Chemotherapy Effectiveness and Prognosis of Gastric Cancer Influenced by PTPN11 Polymorphisms.

OBJECTIVE: Since gastric cancer (GC) cells exhibited higher grades of SHP-2 encoded by PTPN11 than normal cells, it would be intriguing to explore whether PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy effectiveness and GC prognosis among a Chinese population. METHODS: Altogether 430 late-stage GC patients and 960 healthy controls matched with age and sex were incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4 cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. Survival curves were plotted with Kaplan-Meier method and the COX proportional hazard model was used to analyze independent factors for GC prognosis. RESULTS: For rs12229892, AA and GA genotypes would cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60; 95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly associated with a decrease in the risk of GC when compared with G allele (OR = 0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle chemotherapy suggested that chemotherapy was significantly more effective for GA and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides, the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking, family history, intake of processed food and H .pylori infection) on GC risk was considered as positive interaction, while that of rs2301756 (AA) and the above parameters was deemed as negative interaction. Finally, differentiation degree, axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent risk factors for GC development (all P < 0.05). CONCLUSION: Since rs2301756 polymorphism of PTPN11 was associated with reduced risk of GC and better effects of chemotherapy on GC, it can be considered as a predictor of GC prognosis and the treatment target for GC.

Characterizing the clinical heterogeneity of early symptomatic Alzheimer's disease: a data-driven machine learning approach.

Introduction: Alzheimer's disease (AD) is highly heterogeneous, with substantial individual variabilities in clinical progression and neurobiology. Amyloid deposition has been thought to drive cognitive decline and thus a major contributor to the variations in cognitive deterioration in AD. However, the clinical heterogeneity of patients with early symptomatic AD (mild cognitive impairment or mild dementia due to AD) already with evidence of amyloid abnormality in the brain is still unknown. Methods: Participants with a baseline diagnosis of mild cognitive impairment or mild dementia, a positive amyloid-PET scan, and more than one follow-up Alzheimer's Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) administration within a period of 5-year follow-up were selected from the Alzheimer's Disease Neuroimaging Initiative database (n = 421; age = 73±7; years of education = 16 ± 3; percentage of female gender = 43%; distribution of APOE4 carriers = 68%). A non-parametric k-means longitudinal clustering analysis in the context of the ADAS-Cog-13 data was performed to identify cognitive subtypes. Results: We found a highly variable profile of cognitive decline among patients with early AD and identified 4 clusters characterized by distinct rates of cognitive progression. Among the groups there were significant differences in the magnitude of rates of changes in other cognitive and functional outcomes, clinical progression from mild cognitive impairment to dementia, and changes in markers presumed to reflect neurodegeneration and neuronal injury. A nomogram based on a simplified logistic regression model predicted steep cognitive trajectory with an AUC of 0.912 (95% CI: 0.88 - 0.94). Simulation of clinical trials suggested that the incorporation of the nomogram into enrichment strategies would reduce the required sample sizes from 926.8 (95% CI: 822.6 - 1057.5) to 400.9 (95% CI: 306.9 - 516.8). Discussion: Our findings show usefulness in the stratification of patients in early AD and may thus increase the chances of finding a treatment for future AD clinical trials.

Insulin Resistance/Diabetes and Schizophrenia: Potential Shared Genetic Factors and Implications for Better Management of Patients with Schizophrenia.

Schizophrenia is a complex psychotic disorder with co-occurring conditions, including insulin resistance and type 2 diabetes (T2D). It is well established that T2D and its precursors (i.e., insulin resistance) are more prevalent in patients with schizophrenia who are treated with antipsychotics, as well as in antipsychotic-naïve patients experiencing their first episode of psychosis, compared with the general population. However, the mechanism(s) underlying the increased susceptibility, shared genetics, and possible cause-effect relationship between schizophrenia and T2D remain largely unknown. The objective of this narrative review was to synthesize important studies, including Mendelian randomization (MR) analyses that have integrated genome-wide association studies (GWAS), as well as results from in vitro models, in vivo models, and observational studies of patients with schizophrenia. Both GWAS and MR studies have found that schizophrenia and T2D/insulin resistance share genetic risk factors, and this may mediate a connection between peripheral or brain insulin resistance and T2D with cognition impairment and an increased risk of developing prediabetes and T2D in schizophrenia. Moreover, accumulating evidence supports a causal role for insulin resistance in schizophrenia and emphasizes the importance of a genetic basis for susceptibility to T2D in patients with schizophrenia before they receive psychotic treatment. The present findings and observations may have clinical implications for the development of better strategies to treat patients with schizophrenia, with both pharmacological (i.e., samidorphan, empagliflozin) and/or nonpharmacological (i.e., lifestyle changes) approaches. Additionally, this review may benefit the design of future studies by physicians and clinical investigators.

