Low-frequency rTMS induces modifications in cortical structural connectivity - functional connectivity coupling in schizophrenia patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC-FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC-FC coupling compared to healthy controls. Notably, SC-FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC-FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC-FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low-frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.

The impact of depressive and anxious symptoms on non-suicidal self-injury behavior in adolescents: a network analysis.

PURPOSE: Conceptualizing adolescent NSSI and emotional symptoms as a system of causal elements could provide valuable insights into the development of non-suicidal self-injury (NSSI) in adolescent. This study aimed to explore the intricate relationship between NSSI, depressive symptoms, and anxious symptoms in adolescents, identifying key symptoms to establish a theoretical foundation for targeted and effective interventions addressing NSSI behaviors in this population. METHODS: A total of 412 adolescents with NSSI behaviors were selected from outpatients. Generalized anxious disorder scale (GAD-7) and patient health questionnaire (PHQ-9) were employed to measure anxious symptoms and depressive symptoms, respectively. The adolescent non-suicidal self-injury assessment questionnaire (ANSSIAQ) was used to evaluate NSSI of adolescent. Using network analysis, the NSSI、depressive symptoms and anxious symptoms network were constructed to identify the most central symptoms and the bridge symptoms within the networks. RESULTS: The findings revealed that the NSSI functional nodes "coping with sadness and disappointment" and "relieving stress or anxious" exhibited the strongest correlation, with a regularized partial correlation coefficient was 0.401. The symptoms "having a desire to harm oneself and unable to stop" and the node "depressive symptoms" had the highest strength centrality in the network, and their strength centrality indices were 1.267 and 1.263, respectively. The bridge nodes were "having a desire to harm oneself and unable to stop" and "expressing one's despair and hopelessness", with expected impact indices of 0.389 and 0.396, respectively. CONCLUSION: In adolescents, the network revealed a closer connection between NSSI and depressive symptoms. "The desire to not stop hurting oneself" is not only broadly connected to other nodes but also could activate other nodes to maintain NSSI behavior. In light of these findings, precise targets for pharmacological treatment, psychotherapy, physical therapy, etc., are identified for adolescents with NSSI. Targeting this specific aspect in interventions may contribute to preventing and reducing NSSI behavior in adolescents.

Cerebral blood flow changes in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.

Auditory verbal hallucinations (AVH) are a prominent symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been evidenced to improve the treatment of AVH in schizophrenia. Although abnormalities in resting-state cerebral blood flow (CBF) have been reported in schizophrenia, the perfusion alterations specific to schizophrenia patients with AVH during rTMS require further investigation. In this study, we used arterial spin labeling (ASL) to investigate changes in brain perfusion in schizophrenia patients with AVH, and their associations with clinical improvement following low-frequency rTMS treatment applied to the left temporoparietal junction area. We observed improvements in clinical symptoms (e.g., positive symptoms and AVH) and certain neurocognitive functions (e.g., verbal learning and visual learning) following treatment. Furthermore, at baseline, the patients showed reductions in CBF in regions associated with language, sensory, and cognition compared to controls, primarily located in the prefrontal cortices (e.g., left inferior frontal gyrus and left middle frontal gyrus), occipital lobe (e.g., left calcarine cortex), and cingulate cortex (e.g., bilateral middle cingulate cortex), compared to controls. Conversely, we observed increased CBF in the left inferior temporal gyrus and bilateral putamen in patients relative to controls, regions known to be involved in AVH. However, the hypoperfusion or hyperperfusion patterns did not persist and instead were normalized, and were related to clinical response (e.g., AVH) in patients during low-frequency rTMS treatment. Importantly, the changes in brain perfusion were related to clinical response (e.g., AVH) in patients. Our findings suggest that low-frequency rTMS can regulate brain perfusion involving critical circuits by its remote effect in schizophrenia, and may play an important mechanistic role in the treatment of AVH.

A cross-lagged analysis of the relationship between short video overuse behavior and depression among college students.

Introduction: Watching short videos on mobile phones is currently a very prevalent phenomenon. It has been found in research that excessive use of short videos is closely related to depression. The aim of this study is to investigate the relationship between short video overuse behavior and depression among college students as well as the gender differences that are present in such relationship. Methods: A follow-up measurement was conducted on 331 college students using the Short Video Usage Behavior Scale and the Epidemic Research Center Depression Scale with an interval of 2 months. Results: (1) Correlation analysis revealed a significant positive correlation between short video overuse behavior and depression, whether measured at the same or different time points, repeated measures ANOVA indicates that short video overuse behavior and depression have strong stability within the interval between two measurements. (2) Pre-test short video overuse behavior could significantly and positively predict post-test depression, whereas pre-test depression could not significantly predict post-test short video overuse behavior. (3) The cross-lagged effect between short video overuse behavior and depression showed no gender differences. Discussion: These findings indicate that, for college students, short video overuse behavior may increase the risk of depression, whereas depression cannot induce short video overuse behavior.

