Publications by authors named "Zhening Liu"

111 Publications

The Role of Military Training in Improving Psychological Resilience and Reducing Depression Among College Freshmen.

Front Psychiatry 2021 17;12:641396. Epub 2021 May 17.

Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.

Military training plays an important protective role in enhancing mental health. However, the effects of military training on psychological resilience and depression among college freshmen in China remain unclear. The present study aimed to evaluate changes in psychological resilience and depression through military training among college freshmen, and to investigate associated psychosocial factors including childhood trauma that may influence its effects on psychological resilience. A prospective and self-comparison study design was employed. College freshmen who received 3 weeks of military training were recruited. Socio-demographic variables were collected and childhood trauma exposure was estimated by the Childhood Trauma Questionnaire (CTQ). The Connor-Davidson Resilience Scale (CD-RISC) and Patient Health Questionnaire (PHQ-9) were used to assess psychological resilience and depression before and after the military-style training. The military training significantly increased the total and subscale scores of CD-RISC ( < 0.001), and decreased the PHQ-9 score ( < 0.001). The proportion of students with clinical depression reduced from 10.5% at baseline to 7.2% after the training ( < 0.001). Improvement of CD-RISC scores was positively affected by male gender and urban area, while negatively affected by older age, and higher baseline scores of PHQ-9 and CTQ. A significant correlation was found between changes in scores of CD-RISC and PHQ-9 through the training ( = -0.238, < 0.001). Military training may have a positive effect on increasing psychological resilience and reducing depressive symptoms among college freshmen, especially in male students and those from an urban area, while older age, childhood trauma, higher depression levels, and resilience at baseline may weaken, or even mask its positive effect. Follow-up research should be considered for the long-term effects of military-style training.
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http://dx.doi.org/10.3389/fpsyt.2021.641396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166047PMC
May 2021

Childhood trauma is linked to decreased temporal stability of functional brain networks in young adults.

J Affect Disord 2021 Jul 2;290:23-30. Epub 2021 May 2.

Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Mental Health Institute of Central South University, Changsha, Hunan, China; China National Clinical Research Center on Mental Disorders, Changsha, Hunan, China. Electronic address:

Background: Both childhood trauma and disruptions in brain functional networks are implicated in the development of psychiatric disorders in early adulthood. However, the relationships between these two factors remain unclear. This study aimed to investigate whether and how childhood trauma would relate to changes of functional network dynamics in young adults.

Methods: Resting-state functional magnetic resonance imaging data were collected from 53 young healthy adults, whose childhood trauma histories were assessed by the Childhood Trauma Questionnaire (CTQ). Network switching rate, a measure of stability of dynamic brain networks over time, was calculated at both global and local levels for each participant. Switching rates at both levels were compared between participants with and without childhood trauma, and further correlated with CTQ total score.

Results: In the current sample, 19 (35.8%) participants reported a history of childhood trauma. At the global level, participants with childhood trauma showed significantly higher network switching rates than those without trauma (F = 10.021, p = 0.003). A significant positive correlation was found between network switching rates and CTQ scores in the entire sample (r = 0.378, p = 0.007). At the local level, these effects were mainly observed in the default-mode, fronto-parietal, cingulo-opercular, and occipital subnetworks.

Conclusions: Our study provides preliminary evidence for a possible long-term effect of childhood trauma on brain functional dynamism. These findings may have potential contributions to psychiatric disorders during adulthood.
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http://dx.doi.org/10.1016/j.jad.2021.04.061DOI Listing
July 2021

Abnormal Large-Scale Network Activation Present in Bipolar Mania and Bipolar Depression Under Resting State.

Front Psychiatry 2021 26;12:634299. Epub 2021 Mar 26.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.

Previous studies have primarily focused on the neuropathological mechanisms of the emotional circuit present in bipolar mania and bipolar depression. Recent studies applying resting-state functional magnetic resonance imaging (fMRI) have raise the possibility of examining brain-wide networks abnormality between the two oppositional emotion states, thus this study aimed to characterize the different functional architecture represented in mania and depression by employing group-independent component analysis (gICA). Forty-one bipolar depressive patients, 20 bipolar manic patients, and 40 healthy controls (HCs) were recruited and received resting-state fMRI scans. Group-independent component analysis was applied to the brain network functional connectivity analysis. Then, we calculated the correlation between the value of between-group differences and clinical variables. Group-independent component analysis identified 15 components in all subjects, and ANOVA showed that functional connectivity (FC) differed significantly in the default mode network, central executive network, and frontoparietal network across the three groups. Further -tests showed a gradient descent of activity-depression > HC > mania-in all three networks, with the differences between depression and HCs, as well as between depression and mania, surviving after family wise error (FWE) correction. Moreover, central executive network and frontoparietal network activities were positively correlated with Hamilton depression rating scale (HAMD) scores and negatively correlated with Young manic rating scale (YMRS) scores. Three brain networks heighten activity in depression, but not mania; and the discrepancy regions mainly located in prefrontal, which may imply that the differences in cognition and emotion between the two states is associated with top-down regulation in task-independent networks.
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http://dx.doi.org/10.3389/fpsyt.2021.634299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032940PMC
March 2021

Online Real-Time Monitoring of Exhaled Breath Particles Reveals Unnoticed Transport of Nonvolatile Drugs from Blood to Breath.

Anal Chem 2021 03 16;93(12):5005-5008. Epub 2021 Mar 16.

Institute of Mass Spectrometry and Atmospheric Environment, Jinan University, Guangzhou 510632, China.

We used online secondary electrospray ionization mass spectrometry to measure venlafaxine (VEN), a nonvolatile drug, in the exhaled air of mice intraperitoneally treated with VEN. The breath pharmacokinetic (PK) profile of VEN was recorded, which was in good agreement with that of the blood. Combined with online collection of exhaled breath particles (EBPs), it was shown that VEN existed as part of EBPs rather than gas molecules in the breath. Linear free-energy relationship analysis confirmed that almost completely ionized VEN at physiological conditions unlikely partition from the lung lining fluid (LLF) into breath air. This implies that the occurrence of VEN in exhaled air accompanies the formation of EBPs from the LLF. By comparison with the low breath signals of VEN metabolites, passive membrane permeability and lung/blood partition coefficient are suggested as the main influencing factors for the levels of drugs in the breath. This study advances our knowledge on the mechanism by which nonvolatile drugs are transferred from blood into exhaled breath, providing guidance for breath test-based therapeutic drug monitoring.
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http://dx.doi.org/10.1021/acs.analchem.1c00509DOI Listing
March 2021

Gray matter reorganization underpinnings of antidepressant treatment of persistent depressive disorder.

