Publications by authors named "Jijun Wang"

318 Publications

The therapeutic potential of personalized connectivity-guided transcranial magnetic stimulation target over group-average target for depression.

Brain Stimul 2022 Aug 2. Epub 2022 Aug 2.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China. Electronic address:

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http://dx.doi.org/10.1016/j.brs.2022.07.054DOI Listing
August 2022

Eye movement indices as predictors of conversion to psychosis in individuals at clinical high risk.

Eur Arch Psychiatry Clin Neurosci 2022 Jul 20. Epub 2022 Jul 20.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China.

Eye movement abnormalities have been established as an "endophenotype" of schizophrenia. However, less is known about the possibility of these abnormalities as biomarkers for psychosis conversion among clinical high risk (CHR) populations. In the present study, 108 CHR individuals and 70 healthy controls (HC) underwent clinical assessments and eye-tracking tests, comprising fixation stability and free-viewing tasks. According to three-year follow-up outcomes, CHR participants were further stratified into CHR-converter (CHR-C; n = 21) and CHR-nonconverter (CHR-NC; n = 87) subgroups. Prediction models were constructed using Cox regression and logistic regression. The CHR-C group showed more saccades of the fixation stability test (no distractor) and a reduced saccade amplitude of the free-viewing test than HC. Moreover, the CHR-NC group exhibited excessive saccades and an increased saccade amplitude of the fixation stability test (no distractor; with distractor) compared with HC. Furthermore, two indices could effectively discriminate CHR-C from CHR-NC with an area under the receiver-operating characteristic (ROC) curve of 0.80, including the saccade number of the fixation stability test (no distractor) and the saccade amplitude of the free-viewing test. Combined with negative symptom scores of the Scale of Prodromal Symptoms, the area was 0.81. These findings support that eye movement alterations might emerge before the onset of clinically overt psychosis and could assist in predicting psychosis transition among CHR populations.
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http://dx.doi.org/10.1007/s00406-022-01463-zDOI Listing
July 2022

Antipsychotic prescription, assumption and conversion to psychosis: resolving missing clinical links to optimize prevention through precision.

Schizophrenia (Heidelb) 2022 May 4;8(1):48. Epub 2022 May 4.

Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center (20DZ2253800), Shanghai Key Laboratory of Psychotic Disorders, Shanghai, 200030, People's Republic of China.

The current concept of clinical high-risk(CHR) of psychosis relies heavily on "below-threshold" (i.e. attenuated or limited and intermittent) psychotic positive phenomena as predictors of the risk for future progression to "above-threshold" positive symptoms (aka "transition" or "conversion"). Positive symptoms, even at attenuated levels are often treated with antipsychotics (AP) to achieve clinical stabilization and mitigate the psychopathological severity. The goal of this study is to contextually examine clinicians' decision to prescribe AP, CHR individuals' decision to take AP and psychosis conversion risk in relation to prodromal symptoms profiles. CHR individuals (n = 600) were recruited and followed up for 2 years between 2016 and 2021. CHR individuals were referred to the participating the naturalistic follow-up study, which research procedure was independent of the routine clinical treatment. Clinical factors from the Structured Interview for Prodromal Syndromes (SIPS) and global assessment of function (GAF) were profiled via exploratory factor analysis (EFA), then the extracted factor structure was used to investigate the relationship of prodromal psychopathology with clinicians' decisions to AP-prescription, CHR individuals' decisions to AP-taking and conversion to psychosis. A total of 427(71.2%) CHR individuals were prescribed AP at baseline, 532(88.7%) completed the 2-year follow-up, 377(377/532, 70.9%) were taken AP at least for 2 weeks during the follow-up. EFA identified six factors (Factor-1-Negative symptoms, Factor-2-Global functions, Factor-3-Disorganized communication & behavior, Factor-4-General symptoms, Factor-5-Odd thoughts, and Factor-6-Distorted cognition & perception). Positive symptoms (Factor-5 and 6) and global functions (Factor-2) factors were significant predictors for clinicians' decisions to AP-prescription and CHR individuals' decisions to assume AP, whereas negative symptoms (Factor-1) and global functions (Factor-2) factors predicted conversion. While decisions to AP-prescription, decisions to AP-taking were associated to the same factors (positive symptoms and global functions), only one of those was predictive of conversion, i.e. global functions. The other predictor of conversion, i.e. negative symptoms, did not seem to be contemplated both on the clinician and patients' sides. Overall, the findings indicated that a realignment in the understanding of AP usage is warranted.
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http://dx.doi.org/10.1038/s41537-022-00254-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261109PMC
May 2022

Automatic auditory processing features in distinct subtypes of patients at clinical high risk for psychosis: Forecasting remission with mismatch negativity.

Hum Brain Mapp 2022 Jul 18. Epub 2022 Jul 18.

Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center (20DZ2253800), Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People's Republic of China.

