Spatial and Temporal Abnormalities of Spontaneous Fixational Saccades and Their Correlates With Positive and Cognitive Symptoms in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Visual fixation is a dynamic process, with the spontaneous occurrence of microsaccades and macrosaccades. These fixational saccades are sensitive to the structural and functional alterations of the cortical-subcortical-cerebellar circuit. Given that dysfunctional cortical-subcortical-cerebellar circuit contributes to cognitive and behavioral impairments in schizophrenia, we hypothesized that patients with schizophrenia would exhibit abnormal fixational saccades and these abnormalities would be associated with the clinical manifestations. STUDY DESIGN: Saccades were recorded from 140 drug-naïve patients with first-episode schizophrenia and 160 age-matched healthy controls during ten separate trials of 6-second steady fixations. Positive and negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). STUDY RESULTS: Patients with schizophrenia exhibited fixational saccades more vertically than controls, which was reflected in more vertical saccades with angles around 90° and a greater vertical shift of horizontal saccades with angles around 0° in patients. The fixational saccades, especially horizontal saccades, showed longer durations, faster peak velocities, and larger amplitudes in patients. Furthermore, the greater vertical shift of horizontal saccades was associated with higher PANSS total and positive symptom scores in patients, and the longer duration of horizontal saccades was associated with lower MCCB neurocognitive composite, attention/vigilance, and speed of processing scores. Finally, based solely on these fixational eye movements, a K-nearest neighbors model classified patients with an accuracy of 85%. Conclusions: Our results reveal spatial and temporal abnormalities of fixational saccades and suggest fixational saccades as a promising biomarker for cognitive and positive symptoms and for diagnosis of schizophrenia.

The effect of initial antipsychotic treatment on hippocampal and amygdalar volume in first-episode schizophrenia is influenced by age.

BACKGROUND: Antipsychotic treatment has been shown to yield hippocampal and amygdalar volumetric changes in first-episode schizophrenia (FES). However, whether antipsychotic induced volumetric changes interact with age remains unclear. METHODS: The current study includes data from 120 medication naïve FES patients and 110 matched healthy controls (HC). Patients underwent MRI scans before (T1) and after (T2) antipsychotic treatment. HCs underwent MRI scans at baseline only. The hippocampus and amygdala were segmented via Freesurfer 7. General linear models were conducted to investigate the effect of age by diagnosis interaction on baseline volume. Linear mixed models (LMM) were used to detect the effect of age on volumetric changes from pre to post treatment in FES. RESULTS: GLM revealed a trending effect (F = 3.758, p = 0.054) of age by diagnosis interaction on the baseline volume of the left (whole) hippocampus, with older FES patients showing smaller hippocampal volumes, relative to HC, when controlled sex, education years, and ICV. LMM showed a significant age by time-point interaction effect (F = 4.194, estimate effect = -1.964, p = 0.043) on left hippocampal volume in all FES and significant time effect(F = 6.608,T1-T2(estimate effect) = 62.486, p = 0.011), whereby younger patients showed greater hippocampal volumetric decreases following treatment. At the subfield level, a significant time effect emerged in left molecular_layer_HP (F = 4.509,T1-T2(estimate effect) = 12.424, p = 0.032, FDR corrected) and left cornu ammonis(CA)4 (F = 4.800,T1-T2(estimate effect) = 7.527, p = 0.046, FDR corrected), implying volumetric reduction after treatment in these subfields. CONCLUSIONS: Our findings suggest that age plays an important role in the neuroplastic mechanisms of initial antipsychotics on the hippocampus and amygdala of schizophrenia.

Symptom-circuit mappings of the schizophrenia connectome.