Eur Neuropsychopharmacol 2021 Feb 3;43:129-138. Epub 2021 Jan 3.

New York State Psychiatric Institute, New York, NY, USA; Columbia University College of Physicians and Surgeons, New York, NY, USA.

Brain gray matter is organized in a manner with interconnected brain regions, resulting in a notable covariance pattern that recapitulates either the functional coactivation or structural connectivity of brain regions, which is believed to underpin psychiatric disorders such as depression. This study aimed to investigate whether and how antidepressants took effect in treating depression and reducing symptoms by altering the gray matter covariance pattern. We combined structural magnetic resonance imaging (MRI) scans acquired in two randomized, double-blind, placebo-controlled trial (RCT) studies of the treatment using serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant medications in patients with persistent depressive disorder (PDD). One was an RCT of 10-week duloxetine medication that consisted of patients who received duloxetine (N = 21) or placebo (N = 21), and the other was an RCT of 12-week desvenlafaxine medication that consisted of 19 and 17 patients respectively who received desvenlafaxine or placebo. We examined treatment effect on gray matter volume (GMV) and topological organization of GMV covariance pattern (i.e., GMV-based network). We found a treatment-by-time effect on GMV in the angular gyrus and cuneus areas, whereas the GMV change rate of the cuneus was inversely correlated with the response rate. We observed a significant increase in the local efficiency of the GMV-based network following medication treatment compared with placebo. Our findings provide preliminary evidence for a GMV-based network-specific reconfiguration caused by antidepressants compared to placebo and the cuneus may be a possible candidate region to predict antidepressant response.
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http://dx.doi.org/10.1016/j.euroneuro.2020.12.009DOI Listing
February 2021

Decreased integration of the frontoparietal network during a working memory task in major depressive disorder.

Aust N Z J Psychiatry 2021 Jun 16;55(6):577-587. Epub 2020 Dec 16.

Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China.

Background: Working memory deficits are a common feature in major depressive disorder and are associated with poor functional outcomes. Intact working memory performance requires the recruitment of large-scale brain networks. However, it is unknown how the disrupted recruitment of distributed regions belonging to these large-scale networks at the whole-brain level brings about working memory impairment seen in major depressive disorder.

Methods: We used graph theory to examine the functional connectomic metrics (local and global efficiency) at the whole-brain and large-scale network levels in 38 patients with major depressive disorder and 41 healthy controls during a working memory task. Altered connectomic metrics were studied in a moderation model relating to clinical symptoms and working memory accuracy in patients, and a machine learning method was employed to assess whether these metrics carry enough illness-specific information to discriminate patients from controls.

Results: Global efficiency of the frontoparietal network was reduced in major depressive disorder (false discovery rate corrected,  = 0.014); this reduction predicted worse working memory performance in patients with less severe illness burden indexed by Brief Psychiatric Rating Scale (β =-0.43,  = 0.035,  =-2.2, 95% confidence interval = [-0.043,-0.002]). We achieved a classification accuracy and area under the curve of 73.42% and 0.734, respectively, to discriminate patients from controls based on connectomic metrics, and the global efficiency of the frontoparietal network contributed most to the diagnostic classification.

Conclusions: We report a putative mechanistic link between the global efficiency of the frontoparietal network and impaired n-back performance in major depressive disorder. This relationship is more pronounced at lower levels of symptom burden, indicating the possibility of multiple pathways to cognitive deficits in severe major depressive disorder.
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http://dx.doi.org/10.1177/0004867420978284DOI Listing
June 2021

Bipolar Mood State Reflected in Functional Connectivity of the Hate Circuit: A Resting-State Functional Magnetic Resonance Imaging Study.

Front Psychiatry 2020 27;11:556126. Epub 2020 Oct 27.

Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: Previous studies suggested bipolar disorder caused an aberrant alteration in the insular, putamen, and left superior frontal gyrus, which are the main components of the hate circuit. However, the relationship between the hate circuit and the pathophysiologic substrate underlying different phases of bipolar disorder remain unclear. In this study, we aimed to identify group differences of resting-state functional connectivity within the hate circuit in healthy controls (HCs) and bipolar patients in different mood states.

Methods: Resting-state functional magnetic resonance imaging of the brain were acquired from 54 HCs and 81 patients with bipolar disorder including 20 with bipolar mania (BM), 35 with bipolar depression (BD), and 26 with bipolar euthymia (BE). We selected bilateral insula (L.INS and R.INS), bilateral putamen (L.PUT and R.PUT), and left superior frontal gyrus (L.SFGd) as seed regions, and conducted the seed-based functional connectivity analysis to identify group differences of connectivity strength within the hate circuit. Spearman correlations were performed to evaluate the relationship between the hate circuit and manic/depressive symptoms.

Results: Significant group differences of connectivity strength within the hate circuit were found in links of the R.INS-L.SFGd, R.PUT-L.SFGd, and L.INS- R.PUT after false discovery rate was corrected. The BM group showed an opposite hate circuit pattern to BD, BE, and HCs. The BD group showed decreased hate circuit connectivity in the L.INS-R.PUT compared with the BE group. No significant difference was detected among BD, BE, and HCs. Furthermore, functional connectivity of the R.INS-L.SFGd and R.PUT-L.SFGd were positively correlated with manic symptoms, while the L.INS- R.PUT was negatively correlated with depressive symptoms.

Conclusions: Our preliminary findings suggest that altered functional connectivity of the hate circuit in different mood phases may be related to state markers and underpin the neuropathological basis of bipolar disorder.
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http://dx.doi.org/10.3389/fpsyt.2020.556126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652934PMC
October 2020

Drug-naïve first-episode schizophrenia spectrum disorders: Pharmacological treatment practices in inpatient units in Hunan Province, China.

Early Interv Psychiatry 2020 Sep 14. Epub 2020 Sep 14.

Department of Psychiatry, Second Xiangya Hospital of Central South University, Changsha, China.

Aim: This study describes antipsychotic prescription patterns for drug-naïve inpatients diagnosed with first-episode schizophrenia-spectrum (FES) disorders and factors associated with practices deviating from China's current guidelines.

Methods: All inpatients aged 7 to 45 years experiencing a first episode of schizophrenia-spectrum disorder with a duration of untreated illness of less than 18 months and admitted between 1 August 2016 and 1 August 2017 to one of eight psychiatric hospitals in Hunan were included. Demographics, clinical characteristics and prescriptions at discharge were collected from electronic medical records. Logistic regression and random forest methods were used to model relationships between demographic and clinical factors and deviations from China's guidelines.

