Circular RNAs in early brain development and their influence and clinical significance in neuropsychiatric disorders.

Neuropsychiatric disorders represent a set of severe and complex mental illnesses, and the exact etiologies of which are unknown. It has been well documented that impairments in the early development of the brain contribute to the pathogenesis of many neuropsychiatric disorders. Currently, the diagnosis of neuropsychiatric disorders largely relies on subjective cognitive assessment, because there are no widely accepted biochemical or genetic biomarkers for diagnosing mental illness. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA (ncRNA) with a closed-loop structure. In recent years, there have been tremendous advances in our understanding of the expression profiles and biological roles of circRNAs. In the brain, circRNAs are particularly enriched and are expressed more abundantly in contrast to linear counterpart transcripts. They are highly active at neuronal synapses. These features make circRNAs uniquely crucial for understanding brain health, disease, and neuropsychiatric disorders. This review focuses on the role of circRNAs in early brain development and other brain-related processes that have been associated with the development of neuropsychiatric disorders. In addition, we discuss the potential for blood or cerebrospinal fluid circRNAs to be used as novel biomarkers in the early diagnosis of neuropsychiatric disorders. The findings reviewed here may provide new insight into the pathological mechanisms underlying the onset and progression of neuropsychiatric disorders.

Brain function differences in drug-naïve first-episode auditory verbal hallucination-schizophrenia patients with versus without insight.

BACKGROUND: Few studies have reported brain function differences in drug-naïve first-episode schizophrenia patients who had auditory verbal hallucinations (AVH) with insight vs. those without insight. This study aimed to investigate brain function differences between drug-naïve first-episode AVH-schizophrenia patients with and without insight. METHODS: Forty first-episode drug-naïve AVH-schizophrenia patients with or without insight and 40 healthy controls between December 2016 and December 2018 were recruited in this study. The auditory hallucinations rating scale (AHRS) was used to assess AVH severity, while the insight and treatment attitudes questionnaire was used to distinguish insight. The global functional connectivity density (gFCD) between different groups was compared using a voxel-wise one-way analysis of covariance. The relationship between gFCD and AHRS total scores were analyzed using voxel-wise multiple regression. RESULTS: Finally, 13 first-episode drug-naïve AVH-schizophrenia patients with insight, 15 AVH-schizophrenia patients without insight, and 20 healthy controls were included for analysis. Except for global assessment of functioning scores, there were no significant differences in sociodemographic information between the AVH-schizophrenia and healthy groups (P > 0.05). Compared to the healthy controls, AVH-schizophrenia patients with insight demonstrated a decreased gFCD in the supra-marginal gyrus within the primary auditory cortex, while those without insight demonstrated an increased gFCD in the inferior frontal gyrus and superior temporal gyrus and decreased gFCD in the supplemental motor area. Compared to the AVH-schizophrenia patients with insight, those without insight demonstrated an increased gFCD in the supra-marginal gyrus and posterior superior temporal lobule and a decreased gFCD in the frontal lobe. No significant correlation between gFCD and AVH severity (AHRS total score: r = 0.23, P = 0.590; and frequency: r = 0.42, P = 0.820) was found in both AVH-schizophrenia groups. CONCLUSIONS: The gFCD-aberrant brain regions in the AVH-schizophrenia patients without insight were wider compared to those with insight, although the AHRS scores were not significantly different. The AVH-schizophrenia patients without insight had wide functional impairment in the frontal lobule, which may underlie the lack of insight and the abnormal hyperactivity in the inferior frontal gurus and temporal lobe related to the AVH symptoms.

Antidepressant Effects of Electroconvulsive Therapy Unrelated to the Brain's Functional Network Connectivity alterations at an Individual Level.

