Repetitive transcranial magnetic stimulation (rTMS) is a rapid and effective therapy for major depressive disorder; however, there is significant variability in therapeutic outcomes both within and across individuals, with approximately 50% of patients showing no response to rTMS treatment. Many studies have personalized the stimulation parameters of rTMS (e.g., location and intensity of stimulation) according to the anatomical and functional structure of the brain. In addition to these parameters, the internal states of the individual, such as circadian rhythm, behavior/cognition, neural oscillation, and neuroplasticity, also contribute to the variation in rTMS effects. In this review, we summarize the current literature on the interaction between rTMS and internal states. We propose two possible methods, multimodal treatment, and adaptive closed-loop treatment, to integrate patients' internal states to achieve better rTMS treatment for depression.
Humans ; Transcranial Magnetic Stimulation/methods* ; Depressive Disorder, Major/physiopathology* ; Neuronal Plasticity/physiology* ; Brain/physiopathology*

BACKGROUNDEarly-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia.

METHODSIn total, 547 out-patients aged 18-65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4 th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator.

RESULTSEarly-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies.

CONCLUSIONSEOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment.

Adult ; Age of Onset ; Aged ; Anxiety Disorders ; etiology ; Depressive Disorder, Major ; physiopathology ; psychology ; Female ; Humans ; Male ; Middle Aged ; Neuroticism ; Quality of Life ; Young Adult

OBJECTIVETo investigate the changes in brain regional homogeneity in first-onset major depressive disorders (MDDs) using resting-state functional magnetic resonance imaging (fMRI).

METHODSEighteen patients with first-onset MDDs and twenty gender- and age-matched healthy controls underwent resting-state fMRI scans to compare the regional homogeneities of the brain regions.

RESULTSCompared with the normal controls, the patients with MDDs showed significantly decreased regional homogeneity in the left posterior cingulated gyrus, bilateral inferior temporal gyrus, bilateral superior temporal gyrus, left inferior frontal gyrus, left hippocampa gyrus, left posterior central gyrus, left angular gyrus, right amygdala, right orbital frontal gyrus, right supplementary motor area, and right cerebellar lobe.

CONCLUSIONPatients with first-onset MDDs have dysfunctions in the brain regions closed related with cognition and emotional control.

Amygdala ; Brain ; physiopathology ; Case-Control Studies ; Cerebellum ; Cognition ; Depressive Disorder, Major ; diagnosis ; Emotions ; Frontal Lobe ; Humans ; Magnetic Resonance Imaging ; Temporal Lobe

We investigated the baseline brain activity level in patients with major depressive disorder (MDD) by am plitude of low-frequency fluctuation (ALFF) based on resting-state functional MRI (fMRI). We examined 13 patients in the MDD group and 14 healthy volunteers in the control group by resting-state fMRI on GE Signa 3.0T. We calculated and compared the ALFF values of the two groups. In the MDD group, ALFF values in the right medial prefrontal were higher than those in control group, with statistically significant differences (P < 0.001). ALFF values in the left parietal in the MDD group were lower than those in control group with statistically significant differences (P < 0.001). This resting-state fMRI study suggested that the alteration brain activity in the right medial prefrontal and left parietal ALFF contributed to the understanding of the pathophysiological mechanism of MDD patients.
Brain ; physiopathology ; Brain Mapping ; Case-Control Studies ; Depressive Disorder, Major ; physiopathology ; Humans ; Magnetic Resonance Imaging

OBJECTIVETo compare skin sympathetic response(SSR) between patients with generalized anxiety disorder(GAD) and patients with major depression disorder(MDD).

METHODSThe latency and amplitude of SSR wave were measured in 30 GAD patients and 30 MDD patients, before and after 8-week treatment of anti-anxiety or anti-depression drugs. Thirty age and sex-matched healthy subjects served as healthy controls (HC).