Results: Of the 602 inpatients included in the study, 598 (99.3%) were prescribed antipsychotics, and no patients were discharged on long-acting injectable antipsychotics. Polypharmacy (more than one antipsychotic prescribed) was present in 121 (20.2%) participants. Clozapine was prescribed to 45 (7.5%) patients. Adults receiving polypharmacy were more likely to be prescribed high-dose antipsychotics than those receiving a single antipsychotic. Minors under 13 years of age were more likely to receive polypharmacy and unapproved antipsychotics than those older than 13 years.

Conclusions: Our findings suggest that most of the inpatients were prescribed a single antipsychotic at discharge, consistent with China's guidelines. Minors with FES and patients discharged on polypharmacy and clozapine may require more intense monitoring and management. With the current implementation of China's National Mental Health Working Plan, these results will assist decision-makers in allocating resources and conducting reforms to facilitate best practice treatment for FES.
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http://dx.doi.org/10.1111/eip.13046DOI Listing
September 2020

Abnormal Thalamocortical Circuit in Adolescents With Early-Onset Schizophrenia.

J Am Acad Child Adolesc Psychiatry 2021 04 10;60(4):479-489. Epub 2020 Aug 10.

Central South University, Changsha, Hunan, China; the Medical Psychological Institute of Central South University, Changsha, Hunan, China; and the National Clinical Research Center for Mental Disorders, Changsha, Hunan, China; National University of Defense Technology, Changsha, Hunan, China. Electronic address:

Objective: Thalamic circuit imbalance characterized by increased sensorimotor-thalamic connectivity and decreased prefrontal-thalamic connectivity has been consistently observed in adult-onset schizophrenia (AOS), although it is unclear whether this pattern is also a feature of early-onset schizophrenia (EOS). If this is the case, thalamic circuit imbalance can be considered as a core mechanistic defect in schizophrenia, unconfounded by the age of onset.

Method: A total of 116 adolescents with EOS (63 drug-naive EOS) and 55 matched healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging scans. To define the specific location of the thalamic subregions in thalamocortical circuit, 16 atlas-based thalamic subdivisions were used in functional connectivity analysis.

Results: The EOS group showed increased sensorimotor-thalamic connectivity and decreased prefrontal-cerebello-thalamic connectivity, consistent with AOS. Sensorimotor-thalamic hyperconnectivity was more prominent than prefrontal-thalamic hypoconnectivity, which was circumscribed to the medial prefrontal cortex (mPFC), in EOS. Of note, the EOS group specifically exhibited strengthened thalamic connectivity with the salience network (SN). In addition, the EOS showed a more prominent disruption of the lateral thalamic nuclear connectivity.

Conclusion: Thalamic dysconnectivity observed in the EOS extends the observations from adult patients. Sensorimotor-thalamic hyperconnectivity is critical for the expression of schizophrenia phenotype irrespective of the age of onset, raising the possibility of aberrant but accelerated functional network maturation in EOS. The specific thalamocortical dysconnectivity involving the SN and mPFC may underlie the distinctive features of multi-modal hallucinations and heightened emotional valence of psychosis seen in EOS.
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http://dx.doi.org/10.1016/j.jaac.2020.07.903DOI Listing
April 2021

Reduced Cortical Thickness in the Right Caudal Middle Frontal Is Associated With Symptom Severity in Betel Quid-Dependent Chewers.

Front Psychiatry 2020 10;11:654. Epub 2020 Jul 10.

National Clinical Research Centre for Mental Disorders, Institute of Mental Health and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China.

Background: Findings from brain structural imaging studies on betel quid dependence have supported relations between betel quid chewing and alterations in gray matter volume and white matter integrity. However, the effect of betel quid chewing on cortical thickness and the link between cortical thickness and symptom severity remains unascertained.

Methods: In this observational study, we compared cortical thickness measures from 24 male betel quid-dependent chewers with 27 male healthy controls. Using FreeSufer, we obtained three-dimensional T1-weighted images that were used to compute the thickness of the cerebral cortex throughout the cortical layer.

Results: Compared to healthy controls, betel quid dependent chewers displayed significant decreased cortical thickness in the precuneus, entorhinal, right paracentral, middle temporal, and caudal middle frontal gyri. Betel quid dependence scale scores negatively correlated (r = -0.604; = 0.002) with reduced cortical thickness in the right caudal middle frontal of betel quid-dependent chewers.

Conclusion: The findings provide evidence for cortical thickness abnormality in betel dependent chewers and further propose that the severity of betel quid symptoms may be a critical aspect associated with the cortical alterations. The observed alterations may serve as potential mechanisms to explain why BQ chewing behavior is persistent among individuals with betel quid dependence.
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http://dx.doi.org/10.3389/fpsyt.2020.00654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366340PMC
July 2020

A multivariate pattern analysis of resting-state functional MRI data in Naïve and chronic betel quid chewers.

Brain Imaging Behav 2020 Jul 25. Epub 2020 Jul 25.

Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Betel quid (BQ) is the fourth most commonly consumed psychoactive substance in the world. However, comprehensive functional magnetic resonance imaging (fMRI) studies exploring the neurophysiological mechanism of BQ addiction are lacking. Betel-quid-dependent (BQD) individuals (n = 24) and age-matched healthy controls (HC) (n = 26) underwent fMRI before and after chewing BQ. Multivariate pattern analysis (MVPA) was used to explore the acute effects of BQ-chewing in both groups. A cross-sectional comparison was conducted to explore the chronic effects of BQ-chewing. Regression analysis was used to investigate the relationship between altered circuits of BQD individuals and the severity of BQ addiction. MVPA achieved classification accuracies of up to 90% in both groups for acute BQ-chewing. Suppression of the default-mode network was the most prominent feature. BQD showed more extensive and intensive within- and between-network dysconnectivity of the default, frontal-parietal, and occipital regions associated with high-order brain functions such as self-awareness, inhibitory control, and decision-making. In contrast, the chronic effects of BQ on the brain function were mild, but impaired circuits were predominately located in the default and frontal-parietal networks which might be associated with compulsive drug use. Simultaneously quantifying the effects of both chronic and acute BQ exposure provides a possible neuroimaging-based BQ addiction foci. Results from this study may help us understand the neural mechanisms involved in BQ-chewing and BQ dependence.
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http://dx.doi.org/10.1007/s11682-020-00322-6DOI Listing
July 2020

Medication adherence and its correlates among patients affected by schizophrenia with an episodic course: A large-scale multi-center cross-sectional study in China.