Targeting auditory verbal hallucinations in schizophrenia: effective connectivity changes induced by low-frequency rTMS.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

The efficacy of low frequency repetitive transcial magnetic stimulation for treating auditory verbal hallucinations in schizophrenia: Insights from functional gradient analyses.

Background: Auditory Verbal Hallucinations (AVH) constitute a prominent feature of schizophrenia. Although low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic benefits in ameliorating AVH, the underlying mechanisms of its efficacy necessitate further elucidation. Objective: This study investigated the cortical gradient characteristics and their associations with clinical responses in schizophrenia patients with AVH, mediated through 1 Hz rTMS targeting the left temporoparietal junction. Method: Functional gradient metrics were employed to examine the hierarchy patterns of cortical organization, capturing whole-brain functional connectivity profiles in patients and controls. Results: The 1 Hz rTMS treatment effectively ameliorated the positive symptoms in patients, specifically targeting AVH. Initial evaluations revealed expanded global gradient distribution patterns and specific principal gradient variations in certain brain regions in patients at baseline compared to a control cohort. Following treatment, these divergent global and local patterns showed signs of normalizing. Furthermore, there was observed a closer alignment in between-network dispersion among various networks after treatment, including the somatomotor, attention, and limbic networks, indicating a potential harmonization of brain functionality. Conclusion: Low-frequency rTMS induces alternations in principal functional gradient patterns, may serve as imaging markers to elucidate the mechanisms underpinning the therapeutic efficacy of rTMS on AVH in schizophrenia.

Alterations in brain connectivity patterns in schizophrenia patients with auditory verbal hallucinations during low frequency repetitive transcranial magnetic stimulation.

OBJECTIVE: Auditory verbal hallucinations (AVH) are a characteristic symptom of schizophrenia. Although low-frequency repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to alleviate the severity of AVH, its exact neurophysiological mechanisms remain unclear. This study aimed to elucidate the alterations in brain connectivity patterns in schizophrenia patients with AVH after low frequency rTMS. Furthermore, the relationship between these alterations and clinical outcomes was examined, thereby identifying potential biomarkers for rTMS treatment efficacy. METHODS: A total of 30 schizophrenia patients with AVH and 33 healthy controls were recruited. The patients received 1 Hz rTMS applied to the left temporoparietal junction region over 15 days. Resting-state functional magnetic resonance imaging scans were conducted for all participants. Subsequently, degree centrality (DC) and seed-based functional connectivity (FC) analyses were employed to identify specific alterations in brain connectivity patterns after rTMS treatment. RESULTS: At baseline, patients exhibited divergent DC patterns in the frontal, occipital, and limbic lobes compared to healthy controls. In addition, prior to treatment, patients demonstrated altered FC from the superior frontal gyrus seeds that linked to the frontal, temporal, and somatosensory regions. Following rTMS treatment, these abnormalities were notably reversed, correlating with improved clinical outcomes. CONCLUSIONS: These findings demonstrate that schizophrenia patients with AVH exhibited atypical interactions within the frontal and temporal lobes. These alterations might be crucial biomarkers for predicting the efficacy of low frequency rTMS.

Impact of low-frequency repetitive transcranial magnetic stimulation on functional network connectivity in schizophrenia patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has shown potential in the treatment of AVH. However, the underlying neural mechanismof rTMS in the treatment of AVH remains largely unknown. In this study, we used a static and dynamic functional network connectivity approach to investigate the connectivity changes among the brain functional networks in schizophrenia patients with AVH receiving 1 Hz rTMS treatment. The static functional network connectivity (sFNC) analysis revealed that patients at baseline had significantly decreased connectivity between the default mode network (DMN) and language network (LAN), and within the executive control network (ECN) as well as within the auditory network (AUD) compared to controls. However, the abnormal network connectivity patterns were normalized or restored after rTMS treatment in patients, instead of increased connectivity between the ECN and LAN, as well as within the AUD. Moreover, the dynamic functional network connectivity (dFNC) analysis showed that the patients at baseline spent more time in this state that was characterized by strongly negative connectivity between the ENC and AUD, as well as within the AUD relative to controls. While after rTMS treatment, the patients showed a higher occurrence rate in this state that was characterized by strongly positive connectivity among the LAN, DMN, and ENC, as well as within the ECN. In addition, the altered static and dynamic connectivity properties were associated with reduced severity of clinical symptoms. Both sFNC and dFNC analyses provided complementary information and suggested that low-frequency rTMS treatment could induce intrinsic functional network alternations and contribute to improvements in clinical symptoms in patients with AVH.

