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The determination of sunitinib (STB) as a significant anticancer drug is very important. In the present research, a novel and effective electrochemical sensing device for STB was manufactured using the modification of a glassy carbon electrode (GCE) with the 2D layered metal-organic framework-carbon nanotubes (2DMOF-CNTs) nanocomposite. The electro-oxidation of STB exhibited a notable enhancement in the anodic current at +0.70 V, which may be due to the catalytic character of the 2DMOF-CNTs modifier. The key experimental parameters affecting the efficiency of the STB sensor including amount of 2DMOF-CNTs and solution pH of were evaluated and optimized. The 2DMOF-CNTs/GCE demonstrated a linear response in detecting STB, covering a range from 0.02 µM to 30 µM. In addition, the established sensor showed a good detection limit of 5 nM based on signal-to-noise ratio of 3. The successful evaluation of the practical implementation of the 2DMOF-CNTs/GCE for STB detection in serum samples as the real sample was accomplished. The novel electrochemical device possesses several remarkable properties, such as broad linear range, low limit of detection, quick analysis time, high selectivity, and convenient operation.

Abstract Background Norepinephrine transporter (NET) is encoded by the SLC6A2 gene and is a potential target for studying the pathogenesis of PTSD. To the best of our knowledge, no prior investigations have examined SLC6A2 polymorphism-related neuroimaging abnormalities in PTSD patients. Methods In 218 Han Chinese adults who had lost their sole child, we investigated the association between the T-182 C SLC6A2 genotype and gray matter volume (GMV). Participants included 57 PTSD sufferers and 161 non-PTSD sufferers, and each group was further separated into three subgroups based on each participant’s SLC6A2 genotype (TT, CT, and CC). All participants received magnetic resonance imaging (MRI) and clinical evaluation. To assess the effects of PTSD diagnosis, genotype, and genotype × diagnosis interaction on GMV, 2 × 3 full factorial designs were used. Pearson’s correlations were used to examine the association between GMV and CAPS, HAMD, and HAMA. Results The SLC6A2 genotype showed significant main effects on GMV of the left superior parietal gyrus (SPG) and the bilateral middle cingulate gyrus (MCG). Additionally, impacts of the SLC6A2 genotype-diagnosis interaction were discovered in the left superior frontal gyrus (SFG). The CAPS, HAMA, and HAMD scores, as well as the genotype main effect and diagnostic SLC6A2 interaction, did not significantly correlate with each other. Conclusion These findings indicate a modulatory effect that the SLC6A2 polymorphism exerts on the SPG and MCG, irrespective of PTSD diagnosis. We found evidence to suggest that the SLC6A2 genotype-diagnosis interaction on SFG may potentially contribute to PTSD pathogenesis in adults who lost their sole child.

Abstract Background Dysfunctional attitudes, which are characterized by distorted self-cognitions, were considered to be linked to personality traits. It was found that certain personality traits may predict dysfunctional attitudes in patients with major depressive disorder (MDD). Nonetheless, the relationship between personality traits and dysfunctional attitudes remains under-researched. Aims The aim of this study is to examine the relationship between specific domains of Sixteen Personality Factor (16PF) and dysfunctional attitudes in Chinese participants with or without MDD. In addition, the present study explores the associations between 16PF and eight subtypes of dysfunctional attitudes, based on the proposed eight-factor structure of the Chinese version of the Dysfunctional Attitude Scale-Form A (C-DAS-A). Methods One hundred and sixty-eight participants with MDD and 130 healthy participants were included in the study (Trial Registration Number: ChiCTR1800014591). Personality was assessed using the 16PF Questionnaire. Dysfunctional attitudes were measured through the C-DAS-A. Results The 16PF dimensions associated with dysfunctional attitudes and the eight subtypes were mainly concentrated in the four anxiety facets including factors C, L, O, and Q4, in both MDD and HC groups. There were significant differences in the 16 PF dimensions that would explain dysfunctional attitudes between the two groups, which were as follows: factors C, G, and O in the MDD group, and factors L and Q4 in the HC group. Conclusions Personality traits, especially the anxiety-related personality traits, were distinctly associated with the development of dysfunctional attitudes in people with or without MDD.

Abstract Background Associations between adverse childhood experiences (ACEs) and common psychiatric disorders among older Chinese individuals have not been well reported. The objectives of this study are to examine the prevalence of ACEs and the associations of ACEs with common psychiatric disorders among older adults in China. Methods The study used data from the China Mental Health Survey (CMHS), a nationally representative epidemiological survey, which used computer-assisted personal interviewing (CAPI), logistic regression models were used to examine community-based adult psychiatric disorders and associated risk factors. Finally, 2,317 individuals aged 60 years or over were included in the CMHS. The national prevalence of ACEs in older adults were estimated and logistic regression were used to analyse the association between ACEs and past-year psychiatric disorders. Results Prevalence of ACEs among older adults in China was 18.1%. The three most common types of ACEs were neglect (11.6%), domestic violence (9.2%), and parental loss (9.1%). This study proved the association between ACEs and common past-year psychiatric disorders in older adults. ACEs increased the risk of past-year psychiatric disorders in older adults. After adjustment for age, sex, marital status, employment status, education, rural or urban residence, region, and physical diseases, the association between ACEs and past-year psychiatric disorders were still significant. Conclusions ACEs are linked to an increased risk for past-year psychiatric disorders in older adults. ACEs may have long-term effects on older adults’ mental well-being. Preventing ACEs may help reduce possible adverse health outcomes in later life.

Abstract Background Previous studies suggested that childhood maltreatment is associated with poor health outcomes. While not everyone who experiences abuse as a child goes on to experience poor mental health, some traumatized people are grown to be more resilient than others. Few studies have examined the association between childhood maltreatment and adult resilience. This study aimed to determine different relationships between specific types and features of childhood maltreatment with adult resilience among Chinese with Major Depressive Disorder (MDD) and healthy controls (HCs). Methods A total of 101 patients with MDD and 116 participants in the healthy control (HC) group from Zhumadian Psychiatric Hospital and its nearby communities were included in this analysis. Childhood maltreatment was assessed retrospectively using Childhood Trauma Questionnaire (CTQ). Adults’ resilience was assessed by the Connor-Davidson Resilience Scale (CD-RISC). Generalized linear models were applied between childhood maltreatment (specific types and features) and resilience adjusting for covariates. Results The total score of CD-RISC and factor scores of strength, optimism, and tenacity in the HC group were higher than those in the MDD group. CTQ total score had a negative association with optimism score among participants in MDD (β=-0.087, P

Abstract Background Depression is the second most important cause of disability worldwide. Reducing this major burden on global health requires a better understanding of the etiology, risk factors, and course of the disorder. With the goal of improving the prevention, recognition, and appropriate management of depressive disorders in China, the China Depression Cohort Study will establish a nationally representative sample of at least 85,000 adults (the China Depression Cohort Study-I) and 15,000 middle school students (the China Depression Cohort Study-II) and follow them over time to identify factors that influence the onset, characteristics, and course of depressive disorders. This protocol describes the China Depression Cohort Study-I. Methods A multistage stratified random sampling method will be used to identify a nationally representative community-based cohort of at least 85,000 adults (i.e., ≥ 18 years of age) from 34 communities in 17 of mainland China’s 31 provincial-level administrative regions. Baseline data collection includes 1) demographic, social and clinical data, 2) diagnostic information, 3) biological samples (i.e., blood, urine, hair), 4) brain MRI scans, and 5) environmental data (e.g., community-level metrics of climate change, air pollution, and socio-economic characteristics). Baseline findings will identify participants with or without depressive disorders. Annual reassessments will monitor potential risk factors for depression and identify incident cases of depression. Cox Proportional-Hazards Regression, Network analysis, Disease trajectory modelling, and Machine learning prediction models will be used to analyze the collected data. The study’s main outcomes are the occurrence of depressive disorders; secondary outcomes include adverse behaviors (e.g., self-harm, suicide), the recurrence of depression and the incidence other mental disorders. Discussion The China Depression Cohort Study-I will collect a comprehensive, nationally representative set of individual-level and community-level variables over time. The findings will reframe the understanding of depression from a ‘biology-psychology-society’ perspective. This perspective will improve psychiatrists’ understanding of depression and, thus, promote the development of more effective subgroup-specific antidepressant drugs and other interventions based on the new biomarkers and relationships identified in the study. Trail registration The protocol has been registered on the Chinese Clinical Trial Registry (No. ChiCTR2200059016).