OBJECTIVE: This paper aims to model the anatomical circuits underlying schizophrenia symptoms, and to explore patterns of abnormal connectivity among brain networks affected by psychopathology. METHODS: T1 magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), and resting-state functional MRI (rsfMRI) were obtained from a total of 126 patients with schizophrenia who were recruited for the study. The images were processed using the Omniscient software (https://www.o8t. com). We further apply the use of the Hollow-tree Super (HoTS) method to gain insights into what brain regions had abnormal connectivity that might be linked to the symptoms of schizophrenia. RESULTS: The Positive and Negative Symptom Scale is characterised into 6 factors. Each symptom is mapped with specific anatomical abnormalities and circuits. Comparison between factors reveals co-occurrence in parcels in Factor 1 and Factor 2. Multiple large-scale networks are involved in SCZ symptomatology, with functional connectivity within Default Mode Network (DMN) and Central Executive Network (CEN) regions most frequently associated with measures of psychopathology. CONCLUSION: We present a summary of the relevant anatomy for regions of the cortical areas as part of a larger effort to understand its contribution in schizophrenia. This unique machine learning-type approach maps symptoms to specific brain regions and circuits by bridging the diagnostic subtypes and analysing the features of the connectome.

Effective differentiation between depressed patients and controls using discriminative eye movement features.

BACKGROUND: Depression is a common debilitating mental disorder caused by various factors. Identifying and diagnosing depression are challenging because the clinical evaluation of depression is mainly subjective, lacking objective and quantitative indicators. The present study investigated the value and significance of eye movement measurements in distinguishing depressed patients from controls. METHODS: Ninety-five depressed patients and sixty-nine healthy controls performed three eye movement tests, including fixation stability, free-viewing, and anti-saccade tests, and eleven eye movement indexes were obtained from these tests. The independent t-test was adopted for group comparisons, and multiple logistic regression analysis was employed to identify diagnostic biomarkers. Support vector machine (SVM), quadratic discriminant analysis (QDA), and Bayesian (BYS) algorithms were applied to build the classification models. RESULTS: Depressed patients exhibited eye movement anomalies, characterized by increased saccade amplitude in the fixation stability test; diminished saccade velocity in the anti-saccade test; and reduced saccade amplitude, shorter scan path length, lower saccade velocity, decreased dynamic range of pupil size, and lower pupil size ratio in the free-viewing test. Four features mentioned above entered the logistic regression equation. The classification accuracies of SVM, QDA, and BYS models reached 86.0%, 81.1%, and 83.5%, respectively. CONCLUSIONS: Depressed patients exhibited abnormalities across multiple tests of eye movements, assisting in differentiating depressed patients from healthy controls in a cost-effective and non-invasive manner.

Comparison of electroconvulsive therapy and magnetic seizure therapy in schizophrenia: Structural changes/neuroplasticity.

Electroconvulsive therapy (ECT) can effectively reduce the symptoms of schizophrenia, but may also impair cognitive function. A potential alternative is magnetic seizure therapy (MST), which has shown comparable efficacy with less severe cognitive disruption. This study compared ECT to MST for clinical efficacy and cognitive side effects. In addition, we examined the possible contributions of hippocampal volume changes and enhanced brain derived neurotrophic factor (BDNF) signaling to the therapeutic responses. Thirty-four confirmed schizophrenia patients were allocated to receive ECT (n = 16) or MST (n = 18) over a 4-week period. Schizophrenia symptoms were measured by PANSS, cognition by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum BDNF and its precursor proBDNF by ELISA at baseline and following ECT or MST. Both treatments reduced PANSS scores with comparable efficacy, while MST was superior for preservation of RBANS language score. ECT significantly increased the volumes of the bilateral hippocampus and multiple subfields, while MST had no effect on hippocampal volume. The change in right hippocampal volume was correlated with proBDNF change among ECT and MST non-responders (< 25% decrease in PANSS score). MST reduced schizophrenia symptoms as effectively as ECT with slightly better preservation of cognitive function.

Functional reconfiguration of cerebellum-cerebral neural loop in schizophrenia following electroconvulsive therapy.