The Static and dynamic functional connectivity characteristics of the left temporoparietal junction region in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.

Background: Auditory verbal hallucinations (AVH) are a core symptom of schizophrenia. Low-frequency (e.g., 1 Hz) repetitive transcranial magnetic stimulation (rTMS) targeting language processing regions (e.g., left TPJ) has been evident as a potential treatment for AVH. However, the underlying neural mechanisms of the rTMS treatment effect remain unclear. The present study aimed to investigate the effects of 1 Hz rTMS on functional connectivity (FC) of the temporoparietal junction area (TPJ) seed with the whole brain in schizophrenia patients with AVH. Methods: Using a single-blind placebo-controlled randomized clinical trial, 55 patients with AVH were randomly divided into active treatment group (n = 30) or placebo group (n = 25). The active treatment group receive 15-day 1 Hz rTMS stimulation to the left TPJ, whereas the placebo group received sham rTMS stimulation to the same site. Resting-state fMRI scans and clinical measures were acquired for all patients before and after treatment. The seed-based (left TPJ) static and DFC was used to assess the connectivity characteristics during rTMS treatment in patients with AVH. Results: Overall, symptom improvement following 1 Hz rTMS treatment was found in the active treatment group, whereas no change occurred in the placebo group. Moreover, decreased static FC (SFC) of the left TPJ with the right temporal lobes, as well as increased SFC with the prefrontal cortex and subcortical structure were observed in active rTMS group. Increased dynamic FC (DFC) of the left TPJ with frontoparietal areas was also found in the active rTMS group. However, seed-based SFC and DFC were reduced to a great extent in the placebo group. In addition, these changed FC (SFC) strengths in the active rTMS group were associated with reduced severity of clinical outcomes (e.g., positive symptoms). Conclusion: The application of 1 Hz rTMS over the left TPJ may affect connectivity characteristics of the targeted region and contribute to clinical improvement, which shed light on the therapeutic effect of rTMS on schizophrenia with AVH.

Mental health status and related influencing factors in patients with COVID-19.

BACKGROUND: The outbreak of the Corona Virus Disease 2019 (COVID-2019) has resulted in a significant number of diagnosed patients requiring treatment in designated hospitals. However, limited evidence exists regarding the prevalence of mental health problems and associated psychological factors in COVID-19 patients. OBJECTIVES: This study investigated the prevalence rates of anxiety, depression, and insomnia among COVID-19 patients, as well as explored the associations between these mental health problems and psychological factors. METHODS: A cross-sectional study was conducted among 387 COVID-19 patients in a designated shelter hospital. Online measures were used to assess anxiety, depression, insomnia, social support, coping styles, and emotional regulation. Data were analyzed to determine the prevalence rates of mental health problems and examine the associations between these problems and the psychological factors. RESULTS: The results revealed high prevalence rates of anxiety (21.80%), depression (49.0%), and insomnia (63.70%) among COVID-19 patients. Objective social support scores and positive coping style scores were significantly associated with lower levels of anxiety, depression, and insomnia, respectively. Conversely, high negative coping style scores, higher education level, and self-perceived illness severity, were significantly related to higher levels of anxiety, depression, or insomnia symptoms. Emotional regulation scores did not show a significant association with any of the examined mental health problems. CONCLUSIONS: These findings have implications for guiding psychological interventions tailored to COVID-19 patients in future outbreaks. By targeting social support and promoting adaptive coping strategies, psychological interventions can address the psychological distress experienced by COVID-19 patients.

Rich-club reorganization of white matter structural network in schizophrenia patients with auditory verbal hallucinations following 1 Hz rTMS treatment.

