Can Fluoxetine Combined with Cognitive Behavioral Therapy Reduce the Suicide and Non-Suicidal Self-Injury Incidence and Recurrence Rate in Depressed Adolescents Compared with Fluoxetine Alone? A Meta-Analysis.

Objective: The efficacy of medication and psychotherapy for adolescent depression is controversial, so we conducted a meta-analysis to evaluate the efficacy of combination therapy. Methods: We followed the PRISMA checklist in completing the meta-analysis. Relevant literature was searched in PubMed, Web of Science and Embase, Chinese databases CNKI and WanFang Data. We included the literature on the comparison of the fluoxetine plus psychotherapy or cognitive-behavioral therapy (CBT) and each treatment alone for adolescent depression published in 1980-2021. All statistical analyses were performed using Stata software. Results: After careful review, a total of 489 relevant articles were retrieved, and 13 studies were finally included. In comparison with the control group (fluoxetine alone), fluoxetine plus CBT achieved higher response rate (RR=1.12, 95% CI: 1.04, 1.21), lower incidence of adverse Reactions (RR=0.62,95% CI:0.40,0.96), lower proportion of suicide or self-injury (RR=0.94,95% CI:0.74,1.20), and lower one-year recurrence rate (RR=0.27, 95% CI: 0.16, 0.45). Before treatment, there were no significant differences in Hamilton Depression Scale score (HAMD), Children's Depression Rating Scale Revised (CDRS-R) score, and Clinical Global Impression (CGI) Severity score. After treatment, HAMD score (SMD=-1.01, 95% CI:-1.39,-0.63), CDRS-R score (SMD= -0.10,95% CI:-0.26,-0.07), and CGI score (SMD = -0.22, 95% CI: -0.54, -0.10) were significantly lower in the combined treatment group than in the control group. Conclusion: Adolescents simultaneously treated with fluoxetine and CBT had significantly reduced incidence of depressive symptoms, suicide or NSSI, adverse reactions, and one-year recurrence of symptoms, than adolescents treated with fluoxetine alone. This indicates fluoxetine plus CBT may be superior to fluoxetine alone for the clinical treatment of adolescent depression.

Electroconvulsive Therapy-Induced Changes in Functional Brain Network of Major Depressive Disorder Patients: A Longitudinal Resting-State Electroencephalography Study.

Objectives: Several studies have shown abnormal network topology in patients with major depressive disorder (MDD). However, changes in functional brain networks associated with electroconvulsive therapy (ECT) remission based on electroencephalography (EEG) signals have yet to be investigated. Methods: Nineteen-channel resting-state eyes-closed EEG signals were collected from 24 MDD patients pre- and post-ECT treatment. Functional brain networks were constructed by using various coupling methods and binarization techniques. Changes in functional connectivity and network metrics after ECT treatment and relationships between network metrics and clinical symptoms were explored. Results: ECT significantly increased global efficiency, edge betweenness centrality, local efficiency, and mean degree of alpha band after ECT treatment, and an increase in these network metrics had significant correlations with decreased depressive symptoms in repeated measures correlation. In addition, ECT regulated the distribution of hubs in frontal and occipital lobes. Conclusion: ECT modulated the brain's global and local information-processing patterns. In addition, an ECT-induced increase in network metrics was associated with clinical remission. Significance: These findings might present the evidence for us to understand how ECT regulated the topology organization in functional brain networks of clinically remitted depressive patients.

Fecal microbiota transplantation ameliorates stress-induced depression-like behaviors associated with the inhibition of glial and NLRP3 inflammasome in rat brain.