Microglia and cognitive impairment in schizophrenia: translating scientific progress into novel therapeutic interventions.

Cognitive impairment is a core clinical feature of schizophrenia, exerting profound adverse effects on social functioning and quality of life in a large proportion of patients with schizophrenia. However, the mechanisms underlying the pathogenesis of schizophrenia-related cognitive impairment are not well understood. Microglia, the primary resident macrophages in the brain, have been shown to play important roles in psychiatric disorders, including schizophrenia. Increasing evidence has revealed excessive microglial activation in cognitive deficits related to a broad range of diseases and medical conditions. Relative to that about age-related cognitive deficits, current knowledge about the roles of microglia in cognitive impairment in neuropsychiatric disorders, such as schizophrenia, is limited, and such research is in its infancy. Thus, we conducted this review of the scientific literature with a focus on the role of microglia in schizophrenia-associated cognitive impairment, aiming to gain insight into the roles of microglial activation in the onset and progression of such impairment and to consider how scientific advances could be translated to preventive and therapeutic interventions. Research has demonstrated that microglia, especially those in the gray matter of the brain, are activated in schizophrenia. Upon activation, microglia release key proinflammatory cytokines and free radicals, which are well-recognized neurotoxic factors contributing to cognitive decline. Thus, we propose that the inhibition of microglial activation holds potential for the prevention and treatment of cognitive deficits in patients with schizophrenia. This review identifies potential targets for the development of new treatment strategies and eventually the improvement of care for these patients. It might also help psychologists and clinical investigators in planning future research.

Low-dose lithium adjunct to atypical antipsychotic treatment nearly improved cognitive impairment, deteriorated the gray-matter volume, and decreased the interleukin-6 level in drug-naive patients with first schizophrenia symptoms: a follow-up pilot study.

This study was conducted to investigate the effects of long-term low-dose lithium adjunct to antipsychotic agent use on the cognitive performance, whole-brain gray-matter volume (GMV), and interleukin-6 (IL-6) level in drug-naive patients with first-episode schizophrenia, and to examine relationships among these factors. In this double-blind randomized controlled study, 50 drug-naive patients with first-episode schizophrenia each took low-dose (250 mg/day) lithium and placebo (of the same shape and taste) adjunct to antipsychotic agents (mean, 644.70 ± 105.58 and 677.00 ± 143.33 mg/day chlorpromazine equivalent, respectively) for 24 weeks. At baseline and after treatment completion, the MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognitive performance, 3-T magnetic resonance imaging was performed to assess structural brain alterations, and serum IL-6 levels were quantified by immunoassay. Treatment effects were assessed within and between patient groups. Relationships among cognitive performance, whole-brain GMVs, and the IL-6 level were investigated by partial correlation analysis. Relative to baseline, patients in the lithium group showed improved working memory, verbal learning, processing speed, and reasoning/problem solving after 24 weeks of treatment; those in the placebo group showed only improved working memory and verbal learning. The composite MCCB score did not differ significantly between groups. The whole-brain GMV reduction was significantly lesser in the lithium group than in the placebo group (0.46% vs. 1.03%; P < 0.001). The GMV and IL-6 reduction ratios correlated with each other in both groups (r = -0.17, P = 0.025). In the lithium group, the whole-brain GMV reduction ratio correlated with the working memory improvement ratio (r = -0.15, P = 0.030) and processing speed (r = -0.14, P = 0.036); the IL-6 reduction ratio correlated with the working memory (r = -0.21, P = 0.043) and verbal learning (r = -0.30, P = 0.031) improvement ratios. In the placebo group, the whole-brain GMV reduction ratio correlated only with the working memory improvement ratio (r = -0.24, P = 0.019); the IL-6 reduction ratio correlated with the working memory (r = -0.17, P = 0.022) and verbal learning (r = -0.15, P = 0.011) improvement ratios. Both treatments implemented in this study nearly improved the cognitive performance of patients with schizophrenia; relative to placebo, low-dose lithium had slightly greater effects on several aspects of cognition. The patterns of correlation among GMV reduction, IL-6 reduction, and cognitive performance improvement differed between groups.