Asian J Psychiatr 2020 Oct 8;53:102198. Epub 2020 Jun 8.

Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA.

The Medication Adherence Rating Scale (MARS) is a fast, non-intrusive way of measuring adherence to medication in order to improve the management of patients with schizophrenia. The current cross-sectional study evaluated the reliability of the Chinese (Mandarin) version of the MARS and explored clinical and demographic correlates to medication adherence in a large sample of patients affected by schizophrenia with an episodic course in China. 1198 patients were recruited from 37 different hospitals in 17 provinces/municipalities of China and evaluated with the Medication Adherence Rating Scale (MARS), Clinical Global Impression-Severity of Illness (CGI-SI) and Sheehan Disability Scale-Chinese version (SDS-C). The MARS showed good internal consistency; Cronbach's alpha of total MARS was 0.83. Among the cohort of patients affected by schizophrenia with an episodic course, 28.5 % met the criteria of good adherence to antipsychotic medication; age, steady income, and severity of illness had significant effects on medication adherence. Medication adherence of patients affected by schizophrenia in mainland China was found to be relatively low, calling for urgent attention and intervention. Risk factors for non-adherence to medication among patients affected by schizophrenia with an episodic course include older age, unsteady income, being in the acute period of the disease, and severity of illness.
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http://dx.doi.org/10.1016/j.ajp.2020.102198DOI Listing
October 2020

Altered Temporal Variability of Local and Large-Scale Resting-State Brain Functional Connectivity Patterns in Schizophrenia and Bipolar Disorder.

Front Psychiatry 2020 12;11:422. Epub 2020 May 12.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.

Schizophrenia and bipolar disorder share some common clinical features and are both characterized by aberrant resting-state functional connectivity (FC). However, little is known about the common and specific aberrant features of the dynamic FC patterns in these two disorders. In this study, we explored the differences in dynamic FC among schizophrenia patients ( = 66), type I bipolar disorder patients ( = 53), and healthy controls ( = 66), by comparing temporal variabilities of FC patterns involved in specific brain regions and large-scale brain networks. Compared with healthy controls, both patient groups showed significantly increased regional FC variabilities in subcortical areas including the thalamus and basal ganglia, as well as increased inter-network FC variability between the thalamus and sensorimotor areas. Specifically, more widespread changes were found in the schizophrenia group, involving increased FC variabilities in sensorimotor, visual, attention, limbic and subcortical areas at both regional and network levels, as well as decreased regional FC variabilities in the default-mode areas. The observed alterations shared by schizophrenia and bipolar disorder may help to explain their overlapped clinical features; meanwhile, the schizophrenia-specific abnormalities in a wider range may support that schizophrenia is associated with more severe functional brain deficits than bipolar disorder. Together, these findings highlight the potentials of using dynamic FC as an objective biomarker for the monitoring and diagnosis of either schizophrenia or bipolar disorder.
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http://dx.doi.org/10.3389/fpsyt.2020.00422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235354PMC
May 2020

Connectomic signatures of working memory deficits in depression, mania, and euthymic states of bipolar disorder.

J Affect Disord 2020 09 24;274:190-198. Epub 2020 May 24.

Institute of Mental Health, the Second Xiangya Hospital, Central South University, Changsha, PR China; Department of Psychiatry, University of Western Ontario, London, ON, Canada; Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada. Electronic address:

Background: Working memory (WM) deficit is a feature persistently reported across mania, depression, and euthymic periods of bipolar disorder (BD). WM capacity relates to distributed brain regions that are systemically organized at the connectome level. It is not clear whether the same disruption of this network-level organization underlies the WM impairment seen in different phases of BD.

Methods: We used graph theory to examine the topology of the functional connectome in different granularity in 143 subjects (72 with BD [32 depression; 15 mania; 25 euthymic] and 71 healthy controls) during a n-back task. Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients.

Results: Altered topological properties characterised by an increase in small-worldness of the whole-brain connectome, were specific for bipolar depressed, but not in manic and euthymic states. Depressed subjects showed a shift in the distribution of the number of connections per brain region (degree) within the connectome during WM task. Increased small-worldness related to worse WM accuracy in patients with more severe depression, anxiety and illness burden.

Limitations: We used only 2-back load, limiting our ability to study the parametric effects of task demand.

Conclusions: We demonstrate a putative state-dependent mechanistic link between connectome topology, hub re-distribution and impaired n-back performance in bipolar disorder. The aberrant task-dependent modulation of the connectome relates to worse WM performance especially when anxiety and depression are prominent in BD.
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http://dx.doi.org/10.1016/j.jad.2020.05.058DOI Listing
September 2020

Acute and Chronic Effects of Betel Quid Chewing on Brain Functional Connectivity.

Front Psychiatry 2020 17;11:198. Epub 2020 Mar 17.

Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.

Background: The active alkaloid in Betel quid is arecoline. Consumption of betel quid is associated with both acute effects and longer-term addictive effects. Despite growing evidence that betel quid use is linked with altered brain function and connectivity, the neurobiology of this psychoactive substance in initial acute chewing, and long-term dependence, is not clear.

Methods: In this observational study, functional magnetic resonance imaging in a resting-state was performed in 24 male betel quid-dependent chewers and 28 male controls prior to and promptly after betel quid chewing. Network-based statistics were employed to determine significant differences in functional connectivity between brain networks for both acute effects and in long-term betel users versus controls. A support vector machine was employed for pattern classification analysis.

Results: Before chewing betel quid, higher functional connectivity in betel quid-dependent chewers than in controls was found between the temporal, parietal and frontal brain regions (right medial orbitofrontal cortex, right lateral orbital frontal cortex, right angular gyrus, bilateral inferior temporal gyrus, superior parietal gyrus, and right medial superior frontal gyrus). In controls, the effect of betel quid chewing was significantly increased functional connectivity between the subcortical regions (caudate, putamen, pallidum, and thalamus), and the visual cortex (superior occipital gyrus and right middle occipital gyrus).

Conclusion: These findings show that individuals who chronically use betel quid have higher functional connectivity than controls of the orbitofrontal cortex, and inferior temporal and angular gyri. Acute effects of betel quid are to increase the functional connectivity of some visual cortical areas (which may relate to the acute symptoms) and the basal ganglia and thalamus.
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http://dx.doi.org/10.3389/fpsyt.2020.00198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094756PMC
March 2020

Salience-thalamic circuit uncouples in major depressive disorder, but not in bipolar depression.