Abstract Background The pandemic of coronavirus disease 2019 lastingly affects public mental health. Many studies have described symptoms of anxiety and depression in pregnant women before the pandemic. However, the limited study focuses on the prevalence and risk factors of mood symptoms among first-trimester females and their partners during the pandemic in China, which was the aim of the study. Methods One hundred and sixty-nine first-trimester couples were enrolled. The Edinburgh Postnatal Depression Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-Item, Family Assessment Device-General Functioning (FAD-GF), and Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF) were applied. Data were mainly analyzed through logistic regression analysis. Results 17.75% and 5.92% of first-trimester females had depressive and anxious symptoms, respectively. Among partners, 11.83% and 9.47% had depressive and anxious symptoms, respectively. In females, higher scores of FAD-GF (OR = 5.46 and 13.09; P

Abstract Background Suboptimal medication adherence is a major reason for failure in the management of major depressive disorder (MDD), childhood trauma might be an essential risk factor of suboptimal medication adherence. This study aimed to comprehensively explore the associations between different types of childhood trauma and medication adherence among patients with MDD, and to test whether resilience has moderating effects on the foregoing associations. Methods Participants were from the Depression Cohort in China (ChiCTR registry number 1900022145), 282 MDD patients with completed both baseline and 12-weeks follow-up investigations were included in this study. The diagnosis of MDD was assessed by trained psychiatrists using the Mini-International Neuropsychiatric Interview (M.I.N.I.). Childhood trauma was evaluated using the Childhood Trauma Questionnaire-28 item Short Form (CTQ-SF), and resilience was evaluated using the Connor-Davidson Resilience Scale (CD-RISC). Demographic characteristics, depression symptoms, anxiety symptoms, suicidal ideation, suicidal attempt, insomnia symptoms, and painful somatic symptoms were also investigated. Participants were divided into groups of optimal and suboptimal adherence based on their Medication Adherence Rating Scale scores. Logistic regression and stratified analyses were performed. Results A total of 234 participants (83%) reported suboptimal medication adherence. After adjusting for covariates, CTQ total scores (AOR = 1.03, 95%CI = 1.01–1.06), CTQ measures of sexual abuse (AOR = 1.17, 95%CI = 1.01–1.37), and CTQ measures of physical neglect (AOR = 1.12, 95%CI = 1.02–1.23) were all associated with an increased likelihood of suboptimal adherence. There were significant moderating effects of resilience on the associations of childhood trauma (P = 0.039) and physical neglect (P = 0.034) with medication adherence. The stratification analyses showed that CTQ total scores and CTQ measures of physical neglect were independently associated with an increased risk of suboptimal adherence among patients with MDD with low-resilience or moderate-resilience, while not significantly associated with suboptimal adherence in those with high-resilience. Conclusion Childhood trauma was a significant risk factor of suboptimal adherence among patients with MDD, and resilience moderated the foregoing association. Obtaining a history of childhood trauma and assessing resilience may help identify patients with suboptimal adherence when providing MDD pharmacotherapy. Psychiatrists may consider enhancing resilience to cope with the adverse effects of childhood trauma on medication adherence.

IntroductionMajor depressive disorder (MDD) is associated with low-grade inflammation, and anti-inflammatory treatment can help improve depressive symptoms. A recent study found that fluvoxamine (FLV) can reduce Interleukin-6 (IL-6) production via sigma-1 receptor in inflammation models. However, the anti- IL-6 effect of FLV in treating patients with MDD and whether it can contribute to antidepressant effects remain unclear.MethodsA total of 65 patients with MDD and 34 healthy controls were recruited at baseline, and 50 patients completed the FLV treatment for 2 months. We assessed depression and anhedonia and collected plasma IL-6 levels at baseline, 1 month, and 2 months after baseline. This study evaluated the changes in clinical measures and IL-6 during treatment and analyzed their association. Further subgroup analyses were conducted in patients with MDD with high, medium, or low IL-6.ResultsDepression and anhedonia were significantly improved in patients with MDD, while the IL-6 did not significantly change after the FLV treatment. However, IL-6 significantly declined after the FLV treatment among patients with MDD with higher baseline IL-6. No significant associations were found between the changes in depressive symptoms and IL-6.ConclusionOur study provided preliminary evidence suggesting that the anti-IL-6 effect of FLV might not play a vital role in its antidepressant treatment, at least in patients with MDD with low inflammation. However, for patients with MDD with higher IL-6, FLV can help reduce IL-6 significantly in the antidepressant treatment, which may help guide the individual treatment of MDD with higher IL-6 levels.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04160377, identifier NCT04160377.

IntroductionFamily functioning has been found to significantly impact each family member’s health mentally, physically, and socially. A number of the research has focused on the impact of impaired family functioning in general, but limited studies explore family functioning in the vulnerable period, early pregnancy. Therefore, the study aimed to investigate the characteristics and related factors in Chinese females and partners during early pregnancy.MethodsThe cross-sectional study enrolled 226 pregnant women and 166 partners. Assessment tools included the McMaster Family Assessment Device (FAD), Edinburgh Postnatal Depression Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-Item, Social Support Rating Scale, and Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form. Correlation analysis was applied to investigate the related factors.ResultsIn the present study, FAD-Behavior Control (BC) was the only dysfunctional dimension and had the highest dysfunctional rates than other dimensions. Length of time living with a partner, depressive and anxious symptoms, and quality of life were all associated with the dysfunctional family functioning of BC.ConclusionsThe study reinforced the important clues of family functioning during early pregnancy. Also, it provided new entry points for the general population and healthcare providers to minimize the negative impact that impaired family function might bring to a family.

BackgroundThe presence of heterogenous somatic symptoms frequently obscures the recognition of depression in primary care. We aimed to explore the association between somatic symptoms and subthreshold depression (SD) and Major Depressive Disorder (MDD), as well as to determine the predictive potential of somatic symptoms in identifying SD and MDD in primary care.MethodsData were derived from the Depression Cohort in China study (ChiCTR registry number: 1900022145). The Patient Health Questionnaire-9 (PHQ-9) was used to assess SD by trained general practitioners (GPs), and the Mini International Neuropsychiatric Interview depression module was used to diagnose MDD by professional psychiatrists. Somatic symptoms were assessed using the 28-item Somatic Symptoms Inventory (SSI).ResultsIn total of 4,139 participants aged 18–64 years recruited from 34 primary health care settings were included. The prevalence of all 28 somatic symptoms increased in a dose-dependent manner from non-depressed controls to SD, and to MDD (P for trend

Accumulating evidence showed that major depressive disorder (MDD) is characterized by a dysfunction of serotonin neurotransmission. Raphe nuclei are the sources of most serotonergic neurons that project throughout the brain. Incorporating measurements of activity within the raphe nuclei into the analysis of connectivity characteristics may contribute to understanding how neurotransmitter synthesized centers are involved in the pathogenesis of MDD. Here, we analyzed the resting-state functional magnetic resonance imaging (RS-fMRI) dataset from 1,148 MDD patients and 1,079 healthy individuals recruited across nine centers. A seed-based analysis with the dorsal raphe and median raphe nuclei was performed to explore the functional connectivity (FC) alterations. Compared to controls, for dorsal raphe, the significantly decreased FC linking with the right precuneus and median cingulate cortex were found; for median raphe, the increased FC linking with right superior cerebellum (lobules V/VI) was found in MDD patients. In further exploratory analyzes, MDD-related connectivity alterations in dorsal and median raphe nuclei in different clinical factors remained highly similar to the main findings, indicating these abnormal connectivities are a disease-related alteration. Our study highlights a functional dysconnection pattern of raphe nuclei in MDD with multi-site big data. These findings help improve our understanding of the pathophysiology of depression and provide evidence of the theoretical foundation for the development of novel pharmacotherapies.