The human brain comprises a large-scale structural network of regions and interregional pathways, including a selectively defined set of highly central and interconnected hub regions, often referred to as the "rich club", which may play a pivotal role in the integrative processes of the brain. A quintessential symptom of schizophrenia, auditory verbal hallucinations (AVH) have shown a decrease in severity following low-frequency repetitive transcranial magnetic stimulation (rTMS). However, the underlying mechanism of rTMS in treating AVH remains elusive. This study investigated the effect of low-frequency rTMS on the rich-club organization within the brain in patients diagnosed with schizophrenia who experience AVH using diffusion tensor imaging data. Through by constructing structural connectivity networks, we identified several critical rich hub nodes, which constituted a rich-club subnetwork, predominantly located in the prefrontal cortices. Notably, our findings revealed enhanced connection strength and density within the rich-club subnetwork following rTMS treatment. Furthermore, we found that the decreased connectivity within the subnetwork components, including the rich-club subnetwork, was notably enhanced in patients following rTMS treatment. In particular, the increased connectivity strength of the right median superior frontal gyrus, which functions as a critical local bridge, with the right postcentral gyrus exhibited a significant correlation with improvements in both positive symptoms and AVH. These findings provide valuable insights into the role of rTMS in inducing reorganizational changes within the rich-club structural network in schizophrenia and shed light on potential mechanisms through which rTMS may alleviate AVH.

Increased thalamic gray matter volume induced by repetitive transcranial magnetic stimulation treatment in patients with major depressive disorder.

Purpose: Repetitive transcranial magnetic stimulation (rTMS) is an effective therapy in improving depressive symptoms in MDD patients, but the intrinsic mechanism is still unclear. In this study, we investigated the influence of rTMS on brain gray matter volume for alleviating depressive symptoms in MDD patients using structural magnetic resonance imaging (sMRI) data. Methods: Patients with first episode, unmedicated patients with MDD (n = 26), and healthy controls (n = 31) were selected for this study. Depressive symptoms were assessed before and after treatment by using the HAMD-17 score. High-frequency rTMS treatment was conducted in patients with MDD over 15 days. The rTMS treatment target is located at the F3 point of the left dorsolateral prefrontal cortex. Structural magnetic resonance imaging (sMRI) data were collected before and after treatment to compare the changes in brain gray matter volume. Results: Before treatment, patients with MDD had significantly reduced gray matter volumes in the right fusiform gyrus, left and right inferior frontal gyrus (triangular part), left inferior frontal gyrus (orbital part), left parahippocampal gyrus, left thalamus, right precuneus, right calcarine fissure, and right median cingulate gyrus compared with healthy controls (P < 0.05). After rTMS treatment, significant growth in gray matter volume of the bilateral thalamus was observed in depressed patients (P < 0.05). Conclusion: Bilateral thalamic gray matter volumes were enlarged in the thalamus of MDD patients after rTMS treatment and may be the underlying neural mechanism for the treatment of rTMS on depression.

Low-frequency rTMS treatment alters the topographical organization of functional brain networks in schizophrenia patients with auditory verbal hallucination.

Auditory verbal hallucinations (AVH) are an important characteristic of schizophrenia. Repeated transcranial magnetic stimulation (rTMS) has been evidence to be effective in treating AVH. We evaluated the topological properties of resting-state functional brain networks in schizophrenia patients with AVH (n = 32) who received 1-Hz rTMS treatment and matched healthy controls (n = 33). The results showed that the psychotic symptoms and certain neurocognitive performances in patients were improved by rTMS treatment. Furthermore, the pretreatment patients showed abnormal global topological metrics compared with the controls, including lower global efficiency (Eglob, represents the relative quality of information transmission between all nodes in the network) and higher characteristic path length (Lp, characterizes the mean shortest distance between any two nodes in the network). The pretreament patients also showed decreased local topological metrics relative to the controls, including the nodal shortest path (NLp, quantifies the mean distance between the given node and the other nodes in the network) and nodal efficiency (Ne, measures the information interchange among the neighbor nodes when one node is removed), mainly located in the prefrontal cortex, occipital cortex, and subcortical regions. While the abnormal global and local topological patterns were normalized in patients after rTMS treatment. The multiple linear regression analysis indicated that the baseline topological metrics could be associated with the clinical responses after treatment in the patient group. The results suggested that the topological organization of the functional brain network was globally and regionally altered in schizophrenia patients with AVH after rTMS treatment and may be a potential therapeutic effect for AVH in schizophrenia.