J Affect Disord 2020 05 3;269:43-50. Epub 2020 Mar 3.

The China National Clinical Research Center for Mental Health Disorders, Changsha, China; Medical Psychological Center, the Second Xiangya Hospital, Central South University, Changsha, Hunan , China. Electronic address:

Background: Bipolar depression (BDD) and major depressive disorder (MDD) are two diseases both characterized by depressed mood and diminished interest or pleasure. Recent neuroimaging studies have implicated the thalamo-cortical circuit in mood disorders, and the present study aimed to map thalamo-cortical connectivity to explore the dissociable and common abnormalities between bipolar and major depression in this circuit.

Method: Applying resting-state functional magnetic resonance imaging (fMRI), we mapped the thalamo-cortical circuit using a fine-grained thalamic atlas with 8 sub-regions bilaterally in 38 BDD patients, 42 MDD patients and 39 healthy controls (HCs). Correlation analysis was then performed between thalamo-cortical connectivity and clinical variables.

Result: The findings showed that both patient groups exhibited prefronto-thalamo-cerebellar and sensorimotor-thalamic hypoconnectivity, while the abnormalities in MDD were more extensive. Particularly, MDD group showed decreased thalamic connectivity with the salience network including the insula, anterior cingulate cortex (ACC), and striatum. No correlations were found between the abnormal thalamo-cortical connectivity and clinical symptoms in either patient group.

Limitation: Most patients in our study were taking drugs at the time of scanning, which may confound our findings.

Conclusion: Our finding suggest that the thalamo-cortical hypofunction is a common neuro-substrate for BDD and MDD. Specifically, the hypoconnectivity between the thalamus and salience network including the insula, ACC and striatum may be a distinguished biomarker for MDD, which may help to differentiate these two emotional disorders.
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http://dx.doi.org/10.1016/j.jad.2020.03.007DOI Listing
May 2020

Psychological resilience negatively correlates with resting-state brain network flexibility in young healthy adults: a dynamic functional magnetic resonance imaging study.

Ann Transl Med 2019 Dec;7(24):809

Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha 410011, China.

Background: Psychological resilience is an important personality trait whose decrease is associated with many common psychiatric disorders, but the neural mechanisms underlying it remain largely unclear. In this study, we aimed to explore the neural correlates of psychological resilience in healthy adults by investigating its relationship with functional brain network flexibility, a fundamental dynamic feature of brain network defined by switching frequency of its modular community structures.

Methods: Resting-state functional magnetic resonance imaging (fMRI) scans were acquired from 41 healthy adults, whose psychological resilience was quantified by the Connor-Davidson Resilience Scale (CD-RISC). Dynamic functional brain network was constructed for each subject, whose flexibility was calculated at all the global, subnetwork and region-of-interest (ROI) levels. After that, the associations between CD-RISC score and brain network flexibility were assessed at all levels by partial correlations controlling for age, sex, education and head motion. Correlation was also tested between the CD-RISC score and modularity of conventional static brain network for comparative purposes.

Results: The CD-RISC score was significant negatively correlated with the brain network flexibility at global level (r=-0.533, P=0.001), and with flexibility of the visual subnetwork at subnetwork level (r=-0.576, corrected P=0.002). Moreover, significant (corrected P<0.05) or trends for (corrected P<0.10) negative correlations were found between the CD-RISC score and flexibilities of a number of visual and default-mode areas at ROI level. Meanwhile, the modularity of static brain network did not reveal significant correlation with CD-RISC score (P>0.05).

Conclusions: Our results suggest that excessive fluctuations of the functional brain community structures during rest may be indicative of a lower psychological resilience, and the visual and default-mode systems may play crucial roles in such relationship. These findings may provide important implications for improving our understanding of the psychological resilience.
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http://dx.doi.org/10.21037/atm.2019.12.45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989886PMC
December 2019

Connectomic Underpinnings of Working Memory Deficits in Schizophrenia: Evidence From a replication fMRI study.

Schizophr Bull 2020 07;46(4):916-926

Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, PR China.

Background: Working memory (WM) deficit is a key feature of schizophrenia that relates to a generalized neural inefficiency of extensive brain areas. To date, it remains unknown how these distributed regions are systemically organized at the connectome level and how the disruption of such organization brings about the WM impairment seen in schizophrenia.

Methods: We used graph theory to examine the neural efficiency of the functional connectome in different granularity in 155 patients with schizophrenia and 96 healthy controls during a WM task. These analyses were repeated in another independent dataset (81 patients and 54 controls). Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients. A machine-learning approach was adopted to study the ability of multivariate connectome features from one dataset to discriminate patients from controls in the second dataset.

Results: Small-worldness of the whole-brain connectome was significantly increased in schizophrenia during the WM task; this increase is related to better (though subpar) WM accuracy in patients with more severe negative symptom burden. There was a shift in the degree distribution to a more homogeneous form in patients. The machine-learning approach classified a new set of patients from controls with 84.3% true-positivity rate for schizophrenia and 71.6% overall accuracy.

Conclusions: We demonstrate a putative mechanistic link between connectome topology, hub redistribution, and impaired n-back performance in schizophrenia. The task-dependent modulation of the connectome relates to, but remains inefficient in, improving the performance above par in the presence of severe negative symptoms.
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http://dx.doi.org/10.1093/schbul/sbz137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345823PMC
July 2020

Altered resting-state dynamic functional brain networks in major depressive disorder: Findings from the REST-meta-MDD consortium.

Neuroimage Clin 2020 7;26:102163. Epub 2020 Jan 7.

Faculty of Psychology, Southwest University, Chongqing 400716, China.

Background: Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach.

Methods: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels.

Results: The group of MDD patients showed significantly higher temporal variability, lower temporal correlation coefficient (indicating decreased temporal clustering) and shorter characteristic temporal path length (indicating increased temporal efficiency) compared with healthy controls (corrected p < 3.14×10). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients.

Conclusions: Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.
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http://dx.doi.org/10.1016/j.nicl.2020.102163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229351PMC
February 2021

Morphological Profiling of Schizophrenia: Cluster Analysis of MRI-Based Cortical Thickness Data.

Schizophr Bull 2020 04;46(3):623-632

Institute of Mental Health, Second Xiangya Hospital, Central South University, Changsha, PR China.