BACKGROUND: Electroconvulsive therapy (ECT) can alleviate the symptoms of treatment-resistant depression (TRD). Functional network connectivity (FNC) is a newly developed method to investigate the brain's functional connectivity patterns. The first aim of this study was to investigate FNC alterations between TRD patients and healthy controls. The second aim was to explore the relationship between the ECT treatment response and pre-ECT treatment FNC alterations in individual TRD patients. METHODS: This study included 82 TRD patients and 41 controls. Patients were screened at baseline and after 2 weeks of treatment with a combination of ECT and antidepressants. Group information guided-independent component analysis (GIG-ICA) was used to compute subject-specific functional networks (FNs). Grassmann manifold and step-wise forward component selection using support vector machines were adopted to perform the FNC measure and extract the functional networks' connectivity patterns (FCP). Pearson's correlation analysis was used to calculate the correlations between the FCP and ECT response. RESULTS: A total of 82 TRD patients in the ECT group were successfully treated. On an average, 8.50 ± 2.00 ECT sessions were conducted. After ECT treatment, only 42 TRD patients had an improved response to ECT (the Hamilton scores reduction rate was more than 50%), response rate 51%. 8 FNs (anterior and posterior default mode network, bilateral frontoparietal network, audio network, visual network, dorsal attention network, and sensorimotor network) were obtained using GIG-ICA. We did not found that FCPs were significantly different between TRD patients and healthy controls. Moreover, the baseline FCP was unrelated to the ECT treatment response. CONCLUSIONS: The FNC was not significantly different between the TRD patients and healthy controls, and the baseline FCP was unrelated to the ECT treatment response. These findings will necessitate that we modify the experimental scheme to explore the mechanisms underlying ECT's effects on depression and explore the specific predictors of the effects of ECT based on the pre-ECT treatment magnetic resonance imaging.

Suicidal ideation among Chinese cancer inpatients of general hospitals: prevalence and correlates.

Cancer patients are at high risk for suicide, particularly when they are informed about the cancer diagnosis or hospitalized for cancer treatment. Therefore, oncology healthcare settings such as large general hospitals in China, may represent an ideal setting to identify and treat suicidality in cancer patients. However, the clinical epidemiology of suicidality of Chinese cancer patients remains largely unknown. This study examined the prevalence and correlates of suicidal ideation among Chinese cancer inpatients of large general hospitals. A total of 517 cancer inpatients were consecutively recruited from two tertiary general hospitals of a metropolitan city in northern China, and administered with standardized questionnaires to collect data on sociodemographics, mental health, and cancer-related clinical characteristics. Suicidal ideation and mental health were measured with a single self-report question "In the past month, did you think about ending your life?" and Hospital Anxiety and Depression Scale, respectively. The one-month prevalence of suicidal ideation was 15.3% in Chinese cancer inpatients. In multivariable Logistic regression, depression, anxiety, moderate-to-severe pain, metastatic cancer, poor performance status, surgery, and palliative care were significantly associated with suicidal ideation. Cancer inpatients of large Chinese general hospitals have high prevalence of suicidal ideation and therefore potentially at high risk for suicide. Suicide prevention efforts for cancer inpatients should include periodic evaluation of suicidality, effective pain management, psychooncological supports, and, when necessary, psychiatric treatment and crisis intervention.

Reduction of Interhemispheric Functional Connectivity in Sensorimotor and Visual Information Processing Pathways in Schizophrenia.

BACKGROUND: Previous studies have demonstrated interhemispheric functional connectivity alterations in schizophrenia. However, the relationship between these alterations and the disease state of schizophrenia is largely unknown. Therefore, we aimed to investigate this relationship using voxel-mirrored homotopic connectivity (VMHC) method. METHODS: This study enrolled 36 schizophrenia patients with complete remission, 58 schizophrenia patients with incomplete remission and 55 healthy controls. The VMHC was calculated based on resting-state functional magnetic resonance imaging data. Differences in VMHC among three groups were compared using one-way analysis of variance. A brain region with a significant difference in VMHC was defined as a region of interest (ROI), and the mean VMHC value in the ROI was extracted for the post hoc analysis, i.e., pair-wise comparisons across the three groups. RESULTS: VMHC in the visual region (inferior occipital and fusiform gyri) and the sensorimotor region (paracentral lobule) showed significant differences among the three groups (P < 0.05, a false discovery rate method corrected). Pair-wise comparisons in the post hoc analysis showed that VMHC of the visual and sensorimotor regions in schizophrenia patients with complete remission and incomplete remission was lower than that in healthy controls (P < 0.05, Bonferroni corrected); however, there was no significant difference between the two patient subgroups. CONCLUSIONS: Interhemispheric functional connectivity in the sensorimotor and visual processing pathways was reduced in patients with schizophrenia, but this reduction was unrelated to the disease state; thus, this reduction may serve as a trait marker of schizophrenia.

