a high suicide risk. Some evidence suggests that uric acid (UA) may be involved in the pathophysiology of MDD. The purpose of this study was to ...evaluate whether serum UA levels were associated with suicide risk in MDD patients.
One hundred four female patients with MDD (52 patients with suicide risk and 52 patients without suicide risk) and 52 healthy individuals were included in this study. The suicide risk was evaluated by Mini International Neuropsychiatric Interview (M.I.N.I.). Fasting serum levels of UA, as well as glucose, lipid and renal function indicators were measured.
Serum UA levels in MDD patients with suicide risk (245.01 ± 55.44 μmol/L) were significantly lower than those in MDD patients without suicide risk (274.17 ± 72.65 μmol/L) (p = 0.017) and healthy controls (271.42 ± 55.25 μmol/L) (p = 0.030). There was no difference in serum UA levels between the MDD patients without suicide risk and healthy controls (p = 0.821). Binary logistic regression analysis revealed a significant relationship between suicide risk and decreased serum UA levels (OR = 0.989, p = 0.010) in MDD patients.
Decreased serum UA levels were associated with suicide risk in MDD patients. Purinergic system dysfunction may be involved in the neurobiological basis of suicide risk in these patients.
Objective
Bulimia nervosa (BN) is an eating disorder associated with the dysfunction of intrinsic brain networks. However, whether the network disruptions in BN patients manifest as dysconnectivity ...or imbalances of network modular segregation remains unclear.
Method
We collected data from 41 women with BN and 41 matched healthy control (HC) women. We performed graph theory analysis based on resting‐state functional magnetic resonance imaging (RS‐fMRI) data; then, we computed the participation coefficient (PC) among brain modules to characterize the modular segregation for the BN and HC groups. The number of intra‐ and inter‐modular connections was calculated to explain the PC changes. Additionally, we examined the potential associations of the measures mentioned above with clinical variables within the BN group.
Results
Compared with the HC group, the BN group showed significantly decreased PC in the fronto‐parietal network (FPN), cingulo‐opercular network (CON), and cerebellum (Cere). Additionally, the number of intra‐modular connections of the default mode network (DMN) and the number of the inter‐modular connections between the DMN and CON, FPN and Cere, and CON and Cere in the BN group were lower than those in the HC group. The nodal level analysis showed that the BN group had a decreased PC of the anterior prefrontal cortex (aPFC), dorsal frontal cortex (dFC), inferior parietal lobule (IPL), thalamus, and angular gyrus. Further, these metrics were significantly correlated with clinical variables in the BN group.
Discussion
These findings may provide novel insights to capture atypical topologies associated with pathophysiology mechanisms and clinical symptoms underlying BN.
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 review presents a comprehensive overview of 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.
The evaluation tools included HAMD-17 total scores, HAMA total scores, and Clinical Global Impressions Severity Subscale (CGI-S) score. ...short form-12 (SF-12) physical component score (PCS) and ...mental component score (MCS) were used to assess the quality of life of these patients. ...230 patients completed the 6-week follow-up, including 128 patients with early-improvement and 102 early-unimproved patients. According to the logistic regression analysis, the results revealed that the combination with sedative-hypnotic drugs was a significant predictor of early improvement in week 2. Benzodiazepines are primarily used as a sedative-hypnotics in patients with MDD to alleviate anxiety symptom and insomnia, and they might contribute to the response to antidepressants in the first two weeks because they produce a faster onset of effect on anxiety symptoms than antidepressants alone. ...it may be justifiable to combine benzodiazepines as a short-term treatment in patients with MDD and high-level anxiety.
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