Validity and reliability of a Chinese version of the Bergen Work Addiction Scale.

Background: Work addiction (WA), which can impair personal relationships, engagement in recreational activities, and/or health, is a behavioral addiction. A tool for the early detection of WA in China is needed. Objective: The aim of this study was to develop and determine the validity and reliability of a Chinese version of the Bergen Work Addiction Scale (C-BWAS). Methods: Two hundred social workers who provided post-discharge services for adolescents with non-suicidal self-injury (NSSI) were enrolled in this study. The construct validity of the C-BWAS was assessed by confirmatory factor analysis (CFA). Criterion validity was assessed by conducting Pearson correlation analyses of C-CWAS scores with Hamilton Depression Scale (HAM-D) and Hamilton Anxiety Scale (HAM-A) scores. Cronbach's α and the intra-class correlation coefficient (ICC) were used to evaluate the reliability of the C-BWAS. Results: CFA confirmed a one-dimensional structure of the C-BWAS with good construct validity indices [comparative fit index (CFI) = 0.964, Tucker-Lewis index (TLI) = 0.951, root-mean-square error of approximation (RMSEA) = 0.079, and minimum discrepancy C/degrees of freedom (Cmin/DF) = 0.362]. The standardized regression weights ranged from 0.523 to 0.753. All C-BWAS items loaded on one major factor (loading weights, 0.646-0.943). Coefficients of correlation between C-BWAS scores and HAM-D and HAM-A scores were 0.889 and 0.933, respectively. The Cronbach's α coefficient and ICC for the instrument was 0.837 and 0.905, respectively. Conclusion: The presently developed C-BWAS showed very good reliability and acceptably validity. It can be employed as a useful tool for assessing WA severity in social workers who provide post-discharge services for adolescents with NSSI.

Validity and reliability of a Chinese version of the self-evaluation of negative symptoms.

The negative symptoms of schizophrenia can be present at any clinical stage, but evaluating the negative symptoms always remains challenging. To screen the negative symptoms effectively, self-evaluation should be introduced. To date, professional psychiatrists used almost all of the scales available to screen the negative symptoms but could not obtain an accurate outcome. At the same time, an advanced self-assessment scale is needed to accompany the patients' self-feeling-based treatment strategies to understand their feelings about their symptoms. Hence, Chinese self-evaluation of negative symptoms (SNS) should be introduced in China. This study aims to examine the validity and reliability of the Chinese version of SNS. Two hundred patients with schizophrenia were included in this study and were evaluated entirely with the self-assessed negative symptoms by the Chinese version. The correlation analysis was performed between SNS and the Scale for Assessment of Negative Symptoms (SANS) to assess the criterion validity of SNS for screening negative symptoms. Exploratory factor analysis was used to determine the constructive validity of the SNS. Two senior professional psychiatrists were involved in this assessment based on their clinical experience and capability to define the severity of the negative symptoms. Receiver operating characteristic curve (ROC) analysis was performed to assess the cutoff point of SNS. Cronbach's alpha coefficient and intraclass correlation (ICC) coefficient were used to determine the reliability of SNS. We have the following findings: The Chinese version of SNS demonstrated a significant correlation with the SANS (r = .774, p < .05). Exploratory factor analysis demonstrated that the factor loading varies from .442 to .788. ROC analysis demonstrated that at SNS ≥ 8, the patients demonstrated a mild severity of negative symptoms, and at SNS ≥ 15, the patients demonstrated a severe severity of negative symptoms. Subsequently, 9 < SNS < 14 was defined as a moderate severity of negative symptoms. The Cronbach's alpha and ICC coefficients of the Chinese version SNS were .877 and .774, respectively. Our results showed that the acceptable validity and reliability of the Chinese version of SNS confirmed that SNS is an ideal tool for self-assessment of the negative symptoms in patients with schizophrenia.

