Background Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression.Microglia activation can lead to an increase in the levels of proinflammatory cytokines,including TNF-α,which leads to neuronal apoptosis in the specific neural circuits of some brain regions,abnormal cognition and treatment-resistant depression(TRD).Protein kinase C(PKC)is a key regulator of the microglia activation process.We assume that the abnormality in PKC might result in abnormal microglia activation,neuronal apoptosis,significant changes in emotional and cognitive neural circuits,and TRD.In the current study,we plan to target at the PKC signal pathway to improve the TRD treatment outcome.Methods and analysis This is a 12-week,ongoing,randomised,placebo-controlled trial.Patients with TRD(N=180)were recruited from Shanghai Mental Health Center,Shanghai Jiao Tong University.Healthy control volunteers(N=60)were recruited by advertisement.Patients with TRD were randomly assigned to‘escitalopram+golimumab(TNF-αinhibitor)’,‘escitalopram+calcium tablet+vitamin D(PKC activator)’or‘escitalopram+placebo’groups.We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale(HAMD-17).The secondary outcome is defined as changes in anti-inflammatory effects,cognitive function and quality of life.Discussion This study might be the first randomised,placebo-controlled trial to target at the PKC signal pathway in patients with TRD.Our study might help to propose individualised treatment strategies for depression.Trial registration number The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.
Background The prevalence of Alzheimer's disease(AD)comorbid with depression is common.However,the mechanisms of AD with depression remain unclear.Aims To investigate the regional alterations of brain activity of AD with depression in resting-state functional magnetic resonance imaging(rs-fMRI).Methods 154 patients with AD who met the inclusion criteria were recruited from the Zhejiang Provincial People’s Hospital from October 2014 to October 2016.According to whether the core symptoms of depression were present,patients were divided into two groups,22 patients with AD with depression(AD-D)and 52 patients with AD without depression(AD-nD).The amplitude of low frequency fluctuations(ALFF)was compared between two groups by performing independent-samples f-test.Results Compared with the AD-D group,increased ALFF values in the bilateral superior frontal gyrus,left middle frontal gyrus and left inferior frontal gyrus were observed in the AD-nD group.The brain activity in the AD-nD group in the bilateral superior frontal gyrus,left middle frontal gyrus and the left inferior frontal gyrus was higher than the AD-D group.Conclusions Resting-state brain functional alterations may be closely bound up with the pathophysiologic features of patients with AD with depressive symptoms.
LTCCS ARE IMPLICATED IN THE PATHOLOGY OF BIPOLAR DISORDER Bipolar disorder (BPD) is a common mental illness with significant morbidity and mortality.1 Although evidence have suggested changes in oxidative stress, dopamine and inflammation in BPD, it is hard to define the aetiological mechanism of BPD clearly. Recently, some but not all candidate gene association studies, family-based association studies, linkage studies, genome-wide association studies (GWASs) and meta-analyses showed that mutation of L-type voltage-gated calcium chan? nels (LTCCs) gene CACNAlCis implicated in the mechanism of BPD.'-8 These findings support the possibility that BPD might have calcium channelopathy.