Abstract Background Children exposed to natural disasters are vulnerable to developing posttraumatic stress disorder (PTSD). Previous studies using resting-state functional neuroimaging have revealed alterations in graph-based brain topological network metrics in pediatric PTSD patients relative to healthy controls (HC). Here we aimed to apply deep learning (DL) models to neuroimaging markers of classification which may be of assistance in diagnosis of pediatric PTSD. Methods We studied 33 pediatric PTSD and 53 matched HC. Functional connectivity between 90 brain regions from the automated anatomical labeling atlas was established using partial correlation coefficients, and the whole-brain functional connectome was constructed by applying a threshold to the resultant 90 * 90 partial correlation matrix. Graph theory analysis was used to examine the topological properties of the functional connectome. A DL algorithm then used this measure to classify pediatric PTSD vs HC. Results Graphic topological measures using DL provide a potentially clinically useful classifier for differentiating pediatric PTSD and HC (overall accuracy 71.2%). Frontoparietal areas (central executive network), cingulate cortex, and amygdala contributed the most to the DL model’s performance. Conclusions Graphic topological measures based on fMRI data could contribute to imaging models of clinical utility in distinguishing pediatric PTSD from HC. DL model may be a useful tool in the identification of brain mechanisms PTSD participants.

ObjectivePrevious studies on the reliability and validity of the Affective Lability Scale short-form (ALS-SF) have only been evaluated in adults, which may not be able to generalize to the adolescent population. We aimed to examine the factor structure, the reliability and validity of ALS-SF among Chinese adolescents and construct an adolescent form of ALS (ALS-AF).MethodsA total of 1,439 middle school students were investigated with a broad survey including ALS-SF, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Connor-Davidson Resilience Scale 10-item (CD-RISC-10) and non-suicidal self-injury (NSSI) behavior self-report. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to investigate the structural validity of ALS-SF and construct ALS-AF. Cronbach's α was used to assess the internal consistency and reliability of the scale. Factor loading, Average Variance Extracted (AVE) and Composite Reliability (CR) were applied to measure the convergent validity and divergent validity. Besides, Correlation and regression analyses were used to explore the relationship between affective lability and depression, anxiety, NSSI and resilience.ResultsFactor analysis failed to support the original three-factor model of 18-item ALS-SF and confirmed the three-factor model of 15-item ALS-AF. The ALS-AF showed good internal consistency as well as strong convergent and discriminative validity. Besides, ALS-AF was positively correlated with PHQ-9, GAD-7 and self-harm, and was negatively associated with resilience.ConclusionOur study shows that the ALS-AF has good reliability and validity for testing affective lability in Chinese adolescents.

Background Family functioning is associated with anxiety and depression. Perinatal depression and anxiety are common and influence the well-being of women, partners and their offspring. However, little is known about differences in associations between family functioning and mood symptoms in women and their partners in early pregnancy. Aims Investigating differences in associations between family functioning and anxious and depressive symptoms in women and their partners in early pregnancy. Method In total, 171 woman–partner pairs were enrolled. The Edinburgh Postnatal Depression Scale (EPDS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-Item scale (GAD-7) and Family Assessment Device (FAD) were performed. Correlation analysis and multiple linear regression analysis were applied to investigate the associations. Results In pregnant women, all the subscale scores on the FAD were correlated with total scores on the EPDS and GAD-7 (all P < 0.05), whereas only the Roles subscale showed a predicting effect in regression models (P < 0.01). In partners, all the subscale scores on the FAD were related to total scores on the PHQ-9 (all P < 0.05), whereas only the Problem Solving subscale showed a predicting effect (P = 0.029). Conclusions Our findings indicate that family functioning in the domain of roles is associated with anxious and depressive symptoms in pregnant women and functioning in the domain of problem solving is associated with depressive symptoms in partners. Clinicians should pay special attention to roles and problem solving when assessing mood symptoms in pregnant women and their partners. This study also provides a basis for family health education in early pregnancy.

For children and adolescents, there is a high risk of developing post-traumatic stress disorder (PTSD) after suffering from catastrophic events. Previous studies have identified brain functionally and subcortical brain volumes structurally abnormalities in this population. However, up till now, researches exploring alterations of regional cortical thickness (CTh) and brain interregional structural covariance networks (SCNs) are scarce. In this cross-sectional study, CTh measures are derived from 3-Tesla Tl-weighted MRI imaging data in a well-characterized combined group of children and adolescents with PTSD after an earthquake (N = 35) and a traumatized healthy control group (N = 24). By using surface-based morphometry (SBM) techniques, the regional CTh analysis was conducted. To map interregional SCNs derived from CTh, twenty-five altered brain regions reported in the PTSD population were selected as seeds. Whole-brain SBM analysis discovered a significant thickness reduction in the left medial orbitofrontal cortex for the subjects with PTSD. Similarly, analysis of SCNs associated with “seed” regions primarily located in default mode network (DMN), midline cortex structures, motor cortex, auditory association cortex, limbic system, and visual cortex demonstrated that children and adolescents with PTSD are associated with altered structural covariance with six key regions. This study provides evidence for distinct CTh correlates of PTSD that are present across children and adolescents, suggesting that brain cortical abnormalities related to trauma exposure are present in this population, probably by driving specific symptom clusters associated with disrupted extinction recall mechanisms for fear, episodic memory network and visuospatial attention.

Background: The mechanism by which antidepressants normalizing aberrant resting-state functional connectivity (rsFC) in patients with major depressive disorder (MDD) is still a matter of debate. The current study aimed to investigate aberrant rsFC and whether antidepressants would restore the aberrant rsFC in patients with MDD. Methods: A total of 196 patients with MDD and 143 healthy controls (HCs) received the resting-state functional magnetic resonance imaging and clinical assessments at baseline. Patients with MDD received antidepressant treatment after baseline assessment and were re-scanned at the 6-month follow-up. Network-based statistics were employed to identify aberrant rsFC and rsFC changes in patients with MDD and to compare the rsFC differences between remitters and non-remitters. Results: We identified a significantly decreased sub-network and a significantly increased sub-network in MDD at baseline. Approximately half of the aberrant rsFC remained significantly different from HCs after 6-month treatment. Significant overlaps were found between baseline reduced sub-network and follow-up increased sub-network, and between baseline increased sub-network and follow-up decreased sub-network. Besides, rsFC at baseline and rsFC changes between baseline and follow-up in remitters were not different from non-remitters. Conclusions: Most aberrant rsFC in patients with MDD showed state-independence. Although antidepressants may modulate aberrant rsFC, they may not specifically target these aberrations to achieve therapeutic effects, with only a few having been directly linked to treatment efficacy.