Increased Local Spontaneous Neural Activity in the Left Precuneus Specific to Auditory Verbal Hallucinations of Schizophrenia.

BACKGROUND: Auditory verbal hallucinations (AVHs) of schizophrenia have been associated with structural and functional alterations of some brain regions. However, the brain regional homogeneity (ReHo) alterations specific to AVHs of schizophrenia remain unclear. In the current study, we aimed to investigate ReHo alterations specific to schizophrenic AVHs. METHODS: Thirty-five schizophrenic patients with AVH, 41 schizophrenic patients without AVHs, and fifty healthy subjects underwent resting-state functional magnetic resonance imaging. ReHo differences across the three groups were tested using a voxel-wise analysis. RESULTS: Compared with the healthy control group, the two schizophrenia groups showed significantly increased ReHo in the right caudate and inferior temporal gyrus and decreased ReHo in the bilateral postcentral gyrus and thalamus and the right inferior occipital gyrus (false discovery rate corrected, P < 0.05). More importantly, the AVH group exhibited significantly increased ReHo in the left precuneus compared with the non-AVH group. However, using correlation analysis, we did not find any correlation between the auditory hallucination rating scale score and the ReHo of brain regions. CONCLUSIONS: Our results suggest that increased ReHo in the left precuneus may be a pathological feature exclusive to schizophrenic AVHs.

Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress.

Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

Nonspecific Effect of Stress on Brain Gray Matter Volume in Drug-naive Female Patients with First Depressive Episode.

BACKGROUND: This study aimed to observe the differences in brain gray matter volume in drug-naive female patients after the first episode of major depression with and without stressful life events (SLEs) before the onset of depression. METHODS: Forty-three drug-naive female patients voluntarily participated in the present study after the first major depressive episode. The life event scale was used to evaluate the severity of the impact of SLEs during 6 months before the onset of the major depressive episode. High-field magnetic resonance imaging (MRI) scans were obtained, and the VBM and SPM8 software process were used to process and analyze the MRI. RESULTS: Compared to that in patients without SLEs, the volume of brain gray matter was lower in the bilateral temporal lobe, right occipital lobe, and right limbic lobe in the SLE group. However, the gray matter volume did not differ significantly between the two groups after the application of false discovery rate (FDR) correction. CONCLUSIONS: Although the results of the present study suggest the absence of significant differences in brain gray matter volume between female drug-naive patients after the first episode of major depression with and without SLEs after FDR correction, the study provides useful information for exploring the definitive role of stress in the onset of depression.

A randomised controlled trial of combined EEG feedback and methylphenidate therapy for the treatment of ADHD.

PURPOSE: To evaluate the efficacy of combined methylphenidate and EEG feedback treatment for children with ADHD. METHODS: Forty patients with ADHD were randomly assigned to the combination group (methylphenidate therapy and EEG feedback training) or control group (methylphenidate therapy and non-feedback attention training) in a 1:1 ratio using the double-blind method. These patients, who met the DSM-IV diagnostic criteria and were aged between 7 and 16 years, had obtained optimal therapeutic effects by titrating the methylphenidate dose prior to the trial. The patients were assessed using multiple parameters at baseline, after 20 treatment sessions, after 40 treatment sessions, and in 6-month follow-up studies. RESULTS: Compared to the control group, patients in the combination group had reduced ADHD symptoms and improved in related behavioural and brain functions. CONCLUSION: The combination of EEG feedback and methylphenidate treatment is more effective than methylphenidate alone. The combined therapy is especially suitable for children and adolescents with ADHD who insufficiently respond to single drug treatment or experience drug side effects.