BACKGROUND: Evidence from previous studies has demonstrated that the gut-microbiota-brain axis is vital in regulating of behavior and neuroinflammation in the central nervous system. Considering the putative connection among gut microbiota, neural function, and behavior, the present study investigated the potential signaling of gut microbiota to modulate depression-like behaviors and neuroinflammation. METHODS: Rats showing depression-like behaviors induced by chronic unpredictable mild stress received fecal microbiota treatment or vehicle for 14 days, and alterations in behavior and neuroinflammation were assessed. ELISA, immunofluorescence staining and Western blot were used to analysis the activation of glial cells and NLRP3 inflammasome. RESULTS: Treatment with fecal microbiota transplantation ameliorated depression-like behaviors. 5-Hydroxytryptamine decreased in the chronic unpredictable mild stress rat model but significantly increased after fecal microbiota transplantation. The treatment with fecal microbiota transplantation decreased the production of IL-1ß and TNF-α. Moreover, fecal microbiota transplantation administration suppressed the activation of Iba1 positive microglia cells and GFAP positive astrocytes cells and reduced the expression of NLRP3, ASC, Caspase-1, and IL-1ß pathway in the prefrontal cortex and hippocampus. CONCLUSIONS: Fecal microbiota transplantation can improve depression-like behaviors induced by chronic unpredictable mild stress. The anti-depression effects of fecal microbiota transplantation were associated with the suppressed activation of glial cells and NLRP3 inflammasome in the brain.

Fecal microbiota transplantation ameliorates gut microbiota imbalance and intestinal barrier damage in rats with stress-induced depressive-like behavior.

The gut-microbiota-brain axis is the most important complex and bidirectional pathway between the gastrointestinal tract and the central nervous system. This study investigated the potential of microbe-induced gut-to-brain signaling to modulate the effect of stress on depressive-like behavior, intestinal barrier, and neuroinflammation. Result showed that fecal microbiota transplantation increased the consumption of sucrose solutions and decreased the immobility time in forced swimming test. This treatment also increased Firmicutes and decreased Bacteroidetes and Desulfobacterota at phylum levels; reduced the loss of villi and epithelial cells; suppressed the inflammatory cell infiltration in the ileum; increased the expression of ZO-1, occludin; protected the mucosal layer function; and suppressed the high levels of inflammasomes (NLRP3, ASC, caspase-1, and IL-1ß) in rat brain. In summary, fecal microbiota transplantation improves the depressive-like behavior, alters the gut microbiota imbalance, and alleviates the intestinal tract inflammation, intestinal mucosa disruption, and neuroinflammation in rats induced by chronic unpredictable mild stress.

Strategies to solve the reverse inference fallacy in future MRI studies of schizophrenia: a review.

Few advances in schizophrenia research have been translated into clinical practice, despite 60 years of serum biomarkers studies and 50 years of genetic studies. During the last 30 years, neuroimaging studies on schizophrenia have gradually increased, partly due to the beautiful prospect that the pathophysiology of schizophrenia could be explained entirely by the Human Connectome Project (HCP). However, the fallacy of reverse inference has been a critical problem of the HCP. For this reason, there is a dire need for new strategies or research "bridges" to further schizophrenia at the biological level. To understand the importance of research "bridges," it is vital to examine the strengths and weaknesses of the recent literature. Hence, in this review, our team has summarized the recent literature (1995-2018) about magnetic resonance imaging (MRI) of schizophrenia in terms of regional and global structural and functional alterations. We have also provided a new proposal that may supplement the HCP for studying schizophrenia. As postulated, despite the vast number of MRI studies in schizophrenia, the lack of homogeneity between the studies, along with the relatedness of schizophrenia with other neurological disorders, has hindered the study of schizophrenia. In addition, the reverse inference cannot be used to diagnose schizophrenia, further limiting the clinical impact of findings from medical imaging studies. We believe that multidisciplinary technologies may be used to develop research "bridges" to further investigate schizophrenia at the single neuron or neuron cluster levels. We have postulated about future strategies for overcoming the current limitations and establishing the research "bridges," with an emphasis on multimodality imaging, molecular imaging, neuron cluster signals, single transmitter biomarkers, and nanotechnology. These research "bridges" may help solve the reverse inference fallacy and improve our understanding of schizophrenia for future studies.

Abberant inverted U-shaped brain pattern and trait-related retinal impairment in schizophrenia patients with combined auditory and visual hallucinations: a pilot study.