RESULTSBefore the treatment, the latency of SSR in GAD patients was significantly shorter than that in HC group, while the amplitude was significantly higher than that in the HC (P<0.05). In MDD group, the latency before the treatment was significantly longer than that in the HC,while the amplitude was significantly lower than that in the HC (P <0.05). After treatment,the latency of SSR in GAD group was extended compared to the baseline level, and close to the level of the HC. The amplitude of SSR in GAD group became lower after treatment, but still higher than that of control group. The latency of SSR in MDD patients was significantly shorter after treatment compared to baseline level (P <0.05). In addition, the latency of SSR in MDD group was still longer than that in GAD group (P<0.05); meanwhile,the amplitude of SSR in MDD group was significantly lower that in GAD group (P<0.001). SSR parameters were positively correlated with HAMA and HAMD scores with a correlation coefficient of 0.57 and 0.73, respectively.

CONCLUSIONThere are significant differences in SSR parameters between patients with GAD and patients with MDD,indicating that SSR can be used as an objective index to distinguish anxiety from depression.

Adolescent ; Adult ; Anti-Anxiety Agents ; therapeutic use ; Antidepressive Agents ; therapeutic use ; Anxiety Disorders ; drug therapy ; physiopathology ; Case-Control Studies ; Depressive Disorder, Major ; drug therapy ; physiopathology ; Female ; Galvanic Skin Response ; Humans ; Male ; Middle Aged ; Skin ; physiopathology ; Sympathetic Nervous System ; physiopathology ; Young Adult

Major depression disorder is an increasing heavy burden in modem society, but its pathological mechanism is still vague. Recent evidence indicated that two pore potassium channel, TREK1, is one of the important drug targets of antidepressants. The structural and functional research progress of TREK1 potassium channel were reviewed with an emphasis on its roles in anti-depression, neuronal protection, and neuronal plasticity. The complicated interactions between TREK1 potassium channel and monoamine transmitters-receptors were also reviewed and future directions to explore the underline mechanism were also discussed.
Animals ; Antidepressive Agents ; pharmacology ; Depressive Disorder, Major ; genetics ; metabolism ; physiopathology ; Drug Delivery Systems ; Gene Knockout Techniques ; Humans ; Neuronal Plasticity ; Polymorphism, Genetic ; Potassium Channels, Tandem Pore Domain ; genetics ; metabolism ; physiology ; Receptors, Serotonin ; metabolism ; Receptors, Serotonin, 5-HT4 ; Serotonin ; pharmacology

BACKGROUNDReports on mood regulating circuit (MRC) indicated different activities between depressed patients and healthy controls. The functional networks based on MRC have not been described in major depression disorder (MDD). Both the anterior cingulate cortex (ACC) and thalamus are all the key regions of MRC. This study was to investigate the two functional networks related to ACC and thalamus in MDD.

METHODSSixteen patients with MDD on first episode which never got any medication and sixteen matched health controls were scanned by 3.0 T functional magnetic resonance imaging (fMRI) during resting-state. The pregenual anterior cingulate cortex (pgACC) was used as seed region to construct the functional network by cortex section. The thalamus was used as seed region to construct the functional network by limbic section. Paired-t tests between-groups were performed for the seed-target correlations based on the individual fisher z-transformed correlation maps by SPM2.

RESULTSDepressed subjects exhibited significantly great functional connectivity (FC) between pgACC and the parahippocampus gyrus in one cluster (size 923) including left parahippocampus gyrus (-21, -49, 7), left parietal lobe (-3, -46, 52) and left frontal lobe (-27, -46, 28). The one cluster (size 962) of increased FC on thalamus network overlapped the precuneus near to right parietal lobe (9, -52, 46) and right cingulate gyrus (15, -43, 43) in health controls.

CONCLUSIONSAbnormal functional networks exist in earlier manifestation of MDD related to MRC by both cortex and limbic sections. The increased functional connectivity of pgACC and decreased functional connectivity of thalamus is mainly involved in bias mood processing and cognition.