Spot detection has attracted continuous attention for laser sensors with applications in communication, measurement, etc. The existing methods often directly perform binarization processing on the original spot image. They suffer from the interference of the background light. To reduce this kind of interference, we propose a novel method called annular convolution filtering (ACF). In our method, the region of interest (ROI) in the spot image is first searched by using the statistical properties of pixels. Then, the annular convolution strip is constructed based on the energy attenuation property of the laser and the convolution operation is performed in the ROI of the spot image. Finally, a feature similarity index is designed to estimate the parameters of the laser spot. Experiments on three datasets with different kinds of background light show the advantages of our ACF method, with comparison to the theoretical method based on international standard, the practical method used in the market products, and the recent benchmark methods AAMED and ALS.

Abstract Major depressive disorder (MDD) is a prevailing chronic mental disorder with lifetime recurring episodes. Recurrent depression (RD) has been reported to be associated with greater severity of depression, higher relapse rate and prominent functioning impairments than first-episode depression (FED), suggesting the progressive nature of depression. However, there is still little evidence regarding brain functional connectome. In this study, 95 medication-free MDD patients (35 with FED and 60 with RD) and 111 matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scanning. After six months of treatment with paroxetine, 56 patients achieved clinical remission and finished their second scan. Network-based statistics analysis was used to explore the changes in functional connectivity. The results revealed that, compared with HCs, patients with FED exhibited hypoconnectivity in the somatomotor, default mode and dorsal attention networks, and RD exhibited hyperconnectivity in the somatomotor, salience, executive control, default mode and dorsal attention networks, as well as within and between salience and executive control networks. Moreover, the disrupted components in patients with current MDD did not change significantly when the patients achieved remission after treatment, and sub-hyperconnectivity and sub-hypoconnectivity were still found in those with remitted RD. Additionally, the hypoconnectivity in FED and hyperconnectivity in RD were associated with the number of episodes and total illness duration. This study provides initial evidence supporting that impairment of intrinsic functional connectivity across the course of depression is a progressive process.

BackgroundDepression is associated with significant morbidity and human capital costs globally. Early screening for depressive symptoms and timely depressive disorder case identification and intervention may improve health outcomes and cost-effectiveness among affected individuals. China’s public and academic communities have reached a consensus on the need to improve access to early screening, diagnosis, and treatment of depression. ObjectiveThis study aims to estimate the screening prevalence and associated factors of subthreshold depressive symptoms among Chinese residents enrolled in the cohort study using a mobile app–based integrated mental health care model and investigate the 12-month incidence rate and related factors of major depressive disorder (MDD) among those with subthreshold depressive symptoms. MethodsData were drawn from the Depression Cohort in China (DCC) study. A total of 4243 community residents aged 18 to 64 years living in Nanshan district, Shenzhen city, in Guangdong province, China, were encouraged to participate in the DCC study when visiting the participating primary health care centers, and 4066 (95.83%) residents who met the DCC study criteria were screened for subthreshold depressive symptoms using the Patient Health Questionnaire-9 at baseline. Of the 4066 screened residents, 3168 (77.91%) with subthreshold depressive symptoms were referred to hospitals to receive a psychiatric diagnosis of MDD within 12 months. Sleep duration, anxiety symptoms, well-being, insomnia symptoms, and resilience were also investigated. The diagnosis of MDD was provided by trained psychiatrists using the Mini-International Neuropsychiatric Interview. Univariate and multivariate logistic regression models were performed to explore the potential factors related to subthreshold depressive symptoms at baseline, and Cox proportional hazards models were performed to explore the potential factors related to incident MDD. ResultsAnxiety symptoms (adjusted odds ratio [AOR] 1.63, 95% CI 1.42-1.87) and insomnia symptoms (AOR 1.13, 95% CI 1.05-1.22) were associated with an increased risk of subthreshold depressive symptoms, whereas well-being (AOR 0.93, 95% CI 0.87-0.99) was negatively associated with depressive symptoms. During the follow-up period, the 12-month incidence rate of MDD among participants with subthreshold depressive symptoms was 5.97% (189/3168). After incorporating all significant variables from the univariate analyses, the multivariate Cox proportional hazards model reported that a history of comorbidities (adjusted hazard ratio [AHR] 1.49, 95% CI 1.04-2.14) and anxiety symptoms (AHR 1.13, 95% CI 1.09-1.17) were independently associated with an increased risk of incident MDD. The 5-item World Health Organization Well-Being Index was associated with a decreased risk of incident MDD (AHR 0.90, 95% CI 0.86-0.94). ConclusionsElevated anxiety symptoms and unfavorable general well-being were significantly associated with subthreshold depressive symptoms and incident MDD among Chinese residents in Shenzhen. Early screening for subthreshold depressive symptoms and related factors may be helpful for identifying populations at high risk of incident MDD.

Abstract The continued spread of the coronavirus disease 2019 (COVID-19) has a serious impact on everyone across the globe, both physically and psychologically. In addition to proactive measures addressing physical survival needs and health protection, China has launched a mental health support system to cope with the widespread psychological stress during the pandemic and its aftermath. In this debate, the authors attempted to depict and reflect upon the overall framework of China’s mental health support, with particular reference to the psychological intervention in response to COVID-19 over the last few months. Although a lot of effort has been made to meet the mental health needs, the accessibility, acceptability and effectiveness of the support system still have much room for improvement. Therefore, it is very important to re-think the predicament and challenge on ways of enhancing public mental health emergency responses in China. The concepts of universality, timeliness and scientific rigour were proposed as a possible reform in preparation for large-scale natural or man-made disasters in the coming future.

Although observational studies have suggested associations between circulating antioxidants and many mental disorders, causal inferences have not been confirmed. Mendelian randomization (MR) analyses were conducted using summary-level statistics from genome-wide association studies (GWASs) to explore whether genetically determined absolute circulating antioxidants (i.e., ascorbate, retinol, β-carotene, and lycopene) and metabolites (i.e., α- and γ-tocopherol, ascorbate, and retinol) were causally associated with the risk of six major mental disorders, including anxiety disorders (AD), major depressive disorder (MDD), bipolar disorder (BIP), schizophrenia (SCZ), post-traumatic stress disorder (PTSD), and obsessive–compulsive disorder (OCD). MR analyses were performed per specific-outcome databases, including the largest GWAS published to date (from 9725 for OCD to 413,466 for BIP participants), UK Biobank (over 370,000 participants), and FinnGen (over 270,000 participants), followed by meta-analyses. We found no significant evidence that genetically determined diet-derived circulating antioxidants were significantly causally associated with the risk of the six above-mentioned major mental disorders. For absolute antioxidant levels, the odds ratios (ORs) ranged from 0.91 (95% CI, 0.67–1.23) for the effect of β-carotene on OCD to 1.18 (95% CI, 0.90–1.54) for the effect of ascorbate on OCD. Similarly, for antioxidant metabolites, ORs ranged from 0.87 (95% CI, 0.55–1.38) for the effect of ascorbate on MDD to 1.08 (95% CI, 0.88–1.33) for the effect of ascorbate on OCD. Our study does not support significant causal associations of genetically determined diet-derived circulating antioxidants with the risk of major mental disorders.