Schizophrenic patients often experience auditory hallucinations (AHs) and visual hallucinations (VHs). However, brain and retinal alterations associated with combined AHs and VHs in schizophrenic patients are unknown. This study aimed o investigate brain and retinal alterations in first episode un-treated schizophrenic patients with combined AHs and VHs (FUSCHAV). FUSCHAV patients (n = 120), divided into four groups according to severity of AH and VH symptoms, were compared to healthy controls (n = 30). Gray matter volume (GMV) and global functional connectivity density (gFCD) were recorded to reflect brain structure and functional alterations. Total retinal thickness was acquired by optical coherence tomography to assess retinal impairment. The majority of FUSCHAV patients (85.8%) demonstrated both GMV reduction and gFCD increases along with retinal thinning compared to healthy controls. The severity of GMV reduction and gFCD increase differed between patient groups, ranked from highest to lowest severity as follows: severe AHs combined with severe VHs (FUSCHSASV, 20 patients), moderate AHs combined with severe VHs (FUSCHMASV, 23 patients), severe AHs combined with moderate VHs (FUSCHSAMV, 28 patients), and moderate AHs combined with moderate VHs (FUSCHMAMV, 26). Retinal impairment was similar among the four FUSCHAV groups. GMV reduction and gFCD increases in the frontal-parietal lobule show an inverted U-shaped pattern among FUSCHAV patients according to AH and VH severity, while retinal impairment remains stable among FUSCHAV groups. These findings indicate a reciprocal deterioration in auditory and visual disturbances among FUSCHAV patients.

A typical antipsychotic treatment induced gradually expanding white matter alterations in healthy individuals with persistent auditory verbal hallucinations-an artificially controlled pilot study.

OBJECTIVE: The aim of this study was to explore the effects of atypical antipsychotics (AaPs) on brain white matter (WM) tracts in healthy individuals with auditory verbal hallucinations (Hi-AVHs). METHODS: We analyzed neuroimaging, AVH symptoms, and cognitive assessment data obtained from 39 Hi-AVHs who reported being distressed by persistent AVHs and volunteered to receive AaP treatment. We used tract-based spatial statistics (TBSS) and t tests to explore AaP pharmacotherapy effects on AVH symptoms and brain WM alterations in Hi-AVH subjects. RESULTS: TBSS and t tests revealed WM alterations after AaP treatment, relative to pretreatment observations. Although AaPs alleviated AVH symptoms, WM alterations in these subjects expanded over 8 months of AaP treatment, encompassing most major WM tracts by the end of the observation period, including the corpus callosum, arcuate fasciculus, cortico-spinal tracts, anterior commissure, and posterior commissure. CONCLUSIONS: The worsening of AaP-associated WM alterations observed in this study suggest that AaPs may not be a good choice for the treatment of Hi-AVHs despite their ability to alleviate AVHs.

Efficacy of Sertraline Combined with Cognitive Behavioral Therapy for Adolescent Depression: A Systematic Review and Meta-Analysis.

OBJECTIVE: The efficacy of antidepressant drugs combined with psychotherapy is controversial; hence, this meta-analysis was conducted to assess the efficacy of the combination therapy. METHODS: Relevant literature was searched in PubMed, Web of Science and Embase, Chinese databases CNKI, and WanFang Data. We included the literature on the comparison of the sertraline combined with cognitive behavioral therapy (CBT) and each treatment alone for adolescent depression published in 2000-2021. Meta-analysis was performed using Stata16.0 software. RESULTS: A total of 421 relevant articles were retrieved, and 14 studies were finally included. In comparison with the control group (sertraline), sertraline combined with CBT achieved higher response rate (OR = 5.07, 95% CI: 3.00, 8.58) and lower incidence of adverse reactions (OR = 0.43, 95% CI: 0.24, 0.75). Before treatment, there were no significant differences in depression score, anxiety score, and symptom self-rating scale score between the two groups. After treatment, depression score (SMD = -2.79, 95% CI: -3.64, -1.94), anxiety score (SMD = -1.22, 95% CI: -1.96, -0.47), and symptom self-rating scale score (SMD = -1.73, 95% CI: -3.19, -0.27) were significantly lower in the combined treatment group than in the control group. CONCLUSION: Although the number of comparative trials is small, this study shows that sertraline is effective for adolescent depression, but sertraline combined with CBT is more effective. The latter can significantly reduce the incidence of depressive symptoms, anxiety, and adverse reactions in patients. Therefore, this combination therapy is recommended for the clinical treatment of adolescent depression.