Adult ; Depressive Disorder, Major ; physiopathology ; Female ; Gyrus Cinguli ; physiopathology ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Thalamus ; physiopathology

This study sought to reveal the difference in resting-state brain functions between subjects with major depressive disorder and normal controls. Fifty-three depressed patients diagnosed with DSM-IV and 38 normal controls underwent resting-state functional magnetic resonance imaging (fMRI), and the data were analyzed using a new method called Regional Homogeneity (ReHo). Then voxel wised comparison was made to derive the resting-state brain function differences between groups. Compared with normal controls, depressed subjects showed decreased ReHo in bilateral anterior cingulate cortex (ACC), left medial frontal gyrus, and left middle temporal gyrus. Significant decreased ReHo in ACC might suggest less spontaneous neuronal activities or lower baseline brain activities of ACC in depressed subjects in comparison with normal controls.
Adult ; Brain ; physiopathology ; Case-Control Studies ; Depressive Disorder, Major ; physiopathology ; Female ; Gyrus Cinguli ; physiopathology ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Young Adult

BACKGROUNDPainful physical symptoms (PPS) may present as a component of major depressive disorder (MDD). Their effect in Chinese patients has not been investigated. This analysis reports the changes in disease severity, treatment patterns, quality of life and outcomes in a Chinese cohort according to the presence (PPS+) or absence (PPS-) of painful physical symptoms.

METHODSA subgroup of Chinese patients from a large observational 3-month study of patients from Asian countries and regions of China were classified using the modified Somatic Symptom Inventory (SSI) as PPS+ (mean score >or= 2) or PPS- (mean score < 2). Depression severity was assessed with the Clinical Global Impression of Severity (CGI-S) scale and 17-item Hamilton depression rating scale (HAMD(17)). Pain severity was measured using a visual analogue scale (VAS), while the EuroQoL (EQ-5D) assessed patient well-being. Antidepressants were compared with regard to their efficacy.

RESULTSOf the 299 Chinese patients enrolled in the study, 105 were classified as PPS+ (73/105, 70% women). At baseline, PPS+ patients reported greater pain severity (VAS, mean (SD): 49.56 (26.49) vs. 16.60 (20.99) for PPS-, P < 0.01), were more depressed (HAMD(17), mean (SD): 25.32 (5.47) vs. 23.33 (5.24) for PPS-, P = 0.002) and had poorer quality of life (EQ-5D Health State, mean (SD): 38.48 (22.38) vs. 49.57 (18.54) for PPS-, P < 0.001). PPS+ patients showed less overall improvement in depressive symptom severity (HAMD(17), change from baseline (95%CI): -17.38 (-18.65, -16.12) vs. -19.20 (-20.05, -18.35) for PPS-, P = 0.032; CGI-S, change from baseline (95%CI): -2.85 (-3.11, -2.58) vs. -3.20 (-3.38, -3.02) for PPS-, P = 0.044).

CONCLUSIONSPPS were less frequent than expected compared with previous studies of Asian populations. PPS+ were associated with greater MDD severity and less improvement than PPS- when antidepressants were given.

Adult ; Antidepressive Agents ; therapeutic use ; Asian Continental Ancestry Group ; Depressive Disorder, Major ; drug therapy ; pathology ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Pain ; drug therapy ; pathology ; physiopathology ; Quality of Life ; Severity of Illness Index

Animals ; Brain ; metabolism ; Dehydroepiandrosterone ; therapeutic use ; Depressive Disorder, Major ; drug therapy ; metabolism ; physiopathology ; Humans ; Metyrapone ; therapeutic use ; Mifepristone ; therapeutic use ; Psychotic Disorders ; drug therapy ; metabolism ; physiopathology ; Pyrimidines ; therapeutic use ; Receptors, Corticotropin-Releasing Hormone ; antagonists & inhibitors ; Receptors, Glucocorticoid ; antagonists & inhibitors ; metabolism