Individuals at clinical high risk (CHR) for psychosis exhibit a compromised mismatch negativity (MMN) response, which indicates dysfunction of pre-attentive deviance processing. Event-related potential and time-frequency (TF) information, in combination with clinical and cognitive profiles, may provide insight into the pathophysiology and psychopathology of the CHR stage and predict the prognosis of CHR individuals. A total of 92 individuals with CHR were recruited and followed up regularly for up to 3 years. Individuals with CHR were classified into three clinical subtypes demonstrated previously, specifically 28 from Cluster 1 (characterized by extensive negative symptoms and cognitive deficits), 31 from Cluster 2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 33 from Cluster 3 (characterized by the mildest symptoms and cognitive deficits). Auditory MMN to frequency and duration deviants was assessed. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired using TF analysis. Predictive indices for remission were identified using logistic regression analyses. As expected, reduced frequency MMN (fMMN) and duration MMN (dMMN) responses were noted in Cluster 1 relative to the other two clusters. In the TF analysis, Cluster 1 showed decreased theta and alpha ITC in response to deviant stimuli. The regression analyses revealed that dMMN latency and alpha ERSP to duration deviants, theta ITC to frequency deviants and alpha ERSP to frequency deviants, and fMMN latency were significant MMN predictors of remission for the three clusters. MMN variables outperformed behavioral variables in predicting remission of Clusters 1 and 2. Our findings indicate relatively disrupted automatic auditory processing in a certain CHR subtype and a close affinity between these electrophysiological indexes and clinical profiles within different clusters. Furthermore, MMN indexes may serve as predictors of subsequent remission from the CHR state. These findings suggest that the auditory MMN response is a potential neurophysiological marker for distinct clinical subtypes of CHR.
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http://dx.doi.org/10.1002/hbm.26021DOI Listing
July 2022

Double Cystic Duct: Preoperative use of MRCP Without Being Aware of the Anatomic Anomaly: A Case Report.

Front Surg 2022 27;9:892927. Epub 2022 Jun 27.

Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China.

Introduction: A biliary anomaly is occasionally encountered, however, a double cystic duct is exceedingly rare during surgery. It is pivotal for surgeons to recognize the anatomic variations in Cholangiography which is performed under fluoroscopic guidance Intraoperatively to prevent possible complications.

Case Presentation: Herein, the case of a 66-year-old female patient with acute cholecystitis, in which preoperative Magnetic Resonance Cholangiopancreatograph (MRCP) did not identify a single gallbladder with double cystic ducts, is presented. Intraoperatively we identified a double cystic duct and it was safely ligated with clips. Anatomic variability was also confirmed by Cholangiography which was performed under fluoroscopic guidance. Furthermore, the patient was symptom-free through 1 year of follow-up assessment.

Conclusions: In particular, when we do not identify anatomic variability based on imaging, cholangiography under fluoroscopic guidance during surgery was a powerful tool that may clearly show the anomaly of a single gallbladder with double cystic ducts.
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http://dx.doi.org/10.3389/fsurg.2022.892927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271822PMC
June 2022

Categorical and dimensional deficits in hippocampal subfields among schizophrenia, obsessive-compulsive disorder, bipolar disorder, and major depressive disorder.

Biol Psychiatry Cogn Neurosci Neuroimaging 2022 Jul 5. Epub 2022 Jul 5.

Shanghai Mental Health Center, Shanghai Jiao Tong University Medical School, Shanghai, China. Electronic address:

Background: The hippocampus is a core region of interest for all major mental disorders, and its subfields implement distinctive functions. It is unclear whether the mental disorders exhibit common patterns of hippocampal impairments, and we lack knowledge on whether and how the hippocampal subfields represent deficit spectra across mental disorders.

Methods: Using brain images of 1123 individuals scanned on a single MRI scanner, we examined the commonality, specificity, and symptom associations of the volume of hippocampal subfields across schizophrenia (SZ), obsessive-compulsive disorder (OCD), bipolar disorder (BD), and major depressive disorder (MDD) patients and healthy subjects (HC). We further performed a transdiagnostic analysis of the individual variability of the volume of hippocampal subfields to reflect cross-disease gradients in the hippocampus.

Results: We found common and disease-specific abnormalities in a few hippocampal fields and identified two reliable transdiagnostic factors in the hippocampal subfields, each reflecting a spectrum of mental disorders. The plane spanned by the two most reliable factors provided a clearer view of hippocampal volume abnormality spectra among the major mental disorders. In addition, functional and genetic enrichment analyses supported the different roles of the two hippocampal factors in mental disorders.

Conclusions: The volume of hippocampal subfields reflects some commonality and specificity among the four major mental disorders. We propose a new pathophysiological dimensional view of the hippocampus, reflecting at least two spectra of mental disorders, suggesting multivariate links among the diseases. This work highlights the value of the complementary categorical and dimensional view of the hippocampal deficits in mental disorders.
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http://dx.doi.org/10.1016/j.bpsc.2022.06.011DOI Listing
July 2022

Effects of transcranial direct current stimulation on brain changes and relation to cognition in patients with schizophrenia: a fMRI study.

Brain Imaging Behav 2022 Jul 4. Epub 2022 Jul 4.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai, 200030, China.