The diagnosis of schizophrenia is thought to embrace several distinct subgroups. The manifold entities in a single clinical patient group increase the variance of biological measures, deflate the group-level estimates of causal factors, and mask the presence of treatment effects. However, reliable neurobiological boundaries to differentiate these subgroups remain elusive. Since cortical thinning is a well-established feature in schizophrenia, we investigated if individuals (patients and healthy controls) with similar patterns of regional cortical thickness form naturally occurring morphological subtypes. K-means algorithm clustering was applied to regional cortical thickness values obtained from 256 structural MRI scans (179 patients with schizophrenia and 77 healthy controls [HCs]). GAP statistics revealed three clusters with distinct regional thickness patterns. The specific patterns of cortical thinning, clinical characteristics, and cognitive function of each clustered subgroup were assessed. The three clusters based on thickness patterns comprised of a morphologically impoverished subgroup (25% patients, 1% HCs), an intermediate subgroup (47% patients, 46% HCs), and an intact subgroup (28% patients, 53% HCs). The differences of clinical features among three clusters pertained to age-of-onset, N-back performance, duration exposure to treatment, total burden of positive symptoms, and severity of delusions. Particularly, the morphologically impoverished group had deficits in N-back performance and less severe positive symptom burden. The data-driven neuroimaging approach illustrates the occurrence of morphologically separable subgroups in schizophrenia, with distinct clinical characteristics. We infer that the anatomical heterogeneity of schizophrenia arises from both pathological deviance and physiological variance. We advocate using MRI-guided stratification for clinical trials as well as case-control investigations in schizophrenia.
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http://dx.doi.org/10.1093/schbul/sbz112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147597PMC
April 2020

Brain-Wide Functional Dysconnectivity in Schizophrenia: Parsing Diathesis, Resilience, and the Effects of Clinical Expression.

Can J Psychiatry 2020 01 28;65(1):21-29. Epub 2019 Nov 28.

Department of Psychiatry, University of Western Ontario, London, Ontario, Canada.

Background: The functional dysconnectivity observed from functional magnetic resonance imaging (fMRI) studies in schizophrenia is also seen in unaffected siblings indicating its association with the genetic diathesis. We intended to apportion resting-state dysconnectivity into components that represent genetic diathesis, clinical expression or treatment effect, and resilience.

Methods: fMRI data were acquired from 28 schizophrenia patients, 28 unaffected siblings, and 60 healthy controls. Based on Dosenbach's atlas, we extracted time series of 160 regions of interest. After constructing functional network, we investigated between-group differences in strength and diversity of functional connectivity and topological properties of undirected graphs.

Results: Using analysis of variance, we found 88 dysconnectivities. Post hoc tests revealed that 62.5% were associated with genetic diathesis and 21.6% were associated with clinical expression. Topologically, we observed increased degree, clustering coefficient, and global efficiency in the sibling group compared to both patients and controls.

Conclusion: A large portion of the resting-state functional dysconnectivity seen in patients represents a genetic diathesis effect. The most prominent network-level disruption is the dysconnectivity among nodes of the default mode and salience networks. Despite their predisposition, unaffected siblings show a pattern of resilience in the emergent connectomic topology. Our findings could potentially help refine imaging genetics approaches currently used in the pursuit of the pathophysiology of schizophrenia.
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http://dx.doi.org/10.1177/0706743719890174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966251PMC
January 2020

Abnormal Connectivity Within Anterior Cortical Midline Structures in Bipolar Disorder: Evidence From Integrated MRI and Functional MRI.

Front Psychiatry 2019 29;10:788. Epub 2019 Oct 29.

Institute of Mental Health, The Second Xiangya Hospital, Central South University, Changsha, China.

Aberrant functional and structural connectivity across multiple brain networks have been reported in bipolar disorder (BD). However, most previous studies consider the functional and structural alterations in isolation regardless of their possible integrative relationship. The present study aimed to identify the brain connectivity alterations in BD by capturing the latent nexus in multimodal neuroimaging data. Structural and resting-state images were acquired from 83 patients with BD and 94 healthy controls (HCs). Combined with univariate methods conducted to detect the dysconnectivity in BD, we also employed a semi-multimodal fusion framework fully utilizing the interrelationship between the two modalities to distinguish patients from HCs. Moreover, one-way analysis of variance was adopted to explore whether the detected dysconnectivity has differences across stages of patients with BD. The semi-multimodal fusion framework distinguished patients from HCs with 81.47% accuracy, 85.42% specificity, and 74.75% sensitivity. The connection between the anterior cingulate cortex (ACC) and superior medial prefrontal cortex (sMPFC) contributed the most to BD diagnosis. Consistently, the univariate method also identified that this ACC-sMPFC functional connection significantly decreased in BD patients compared to HCs, and the significant order of the dysconnectivity is: depressive episode < HCs and remission episode < HCs. Our findings, by adopting univariate and multivariate analysis methods, shed light on the decoupling within the anterior midline brain in the pathophysiology of BD, and this decoupling may serve as a trait marker for this disease.
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http://dx.doi.org/10.3389/fpsyt.2019.00788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829675PMC
October 2019

Longitudinal Trajectories of Psychotic-Like Experiences and Their Relationship to Emergent Mental Disorders Among Adolescents: A 3-Year Cohort Study.

J Clin Psychiatry 2019 07 23;80(4). Epub 2019 Jul 23.

Department of Psychiatry, Yale University, New Haven, Connecticut, USA.

Background: Psychotic-like experiences (PLEs) may be important antecedents of psychosis and other mental disorders.

Objective: To investigate distinct longitudinal trajectories of the frequency of PLEs and their relationship to subsequent development of mental disorders.

Methods: A longitudinal study of self-reported PLEs and concurrent traumatic experiences was conducted among 6,198 adolescents through annual classroom assessments over 3 years (2014-2016) using the Community Assessment of Psychic Experiences and the Trauma History Questionnaire. Diagnoses of mental disorders were based on the Mini-International Neuropsychiatric Interview in the final year. Growth mixture modeling was used to identify distinct growth trajectories in the frequency of PLEs. Logistic regression was then used to explore relationships between different PLE trajectories and emergence of psychiatric disorders, taking account of sociodemographic characteristics and childhood antecedents.

Results: Two different PLE trajectories were identified, one characterized by stable low levels of PLE frequency and the other by progressively increasing PLE frequency. Transition to mental disorder occurred in 3.39% of the increasing-frequency group and 1.28% of the stable low-level group. The increasing-frequency group had a significantly higher risk of transition to any psychiatric disorder (OR = 2.7; 95% CI, 1.56-4.66), to a psychotic disorder (OR = 22.14; 95% CI, 2.30-213.25), and to a nonpsychotic psychiatric disorder (OR = 2.28; 95% CI, 1.27-4.10). Besides increasing PLEs (OR = 3.33; 95% CI, 1.55-7.19), other risk factors for any psychiatric disorder included childhood trauma (OR = 1.17; 95% CI, 1.01-1.36), family divorce (OR = 2.86; 95% CI, 1.24-6.61), and minority ethnicity (OR = 2.91; 95% CI, 1.18-7.20).