Recent evidence highlights the role of the cerebellum-cerebral loop in the pathophysiology of schizophrenia (SZ). Electroconvulsive therapy (ECT) is clinically applied to augment the effect of antipsychotic drugs. The study aims to address whether the cerebellum-cerebral loop is involved in the mechanisms of ECT's augmentation effect. Forty-two SZ patients and 23 healthy controls (HC) were recruited and scanned using resting-state functional MRI (rs-fMRI). Twenty-one patients received modified ECT plus antipsychotics (MSZ group), and 21 patients took antipsychotics only (DSZ group). All patients were re-scanned four weeks later. Brain functional network was constructed according to the graph theory. The sub-network exhibited longitudinal changes after ECT or medications were constructed. For the MSZ group, a sub-network involving default-mode network and cerebellum showed significant longitudinal changes. For the DSZ group, a different sub-network involving the thalamus, frontal and occipital cortex was found to be altered in the follow-up scan. In addition, the changing FC of the left cerebellar crus2 region was correlated with the changing scores of the psychotic symptoms only in the MSZ group but not in the DSZ group. In conclusion, the cerebral-cerebellum loop is possibly involved in the antipsychotic mechanisms of ECT for schizophrenia.

Postpartum depression in mothers and fathers: a structural equation model.

BACKGROUND: Post-partum depression (PPD) is a growing mental health concern worldwide. There is little evidence in the Chinese context of the relationship between paternal PPD and maternal PPD. Given the growing global concerns this relationship requires further exploration. METHODS: A survey was conducted with 950 total couples from March 2017 to December 2018. The study was conducted using a standardized questionnaire that included basic demographic information, information on the relationship between the mother-in-law and daughter-in-law, marital satisfaction (both maternal and paternal), and PPD symptoms. Structural Equation Modelling (SEM) analysis was used to explore the underlying mechanism for PPD symptoms in mothers and fathers. RESULTS: In 4.4% of the couples both the wife and the husband showed depressive symptoms. Maternal marital satisfaction showed a significant mediating effect on paternal PPD (B = -0.114, p < 0.01), and there was a direct effect of maternal PPD on paternal PPD (B = 0.31, p < 0.001). CONCLUSIONS: This is the first study to investigate the possible correlation between maternal PPD, mother-in-law and daughter-in-law relationship satisfaction, maternal marital satisfaction, paternal marital satisfaction, and paternal PPD. It is important for future PPD interventions to target both maternal and paternal mental health, as well as the mechanisms identified that can lead to PPD.

Bullying victimization, bullying witnessing, bullying perpetration and suicide risk among adolescents: A serial mediation analysis.

INTRODUCTION: Prior work suggests that involvement in bullying was associated with a higher suicide risk among adolescents. However, the mechanisms of this association remain unclear. The present study aimed to understand the relationship between direct and indirect involvement in bullying (bullying victimization, bullying perpetration and bullying witnessing) and suicide risk by examining the serial mediation of negative coping styles and depressive symptoms. METHODS: 12,354 Chinese adolescents (mean age = 15.00, 54% male) were recruited from December 2018 to January 2019 in 18 secondary schools. Participants completed questionnaires that measured their direct and indirect involvement in bullying, negative coping styles, depressive symptoms, and suicide risk. RESULTS: The relationship between involvement in bullying and suicide risk was mediated by negative coping styles, depressive symptoms, and also serially mediated by negative coping styles and depressive symptoms. Similar findings were obtained for both direct and indirect involvement in bullying. LIMITATIONS: The present study is limited by a cross-sectional design. Future studies could examine longitudinal changes in the outcome measures CONCLUSIONS: Given the urgent need to reduce the high suicide rate among adolescents in China, our findings suggest that having a less negative coping style is an important protective factor. These results provide direction for the development of prevention strategies and targeted interventions within this population. Additionally, it is essential to develop prevention strategies and interventions not only for those who have been a victim or perpetrator of bullying, but also for those who have witnessed bullying.

Mental health outcomes among Chinese prenatal and postpartum women after the implementation of universal two-child policy.