Disrupted pathways from frontal-parietal cortex to basal ganglia and cerebellum in patients with unmedicated obsessive compulsive disorder as observed by whole-brain resting-state effective connectivity analysis - a small sample pilot study.

OBJECTIVE: To date, a systematic characterization of abnormalities in resting-state effective connectivity (rsEC) in obsessive-compulsive disorder (OCD) is lacking. The present study aimed to systematically characterize whole-brain rsEC in OCD patients as compared to healthy controls. METHODS: Using resting-state fMRI data of 50 unmedicated patients with OCD and 50 healthy participants, we constructed whole-brain rsEC networks using Granger causality analysis followed by univariate and multivariate comparisons between patients and controls. Similar analyses were performed for resting-state functional connectivity (rsFC) networks to examine how rsFC and rsEC differentially capture abnormal brain connectivity in OCD. RESULTS: Univariate comparisons identified 10 rsEC networks that were significantly disrupted in patients, and which were mainly associated with frontal-parietal cortex, basal ganglia, and cerebellum. Conversely, abnormal rsFC networks were widely distributed throughout the whole brain. Multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls using combined whole-brain rsEC and rsFC. CONCLUSIONS: The results of the present study suggest disrupted communication of information from frontal-parietal cortex to basal ganglia and cerebellum in OCD patients. Using combined whole-brain rsEC and rsFC, multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls. The alterations observed in OCD patients could aid in identifying treatment mechanisms for OCD.

Left Cerebral Cortex Complexity in Patients with Major Depression Disorder: A Small-Sample Pilot Study.

Objective: To investigate cerebral cortical complexity (CCC) in patients with first-episode, drug-naive major depressive disorder (MDD) with source-based morphometry (SBM) analyses. Methods: We used the SBM parameters gyrification index (GI) and fractal dimension (FD) to evaluate CCC in 14 first-episode, drug-naive patients diagnosed with MDD. The severity of depression symptoms was assessed with the 17-item Hamilton Depression Scale (HAMD-17). GI and FD alterations in the MDD group, relative to healthy controls (HCs), were correlated with depression symptom severity with GI/FD. Results: Increased GIs in the MDD group, relative to HCs, were found mainly in the left postcentral gyrus, whereas GI reductions were found in the left angular gyrus, left lingual gyrus, left superior temporal gyrus, and left insular cortex. Increased FDs in the MDD group, relative to HCs, were located in the superior frontal gyrus. In contrast, decreased FDs were located in the left superior temporal gyrus and left superior frontal gyrus. Conclusion: Although the group differences in GI and FD values obtained did not withstand family-wise error (FWE) correction, the results show a consistent trend of alterations in left-hemisphere CCC in first-episode, drug-naive patients diagnosed with MDD. These findings support the hypothesis that there is a pattern of subtle neocortical aberrations in early-stage MDD.

Unstructured Group Support Enhances Compliance to Pharmacological Treatment by Improving Social Cognition in Patients with Bipolar Disorder: A Pilot fMRI Study.

Objective: Unstructured group support (UGS) has been shown to improve the prognosis of patients with bipolar disorder (BP). However, objective evidence is needed to support implementation of UGS intervention. This study aimed to investigate the effectiveness of UGS intervention and the associated alterations in the objective indexes, mainly global function connectivity density (gFCD), in BP patients. Methods: Remitted BP patients were enrolled and randomly assigned into a UGS group (received UGS intervention for 26 weekly UGS sessions, and a sham group (received sham intervention). The effects of UGS on adherence to the prescribed medications, social cognition, and quality of life were examined and compared between these 2 groups. Magnetic resonance imaging (MRI) was performed to determine the functional index and gFCD values, as an objective measurement of functional alterations in the brain. Results: The compliance rate was significantly greater in the UGS group than in the sham group at the 2-year follow-up, after 26 weekly intervention sessions. The proportion of patients with increased levels of compliance to pharmacological treatment, improved social cognition, and improved quality of life were significantly higher in the UGS group than in the sham group. Furthermore, consistent with these subjective measurements, the fMRI study revealed that gFCD values significantly increased in the regions of the brain that are related to social cognition, in patients with UGS intervention. Conclusion: UGS improves the compliance to pharmacological treatment, quality of life, and social cognition of remitted BP patients. Notably, these findings offer the first objective evidence that UGS enhances gFCD in BP patients. Thus, UGS implementation can help improve the psychiatric care for BP patients.