Conclusions: The pattern of increasing PLEs predominates in predicting emergent mental disorder, particularly psychosis, along with minority status, trauma, and family divorce, suggesting potential targets for preventive intervention.
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http://dx.doi.org/10.4088/JCP.18m12437DOI Listing
July 2019

A Qualitative Study of Implementation Challenges of Mental Health Clubhouse Rehabilitation Services in China's Hunan Province.

Psychiatr Serv 2019 08 30;70(8):674-680. Epub 2019 Apr 30.

Department of Psychiatry, Yale School of Medicine, Yale New Haven Psychiatric Hospital, New Haven, Connecticut (Li, Rohrbaugh); Psychiatry Department, Second Xiangya Hospital of Central South University, Changsha, China (Deng, Liu).

Objective: Psychosocial rehabilitation has been established as a critical component of client-centered recovery-oriented services for people with serious mental illness. Despite its importance, the implementation of mental health rehabilitation services in low- or middle-income countries has not been well studied. In this study, the authors document the regional challenges of planning and implementing mental health rehabilitation services in clubhouses in Hunan Province in the People's Republic of China.

Methods: Participants were purposively selected and consisted of diverse stakeholders, including rehabilitation directors and psychiatric hospital leaders in Hunan Province, China. Information was collected from 33 individuals by using three focus groups, 23 semistructured interviews of key informants, and participant observation. Interview transcripts were coded and analyzed by using standard qualitative methods.

Results: Implementation challenges were characterized by four themes: skepticism toward psychosocial rehabilitation services, resource shortage, insufficient system integration and incentives, and stigma of mental illness.

Conclusions: Psychosocial rehabilitation is an emerging public health priority in China. This study on clubhouses in Hunan Province used qualitative methods to inform future directions for service development and research. Early identification of regional implementation challenges is a first step in assessing the applicability of psychosocial rehabilitation services locally in Hunan Province. Successful implementation of clubhouse psychosocial rehabilitation services will benefit not only from strong government commitment but also from developing standard evaluations of evidence-based practices, tackling stigma, and addressing low resource investment.
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http://dx.doi.org/10.1176/appi.ps.201800549DOI Listing
August 2019

Structural and Functional Alterations in Betel-Quid Chewers: A Systematic Review of Neuroimaging Findings.

Front Psychiatry 2019 29;10:16. Epub 2019 Jan 29.

Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.

A number of neuroimaging studies have investigated structural, metabolic, and functional connectivity changes in betel quid (BQ) chewers. We present a systematic review of neuroimaging studies with emphasis on key brain systems affected by BQ chewing to bring a better understanding on the neuro mechanisms involved in BQD. All BQ neuroimaging studies were identified by searching PubMed, EMBASE, and Google scholar for English articles published until March 2018 using the key words: Betel-quid, resting state, functional MRI, structural MRI, diffusion tensor imaging (DTI), and betel quid dependence basing on the PRISMA criteria. We also sought unpublished studies, and the rest were obtained from reference lists of the retrieved articles. All neuroimaging studies investigating brain structural, and functional alterations related to BQ chewing and BQ dependence were included. Our systematic review registration number is CRD42018092669. A review of 12 studies showed that several systems in the brain of BQ chewers exhibited structural, metabolic, and functional alterations. BQ chewing was associated with alterations in the reward [areas in the midbrain, and prefrontal cortex (PFC)], impulsivity (anterior cingulate cortex, PFC) and cognitive (PFC, the default mode, frontotemporal, frontoparietal, occipital/temporal, occipital/parietal, temporal/limbic networks, hippocampal/hypothalamus, and the cerebellum) systems in the brain. BQ duration and severity of betel quid dependence were associated with majority of alterations in BQ chewers. Betel quid chewing is associated with brain alterations in structure, metabolism and function in the cognitive, reward, and impulsivity circuits which are greatly influenced by duration and severity of betel quid dependence.
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http://dx.doi.org/10.3389/fpsyt.2019.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361845PMC
January 2019

Structural and Functional Alterations in Betel-Quid Chewers: A Systematic Review of Neuroimaging Findings.

Front Psychiatry 2019 29;10:16. Epub 2019 Jan 29.

Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.

A number of neuroimaging studies have investigated structural, metabolic, and functional connectivity changes in betel quid (BQ) chewers. We present a systematic review of neuroimaging studies with emphasis on key brain systems affected by BQ chewing to bring a better understanding on the neuro mechanisms involved in BQD. All BQ neuroimaging studies were identified by searching PubMed, EMBASE, and Google scholar for English articles published until March 2018 using the key words: Betel-quid, resting state, functional MRI, structural MRI, diffusion tensor imaging (DTI), and betel quid dependence basing on the PRISMA criteria. We also sought unpublished studies, and the rest were obtained from reference lists of the retrieved articles. All neuroimaging studies investigating brain structural, and functional alterations related to BQ chewing and BQ dependence were included. Our systematic review registration number is CRD42018092669. A review of 12 studies showed that several systems in the brain of BQ chewers exhibited structural, metabolic, and functional alterations. BQ chewing was associated with alterations in the reward [areas in the midbrain, and prefrontal cortex (PFC)], impulsivity (anterior cingulate cortex, PFC) and cognitive (PFC, the default mode, frontotemporal, frontoparietal, occipital/temporal, occipital/parietal, temporal/limbic networks, hippocampal/hypothalamus, and the cerebellum) systems in the brain. BQ duration and severity of betel quid dependence were associated with majority of alterations in BQ chewers. Betel quid chewing is associated with brain alterations in structure, metabolism and function in the cognitive, reward, and impulsivity circuits which are greatly influenced by duration and severity of betel quid dependence.
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http://dx.doi.org/10.3389/fpsyt.2019.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361845PMC
January 2019

Crosstalk Between Inflammation and Glutamate System in Depression: Signaling Pathway and Molecular Biomarkers for Ketamine's Antidepressant Effect.

Mol Neurobiol 2019 May 23;56(5):3484-3500. Epub 2018 Aug 23.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.