BACKGROUND: Poor mental health status among both pregnant and postpartum women is commonly reported worldwide. The associations between mental health outcomes and giving birth to the second child since the implementation of China's universal two-child policy have not been identified. METHODS: A large-scale based mental health survey was conducted between March 2017 and December 2018 in Suzhou, China. The survey evaluated the symptoms of anxiety, hypomania, depression and poor sleep quality among both pregnant and postpartum women. RESULTS: A total of 3113 questionnaires were collected, the prevalence of anxiety, hypomanic and depressive symptoms and poor sleep quality in our sample were 3.2% (95%CI: 2.6%-3.9%), 51.7% (95%CI: 49.9%-53.4%), 12.4% (95%CI: 11.3%-13.6%) and 37.8% (95%CI: 36.0%-39.5%), respectively. Logistic regression showed that giving birth to the second child was positively associated with women's age, and was negatively correlated with higher educational level and living in rented housing. Women with the second pregnancy or child were positively associated with anxiety symptoms in the whole sample (OR = 1.75, 95%CI: 1.11-2.75) and among prenatal women (OR = 2.11, 95%CI: 1.16-3.83), while it was inversely correlated with depressive symptoms among postpartum women (OR = 0.63, 95%CI: 0.41-0.99). CONCLUSIONS: Women giving birth a second time were more prone to have anxiety symptoms among the prenatal women and the whole sample, and less likely to have depressive symptoms among the postpartum women. Efficacious measures and interventions are essential to improve maternal mental health.

Altered functional connectivity of the thalamus induced by modified electroconvulsive therapy for schizophrenia.

BACKGROUND: Electroconvulsive therapy (ECT) has been shown to be effective in schizophrenia (SZ), particularly in drug-refractory cases or when rapid symptom relief is needed. However, its precise mechanisms of action remain largely unclear. To clarify the mechanisms underlying modified electroconvulsive therapy (mECT) for SZ, we conducted a longitudinal cohort study evaluating functional connectivity of the thalamus before and after mECT treatment using sub-regions of thalamus as regions of interest (ROIs). METHODS: Twenty-one SZ individuals taking only antipsychotics (DSZ group) for 4 weeks and 21 SZ patients receiving a regular course of mECT combining with antipsychotics (MSZ group) were observed in parallel. All patients underwent magnetic resonance imaging scans at baseline (t1) and follow-up (t2, ~4 weeks) time points. Data were compared to a matched healthy control group (HC group) consisting of 23 persons who were only scanned at baseline. Group differences in changes of thalamic functional connectivity between two SZ groups over time, as well as in functional connectivity among two SZ groups and HC group were assessed. RESULTS: Significant interaction of group by time was found in functional connectivity of the right thalamus to right putamen during the course of about 4-week treatment. Post-hoc analysis showed a significantly enhanced functional connectivity of the right thalamus to right putamen in the MSZ group contrasting to the DSZ group. In addition, a decreased and an increased functional connectivity of the thalamus to sensory cortex were observed within the MSZ and DSZ group after 4-week treatment trial, respectively. CONCLUSION: Our findings suggest that changes in functional connectivity of the thalamus may be associated with the brain mechanisms of mECT for schizophrenia.

ECT-induced brain plasticity correlates with positive symptom improvement in schizophrenia by voxel-based morphometry analysis of grey matter.