Background: Previous studies have shown that childhood maltreatment (CM) is closely associated with social support in the general population. However, little is known about the associations of different types of CM with social support in Chinese patients with major depressive disorder (MDD), which was the goal of the current study.Methods: One hundred and sixty-six patients with moderate-to-severe MDD were enrolled. Participants were assessed by the Childhood Trauma Questionnaire-28 item Short Form, Social Support Rating Scale (SSRS), the 24-item Hamilton rating scale for depression, and the 14-item Hamilton Anxiety Rating Scale. Correlation analysis and Hierarchical multiple linear regression analysis were adopted to investigate associations of types of CM with social support.Results: (1) Physical neglect (PN) and emotional neglect (EN) were the most commonly reported types of CM in patients with MDD. (2) EN was the only type of CM significant in the regression models of the SSRS total score, the score of subjective support, and the score of utilization of support.Limitations: The data of CM was collected retrospectively and recall bias may be introduced. Assessment of CM and social support were self-reported and could be influenced by the depression status.Conclusion: In Chinese patients with MDD, PN and EN are the most prevalent types of CM. EN is the only type of CM associated with low social support in regression models, calling for special attention in the assessment and intervention of EN.

Background: Studies have shown a strong association between childhood maltreatment (CM) and major depressive disorder (MDD). Dysfunctional attitudes (DAs) play a crucial role in the development of MDD. In this study, we aimed to investigate whether (1) DAs are associated with CM, (2) specific CM types predict specific types of DAs, and (3) higher childhood trauma counts (CTCs) predict more DAs.Methods: One hundred seventy-one MDD participants and 156 healthy controls (HCs) were enrolled for the study. CM was assessed retrospectively with the Childhood Trauma Questionnaire. DAs were evaluated using the Chinese version of the Dysfunctional Attitude Scale–Form A (C-DAS-A). A series of analyses, including multiple analyses of covariance and hierarchical regression analyses, were used in this study to examine the hypotheses.Results: The proportion of CM was 60.2% in the MDD group and 44.2% in the HC group. The 2 × 2 analysis of covariance results showed no interaction effect between CM and MDD on C-DAS-A total score. When the factor scores replaced the C-DAS-A total score, a similar trend was observed. Within the MDD group, emotional abuse (EA) predicted two forms of DAs: self-determination type and overall DAs; physical neglect (PN) was predictive of attraction and repulsion-type DAs. Higher childhood trauma counts significantly predicted more types of DAs in the MDD group.Conclusion: DAs are a trait feature of CM. EA and PN predict specific types of DAs in MDD patients. Higher CTCs predict more DAs in MDD patients.

Background: Minimal research has examined utility of PC-PTSD-5 in family members of frontline medical workers. The aims of our study were to develop and elucidate the psychometric properties of the Chinese version of the PC-PTSD-5 and to determine its usefulness in screening for possible PTSD in relatives of Chinese healthcare workers during the COVID-19.Methods: We conducted a cross-sectional research in the relatives of medical staffs working in a general hospital during the COVID-19. Descriptive analysis was used to characterize demographic information of family members to find factors associated with PTSD symptoms. For reliability test, the internal consistency of PC-PTSD-5 was accessed using Cronbach's alpha coefficient. A validity test was assessed by Pearson's correlation between scales. A receiver operating characteristic (ROC) curve was used to evaluate the optimal cutoff score with the maximum Youden Index in this study.Results: The result of demographic information indicated that gender and the type of work undertaken by medical staff in the family have a potential impact on the PTSD symptoms of medical staff's family members. Cronbach's alpha coefficient of PC-PTSD-5 was 0.83, indicating the high reliability. Good validity was also demonstrated by Pearson coefficient. By calculating the Youden index, a cutoff score of 2 was found to be optimal in our study, with sensitivity of 80.74% and specificity of 88.43%.Conclusions: Our study has demonstrated the robust psychometric strengths of the PC-PTSD-5, introducing a reliable tool for screening PTSD among vulnerable and neglected families of these medical workers.

Background: The difficulty in timely evaluating patient response to antidepressants has brought great challenge to the treatment of major depressive disorder (MDD). Some studies found that the electroencephalogram (EEG) microstates might be a reliable marker to evaluate patient response to treatment. The present study aims to evaluate the relationship between EEG microstate parameters and MDD symptoms before and after treatment to identify predictive biological markers for patient response.Methods: Thirty drug-naïve MDD patients (20 females and 10 males) were enrolled in this study. All the patients received effective dosages of selective serotonin reuptake inhibitors, and EEG recordings were collected at baseline and 2 weeks of treatment. Brain activities during the eyes-closed state were recorded using 64-channel electroencephalography, and the patients' microstates were clustered into four maps according to their topography (labeled A, B, C, and D). The differences of EEG microstates before and after treatment were compared using paired t-test. Spearman correlation coefficients were calculated to identify the relationships between the improvement of depression and anxiety symptoms and microstate parameters.Results: The mean duration (69.67 ± 10.33 vs. 64.00 ± 7.70, p < 0.001) and occurrence (4.06 ± 0.69, vs. 3.69 ± 0.70, p = 0.002) of microstate B decreased significantly after treatment. The proportion of microstate B also decreased (27.53 ± 5.81, vs. 23.23 ± 4.61, p < 0.001), while the occurrence of microstate A increased after treatment. A significant negative correlation was found between the change of score of Hamilton Rating Scale for Anxiety and the increase of the occurrence of microstate A (r = −0.431, p < 0.05) after 2 weeks of treatment. The reduction of the duration of microstate B was found to be predictive of patient response to antidepressants after 3 months.Conclusion: This study explored the relationship between changes of EEG microstates and patient response to antidepressants. Depression symptoms might be associated with the duration of microstate B and anxiety symptoms related to the occurrence of microstate A. Therefore, the duration of microstate B and the occurrence of microstate A are potential biological markers for MDD patients' early response and further clinical outcomes.

Background: Losing one’s only child may lead to post-traumatic stress disorder (PTSD), of which re-experiencing is the core symptom. However, neuroimaging studies of sex differences in re-experiencing in the context of the trauma of losing one’s only child and PTSD are scarce; comparisons of the functional networks from the hippocampal subfields to the thalamus might clarify the neural basis.Methods: Thirty couples without any psychiatric disorder who lost their only child (non-PTSD group), 55 patients with PTSD, and 50 normal controls underwent resting-state functional magnetic resonance imaging. The functional connectivity (FC) from the hippocampal subregions to the thalamus and the correlations of FC with re-experiencing symptoms were analyzed within and between the sexes.Results: Compared with husbands without PTSD, wives without PTSD had higher re-experiencing symptoms and weaker FC between the right hippocampal cornu ammonis 3 (RCA3) and the right thalamus (RT; RCA3-RT). Moreover, only the correlation between the RCA3-RT FC and re-experiencing in wives without PTSD was significant. Among the three groups, only the RCA3-RT FC in female subjects was markedly different. Additionally, the RCA3-RT FC in wives without PTSD was remarkably lower relative to female patients with PTSD.Conclusion: Wives without PTSD who lost their only child had worse re-experiencing symptoms relative to their husbands, which was associated with the FC alteration between the hippocampal subregions and the thalamus. Importantly, the low level of the RCA3-RT FC may play a potentially protective role against the development of PTSD in wives who have lost their only child.

Background: Cognitive deficits have shown progressive feature in major depressive disorder (MDD). However, it remains unknown which component of cognitive function is progressively impaired across episodes of MDD. Here we aim to identify the progressively impaired cognitive components in patients with MDD.Methods: A comprehensive neurocognitive test battery was used to assess the cognitive components (executive function, attention, processing speed, memory, working memory, inhibition, shifting, and verbal fluency) in 35 patients with first-episode MDD (FED), 60 patients with recurrent MDD (RD) and 111 matched healthy controls (HCs). After 6 months of treatment with antidepressant, 20 FED and 36 RD patients achieved clinical remission and completed their second-time neurocognitive tests. Statistical analyses were conducted to identify the impaired cognitive components in the FED and RD groups before and after treatment, and to assess the relationship between the cognitive components and the number of episodes and total illness duration in the MDD patient group.Results: At baseline, both the FED and RD groups showed impairments in all of the cognitive components; the FED and RD groups showed no significant difference in all of the components except for shifting. After remission, only shifting in the RD group showed no significant improvement and remained in an impaired status. Furthermore, shifting was the only component negatively correlated with the number of episodes as well as the total illness duration.Conclusions: Shifting may serve as the progressive cognitive deficit across episodes of MDD.Clinical Trials Registration: Registry name: HPA function and MRI study of trauma-related depression; Registration number: ChiCTR1800014591; URL: http://www.chictr.org.cn/edit.aspx?pid=24669&htm=4.