Depression is a worldwide illness with a significant impact on both family and society. Conventional antidepressants are ineffective for more than 30% of patients. In such patients, who have what is called treatment-resistant depression (TRD), inflammatory biomarkers are expressed excessively in both the central nervous system (CNS) and the peripheral blood. Ketamine, a glutamate receptor antagonist, exerts a rapid and sustained therapeutic effect in patients with TRD. Thus, the investigation of the relations between inflammation and glutamate underlying depression has drawn great attention. Inflammation influences glutamate release, transmission, and metabolism, resulting in accumulated extracellular glutamate in the CNS. Downstream of the glutamate receptors, the mammalian target of rapamycin (mTOR) signaling pathway plays a key role in mediating ketamine's antidepressant effect by improving neurogenesis and plasticity. Based on the mechanism and clinical evidence of the inflammatory contribution to the pathogenesis of depression, extensive research has been devoted to inflammatory biomarkers of the clinical response of depression to ketamine. The inconsistent findings from the biomarker investigations are at least partially attributable to the heterogeneity of depression, limited sample size, and complex gene-environment interactions. Deep exploration of the clinical observations and the underlying mechanism of ketamine's antidepressant response can provide new insights into the selection of specific groups of depressed patients for ketamine treatment and to aid in monitoring the therapeutic effect during antidepressant medication. Further, targeting persistent inflammation in patients with TRD and the key molecules mediating ketamine's antidepressant effect may encourage the development of novel therapeutic strategies.
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http://dx.doi.org/10.1007/s12035-018-1306-3DOI Listing
May 2019

Resilience and Cognitive Function in Patients With Schizophrenia and Bipolar Disorder, and Healthy Controls.

Front Psychiatry 2018 29;9:279. Epub 2018 Jun 29.

Department of Psychiatry, Yale University, New Haven, CT, United States.

This study compared adaptive resilience among patients with schizophrenia, bipolar disorder, and healthy controls, and examined the relationship of resilience to cognitive function. A sample of 81 patients diagnosed with schizophrenia, 34 with bipolar disorder, and 52 healthy controls completed the Connor-Davidson Resilience Scale (CD-RISC) and cognitive tests of verbal comprehension, executive functioning, and working memory. Paired comparison of diagnostic groups on CD-RISC and cognitive tests was conducted. Linear regression was used to identify the independent association of clinical diagnoses and neurocognition with resilience deficits. Both patient groups showed significantly lower CD-RISC scores and poorer cognitive function than healthy controls and the schizophrenia group scored lower than bipolar group on these measures as well. CD-RISC scores were positively correlated with all three cognitive measures in the entire sample but not within the diagnostic subgroups. Multiple regression analysis showed differences in CD-RISC between diagnostic groups were not mediated by differences in these three measures of neurocognition. Schizophrenia and bipolar disorder are associated with impairments in both resilience and cognitive function but the impairment in resilience appears to be independent of deficits in cognitive function measured here and may reflect unmeasured dimensions of cognitive function, other impairments or environmental factors.
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http://dx.doi.org/10.3389/fpsyt.2018.00279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033957PMC
June 2018

"Brain Connectivity Deviates by Sex and Hemisphere in the First Episode of Schizophrenia"-A Route to the Genetic Basis of Language and Psychosis?

Schizophr Bull 2019 03;45(2):484-494

Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, PR China.

Schizophrenia is genetic in origin and associated with a fecundity disadvantage. The deficits in schizophrenia have been attributed to variation related to the human capacity for language or brain laterality. How sex influences the relative connectivity of the 2 hemispheres is a route to understanding these 2 functions. Using resting-state functional magnetic resonance imaging (fMRI) we searched for sex- and hemisphere-specific changes in whole-brain functional-connectivity in multi-site datasets (altogether 672 subjects including 286 patients, all right-handed) in the first-episode schizophrenia (illness duration ≤ 1 year, mostly drug naive) and in chronic stages of schizophrenia (illness duration > 1 year), respectively. We used meta-analyses to integrate data from different sources concerning individuals at the same illness stage. We found first-episode male patients are predominantly left-lateralized in aberrant connectivity with a focus on Broca's area. Female patients show a lesser degree of lateralization than males, but to the right particularly in orbital frontal cortex. In the chronic stage, the focus of aberrant connectivity shifted from anterior to posterior structures with prominent involvement of the thalamus and pre- and post-central gyri bilaterally and in both sexes. While the "deviant connectivity" is right-sided in both the first-episode and the chronic stages in females, in males there is a shift between stages from the left to the right hemisphere. We hypothesized that the pathophysiology of schizophrenia may lie in the interaction between sex and lateralization, ie, in genetic mechanisms located on the X and Y chromosomes, intrinsic to the evolution of language.
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http://dx.doi.org/10.1093/schbul/sby061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403095PMC
March 2019

Effects of DISC1 Polymorphisms on Resting-State Spontaneous Neuronal Activity in the Early-Stage of Schizophrenia.

Front Psychiatry 2018 23;9:137. Epub 2018 May 23.

Medical Psychological Center, Second Xiangya Hospital, Central South University, Changsha, China.

Localized abnormalities in the synchrony of spontaneous neuronal activity, measured with regional homogeneity (ReHo), has been consistently reported in patients with schizophrenia (SCZ) and their unaffected siblings. To date, little is known about the genetic influences affecting the spontaneous neuronal activity in SCZ. , a strong susceptible gene for SCZ, has been implicated in neuronal excitability and synaptic function possibly associated with regional spontaneous neuronal activity. This study aimed to examine the effects of variations on the regional spontaneous neuronal activity in SCZ. Resting-state fMRI data were obtained from 28 SCZ patients and 21 healthy controls (HC) for ReHo analysis. Six single nucleotide polymorphisms (SNPs) of gene were genotyped using the PCR and direct sequencing. Significant diagnosis × genotype interactions were noted for three SNPs (rs821616, rs821617, and rs2738880). For rs821617, the interactions were localized to the precuneus, basal ganglia and pre-/post-central regions. Significant interactive effects were identified at the temporal and post-central gyri for rs821616 (Ser704Cys) and the inferior temporal gyrus for rs2738880. Furthermore, analysis revealed that the variations on these SNPs exerted different influences on ReHo between SCZ patients and HC. To our knowledge this is the first study to unpick the influence of variations on spontaneous neuronal activity in SCZ; Given the emerging evidence that ReHo is a stable inheritable phenotype for schizophrenia, our findings suggest the DISC1 variations are possibly an inheritable source for the altered ReHo in this disorder.
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http://dx.doi.org/10.3389/fpsyt.2018.00137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974222PMC
May 2018