We studied brain changes during an N-back task before and after 10 sessions of transcranial direct current stimulation (tDCS) and its relation to cognitive changes. This was a double-blind, sham-controlled, randomized study of tDCS in 27 patients with schizophrenia. They performed an N-back task in a 3 T scanner before and after receiving the 10 tDCS sessions. Cognitive performance outside the fMRI session was assessed using the MATRICS Consensus Cognitive Battery and other tests at baseline and several time points after 10 sessions of tDCS. During the N-back task performed during fMRI scans, comparing the 0-back vs. the 2-back task, the active tDCS group demonstrated a significantly increased activation in the right fusiform, left middle frontal, left inferior frontal gyrus (opercular part) and right inferior frontal gyrus (triangular part) and reduced activation in the left posterior cingulum gyrus with most of these results primarily due to increases in activation during the 0-back rather than 2-back task. There were also significant positive or negative correlations between some of the brain changes and cognitive performance. tDCS modulated prefrontal activation at low working memory load or attention mode, but default mode network at higher working memory load. Changes in brain activation measured during the N-back task were correlated with some dimensions of cognitive function immediately after 10 tDCS sessions and at follow-up times. The results support tDCS could offer a potential novel approach for modulating cortical activity and its relation to cognitive function.
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http://dx.doi.org/10.1007/s11682-022-00676-zDOI Listing
July 2022

Relationships between self-reflectiveness and clinical symptoms in individuals during pre-morbid and early clinical stages of psychosis.

Gen Psychiatr 2022 31;35(3):e100696. Epub 2022 May 31.

Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Self-reflectiveness, one dimension of cognitive insight, plays a protective role in an individual's mental state. Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.

Aims: This study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.

Methods: A total of 181 subjects, including individuals with attenuated positive symptoms (APS, n=122) and patients with first-episode psychosis (FEP, n=59), completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale. All subjects were classified into three groups according to their level of self-reflectiveness: low level (LSR, n=59), medium level (MSR, n=67) and high level (HSR, n=55). Both linear and non-linear relationships between self-reflectiveness and clinical symptoms were explored.

Results: More individuals with APS were classified into the MSR group, while more patients with FEP were classified into the LSR group. The LSR group demonstrated less awareness of illness than the MSR and HSR groups, more stereotyped thinking and poorer impulse control but less anxiety than the MSR group, and lower levels of blunted affect and guilt feelings than the HSR group. The MSR group demonstrated lower stereotyped thinking than the HSR group. Compared to the LSR group, the MSR group had increased self-reflectiveness, improved awareness of illness, decreased stereotyped thinking, and better impulse control, but increased feelings of guilt. The HSR group showed increased stereotyped thinking when compared to the MSR group, but the other variables did not change significantly between these two groups. Overall, self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness, a U-shaped relationship with stereotyped thinking and poor impulse control, and an almost linear relationship with anxiety and guilt feelings.

Conclusions: Self-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level.
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http://dx.doi.org/10.1136/gpsych-2021-100696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161056PMC
May 2022

Fermented Dairy Food Intake and Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis.

Front Oncol 2022 25;12:812679. Epub 2022 May 25.

Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China.

It was highly controversial whether fermented dairy foods protect against colorectal cancer (CRC) because of conflicting results from current human epidemiologic studies; we therefore conducted this meta-analysis based on the case-control and cohort studies to estimate the holistic analyses. Finally, a total of seven case-control studies and ten cohort studies comprising a total of >20,000 cases were incorporated in the quantitative synthesis. Specifically, statistical evidence of significantly decreasing CRC risk in case-control studies was found to be associated with cheese intake (OR = 0.89, 95% CI = 0.82-0.97). In a subgroup analysis, cheese intake was correlated with lower colon cancer (OR = 0.89, 95% CI = 0.79-1.00) and rectal cancer (OR = 0.86, 95% CI = 0.74-1.00) risk in case-control studies. Furthermore, we also found that the higher intake of yogurt may lower the risk of rectal cancer (OR = 0.75, 95% CI = 0.65-0.88) in cohort studies. The consumption of fermented dairy foods may be relevant to decrease CRC risk in this meta-analysis.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021269798, CRD42021269798.
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http://dx.doi.org/10.3389/fonc.2022.812679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174999PMC
May 2022

Editorial: Investigating the Mechanism of TMS Using Brain Imaging Methods.

Front Neurosci 2022 20;16:936219. Epub 2022 May 20.

Center for Cognition and Brain Disorders, Institutes of Psychological Sciences, Hangzhou Normal University, Hangzhou, China.

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http://dx.doi.org/10.3389/fnins.2022.936219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163988PMC
May 2022

Replication of the abnormal niacin response in first episode psychosis measured using laser Doppler flowmeter.

Asia Pac Psychiatry 2022 Jun 2:e12516. Epub 2022 Jun 2.

Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China.

Introduction: Impaired sensitivity of the skin flush response to niacin is found in approximately 30% of patients with schizophrenia. Although the niacin response abnormality (NRA) may serve as a useful endophenotype for schizophrenia, few studies have directly replicated NRA in patients with first-episode psychosis (FEP).

Methods: In total, 204 patients with FEP, 16 with psychotic mood disorder (PMD), and 68 healthy controls (HC) were included. The log (EC ) values represent the concentration of methyl nicotinate required to elicit a half-maximal blood flow (MBF) response, and the MBF value was calculated. The NRA was defined as having log (EC ) molar value above the 90% and an MBF value below the 60% of those in the HC group.

Results: In total, 13.7% of the FEP, 12.5% of the PMD, and 7.4% of the HC group met the definition of NRA. Significant differences were found in the log (EC ) values between the FEP and HC groups (p = .014) and in the MBF between the FEP and PMD groups (p = .011). Patients with FEP and NRA had more severe negative symptoms than those with a normal niacin response.