Previous studies have demonstrated relations between spontaneous neural activity evaluated by resting-state functional magnetic resonance imaging (fMRI) and symptom severity in post-traumatic stress disorder. However, few studies have used brain-based measures to identify imaging associations with illness severity at the level of individual patients. This study applied connectome-based predictive modeling (CPM), a recently developed data-driven and subject-level method, to identify brain function features that are related to symptom severity of trauma survivors. Resting-state fMRI scans and clinical ratings were obtained 10–15 months after the earthquake from 122 earthquake survivors. Symptom severity of post-traumatic stress disorder features for each survivor was evaluated using the Clinician Administered Post-traumatic Stress Disorder Scale (CAPS-IV). A functionally pre-defined atlas was applied to divide the human brain into 268 regions. Each individual’s functional connectivity 268 × 268 matrix was created to reflect correlations of functional time series data across each pair of nodes. The relationship between CAPS-IV scores and brain functional connectivity was explored in a CPM linear model. Using a leave-one-out cross-validation (LOOCV) procedure, findings showed that the positive network model predicted the left-out individual’s CAPS-IV scores from resting-state functional connectivity. CPM predicted CAPS-IV scores, as indicated by a significant correspondence between predicted and actual values (r = 0.30, P = 0.001) utilizing primarily functional connectivity between visual cortex, subcortical-cerebellum, limbic, and motor systems. The current study provides data-driven evidence regarding the functional brain features that predict symptom severity based on the organization of intrinsic brain networks and highlights its potential application in making clinical evaluation of symptom severity at the individual level.

Background Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design. Aims This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934). Method Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups. Results The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine. Conclusions The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.

Some brain abnormalities persist at the remission phase, that is, the state-independent abnormalities, which may be one of the reasons for the high recurrence of major depressive disorder (MDD). Hence, it is of great significance to identify state-independent abnormalities of MDD through longitudinal investigation. Ninety-nine MDD patients and 118 healthy controls (HCs) received diffusion tensor imaging scanning at baseline. After 6-month antidepressant treatment, 68 patients received a second scan, among which 59 patients achieved full clinical remission. Differences in whole-brain structural connectivity (SC) between patients with MDD at baseline and HCs were estimated by two-sample t-tests. Masked with significantly changed SCs in MDD, two-sample t-tests were conducted between the remitted MDD subgroup at follow-up and HCs, and paired t-tests were implemented to compare the differences of SC in the remitted MDD subgroup before and after treatment. Significantly decreased SC between the right insula and the anterior temporal cortex (ATC), between the right ATC and the posterior temporal cortex (PTC), between the left ATC and the auditory cortex as well as increased connectivity between the right posterior cingulate cortex (PCC) and the left medial parietal cortex (MPC) were observed in the MDD group compared with the HC group at baseline (p < 0.05, FDR corrected). The decreased connectivity between the right insula and the ATC and increased connectivity between the right PCC and the left MPC persisted in the remitted MDD subgroup at follow-up (p < 0.05, FDR corrected). The decreased SC between the right insula and the ATC and increased SC between the right PCC and left MPC showed state-independent characters, which may be implicated in the sustained negative attention bias and motor retardation in MDD. In contrast, the decreased SC between the right ATC and the PTC and between the left ATC and the auditory cortex seemed to be state-dependent.

Losing an only child is a devastating life event that a parent can experience and may lead to post-traumatic stress disorder (PTSD). Social support could buffer against the negative influence of this trauma, but the neural mechanism underlying this alleviation effect remains poorly understood. In this study, voxel-based morphometry was conducted on brain MRI of 220 Han Chinese adults who had lost their only child. We performed multiple regression analysis to investigate the associations between social support scores – along with PTSD diagnosis, age, sex, body mass index (BMI) – and brain grey matter (GM) volumes in these bereaved parents. For all trauma-exposed adults, social support-by-diagnosis interaction was significantly associated with medial prefrontal volume (multiple comparisons corrected P ˂ 0.05), where positive correlation was found in adults with PTSD but not in those without PTSD. Besides, PTSD diagnosis was associated with decreased GM volume in medial and middle frontal gyri (P ˂ 0.001, uncorrected); older age was associated with widespread GM volume deficits; male sex was associated with lower GM volume in rolandic operculum, insular, postcentral gyrus (corrected P ˂ 0.05), and lower GM in thalamus but greater GM in parahippocampus (P ˂ 0.001, uncorrected); higher BMI was associated with GM deficits in occipital gyrus (corrected P ˂ 0.05) and precuneus (P ˂ 0.001, uncorrected). In conclusions, social support modulates the association between PTSD diagnosis and medial frontal volume, which may play an important role in the emotional disturbance in PTSD development in adults who lost their only child.

BackgroundStudies have shown that patients with major depressive disorder (MDD) exhibit elevated dysfunctional attitudes (DAs). However, it remains controversial whether the DAs are state-dependent or trait-like features of MDD.MethodsThis study recruited 172 patients and 159 healthy controls (HCs) at baseline. DAs were respectively assessed by the 24-item Hamilton Depression Rating Scale (HAMD24) and the Chinese version of Dysfunctional Attitude Scale form A (C-DAS-A). After baseline, patients received a 6-month antidepressant treatment. General linear models were used to analyze the differences in the C-DAS-A total and factor scores between the acute and remitted MDD groups and the HC group. Paired t tests were used to assess the changes of C-DAS-A total and factor scores in the remitted MDD group before and after treatment.ResultsAt baseline, patients with MDD showed significantly higher scores in C-DAS-A and its subscales than HCs (all P < 0.05). After treatment, the C-DAS-A total and factor scores decreased significantly in the remitted MDD group (all P < 0.05). However, the C-DAS-A total (P = 0.005) and five factors’ scores (vulnerability, attraction and repulsion, perfectionism, compulsion, and dependence) remained elevated in the remitted MDD group as compared with HCs (all P < 0.05). There were moderate correlations between the baseline and remission phase C-DAS-A total and five factors’ scores (all P < 0.05).ConclusionDAs show a mixture of state-dependent and trait-like characteristics in MDD with partial improvement in the remission phase. Special attention should be paid to the residual DAs in the remitted MDD for the prevention of relapse.

BackgroundEven with continuous antidepressant treatment, residual symptoms and the risk of relapse can persist in remitted major depressive disorder (MDD) patients. Hence, having a clear recognition of the persistent abnormalities of the underlying neural substrate in MDD through a longitudinal investigation is of great importance.MethodsA total of 127 adult medication-free MDD patients with an acute depressive episode and 118 matched healthy controls (HCs) underwent diffusion tensor imaging. Over a 6-month treatment course, 62 remitted patients underwent a second scan. Remission was defined as a 24-item Hamilton Depression Rating Scale (HAMD24) score ≤7 for at least two weeks. Diffusion tensor imaging was performed with a 3.0 T scanner. Differences in whole-brain fractional anisotropy (FA) between MDD patients and HCs were assessed by an independent t-test using gender, age, and education as covariates.ResultsSignificant FA reductions in the left insula, left middle occipital gyrus, right thalamus, left pallidum and left precuneus were observed in current MDD (cMDD) patients compared with HCs. Moreover, significant FA reductions in the left insula were observed in remitted (rMDD) patients compared to HCs. However, no significant differences in FA values were found when comparing cMDD and rMDD patients.ConclusionsThe abnormalities in the insula showed state-independent characteristics, while the abnormalities in the middle occipital gyrus, thalamus, pallidum and precuneus seemed to be state-dependent impairments in MDD patients.