A two-year follow-up study on the first manic episode due to mood-incongruent psychosis.

BACKGROUND: Mood-incongruent psychosis during bipolar disorder has been associated with poor outcomes. However, it remains unknown whether this is secondary to persistent affective or psychotic symptoms or both. METHOD: Sixty-eight patients with bipolar disorder between the ages of 16 and 45 were recruited during their first psychiatric hospitalization for mania. These patients were evaluated using structured and semi-structured clinical interview then followed longitudinally. Outcomes during the first twenty-four months of follow-up were compared between patients with mood-incongruent psychosis and those without (i.e., patients with mood-congruent psychosis or no psychosis) during the index manic episode. Specifically, ratings of the percent of weeks during follow-up with the duration of mood incongruent psychotic symptom, any psychotic symptom, affective syndromes, and scores of global outcomes were compared. RESULTS: Comparing the 24-month follow-up results between the two groups, patients with mood incongruent psychotic symptoms had a lower global functional rating scale, efficacy index, while the duration of mood incongruent psychotic symptom, any psychotic symptom, and complete affective symptom showed statistically significant differences between the two groups. There were also statistically significant differences between the two groups in the duration of mood stabilizers, and antidepressants use, typical antipsychotics, and atypical antipsychotics. Partial correlation analysis reveals the scores of the global assessment of functioning scale (GAF) after 24 months showed a significant negative correlation with the length of time of incongruent psychotic symptoms. Still, the correlation was intermediate (correlation coefficients less than 0.5，r2 = -0.471, P < 0.001). CONCLUSION: Mood-incongruent psychosis that occurs during the first manic episode appears to predict an increased likelihood of persistent psychotic symptoms during the subsequent twenty-four months. This persistence of psychosis is associated with a worse overall course of illness than patients without mood-incongruent psychosis. LIMITATIONS: These results apply to a relatively short outcome period, and the sample size is relatively small.

A network analysis of social problem-solving and anxiety/depression in adolescents.

Social problem-solving (SPS) involves the cognitive-behavioral processes through which an individual identifies and copes with everyday problems; it is considered to contribute to anxiety and depression. The Social Problem-Solving Inventory Revised is a popular tool measuring SPS problem orientations and problem-solving styles. Only a negative problem orientation (NPO) is considered strongly related to anxiety and depression. In the present study, we investigated the detailed connections among the five components of SPS and 14 anxiety-depression symptoms and specified the role of NPO and other components in the anxiety-depression network. We employed network analysis, constructed circular and multi-dimensional scaling (MDS) networks, and calculated the network centrality, bridge centrality, and stability of centrality indices. The results were as follows: (1) the MDS network showed a clustering of anxiety and depression symptoms, with NPO and avoidance style components from SPS being close to the anxiety-depression network (demonstrated by large bridge betweenness and bridge closeness); (2) the NPO and positive problem orientation from SPS were most influential on the whole network, though with an opposite effect; (3) strength was the most stable index [correlation stability (CS) coefficient = 0.516] among the centrality indices with case-dropping bootstraps. We also discussed this network from various perspectives and commented on the clinical implications and limitations of this study.

A borderline personality assessment for adolescents: Validity and reliability of the Chinese languages borderline personality features scale (short form version) for adolescents/children.

Background: Borderline personality disorder (BPD) is characterized by behavioral patterns that promote suffering in many adolescents and their guardians. Currently, early diagnosis of BPD mainly depends on the effective assessment of pathological personality traits (i.e., borderline personality features) and using the indicated scales. The Borderline Personality Features Scale for Children-Short Form (BPFSC-SF) is widely used and the introduction of a Chinese version of the BPFSC-SF, can improve the diagnosis and prognosis of Chinese patients with BPD. Objective: The aim of the present study was to assess the validity and reliability of the Chinese version of the BPFSC-SF. Method: 120 adolescents with BPD were enrolled in the present study and completed the BPFSC-SF and the Personality Belief Questionnaire-Short Form (PBQ-SF) assessments. Confirmatory factor analysis (CFA) was used to test assessment validity. Test-retest correlations and the Cronbach's α coefficients were used to determine reliability. Results: CFA analysis identified primary factors of BPFSC, with each item ranging from 0.597~0.899. The Spearman rank correlation coefficient was 0.877 between CL-BFSFC-SF and the state vs. trait loneliness scale. The Cronbach's α of the scale was 0.854 in the clinical group. The test-retest reliability correlation coefficient (interclass correlation coefficients.ICC) was 0.937. Conclusion: The Chinese version of BPFSC-SF is a valid and reliable tool for adolescent Chinese patients with BPD.