Discussion: These data represent the NRA in patients with FEP, defining a small subgroup of patients with early-phase psychosis possessing a clinically significant phospholipid-signaling defect.
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http://dx.doi.org/10.1111/appy.12516DOI Listing
June 2022

Omentin-1 circulating levels as predictor of heart diseases: a systematic review and meta-analysis.

Rev Assoc Med Bras (1992) 2022 04;68(4):542-548

The Fourth People's Hospital of Jinan, Department of Traditional Chinese Medicine - Jinan, China.

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http://dx.doi.org/10.1590/1806-9282.20211111DOI Listing
April 2022

Thalamo-hippocampal dysconnectivity is associated with serum cholesterol level in drug-naïve patients with first-episode schizophrenia.

J Psychiatr Res 2022 07 12;151:497-506. Epub 2022 May 12.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China; CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, Shanghai, 200031, China; Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:

Hippocampal deficits and metabolic dysregulations such as dyslipidemia have been frequently reported in schizophrenia and are suggested to contribute to the pathophysiology of schizophrenia. Hippocampus is particularly susceptible to environmental challenges including metabolism and inflammation. However, evidence linking hippocampal alterations and metabolic dysregulations are quite sparse in drug-naïve schizophrenia. A total of 166 drug-naïve patients with first-episode schizophrenia (FES) and 78 healthy controls (HC) underwent measures for several serum metabolic markers, structural and resting-state functional magnetic resonance imaging (rs-fMRI), as well as diffusion tensor imaging (DTI). Seed-to-voxel functional connectivity (FC) and probabilistic tractography were performed to assess the functional and microstructural connectivity of the bilateral hippocampi. Clinical symptoms were evaluated with Positive and Negative Syndrome Scale (PANSS). Patients with FES showed significantly decreased total cholesterol (Chol) level. Patients showed elevated FC between the left hippocampus and bilateral thalami while showing decreased microstructural connectivity between the left hippocampus and bilateral thalami. Multiple regression analyses showed that FC from the left hippocampus to the right superior frontal gyrus (SFG), bilateral frontal pole (FP), and right thalamus were negatively associated with the Chol level, while no association was observed in the HC group. Our study validated alterations in both functional and microstructural thalamo-hippocampal connectivities, and abnormal cholesterol level in FES. Moreover, decreased cholesterol level is associated with elevated thalamo-hippocampal functional connectivity in patients with FES, suggesting that dyslipidemia may interact with the hippocampal dysfunction in FES.
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http://dx.doi.org/10.1016/j.jpsychires.2022.05.013DOI Listing
July 2022

The impact of COVID-19 pandemic on individuals at clinical high-risk for psychosis: Evidence from eye-tracking measures.

Prog Neuropsychopharmacol Biol Psychiatry 2022 08 23;118:110578. Epub 2022 May 23.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China; CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, Shanghai 201203, PR China; Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai 200030, PR China. Electronic address:

Emerging evidence suggested that people with severe mental disorders were more vulnerable to the negative effects of the COVID-19 pandemic. However, few researches investigated the influence of global pandemics on people at clinical high risk (CHR) for psychosis. This study aimed to investigate the impact of the COVID-19 pandemic on clinical symptoms, psychological distress, and eye-tracking characteristics in CHR individuals and healthy participants. Forty-nine CHR individuals and 50 healthy controls (HC) were assessed by PTSD Checklist for DSM-5 (PCL-5), Perceived Stress Scale, 10-item version (PSS-10), and Coronavirus Impact Scale (CIS). Eye movement performances were measured by the tests of fixation stability, free-viewing, and anti-saccade. According to the mean score of CIS, participants were stratified into high-impact (n = 35) and low-impact (n = 64) subgroups. Compared with the HC group, CHR participants reported significantly higher levels of post-traumatic symptoms caused by the COVID-19 pandemic and showed abnormalities in most of the eye movement indexes. Among the altered indexes, the saccade amplitude of fixation stability test (far distractor), the scan path length of free-viewing test, and the accuracy of anti-saccade test were negatively affected by the severity of impact level in the CHR group. Moreover, the altered eye movement indexes were significantly associated with the total scores of CIS, PCL-5, and subscales of the Scale of Prodromal Syndromes (SOPS) among CHR individuals. Overall, our findings suggested the negative impact of the COVID-19 pandemic on the eye movement characteristics of CHR individuals. The present study provides valuable information on physiological distress related to the COVID-19 pandemic and sensitive neuropsychological biomarkers that interacted with social and environment stress in the CHR population.
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http://dx.doi.org/10.1016/j.pnpbp.2022.110578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126616PMC
August 2022

Impact of Annealing and Controlled Ice Nucleation on Properties of A Lyophilized 50 mg/ml MAB Formulation.

J Pharm Sci 2022 May 22. Epub 2022 May 22.

Pharmaceutical Research and Development, BioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Chesterfield, MO 63017, USA.

We compared "ice-fog" controlled ice nucleation at -6 °C to annealing at the same temperature for a 50 mg/mL monoclonal antibody formulation, using shelf-ramp freezing as a control. Cake structure, drying time, reconstitution time, specific surface area, calculated cake resistance and size exclusion chromatography were all compared. Controlled nucleation resulted in the fastest reconstitution, shortest primary drying, lowest calculated cake resistance, lowest specific surface area and highest moisture content. There was no effect upon the results for size exclusion chromatography. Results for annealing were between those for controlled nucleation and shelf-ramp freezing. All results were consistent with "ice-fog" controlled nucleation at -6 °C having greater impact upon the ice crystal morphology than annealing at the same temperature for 3 h.
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http://dx.doi.org/10.1016/j.xphs.2022.05.016DOI Listing
May 2022

Clinical high risk for psychosis provides new opportunities for schizophrenia intervention strategies.