Plasma Orexin Levels Related to Altered Brain Activity During Abstinence in Patients with Alcohol Dependence.

Objectives: In vivo studies have correlated brain activity with alcohol-seeking behavior, while clinical studies have identified altered brain activity in patients with alcohol dependence (AD) even during abstinence. We aimed to explore the relationship between plasma orexin levels, brain activity, and alcohol-craving scores in patients with AD. Methods: In this pilot study, we evaluated 24 male patients with AD in remission and 25 male controls. Alcohol craving was assessed using the Obsessive Compulsive Drinking Scale (OCDS). An adapted MRI technique was used to assess global functional connectivity density (gFCD), and plasma orexin concentrations were measured by radioimmunoassay. Associations were analyzed by the Pearson correlation. Results: Plasma orexin levels in AD patients in remission were significantly higher than those in the controls. OCDS scores correlated to orexin concentrations (r = 0.47, P < .05). Compared to the controls, all AD patients demonstrated reduced gFCD, primarily in the frontal, temporal, and parietal lobes, and increased gFCD in the accumbens nuclei and posterior insular cortex. Mean gFCD values in the accumbens nuclei significantly correlated to craving scores (r = 0.55, P < .05). Although assessed during abstinence, the reward circuits in AD patients exhibited increased activity. Orexin levels correlated to increased activity in the accumbens nuclei and craving scores. Conclusions: The potential clinical utility of plasma orexin levels to assess the risk of relapse in AD patients in treatment and prevention programs deserves further study.

The Impact of Adverse Childhood Experiences on Mobile Phone Addiction in Chinese College Students: A Serial Multiple Mediator Model.

Mobile phone addiction is a universal phenomenon that has attracted a lot of attention in recent years. Previous researches revealed a significant relation between adverse childhood experiences (ACEs) and addiction. This study further investigated the association between ACEs and mobile phone addiction, and the mediating effects of attachment styles and interpersonal relationships. The cross-sectional design and multiple questionnaires, namely, the Revised Adverse Childhood Experience Questionnaire, the Mobile Phone Addiction Index, the Revised Adult Attachment Scale (AAS), and the Interpersonal Relationship Comprehensive Diagnostic Scale (IRCDS) were used in the sample of 345 university students. Correlation analysis revealed that adverse childhood experience, attachment anxiety, attachment avoidance, interpersonal relationship, and mobile phone addiction were significantly positively correlated with each other. Results of regression analysis showed that attachment style and interpersonal relationship played multiple mediation roles in the association between adverse childhood experience and mobile phone addiction. That is, (1) adverse childhood experience was positively related to mobile phone addiction, (2) both attachment anxiety and interpersonal relationship played partial and parallel mediating roles between adverse childhood experience and mobile phone addiction, and (3) attachment anxiety/avoidance and interpersonal relationship mediated the relationship between adverse childhood experience and mobile phone addiction sequentially. These results indicated that mobile phone addiction among college students who had adverse childhood experience can be relieved by way of the remission of attachment anxiety, reduction of attachment avoidance, and improvement of interpersonal relationship.

Metformin Enhances Antidepressant/Antipsychotic Combination Therapy of Schizophrenia With Comorbid Depression in a Murine Model.

Comorbid depressive disorders confound the diagnosis and therapy of schizophrenia. Using a murine model incorporating both MK801 and chronic unpredictable mild stress exposures, we successfully replicated both psychosis and depression. Ex vivo patch clamp recordings and in vivo calcium imaging demonstrated impaired neural activity in the prefrontal cortex (PFC). We then administered triple-drug combinations consisting of two antidepressants (mirtazapine and venlafaxine) plus an antipsychotic (either clozapine or olanzapine), and found improved PFC neuronal activity and performance in behavioral assays. Moreover, the addition of metformin to both psychotropic drug combinations brought further improvements in depressive and schizophrenic-like behaviors and physiological parameters. In summary, our data modeled the neuropathophysiology of schizophrenia with comorbid depression, and may inform drug intervention strategies.