Baseline global brain structural and functional alterations at the time of symptom onset can predict subsequent cognitive deterioration in drug-naïve first-episode schizophrenia patients: Evidence from a follow-up study.

Alterations in the global brain gray matter volume (gGMV) and global functional connectivity density (gFCD) play a pivotal role in the cognitive impairment and further deterioration in schizophrenia. This study aimed to assess the correlation between alterations in the gGMV and gFCD at baseline (ΔgGMV and ΔgFCD), and the subsequent alterations of cognitive function in schizophrenia patients after 2-year antipsychotic treatment. Global-brain magnetic resonance imaging scans were acquired from 877 drug-naïve, first-episode schizophrenia patients at baseline and after two years of antipsychotic treatment with adequate dosage and duration, and 200 healthy controls. According to ΔgGMV at baseline, schizophrenia patients were divided into mild, moderate, and severe alteration groups. The MATRICS consensus cognitive battery and Global Deficit Score (GDS) were used to assess cognitive impairment. We found that ΔgGMV and ΔgFCD at baseline were significantly correlated with the severity of the cognitive deterioration (ΔGDS). The correlation coefficient indicated a significant positive correlation between baseline ΔgFCD and subsequent cognitive deterioration, with a relatively stronger relation in the mild alteration group (r = 0.31). In addition, there was a significant positive correlation between baseline ΔgGMV and subsequent cognitive deterioration, with a stronger relation in the moderate and severe alteration groups (r = 0.303; r = 0.302, respectively). Our results showed that ΔgGMV and ΔgFCD are correlated with the severity of cognitive deterioration after completion of a 2-year antipsychotic treatment in schizophrenia patients. These findings suggest that baseline alterations in gGMV and gFCD hold potential for predicting subsequent cognitive decline in schizophrenia.

Testing the validity and reliability of the Chinese version of the Staden schizophrenia anxiety rating scale.

Accurate assessment of anxiety disorders and their symptomatology in schizophrenic patients is important for prognosis and treatment. Measuring anxiety on the traditional anxiety assessment scales such as the Hamilton Anxiety Rating (HAMA) Scale or the self-rating depression scale (SAS) is challenging and often considered unsuitable for assessing anxiety symptoms in patients with schizophrenia. The Staden schizophrenia anxiety rating scale (S-SARS) has been shown to reliably measure specified and undifferentiated anxiety in schizophrenia. The present study aims to test the reliability and validity of the S-SARS version, thereby facilitating Chinese psychiatrists in assessing anxiety symptoms in schizophrenic patients. A total of 300 patients meeting ICD-10 diagnostic criteria of schizophrenia were recruited by convenience sampling. We used the exploratory factor analysis (EFA) to evaluate the structural validity of S-SARS and receiver operating characteristic (ROC) curves to acquire the cutoff point of S-SARS to define the severity of anxiety. Internal consistency was assessed using Cronbach's and Krippendorff's α scores. 1-week test-retest reliability was assessed using the intra-class correlation coefficient (ICC). Correlation analysis with HAMA was used to determine the Chinese version of S-SARS criterion validity. We have the following results: Our version of S-SARS showed Cronbach's α score as 0.899, Krippendorff's α as 0.874, and a correlation coefficient of 0.852 between S-SARS and HAMA. The EPA demonstrated that the contribution rate of major factors was 69.45%. All the items of S-SARS were located in one factor and showed a high factor load (0.415-0.837). The correlation coefficient of S-SARS and HAMA was 0.852. Our results indicated that Chinese version of S-SARS showed good constructive validity and reliability. It also showed better criterion validity compared to HAMA. The S-SARS and its Chinese version can thus serve as an effective tool for assessing anxiety symptoms in patients with schizophrenia.

Higher benefit-risk ratio of COVID-19 vaccination in patients with schizophrenia and major depressive disorder versus patients with bipolar disorder when compared to controls.