Gen Psychiatr 2022 26;35(2):e100736. Epub 2022 Apr 26.

Department of Psychiatry, Beth Israel Deaconess Medical Center, Massachusetts Mental Health Center, Harvard Medical School, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1136/gpsych-2021-100736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047877PMC
April 2022

Attenuated niacin-induced skin flush response in individuals with clinical high risk for psychosis.

Gen Psychiatr 2022 24;35(2):e100748. Epub 2022 Apr 24.

Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Impaired sensitivity of the skin flush response to niacin is one of the most replicated findings in patients with schizophrenia. However, prior studies have usually focused on postonset psychosis, and little is known about the clinical high-risk (CHR) phase of niacin sensitivity in psychosis.

Aims: To profile and compare the niacin flush response among CHR individuals (converters and non-converters), patients with first-episode schizophrenia (FES) and healthy controls (HCs).

Methods: Sensitivity to four concentrations (0.1-0.0001 M) of aqueous methylnicotinate was tested in 105 CHR individuals, 57 patients with FES and 52 HCs. CHR individuals were further grouped as converters and non-converters according to the 2-year follow-up outcomes. Skin flush response scores were rated on a 4-point scale.

Results: Of the 105 CHR individuals, 21 individuals were lost during the study, leaving 84 CHR individuals; 16 (19.0%) converted to full psychosis at 2 years of follow-up. Flush response scores identified in the CHR samples were characterised as modest degree levels, intermediate between those of HC individuals and patients with FES. The flush responses in the CHR group mimicked the responses observed in the FES group at higher concentrations (0.01 M, 0.1 M) and longer time points (15 min, 20 min); however, these became comparable with the responses in the HC group at the shorter time points and at lower concentrations. The converters exhibited lower mean flush response scores than the non-converters.

Conclusions: Attenuated niacin-induced flushing emerged during the early phase of psychosis. New devices should be developed and verified for objective quantification of skin responses in the CHR population.
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http://dx.doi.org/10.1136/gpsych-2022-100748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039376PMC
April 2022

Reduced temporal activation during a verbal fluency test in clinical high risk of psychosis: a functional near-infrared spectroscopy-based study.

Gen Psychiatr 2022 28;35(2):e100702. Epub 2022 Apr 28.

EEG and Neuroimaging Department, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Clinical high risk (CHR) of psychosis is a state in which positive symptoms cause the subjects distress but do not approach a severity level that fulfils the criteria for a psychotic episode. CHR exhibits cognitive deficits; however, the underlying neurobiological mechanisms remain unclear. This study aimed to investigate whether brain activation measured by the levels of oxygenated hemoglobin (oxy-Hb) in CHR subjects could be correlated with cognitive deficits.

Methods: Fifty-eight CHR individuals who fulfilled the criteria for attenuated positive syndrome as specified in the Structured Interview for Prodromal Syndrome (SIPS) and the Scale of Prodromal Syndrome (SOPS) and 58 age- and sex-matched healthy participants were included in the study. All subjects completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) that includes tests measuring attention, verbal memory, verbal fluency, executive function, and general intelligence. Functional near-infrared spectroscopy (fNIRS) was used to measure the level of oxy-Hb in the dorsolateral prefrontal and frontotemporal cortices.

Results: We observed significantly decreased oxy-Hb levels in channel 32 (located in the right superior temporal gyrus, rSTG)) within the CHR individuals compared with that in the healthy controls (HCs) (t=-3.44, Bonferroni-corrected p=0.002), indicating lower brain activity. A significant positive correlation was observed between task-related β values and working memory in the CHR group (r=0.35, p=0.008).

Conclusions: The brain activation of rSTG is abnormal among subjects at clinicial high risk for psychosis. This abnormality is probably associated with the neural mechanisms of deficits in the working memory during the early stage of psychosis.
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http://dx.doi.org/10.1136/gpsych-2021-100702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058760PMC
April 2022

Abnormal neural oscillations in clinical high risk for psychosis: a magnetoencephalography method study.

Gen Psychiatr 2022 28;35(2):e100712. Epub 2022 Apr 28.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks. Abnormal neural oscillations have been discovered in patients with schizophrenia. However, there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis (CHR-P). The brain signals recorded by the magnetoencephalography (MEG) technique are not to be disrupted by the skull and scalp.

Methods: In this study, we applied the MEG technique to record the resting-state neural activities in CHR-P. This was followed by a detailed MEG analysis method including three steps: (1) preprocessing, which was band-pass filtering based on the 0.5-60 Hz frequency range, removal of 50 Hz power frequency interference, and removal of electrocardiography (ECG) and electrooculography (EOG) artefacts by independent component analysis; (2) time-frequency analysis, a multitaper time-frequency transformation based on the Hanning window, and (3) source localisation, an exact low-resolution brain electromagnetic tomography. The method was verified by comparing a participant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state.

Results: Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band (4-7 Hz) and the delta frequency band (1-3 Hz). Also, relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band.