Antipsychotic agents deteriorate brain and retinal function in schizophrenia patients with combined auditory and visual hallucinations: A pilot study and secondary follow-up study.

INTRODUCTION: Schizophrenia patients often experience auditory hallucinations (AHs) and visual hallucinations (VHs). However, the degree and type of brain and retinal alterations associated with combined AHs and VHs in schizophrenia patients remain unknown. There is an urgent need for a study that investigates the trajectory of brain and retinal alterations in patients with first-episode untreated schizophrenia accompanied by combined AHs and VHs (FUSCHAV). METHODS: FUSCHAV patients (n = 120), divided into four groups according to AH and VH symptom severity (severe AHs combined with severe VHs [FUSCHSASV, 20 patients]; middle-to-moderate AHs combined with severe VHs [FUSCHMASV, 23 patients]; severe AHs combined with middle-to-moderate VHs [FUSCHSAMV, 28 patients]; and middle-to-moderate AHs combined with middle-to-moderate VHs [FUSCHMAMV, 26 patients]), were compared to healthy controls (n = 30). Gray matter volume (GMV) was adopted for brain structural alteration assessment. Total retinal thickness was adopted as a measure of retinal thickness impairment. RESULTS: In the pilot study, the rate of GMV reduction showed an inverted U-shaped pattern across the different FUSCHAV patient groups according to AH and VH severity. The degree of retinal impairment remained stable across the groups. More notably, in the secondary follow-up study, we observed that, after 6 months of treatment with antipsychotic agents, all the GMV reduction-related differences across the different patient groups disappeared, and both GMV and retinal thickness demonstrated a tendency to deteriorate. CONCLUSIONS: These findings indicate the need for heightened alertness on brain and retinal impairments in patients with FUSCHAV. Further deteriorations induced by antipsychotic agent treatment should be monitored in clinical practice.

A unified model of shared brain structural alterations in patients with different mental disorders who experience own-thought auditory verbal hallucinations-A pilot study.

OBJECTIVE: To explore shared brain structural alterations in patients diagnosed with mental disorders who experience own-thought auditory verbal hallucinations (OTAVHs). METHODS: A cohort of 143 first-diagnosis, nonmedicated patients with OTAVHs was enrolled: 25 with schizophrenia (FUSCH-OTAVH), 20 with major depression disorder (FUMDD-OTAVH), 28 with bipolar disorder (FUBD-OTAVH), 22 patients with posttraumatic stress disorder (FUPTSD-OTAVH), 21 with anxiety disorder (FUAD-OTAVH), and 27 with borderline personality disorder (FUBPD-OTAVH); 25 healthy controls (HCs) participated. The Auditory Hallucinations Rating Scale (AHRS), multiple psychometric scales, voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and multiple regression were used. RESULTS: Compared with HCs, patients had increased occipital cortex, dorsal prefrontal cortex (PFC), and striatum gray matter volumes (GMVs), a reduced insular cortex (IC) GMV, and an impaired frontooccipital fasciculus. The following differences were found versus HCs: FUSCH-OTAVH, reduced PFC and occipital GMVs, increased striatum and thalamus GMVs, impaired arcuate fasciculus, u-shaped bundle, optic tract, and upper longitudinal fasciculus (LF); FUMDD-OTAVH, increased posterior frontotemporal junction and hippocampus GMVs; FUMN-OTAVH, increased posterior frontotemporal junction and parietal cortex GMVs, reduced hippocampus GMV, impaired upper LF; FUPTSD-OTAVH, increased temporal, hippocampus, and nucleus accumbens GMVs; FUBPD-OTAVH, increased frontotemporal junction and hippocampus GMVs, impaired upper/lower LF; and FUAD-OTAVH, increased frontal and temporal cortex, hippocampus GMVs. CONCLUSIONS: The present findings provide evidence consistent with a bottom-up and top-down reciprocal action dysfunction hypothesis of AVHs and with the dopamine hypothesis of AVHs. We observed specific features related to OTAVHs in patients with different mental disorders. The findings, though complex, provide clues for further studies of specific mental disorders.