Patients with major psychiatric disorders (MPD) that include schizophrenia (SCH), bipolar disorder (BP), and major depressive disorder (MDD) are at increased risk for coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccines in MPD patients have not been fully evaluated. This study aimed to investigate adverse events (AEs)/side effects and efficacy of COVID-19 vaccines in MPD patients. This retrospective study included 2034 patients with SCH, BP, or MDD who voluntarily received either BBIBP-CorV or Sinovac COVID-19 vaccines, and 2034 matched healthy controls. The incidence of AEs/side effects and the efficacy of COIVD-19 vaccinations among the two groups were compared. The risk ratio (RR) of side effects in patients with MPD was 0.60 (95% confidence interval [CI]: 0.53-0.68) after the first dose and 0.80 (95% CI: 0.65-0.99) following the second dose, suggesting a significantly lower risk in the MPD group versus healthy controls. The RRs of AEs did not differ between patients and controls. Notably, fully vaccinated patients exhibited a decreased risk of influenza with or without fever compared with controls (RR=0.38, 95% CI: 0.31-0.46; RR=0.23, 95% CI: 0.17-0.30; respectively). Further subgroup comparisons revealed a significantly lower risk of influenza with fever in MDD (RR=0.13, 95% CI: 0.08-0.21) and SCH (RR=0.24, 95% CI: 0.17-0.34) than BP (RR=0.85, 95% CI: 0.69-1.06) compared to controls. We conclude that the benefit-risk ratio of COVID-19 vaccination was more favorable in SCH or MDD versus BP when compared with controls. These data indicate that COVID-19 vaccines are safe and protective in patients with MPD from COVID-19.

Exploration of the cortical pathophysiology underlying visual disturbances in schizophrenia comorbid with depressive disorder-An evidence from mouse model.

INTRODUCTION: Patients with schizophrenia frequently present with visual disturbances including hallucination, and this symptom is particularly prevalent in individuals with comorbid depressive disorders. Currently, little is known about the neurobiological mechanisms of such psychiatric symptoms, and few explanations for the co-occurrence of schizophrenia, depression, and visual disturbances are available. METHODS: In this study, we generated a mouse schizophrenia model in which depressive symptoms were also induced. We adopted in vivo two-photon calcium imaging and ex vivo electrophysiological recording of the primary visual cortex to reveal the synaptic transmission and neural activity in the mouse schizophrenia model. RESULTS: In vivo two-photon calcium imaging and ex vivo electrophysiological recording of the primary visual cortex revealed impaired synaptic transmission and abnormal neural activity in the schizophrenia model, but not in the depression model. These functional deficits were most prominent in the combined schizophrenia and depression model. CONCLUSION: Overall, our data support a mechanism by which the visual cortex plays a role in visual disturbances in schizophrenia.

Patients with first-episode untreated schizophrenia who experience concomitant visual disturbances and auditory hallucinations exhibit co-impairment of the brain and retinas-a pilot study.

There are limited structural brain and retina alteration data from schizophrenia patients who experience visual disturbances (VDs) with or without auditory hallucinations (AHs). We compared brain and retina alterations between first-episode untreated schizophrenia patients with VDs (FUSCH-VDs) with versus without AHs, and between patients and healthy controls (HCs)(N = 30/group). VDs, AHs, gray matter volumes (GMVs), and retinal thicknesses were evaluated with the Bonn Scale for Assessment of Basic Symptoms (BSABS) scale, the Auditory Hallucinations Rating Scale (AHRS), magnetic resonance imaging (MRI), and optical coherence tomography (OCT), respectively. Compared to HCs, FUSCH-VDs had reduced GMVs, mainly in dorsal V3/V3A and V5 regions, the fusiform gyrus, and ventral V4 and V8 regions. Most FUSCH-VDs (85.0%; 51/60) had primary visual cortex-retina co-impairments. FUSCH-VDs with AHs had more serious and larger scope GMV reductions than FUSCH-VDs without AHs. FUSCH-VDs with AHs had significant retinal thickness reductions compared to HCs. Primary visual cortex-retina co-impairments were found to be more common, and more pronounced when present, in FUSCH-VDs with AHs than in FUSCH-VDs without AHs. The present findings support the notion that VDs and AHs may have reciprocal deteriorating actions in patients with schizophrenia.