Conclusions: Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups. Further work will validate these characteristics in CHR-P cohorts.
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http://dx.doi.org/10.1136/gpsych-2021-100712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052050PMC
April 2022

Artificial intelligence-assisted niacin skin flush screening in early psychosis identification and prediction.

Gen Psychiatr 2022 28;35(2):e100753. Epub 2022 Apr 28.

Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1136/gpsych-2022-100753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058756PMC
April 2022

Effect of cognitive insight on clinical insight from pre-morbid to early psychosis stages.

Psychiatry Res 2022 07 10;313:114613. Epub 2022 May 10.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, Shanghai, China; Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Poor cognitive insight, including low self-reflectiveness and high self-certainty, contributes to poor clinical insight, which includes awareness of illness, relabelling of specific symptoms, and treatment compliance. However, inconsistent results regarding cognitive insight among individuals at clinical high risk of psychosis (CHR) have been reported. This study investigated the difference in cognitive insight among groups with different severity of positive symptoms and analysed the effect of cognitive insight on clinical insight in each group. All participants, including CHR individuals with 3 or 4 points (L-P, n = 85) and 5 points (H-P, n = 37) on any positive-symptom item of the Scale of Prodromal Syndromes, and patients with first-episode psychosis (FEP, n = 59), were measured cognitive and clinical insight using the Beck Cognitive Insight Scale and the Schedule of Assessment of Insight, respectively. The self-reflectiveness of cognitive insight was highest in the L-P group and lowest in the FEP group. Self-reflectiveness was positively associated with awareness of illness in the L-P and FEP groups; both self-reflectiveness and self-certainty was positively associated with treatment compliance in the L-P group. Improving self-reflectiveness of cognitive insight may conduce to good clinical insight. Self-certainty may have different implication to individuals with mild prodromal symptoms.
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http://dx.doi.org/10.1016/j.psychres.2022.114613DOI Listing
July 2022

Altered attentive bias towards interpersonal communication information across phases of schizophrenia: an eye-tracking study.

Gen Psychiatr 2022 18;35(2):e100699. Epub 2022 Apr 18.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Eye movement abnormality in schizophrenia has been studied for several decades. However, patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well documented.

Aims: This pilot study used eye-tracking technology to investigate attentive bias towards interpersonal communication information across different clinical phases of schizophrenia.

Methods: This study included 78 persons at clinical high risk (CHR) for schizophrenia, 68 first-episode (FEZ) patients, and 39 chronically ill patients from the Shanghai At Risk for Psychosis Extending Project (SHARP Extending cohort) as well as 74 healthy controls (HCs). The experiment was an unguided-viewing task composed of 24 trials showing three types of pictures which varied in the degree of interpersonal communication. Type 1 was a scenery picture without people, type 2 was a picture with four people not communicating, and type 3 was a picture with four people communicating. We used two measures: (1) initial fixation duration and (2) total fixation duration.

Results: A ratio for both measures was calculated between measures for pictures with more or less interpersonal communication. The ratio of initial fixation duration for pictures with people communicating versus pictures with people not communicating was lowest in chronically ill patients (0.13 (0.34))compared with HCs (0.31 (0.36)), FEZ patients (0.31 (0.46)), and CHR patients (0.36 (0.42)). The difference in the ratios of initial fixation duration for type 2 and type 3 pictures was also significant for female participants (HCs vs chronically ill patients, t=2.706, p=0.009; CHR patients vs chronically ill patients, t=4.079, p<0.001). In addition, the ratio of initial fixation duration on pictures with people not communicating versus pictures without people negatively correlated with participants' high-risk symptoms (r=-0.35, p=0.002) among the CHR group and also correlated with the negative symptom subscore on the Positive and Negative Syndrome Scale (PANSS) among chronically ill patients (r=-0.33, p=0.037). The ratio of initial fixation duration between type 1 and type 3 pictures was associated with PANSS negative symptoms only in female patients with schizophrenia (r=-0.46, p=0.004).

Conclusions: These findings suggest an altered attentive bias towards pictures with a high degree of interpersonal communication information across different clinical phases in schizophrenia. The ratio of initial attentive orienting was associated with negative symptoms in female patients.
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http://dx.doi.org/10.1136/gpsych-2021-100699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016392PMC
April 2022

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants.

Gen Psychiatr 2022 13;35(2):e100703. Epub 2022 Apr 13.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Disrupted white matter (WM) microstructure has been commonly identified in youth at clinical high risk (CHR) for psychosis. Several lines of evidence suggest that fatty acids, especially unsaturated fatty acids (UFAs), might play a crucial role in the WM pathology of early onset psychosis. However, evidence linking UFA and WM microstructure in CHR is quite sparse.

Aims: We investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls (HC).

Methods: Plasma fatty acids were assessed and diffusion tensor imaging (DTI) data were performed with tract-based spatial statistics (TBSS) analysis for 66 individuals at CHR for psychosis and 70 HC.

Results: Both the global and regional diffusion measures showed significant between-group differences, with decreased fractional anisotropy (FA) but increased mean diffusivity (MD) and radial diffusivity (RD) found in the CHR group compared with the HC group. On top of that, we found that in the HC group, plasma arachidic acid showed obvious trend-level associations with higher global FA, lower global MD and lower global RD, which regionally spread over the corpus callosum, right anterior and superior corona radiata, bilateral anterior and posterior limb of the internal capsule, and bilateral superior longitudinal fasciculus. However, there were no associations between global WM measures and any UFA in the CHR group. Conversely, we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group.