The alternations of nucleus accumbent in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce the severity of auditory verbal hallucinations (AVH) and induce beneficial functional and structural alternations of the brain in schizophrenia patients with AVH. The nucleus accumbens (NAcc) as an important component of the ventral striatum is implicated with the pathology in AVH. However, the induced characteristic patterns of NAcc by low-frequency rTMS in schizophrenia with AVH are seldom explored. We investigated the functional and structural characteristic patterns of NAcc by using seed-based functional connectivity (FC) analysis and gray matter volume (GMV) measurement in schizophrenia patients with AVH during 1 Hz rTMS treatment. Although low-frequency rTMS treatment did not affect the volumetric changes of NAcc, the abnormal FC patterns of NAcc, including increased FC of NAcc with the temporal lobes and decreased FC of NAcc with the frontal cortices in the pretreatment patients compared to healthy controls, were normalized or reversed after treatment. These FC changes were associated with improvements in clinical symptoms and neurocognitive functions. Our findings may extend our understanding of the NAcc in the pathology of schizophrenia with AVH and might be a biomarker of clinical effect for low-frequency rTMS treatment in schizophrenia.

Corrigendum: The alternations of nucleus accumbent in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.

[This corrects the article DOI: 10.3389/fpsyt.2022.971105.].

Impaired sustained attention in groups at high risk for antisocial personality disorder: A contingent negative variation and standardized low-resolution tomographic analysis study.

Objective: This study aimed to explore the characteristics of contingent negative variation (CNV) in groups at high risk for antisocial personality disorder. Materials and methods: A classic CNV paradigm was used to compare the characteristics of attention maintenance among a group of individuals with conduct disorder (CD group; n = 27), a group of individuals with antisocial personality traits (AP; n = 29), a group of individuals with conduct disorder and antisocial personality traits (CD + AP group; n = 25), and a group of healthy controls (CG group; n = 30), to examine the characteristics of the amplitude and latency of CNV in different processing stages. Results: Results of the event-related potential analysis were as follows: The mean amplitude analysis between 500 and 1,000 ms revealed that the mean CNV amplitudes in the CD + AP group (-1.388 ± 0.449 µV, P < 0.001) were significantly lower than that in the CG group (-4.937 ± 0.409 µV). The mean amplitude analysis between 1,000 and 1,500 ms revealed that the mean CNV amplitude in the CD + AP group (-0.931 ± 0.646 µV) was significantly lower than that in the CG group (4.809 ± 0.589 µV, P < 0.001). The mean amplitude analysis between 1,500 and 2,000 ms revealed that the mean CNV amplitude in the CG group (3.121 ± 0.725 µV) was significantly higher than that in the CD + AP group (-0.277 ± 0.795 µV, P = 0.012), whereas the mean CNV amplitude in the CD + AP group was not significantly different in the AP group (P = 0.168) and CD group (P > 0.05). Source localization results indicated altered activity in frontal-temporal regions. Conclusion: The CNV amplitude characteristics in the CD + AP group and AP group were more consistent and fluctuated around the baseline, indicating the absence of attention maintenance resulted in impairments in attention allocation and motor preparation in the CD + AP group and AP group.

Corrigendum: rTMS induces brain functional and structural alternations in schizophrenia patient with auditory verbal hallucination.

[This corrects the article DOI: 10.3389/fnins.2021.722894.].

Impact of low-frequency rTMS on functional connectivity of the dentate nucleus subdomains in schizophrenia patients with auditory verbal hallucination.

Despite low-frequency repetitive transcranial magnetic stimulation (rTMS) is effective in treating schizophrenia patients with auditory verbal hallucinations (AVH), the underlying neural mechanisms of the effect still need to be clarified. Using the cerebellar dentate nucleus (DN) subdomain (dorsal and versal DN) as seeds, the present study investigated resting state functional connectivity (FC) alternations of the seeds with the whole brain and their associations with clinical responses in schizophrenia patients with AVH receiving 1 Hz rTMS treatment. The results showed that the rTMS treatment improved the psychiatric symptoms (e.g., AVH and positive symptoms) and certain neurocognitive functions (e.g., visual learning and verbal learning) in the patients. In addition, the patients at baseline showed increased FC between the DN subdomains and temporal lobes (e.g., right superior temporal gyrus and right middle temporal gyrus) and decreased FC between the DN subdomains and the left superior frontal gyrus, right postcentral gyrus, left supramarginal gyrus and regional cerebellum (e.g., lobule 4-5) compared to controls. Furthermore, these abnormal DN subdomain connectivity patterns did not persist and decreased FC of DN subdomains with cerebellum lobule 4-5 were reversed in patients after rTMS treatment. Linear regression analysis showed that the FC difference values of DN subdomains with the temporal lobes, supramarginal gyrus and cerebellum 4-5 between the patients at baseline and posttreatment were associated with clinical improvements (e.g., AVH and verbal learning) after rTMS treatment. The results suggested that rTMS treatment may modulate the neural circuits of the DN subdomains and hint to underlying neural mechanisms for low-frequency rTMS treating schizophrenia with AVH.