BackgroundDysfunctional attitudes play a key role in the development and prognosis of depression. Gender also plays an important role in many clinical features of major depressive disorder (MDD). This study is aimed at investigating the gender differences in dysfunctional attitudes in patients with MDD.MethodsOne hundred and seventy-two patients with MDD and 159 healthy controls (HCs) were enrolled in this study. Dysfunctional attitudes were assessed by the Chinese version of the dysfunctional attitude scale—form A (C-DAS-A) and depression severity was assessed by the 24-item Hamilton rating scale for depression (HAMD24). The 14-item Hamilton Anxiety Rating Scale (HAMA14) was used to measure anxiety. Factorial analysis of variance (ANOVA) of gender and diagnosis on C-DAS-A total and factor scores was adopted with age, education, and body mass index (BMI) controlled. Multiple linear regression analyses of DAS were performed in the MDD group.ResultsFirst, the C-DAS-A score in the MDD group was increased significantly than HCs. Second, female patients with MDD showed significantly higher scores in C-DAS-A total and three-factor scores (seeking applause, dependence, and self-determination attitude), while no significant difference between female HCs and male HCs was detected. Third, five variables (age, gender, smoking history, HAMD24, and HAMA14) had predictive effects on and gender showed the greatest contributions to C-DAS-A total and three-factor scores (seeking applause, dependence, and self-determination attitude).ConclusionFemales with MDD may be linked to more severe cognitive distortion than their male counterparts in seeking applause, dependence, and self-determination attitude, supporting the reasonableness for gender-specific psychosocial interventions.

Introduction: Disrupted topological organization of brain functional networks has been widely observed in posttraumatic stress disorder (PTSD). However, the topological organization of the brain grey matter (GM) network has not yet been investigated in pediatric PTSD who was more vulnerable to develop PTSD when exposed to stress. Materials and methods: Twenty two pediatric PTSD patients and 22 matched trauma-exposed controls who survived a massive earthquake (8.0 magnitude on Richter scale) in Sichuan Province of western China in 2008 underwent structural brain imaging with MRI 8–15 months after the earthquake. Brain networks were constructed based on the morphological similarity of GM across regions, and analyzed using graph theory approaches. Nonparametric permutation testing was performed to assess group differences in each topological metric. Results: Compared with controls, brain networks of PTSD patients were characterized by decreased characteristic path length (P = 0.0060) and increased clustering coefficient (P = 0.0227), global efficiency (P = 0.0085) and local efficiency (P = 0.0024). Locally, patients with PTSD exhibited increased centrality in nodes of the default-mode (DMN), central executive (CEN) and salience networks (SN), involving medial prefrontal (mPFC), parietal, anterior cingulate (ACC), occipital and olfactory cortex and hippocampus. Conclusions: Our analyses of topological brain networks in children with PTSD indicate a significantly more segregated and integrated organization. The associations and disassociations between these grey matter findings and white matter (WM) and functional changes previously reported in this sample may be important for diagnostic purposes and understanding the brain maturational effects of pediatric PTSD. Keywords: Pediatric PTSD, Topological organization, Graph theory, Brain network, MRI, Psychoradiology

Previous studies using resting-state functional MRI (rs-fMRI) have revealed alterations in graphical metrics in groups of individuals with posttraumatic stress disorder (PTSD). To explore the ability of graph measures to diagnose PTSD and capture its essential features in individual patients, we used a deep learning (DL) model based on a graph-theoretic approach to discriminate PTSD from trauma-exposed non-PTSD at the individual level and to identify its most discriminant features. Our study was performed on rs-fMRI data from 91 individuals with PTSD and 126 trauma-exposed non-PTSD patients. To evaluate our DL method, we used the traditional support vector machine (SVM) classifier as a reference. Our results showed that the proposed DL model allowed single-subject discrimination of PTSD and trauma-exposed non-PTSD individuals with higher accuracy (average: 80%) than the traditional SVM (average: 57.7%). The top 10 DL features were identified within the default mode, central executive, and salience networks; the first two of these networks were also identified in the SVM classification. We also found that nodal efficiency in the left fusiform gyrus was negatively correlated with the Clinician Administered PTSD Scale score. These findings demonstrate that DL based on graphical features is a promising method for assisting in the diagnosis of PTSD.

Background Whether there are distinct subtypes of schizophrenia is an important issue to advance understanding and treatment of schizophrenia. Aims To understand and treat individuals with schizophrenia, the aim was to advance understanding of differences between individuals, whether there are discrete subtypes, and how fist-episode patients (FEP) may differ from multiple episode patients (MEP). Method These issues were analysed in 687 FEP and 1880 MEP with schizophrenia using the Positive and Negative Syndrome Scale for (PANSS) schizophrenia before and after antipsychotic medication for 6 weeks. Results The seven Negative Symptoms were correlated with each other and with P2 (conceptual disorganisation), G13 (disturbance of volition), and G7 (motor retardation). The main difference between individuals was in the cluster of seven negative symptoms, which had a continuous unimodal distribution. Medication decreased the PANSS scores for all the symptoms, which were similar in the FEP and MEP groups. Conclusions The negative symptoms are a major source of individual differences, and there are potential implications for treatment.

Background: Major depressive disorder (MDD) is associated with a wide range of cognitive deficits. However, it remains unclear whether there will be a major cognitive deficit independently caused by depression at acute episodes of MDD.Method: A comprehensive neurocognitive test battery was used to assess the executive function, processing speed, attention, and memory in 162 MDD patients and 142 healthy controls (HCs). A multivariate analysis of variance, hierarchical regression analyses and general linear regression analyses were used to explore the possible major cognitive deficits and their predictor variables.Results: MDD patients showed extensive impairment in all four cognitive domains. Impairment of executive function and processing speed were found to persist even with other cognitive domains and clinical variables being accounted for. Executive function and processing speed were further predicted by total disease duration and depression severity, respectively.Conclusions: Executive function and processing speed may be two distinct major deficits at acute episodes of MDD. Furthermore, the executive function is likely originated from the cumulative effect of disease duration and processing speed is possibly derived from the temporary effect of current depressive episode.

Generalized anxiety disorder (GAD) is characterized by excessive and uncontrollable worry about everyday life. Prior neuroimaging studies have demonstrated that GAD is associated with disruptions in specific brain regions; however, little is known about the global functional connectivity maps in adolescents with GAD. Here, first-episode, medication-naive, adolescent GAD patients (N = 36) and healthy controls (N = 28) (HCs) underwent resting-state functional MRI (R-fMRI) and completed a package of questionnaires to assess clinical symptoms. Functional connectivity strength and seed-based functional connectivity were employed to investigate the functional connectivity architecture. GAD patients showed reduced functional connectivity strength in right supramarginal gyrus (SMG) and right superior parietal gyrus (SPG) compared with HCs. Further seed-based functional connectivity analysis revealed that GAD patients displayed decreased functional connectivity between right SMG and left fusiform gyrus, inferior temporal gyrus, parahippocampal gyrus, bilateral precuneus and cuneus, and between right SPG and bilateral supplementary motor area and middle cingulate gyrus, as well as between the SMG-based network and the SPG-based network. Moreover, the disrupted intra-network connectivity (i.e., the SMG-based network and the SPG-based network) and inter-network connectivity between the SMG-based network and the SPG-based network accounted for 25.5% variance of the State and Trait Anxiety Inventory (STAI) and 39.5% variance of the trait subscale of STAI. Our findings highlight the abnormal functional architecture in the SMG-based network and the SPG-based network in GAD, providing novel insights into the pathological mechanisms of this disorder.

Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved.

Objective: Pain and affective disorders have clear clinical relevance; however, very few studies have investigated the association between pain and bipolar disorder. This study investigated the brain activity of patients with bipolar disorder (BPs) undergoing tonic pain and assessed the interaction between pain and emotion.Methods: Ten BPs and ten healthy controls (HCs) were exposed to emotional pictures (positive, neutral, or negative), tonic pain only (pain session), and emotional pictures along with tonic pain (combined session). A moderate tonic pain was induced by the infusion of hypertonic saline (5% NaCl) into the right masseter muscle with a computer-controlled system. Whole-brain blood oxygenation level dependent (BOLD) signals were acquired using 3T functional resonance imaging (fMRI).Results: Ten BPs and ten healthy participants were included in the final analysis. During the pain session, BPs accepted more saline, but showed lower pain rating scores than HCs. When experiencing pain, BPs showed a significant decrease in the BOLD signal in the bilateral insula, left inferior frontal gyrus (IFG), and left cerebellum as compared with HCs. In the combined session, the activated regions for positive mood (pain with positive mood > baseline) in BPs were the left cerebellum, right temporal gyrus, and left occipital gyrus; the activated regions for negative mood (pain with negative mood > baseline) were the right occipital gyrus, left insula, left IFG, and bilateral precentral gyrus.Conclusions: This study presents the preliminary finding of the interaction between pain and emotion in BPs. BPs exhibited lower sensitivity to pain, and the activation of insula and IFG may reflect the interaction between emotion and pain stimulus.

Objectives: While evidence that episodes of mania in bipolar I are associated with changes in bioenergetic and regional cerebral blood flow (rCBF) and cerebral blood flow velocity (rCBFV), both the regions and the extent of these changes have not yet been defined. Therefore, we determined the pattern of regional cerebral perfusion mania patients and using patients with major depressive disorder (MDD) as positive controls and healthy participants as negative controls.Methods: Twenty participants with mania, together with 22 MDD patients and 24 healthy volunteers, were recruited for this study. On all participants, Transcranial Doppler (TCD) was conducted to measure rCBFV parameters, 320-slice CT was conducted to measure rCBF in the different cerebral artery regions, and hematological parameters were assessed. ANOVA and Pearson's tests were used for the statistical analysis.Results: Our data indicated that rCBF in the medial temporal lobe and hippocampus, especially in the left medial temporal lobe and the right hippocampus, was increased in the mania group compared with the control and MDD groups (p < 0.01). In contrast, rCBF in the medial temporal lobe and hippocampus was decreased in the depression group (p < 0.01) compared with healthy controls. In addition, values of rCBFV in the bilateral internal carotid arteries (ICAs) and middle cerebral arteries (MCA) were increased in mania (p < 0.01) in comparison to the MDD group. Whole blood viscosity and hematocrit as well as red blood cell sedimentation rate remained unchanged in all group (p > 0.05).Conclusions: In mania, rCBF is increased in the medial temporal lobe and hippocampus, with a corresponding increase in rCBFV in the same regions.

Several neuropsychiatric diseases have been found to influence the frequency-specific spontaneous functional brain organization (SFBO) in resting state, demonstrating that the abnormal brain activities of different frequency bands are associated with various physiological and psychological dysfunctions. However, little is known about the frequency specificities of SFBO in adolescent generalized anxiety disorder (GAD). Here, a novel complete ensemble empirical mode decomposition with adaptive noise method was applied to decompose the time series of each voxel across all participants (31 adolescent patients with GAD and 28 matched healthy controls; HCs) into four frequency-specific bands with distinct intrinsic oscillation. The functional connectivity density (FCD) of different scales (short-range and long-range) was calculated to quantify the SFBO changes related to GAD within each above frequency-specific band and the conventional frequency band (0.01–0.08 Hz). Support vector machine classifier was further used to examine the discriminative ability of the frequency-specific FCD values. The results showed that adolescent GAD patients exhibited abnormal alterations of both short-range and long-range FCD (S-FCD and L-FCD) in widespread brain regions across three frequency-specific bands. Positive correlation between the State Anxiety Inventory (SAI) score and increased L-FCD in the fusiform gyrus in the conventional frequency band was found in adolescents with GAD. Both S-FCD and L-FCD in the insula in the lower frequency band (0.02–0.036 Hz) had the highest classification performance compared to all other brain regions with inter-group difference. Furthermore, a satisfactory classification performance was achieved by combining the discrepant S-FCD and L-FCD values in all frequency bands, with the area under the curve (AUC) value of 0.9414 and the corresponding sensitivity, specificity, and accuracy of 87.15, 92.92, and 89.83%, respectively. This study indicates that the alterations of SFBO in adolescent GAD are frequency dependence and the frequency-specific FCD can potentially serve as a valuable biomarker in discriminating GAD patients from HCs. These findings may provide new insights into the pathophysiological mechanisms of adolescent GAD.

Generalized anxiety disorder (GAD) is one of common anxiety disorders in adolescents. Although adolescents with GAD are thought to be at high risk for other mental diseases, the disease-specific alterations have not been adequately explored. Recent studies have revealed the abnormal functional connectivity (FC) in adolescents with GAD. Most previous researches have investigated the static FC which ignores the fluctuations of FC over time and focused on the structures of “fear circuit”. To figure out the alterations of dynamic FC caused by GAD and the possibilities of dynamic FC as biomarkers, we propose an effective approach to identify adolescent GAD using temporal features derived from dynamic FC. In our study, the instantaneous synchronization of pairwise signals was estimated as dynamic FC. The Hurst exponent (H) and variance, indicating regularity and variable degree of a time series respectively, were calculated as temporal features of dynamic FC. By leave-one-out cross-validation (LOOCV), a relatively high accuracy of 88.46% could be achieved when H and variance of dynamic FC were combined as features. In addition, we identified the disease-related regions, including regions belonging to default mode (DM) and cerebellar networks. The results suggest that temporal features of dynamic FC could achieve a clinically acceptable diagnostic power and serve as biomarkers of adolescent GAD. Furthermore, our work could be helpful in understanding the pathophysiological mechanism of adolescent GAD.

The serotonin (5-HT) hypothesis of depression has played an important role in the history of psychiatry, yet it has also been criticized for the delayed onset and inadequate efficacy of selective serotonin reuptake inhibitors (SSRIs). With evolvement of neuroscience, the neuroplasticity hypothesis of major depressive disorder (MDD) has been proposed and may provide a better framework for clarification the pathogenesis of MDD and antidepressant efficacy. In this article, we first summarized the evidence challenging the monoamine hypothesis and proposed that the antidepressant efficacy of SSRIs is not derived from elevated monoamine (5-HT, noradrenaline (NE), or dopamine (DA)) concentration or monoamine neurotransmission. Second, we reviewed the role of stress in the pathogenesis of MDD and gave a brief introduction to the neuroplasticity hypothesis of MDD. Third, we explored the possible mechanisms underlying the antidepressant efficacy of typical antidepressants in the context of neuroplasticity theory. Fourth, we tried to provide an explanatory framework for the significant difference in onset of efficacy between typical antidepressants and ketamine. Finally, we provided a brief summarization about this review article and some perspectives for future studies.