Conclusions: Compared with the HC group, CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA, with a neuroprotective effect found in the HC group but not in the CHR group. Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group, highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.
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http://dx.doi.org/10.1136/gpsych-2021-100703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014058PMC
April 2022

Biological mechanisms and clinical efficacy of sulforaphane for mental disorders.

Gen Psychiatr 2022 5;35(2):e100700. Epub 2022 Apr 5.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Current clinical management of major mental disorders, such as autism spectrum disorder, depression and schizophrenia, is less than optimal. Recent scientific advances have indicated that deficits in oxidative and inflammation systems are extensively involved in the pathogenesis of these disorders. These findings have led to expanded considerations for treatment. Sulforaphane (SFN) is a dietary phytochemical extracted from cruciferous vegetables. It is an effective activator of the transcription factor nuclear erythroid-2 like factor-2, which can upregulate multiple antioxidants and protect neurons against various oxidative damages. On the other hand, it can also significantly reduce inflammatory response to pathological states and decrease the damage caused by the immune response via the nuclear factor-κB pathway and other pathways. In this review, we introduce the biological mechanisms of SFN and the pilot evidence from its clinical trials of major mental disorders, hoping to promote an increase in psychiatric clinical studies of SFN.
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http://dx.doi.org/10.1136/gpsych-2021-100700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987744PMC
April 2022

Age-related changes in self-reported psychotic experiences in clinical help-seeking population: From 15 to 45 years.

Early Interv Psychiatry 2022 Apr 23. Epub 2022 Apr 23.

Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center (20DZ2253800), Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China.

Aims: Psychotic experiences differ with age. It is currently unknown whether there were specific patterns and associations between the presentation of psychotic experiences and age. This study aimed to explore age-related differences (15-45 years) in self-reported psychotic experiences in a large-scale clinical population.

Methods: A total of 2542 consecutive new patients aged 15-45 years were recruited on their first visit to the Shanghai Mental Health Center and screened with the PRIME Screen-Revised (PS-R). According to the clinical diagnostic information of patients from their outpatient medical records compiled by their clinicians, four diagnostic categories were applied: 1) psychotic disorder; 2) mood disorder; 3) anxiety disorder and 4) others.

Results: The PS-R scores of self-reported psychotic experiences declined with age, except for two age ranges: ≤18 years for overall sample (≤18 vs. 19-34 years: t = 5.531, df = 2202, p < .001) and 37-40 years for female sample (37-40 vs. >40 years: t = 1.985, df = 138, p = .049), which showed upward trends, contrary to those of others. There were no significant differences in self-reported psychotic experiences between age groups in patients with psychotic disorders, while significant age differences were found in all nonpsychotic patients.

Conclusion: These findings support the view that frequent PS-R screening demonstrated that psychotic experiences decline with age in the clinical population. Early detection of psychosis should focus on not only adolescents but also women aged >36 years.
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http://dx.doi.org/10.1111/eip.13285DOI Listing
April 2022

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

J Affect Disord 2022 06 4;307:237-243. Epub 2022 Apr 4.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China; CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, Shanghai, PR China; Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jad.2022.03.077DOI Listing
June 2022

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

Psychiatry Res 2022 06 22;312:114523. Epub 2022 Mar 22.

Shanghai Key Laboratory of Psychotic Disorders, Department of EEG and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.psychres.2022.114523DOI Listing
June 2022

Common abnormal connectivity in first-episode and chronic schizophrenia in pre- and post-central regions: Implications for neuromodulation targeting.

Prog Neuropsychopharmacol Biol Psychiatry 2022 07 30;117:110556. Epub 2022 Mar 30.

Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China; Department of Computer Science, University of Warwick, Coventry CV4 7AL, UK; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China; Shanghai Center for Mathematical Sciences, Shanghai, China. Electronic address:

Schizophrenia is a neurodevelopmental disorder manifesting differing impairments at early onset and chronic disease stages. Brain imaging research suggests a core pathological region in patients with first-episode schizophrenia is Broca's area. With disease progression, alterations in thalamic connectivity becomes more prevalent. Understanding the common circuitry underlying pathology in these two groups might highlight a critical common network and novel targets for treatment. In this study, 937 subject samples were collected including patients with first-episode schizophrenia and those with chronic schizophrenia. We used hypothesis-based voxel-level functional connectivity analyses to calculate functional connectivity using the left Broca's area and thalamus as regions of interest in those with first-episode and chronic schizophrenia, respectively. We show for the first time that in both patients with first-episode and chronic schizophrenia the greatest functional connectivity disruption ended in the pre- and postcentral regions. At the early-onset stage, the core brain region is abnormally connected to pre- and postcentral areas responsible for mouth movement, while in the chronic stage, it expanded to a wider range of sensorimotor areas. Our findings suggest that expanding the focus on the low-order sensory-motor systems beyond high-order cognitive impairments in schizophrenia may show potential for neuromodulation treatment, given the relative accessibility of these cortical regions and their functional and structural connections to the core region at different stages of illness.
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http://dx.doi.org/10.1016/j.pnpbp.2022.110556DOI Listing
July 2022

The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment.

J Psychiatry Neurosci 2022 Mar-Apr;47(2):E134-E147. Epub 2022 Mar 31.