One-year incidence rate of Treatment Resistant Depression (TRD) and treatment characteristics in China.

BACKGROUND: Little is known about the characteristics of Treatment-Resistant Depression (TRD) in China. In previous studies various identification approaches have led to a wide range of results, and it is unclear how Chinese patients compare to those in other studies. METHODS: This is a retrospective cohort study using electronic health records (EHR) from two major psychiatric hospitals in China. Adult major depressive disorder (MDD) patients who initiated pharmaceutical treatment during 2010-2018 were enrolled and follow-up was 1 year. TRD was primarily identified by consensus definition of two failures of adequate (≥4 weeks) regimens. Alternative regimens of 2-weeks and 6-weeks duration, and a data-driven definition were also applied. RESULTS: In the two hospitals, 12,257 (mean age: 40.8y, 63.6% female) and 8314 (mean age: 42.4y, 68.4% female) eligible patients were included. The 1-year incidence rate of TRD was estimated to be 5.2%-7.7% using the primary definition. TRD patients had mean treatment duration of 302.5 days and 285.7 days; had 3.6 and 3.7 treatment steps on average; 94.0% and 72.6% were prescribed polypharmacy regimens, which were all marginally greater than that of non-TRD patients. Alternative definitions resulted in a wide range of incidence estimates (0.5%-20.0%). LIMITATIONS: Medications were assumed to be consumed as prescribed and lack of rating scales from EHRs may limit our TRD identification. CONCLUSIONS: The incidence of TRD among Chinese MDD patients was comparable to other countries under similar settings and more complex treatment characteristics were observed among TRD patients. Alternative TRD definitions revealed the need for better treatment management in practices.

Altered Brain Function and Causal Connectivity Induced by Repetitive Transcranial Magnetic Stimulation Treatment for Major Depressive Disorder.

Objective: Repetitive transcranial magnetic stimulation (rTMS) can effectively improve depression symptoms in patients with major depressive disorder (MDD); however, its mechanism of action remains obscure. This study explored the neuralimaging mechanisms of rTMS in improving depression symptoms in patients with MDD. Methods: In this study, MDD patients with first-episode, drug-naive (n = 29) and healthy controls (n = 33) were enrolled. Depression symptoms before and after rTMS treatment were assessed using the Hamilton Depression Rating Scale (HAMD-17). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected both before and after the treatment. Changes in the brain function after the treatment were compared using the following two indices: the amplitude of the low-frequency fluctuation (ALFF) and regional homogeneity (ReHo), which are sensitive for evaluating spontaneous neuronal activity. The brain region with synchronous changes was selected as the seed point, and the differences in the causal connectivity between the seed point and whole brain before and after rTMS treatment were investigated via Granger causality analysis (GCA). Results: Before treatment, patients with MDD had significantly lower ALFF in the left superior frontal gyrus (p < 0.01), higher ALFF in the left middle frontal gyrus and left precuneus (p < 0.01), and lower ReHo in the left middle frontal and left middle occipital gyri (p < 0.01) than the values observed in healthy controls. After the rTMS treatment, the ALFF was significantly increased in the left superior frontal gyrus (p < 0.01) and decreased in the left middle frontal gyrus and left precuneus (p < 0.01). Furthermore, ReHo was significantly increased in the left middle frontal and left middle occipital gyri (p < 0.01) in patients with MDD. Before treatment, GCA using the left middle frontal gyrus (the brain region with synchronous changes) as the seed point revealed a weak bidirectional causal connectivity between the middle and superior frontal gyri as well as a weak causal connectivity from the inferior temporal to the middle frontal gyri. After treatment, these causal connectivities were strengthened. Moreover, the causal connectivity from the inferior temporal gyrus to the middle frontal gyri negatively correlated with the total HAMD-17 score (r = -0.443, p = 0.021). Conclusion: rTMS treatment not only improves the local neural activity in the middle frontal gyrus, superior frontal gyrus, and precuneus but also strengthens the bidirectional causal connectivity between the middle and superior frontal gyri and the causal connectivity from the inferior temporal to the middle frontal gyri. Changes in these neuroimaging indices may represent the neural mechanisms underlying rTMS treatment in MDD. Clinical Trial Registration: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019761).