BACKGROUND: Electroconvulsive therapy (ECT) is often considered as an augmentation of antipsychotic treatment for schizophrenia in drug-refractory cases. However, the mechanisms underlying the observed therapeutic effects are still not understood. OBJECTIVE: We aimed to investigate changes in whole brain grey matter volume (GMV) before and after modified ECT. GMV was determined using voxel-based morphometry (VBM) whole brain analysis. Correlations of brain structural changes with clinical improvement were also investigated. METHODS: Twenty-one schizophrenia patients treated with a full course of ECT combined with antipsychotics (ECT group) and 21 schizophrenia patients treated only with antipsychotics (Drug group) were observed in parallel. Magnetic resonance imaging scans were performed at baseline (T1) and follow-up (T2) for each patient. Data were compared to a healthy control group (HC group) of 23 persons who were only scanned at baseline. Demographic data were matched between the three groups. RESULTS: Significant interactions of group by time were found within four brain regions: the left parahippocampal gyrus/hippocampus, right parahippocampal gyrus/hippocampus, right temporal_pole_mid/superior temporal gyrus, and right insula. Post-hoc analysis revealed an increase of GMV across all four regions amongst ECT group, but a decrease of GMV within the Drug group. Furthermore, the ECT group showed a significant positive correlation of GMV change in the right parahippocampal gyrus/hippocampus with a reduction of positive subscore in the positive and negative syndrome scale. Both treatment groups did not differ significantly in terms of GMV from the HC group in these regions either at T1 or at T2. CONCLUSION: Our findings indicate that ECT may induce brain plasticity as indexed by grey matter volume change during the treatment of schizophrenia via distinct mechanics from those by antipsychotic medications. ECT may ameliorate the positive psychotic symptoms of patients suffering from schizophrenia by preferentially targeting limbic brain areas such as the parahippocampal gyrus/hippocampus.

Insular changes induced by electroconvulsive therapy response to symptom improvements in schizophrenia.

Although modified electroconvulsive therapy (MECT) has been employed as a treatment strategy and to resolve medication resistant symptoms in schizophrenia (SZ), its action mechanisms remain unclear. The insula has been demonstrated to associate with clinical symptoms and neuropathology in SZ. This study examined whether insular changes response to MECT outcomes in SZ. Forty-two SZ were divided into two groups according to their treatment strategies. One group (MSZ, n = 21) received 4-weeks MECT together with antipsychotics; another group (DSZ, n = 21) was treated only with antipsychotics. Twenty-three healthy controls (HC) were also included. Structural and functional MRI were scanned twice (baseline and after 4-week treatment) for SZ and once for HC. Firstly, the insula was divided into three subregions based on resting-state functional connectivity (FC). Subsequently, gray matter volume (GMV) and voxel-wise FC were assessed in each subregion. Finally, the relationship between insular changes and symptom improvements was also investigated. Compared with baseline, the DSZ group showed reduced GMV in insular subregions. In contrast, the MSZ group exhibited increased GMV in bilateral posterior insula (PIns); furthermore, the increase in the PIns was correlated with symptom improvements. Second, the decreased FC between right PIns and left orbitofrontal cortex, and left PIns and middle occipital gyrus was observed only in the MSZ group; moreover, these FC changes were associated with symptom improvements. The present study demonstrated that MECT induced insular changes, which may contribute to the mechanisms of MECT.

Effect of Electroconvulsive Therapy on Medial Prefrontal γ-Aminobutyric Acid Among Schizophrenia Patients: A Proton Magnetic Resonance Spectroscopy Study.

OBJECTIVE: Electroconvulsive therapy (ECT) has often been applied to augment antipsychotics for schizophrenia patients. However, the underpinning mechanism is still unclear. Previous studies of major depressive disorder reported an increase in γ-aminobutyric acid (GABA) after ECT. The present study investigated the effects of ECT on medial prefrontal GABA in schizophrenia using a proton magnetic resonance spectroscopy. METHODS: Inpatients fulfilling the diagnostic criteria for schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) were assigned to 2 groups, ECT group (n = 14) receiving ECT plus antipsychotic drugs (APD) and drug group (n = 17) only receiving antipsychotic drugs. Medial prefrontal GABA+/Cr concentrations of all patients were measured with magnetic resonance spectroscopy at baseline and after 4-week treatment. Sex- and age-matched healthy comparisons (n = 19) were scanned at baseline. RESULTS: γ-Aminobutyric acid level did not show a significant difference among 3 groups. However, when 2 patient groups were combined, their GABA level was significantly lower than that in healthy comparisons group. For schizophrenia patients, repeated measures analysis of variance revealed that both the group effect and group × time interaction were insignificant, but the time effect of baseline versus after treatment was significant. Exploratory post hoc paired t test found a significant increase of GABA only in ECT group, but not in drug group. No correlation was found between GABA change and clinical symptom improvement in either group. CONCLUSIONS: γ-Aminobutyric acid level in the medial prefrontal lobe was reduced in schizophrenia patients. An increase in GABA concentration in the medial prefrontal cortex is more significantly associated with ECT plus antipsychotics than antipsychotics alone, possibly supporting the hypothesis of ECT augmentation for GABA mediated neural inhibition.