From the Shanghai Mental Health Centre, Shanghai Jiaotong University, School of Medicine, Shanghai, China (Wang, Xu, Yuan, Li, Zhang, Liu); the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ont. (Su, Samsom, Wong, Liu); the National Clinical Research Centre for Mental Disorders, Beijing AnDing Hospital, Capital Medical University, Beijing, China (Yang, Dong, Zhou); the Department of Pharmacology, University of Toronto, Toronto, Ont. (Samsom, Wong); the Institute of Medical Science, University of Toronto, Toronto, Ont. (Wong, Liu); the Department of Psychiatry, University of Toronto, Toronto, Ont. (Wong, Liu); the Department of Physiology, University of Toronto, Toronto, Ont. (Liu)

Background: For decades, the dopamine D2 receptor (D2R) has been known as the main target of antipsychotic medications, but the mechanism for antipsychotic effects beyond this pharmacological target remains unclear. Disrupted-in-schizophrenia 1 () is a gene implicated in the etiology of schizophrenia, and we have found elevated levels of the D2R-DISC1 complex in the postmortem brain tissue of patients with schizophrenia.

Methods: We used coimmunoprecipitation to measure D2R-DISC1 complex levels in peripheral blood samples from patients with schizophrenia and unaffected controls in 3 cohorts (including males and females) from different hospitals. We also used label-free mass spectrometry to conduct proteomic analysis of these samples.

Results: Levels of the D2R-DISC1 complex were elevated in the peripheral blood samples of patients with schizophrenia from 3 independent cohorts, and were normalized with antipsychotic treatment. Proteomic analysis of the blood samples from patients with high D2R-DISC1 complex levels that were normalized with antipsychotic treatment revealed a number of altered proteins and pathways associated with D2R, DISC1 and the D2R-DISC1 complex. We identified additional proteins and pathways that were associated with antipsychotic treatment in schizophrenia, and that may also be novel targets for schizophrenia treatment.

Limitations: Sample sizes were relatively small, but were sufficient to detect associations between D2R-DISC1 levels, schizophrenia and treatment response. The relevance of leukocyte changes to the symptoms of schizophrenia is unknown. The coimmunoprecipitation lanes included several nonspecific bands.

Conclusion: Levels of the D2R-DISC1 complex were elevated in patients with schizophrenia and reduced with antipsychotic treatment. This finding reinforces the independent role of each protein in schizophrenia. Our results enhanced our understanding of the molecular pathways involved in schizophrenia and in antipsychotic medications, and identified novel potential molecular targets for treating schizophrenia.
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http://dx.doi.org/10.1503/jpn.210145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979657PMC
March 2022

Antipsychotic Exposure in Clinical High Risk of Psychosis: Empirical Insights From a Large Cohort Study.

J Clin Psychiatry 2022 03 21;83(3). Epub 2022 Mar 21.

Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Intelligent Psychological Evaluation and Engineering Technology Research Center (20DZ2253800), Shanghai Key Laboratory of Psychotic Disorders, Shanghai, PR China.

Current treatment guidelines for individuals at clinical high risk (CHR) for psychosis do not recommend the prescription of antipsychotics (not even second-generation ones) as the first treatment option for preventing psychosis. Yet, recent meta-analytic evidence indicates that antipsychotic exposure in CHR is relatively widespread and associated with a higher imminent risk of transition to psychosis. Therefore, we undertook this study to better delineate which clinical characteristics of CHR individuals may lead to the choice of antipsychotic prescription and whether it identifies a subgroup at higher risk for conversion to psychosis.

Consecutively referred CHR individuals (N = 717) were assessed for demographic and clinical characteristics and followed up for 3 years (200 did not reach the end of the follow-up time) from 2016 to 2021. The sample was then dichotomized, on the basis of antipsychotic prescription, to prescribed (CHRAP+, n = 492) or not-prescribed (CHRAP-, n = 225) groups, which were subsequently compared for sociodemographic and clinical characteristics. The risks of conversion to psychosis in CHRAP+ versus CHRAP- groups were tested via survival analysis.

Of the 717 CHR individuals, 492 (68.62%) were prescribed antipsychotics; among these antipsychotics, the highest proportion used was for aripiprazole (n = 152), followed by olanzapine (n = 106), amisulpride (n = 76), and risperidone (n = 64). The CHRAP+ group had younger age ( = 2.138,  = .033), higher proportion of female individuals ( = 5.084,  = .024), psychotic symptoms of greater severity ( = 7.910,  < .001), and more impaired general function ( = 5.846,  < .001) than the CHRAP- group. The CHRAP+ group had greater risk for conversion to psychosis (27.0% in the CHRAP+ group vs 10.9% in the CHRAP- group,  < .001). Factors related to positive symptoms were the most likely to influence doctors' decision-making regarding prescripton of antipsychotics, without influence of age, sex, and education levels.

Clinicians may prescribe antipsychotics mainly based on the severity of positive and disorganization symptoms of CHR individuals. The CHRAP+ group was associated with a higher risk of conversion to psychosis. In pragmatic terms, this finding indicates that baseline antipsychotic prescription in CHR cohorts is a warning flag for higher incipient risk of psychosis and designates as hyper-CHR subgroup as compared to antipsychotic-naive CHR.

ClinicalTrials.gov identifier: NCT04010864.
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http://dx.doi.org/10.4088/JCP.21m14092DOI Listing
March 2022
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