Unified and disease specific alterations to brain structure in patients across six categories of mental disorders who experience own-thought auditory verbal hallucinations: A pilot study.

OBJECTIVE: To explore the unified and disease specific structural features of the brain in patients spanning six mental disorders who experience own-thought auditory verbal hallucinations (OTAVH). METHODS: A pilot study was conducted on 25 patients with schizophrenia (FUSCH-OTAVH), 20 patients with major depression disorder (FUMDD-OTAVH), 28 patients with bipolar disorder (FUBD-OTAVH), 22 patients with posttraumatic stress disorder (FUPTSD-OTAVH), 21 patients with anxiety disorder (FUAD-OTAVH), and 27 patients with borderline personality disorder (FUBPD-OTAVH). Twenty-five healthy controls (HCs) were also recruited. Auditory Hallucinations Rating Scale (AHRS) multiple psychometric scales were adopted to assess the clinical features of voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and multiple regression in all patients. Common and specific brain features of OTAVH among these mental disorders were investigated. RESULTS: Compared to HCs, GMV aberrant pattern across all the six categories patients with OTAVH decreased in the occipital cortex, left parietal lobe, prefrontal cortex (PFC), and insular cortex (IC). Aberrant patterns in white matter (WM) were detected in the corpus callosum and impairment of the fronto-occipital fasciculus. Structural differences in the brain were observed for each mental disorder versus HCs. CONCLUSIONS: The unified brain aberrant features of OTAVH across six mental disorders were characterized by decreased GMV and WM impairments in some regions and the specific brain features of each disease were also characterized. In conclusion, this study provides evidence for the structural basis of OTAVH and potential avenues for investigating disease specific brain features of OTAVH.

Rethinking Schizophrenia and Depression Comorbidity as One Psychiatric Disorder Entity: Evidence From Mouse Model.

Schizophrenia is frequently accompanied by depressive symptoms, but the pathological mechanisms remain to be elucidated. In this study, we used chronic unpredicted mild stress plus MK801 injection to generate a mouse model of schizophrenia with depression, in which in vivo 2-photon calcium imaging and electrophysiological recordings were performed in conjunction with behavioral phenotyping. Compared to mice models with classical depression or to schizophrenia models, the animal models with schizophrenia and depression comorbidity presented worse psychotic and depressive symptoms. These behavioral deficits are associated with impaired neuronal calcium activities in the frontal cortex and thalamic nuclei. Moreover, in sharp contrast to classical models that have a satisfactory response to antipsychotic or antidepressant drugs, this novel schizophrenia with depression model is resilient to combined drug treatment in terms of behavioral and functional recovery. Taken together, these data indicate that schizophrenia with depression likely involves a unique pathophysiology that is different from schizophrenia or depression alone.

Ketamine plus propofol-electroconvulsive therapy (ECT) transiently improves the antidepressant effects and the associated brain functional alterations in patients with propofol-ECT-resistant depression.

New methods for using ketamine in patients with propofol-electroconvulsive therapy-resistant depression (ECT-RD) are needed in the clinic. This study aimed to investigate the therapeutic efficacy of ketamine plus ECT in ECT-RD patients, along with the treatment-induced brain alterations. A total of 28 ECT-RD patients were intravenously injected with ketamine six times and treated with propofol-ECT six times alternately within two weeks. The Hamilton Depression Scale was used to assess the treatment effect. Global functional connectivity density (gFCD) and functional connectivity strength (FCS) were used to evaluate functional brain alterations. As compared with the propofol-ECT treatment group, the addition of ketamine could improve the therapeutic outcomes in patients with ECT-RD. The treatment increased gFCD in the left temporal and subgenual anterior cingulated cortex. Simultaneously, the treatment decreased FCS within the default mode network. Although increased functional connectivity could be sustained for 10 days, the clinical effect was only sustained 7 days, indicating that the clinical effect and functional brain alterations were disjointed. Ketamine plus propofol-ECT can obviously improve the effects of propofol-ECT in ECT-RD patients. However, the effect is limited in 7 days, suggesting the benefit is short-term.