Increased resting-state global functional connectivity density of default mode network in schizophrenia subjects treated with electroconvulsive therapy.

Modified electroconvulsive therapy (MECT) has been widely applied to help treat schizophrenia patients who are treatment-resistant to pharmaceutical therapy. Although the technique is increasingly prevalent, the underlying neural mechanisms have not been well clarified. We conducted a longitudinal study to investigate the alteration of global functional connectivity density (gFCD) in schizophrenia patients undergoing MECT using resting state fMRI (functional magnetic resonance imaging). Two groups of schizophrenia inpatients were recruited. One group received a four-week MECT together with antipsychotic drugs (ECT+Drug, n=21); the other group only received antipsychotic drugs (Drug, n=21). Both groups were compared to a sample of healthy controls (HC, n=23). fMRI scans were obtained from the schizophrenia patients twice at baseline (t1) and after 4-week treatment (t2), and from healthy controls at baseline. gFCD was computed using resting state fMRI. Repeated ANCOVA showed a significant interaction effect of group×time in the schizophrenia patients in left precuneus (Pcu), ventral medial prefrontal cortex (vMPFC), and dorsal medial prefrontal cortex (dMPFC) (GRF-corrected P<0.05), which are mainly located within the default mode network (DMN). Post-hoc analysis revealed that compared with baseline (t1), an increased gFCD was found in the ECT+Drug group in the dMPFC (t=3.87, p=0.00095), vMPFC (t=3.95, p=0.00079) and left Pcu (t=3.33, p=0.0034), but no significant effect was identified in the Drug group. The results suggested that increased global functional connectivity density within the DMN might be one important neural mechanism of MECT in schizophrenia.

Eye Movement Indices in the Study of Depressive Disorder.

BACKGROUND: Impaired cognition is one of the most common core symptoms of depressive disorder. Eye movement testing mainly reflects patients' cognitive functions, such as cognition, memory, attention, recognition, and recall. This type of testing has great potential to improve theories related to cognitive functioning in depressive episodes as well as potential in its clinical application. AIMS: This study investigated whether eye movement indices of patients with unmedicated depressive disorder were abnormal or not, as well as the relationship between these indices and mental symptoms. METHODS: Sixty patients with depressive disorder and sixty healthy controls (who were matched by gender, age and years of education) were recruited, and completed eye movement tests including three tasks: fixation task, saccade task and free-view task. The EyeLink desktop eye tracking system was employed to collect eye movement information, and analyze the eye movement indices of the three tasks between the two groups. RESULTS: (1) In the fixation task, compared to healthy controls, patients with depressive disorder showed more fixations, shorter fixation durations, more saccades and longer saccadic lengths; (2) In the saccade task, patients with depressive disorder showed longer anti-saccade latencies and smaller anti-saccade peak velocities; (3) In the free-view task, patients with depressive disorder showed fewer saccades and longer mean fixation durations; (4) Correlation analysis showed that there was a negative correlation between the pro-saccade amplitude and anxiety symptoms, and a positive correlation between the anti-saccade latency and anxiety symptoms. The depression symptoms were negatively correlated with fixation times, saccades, and saccadic paths respectively in the free-view task; while the mean fixation duration and depression symptoms showed a positive correlation. CONCLUSION: Compared to healthy controls, patients with depressive disorder showed significantly abnormal eye movement indices. In addition patients' anxiety and depression symptoms and eye movement indices were correlated. The pathological meaning of these phenomena deserve further exploration.