Strategies to solve the reverse inference fallacy in future MRI studies of schizophrenia: a review.

Few advances in schizophrenia research have been translated into clinical practice, despite 60 years of serum biomarkers studies and 50 years of genetic studies. During the last 30 years, neuroimaging studies on schizophrenia have gradually increased, partly due to the beautiful prospect that the pathophysiology of schizophrenia could be explained entirely by the Human Connectome Project (HCP). However, the fallacy of reverse inference has been a critical problem of the HCP. For this reason, there is a dire need for new strategies or research "bridges" to further schizophrenia at the biological level. To understand the importance of research "bridges," it is vital to examine the strengths and weaknesses of the recent literature. Hence, in this review, our team has summarized the recent literature (1995-2018) about magnetic resonance imaging (MRI) of schizophrenia in terms of regional and global structural and functional alterations. We have also provided a new proposal that may supplement the HCP for studying schizophrenia. As postulated, despite the vast number of MRI studies in schizophrenia, the lack of homogeneity between the studies, along with the relatedness of schizophrenia with other neurological disorders, has hindered the study of schizophrenia. In addition, the reverse inference cannot be used to diagnose schizophrenia, further limiting the clinical impact of findings from medical imaging studies. We believe that multidisciplinary technologies may be used to develop research "bridges" to further investigate schizophrenia at the single neuron or neuron cluster levels. We have postulated about future strategies for overcoming the current limitations and establishing the research "bridges," with an emphasis on multimodality imaging, molecular imaging, neuron cluster signals, single transmitter biomarkers, and nanotechnology. These research "bridges" may help solve the reverse inference fallacy and improve our understanding of schizophrenia for future studies.

Abberant inverted U-shaped brain pattern and trait-related retinal impairment in schizophrenia patients with combined auditory and visual hallucinations: a pilot study.

Schizophrenic patients often experience auditory hallucinations (AHs) and visual hallucinations (VHs). However, brain and retinal alterations associated with combined AHs and VHs in schizophrenic patients are unknown. This study aimed o investigate brain and retinal alterations in first episode un-treated schizophrenic patients with combined AHs and VHs (FUSCHAV). FUSCHAV patients (n = 120), divided into four groups according to severity of AH and VH symptoms, were compared to healthy controls (n = 30). Gray matter volume (GMV) and global functional connectivity density (gFCD) were recorded to reflect brain structure and functional alterations. Total retinal thickness was acquired by optical coherence tomography to assess retinal impairment. The majority of FUSCHAV patients (85.8%) demonstrated both GMV reduction and gFCD increases along with retinal thinning compared to healthy controls. The severity of GMV reduction and gFCD increase differed between patient groups, ranked from highest to lowest severity as follows: severe AHs combined with severe VHs (FUSCHSASV, 20 patients), moderate AHs combined with severe VHs (FUSCHMASV, 23 patients), severe AHs combined with moderate VHs (FUSCHSAMV, 28 patients), and moderate AHs combined with moderate VHs (FUSCHMAMV, 26). Retinal impairment was similar among the four FUSCHAV groups. GMV reduction and gFCD increases in the frontal-parietal lobule show an inverted U-shaped pattern among FUSCHAV patients according to AH and VH severity, while retinal impairment remains stable among FUSCHAV groups. These findings indicate a reciprocal deterioration in auditory and visual disturbances among FUSCHAV patients.

Left Cerebral Cortex Complexity in Patients with Major Depression Disorder: A Small-Sample Pilot Study.

Objective: To investigate cerebral cortical complexity (CCC) in patients with first-episode, drug-naive major depressive disorder (MDD) with source-based morphometry (SBM) analyses. Methods: We used the SBM parameters gyrification index (GI) and fractal dimension (FD) to evaluate CCC in 14 first-episode, drug-naive patients diagnosed with MDD. The severity of depression symptoms was assessed with the 17-item Hamilton Depression Scale (HAMD-17). GI and FD alterations in the MDD group, relative to healthy controls (HCs), were correlated with depression symptom severity with GI/FD. Results: Increased GIs in the MDD group, relative to HCs, were found mainly in the left postcentral gyrus, whereas GI reductions were found in the left angular gyrus, left lingual gyrus, left superior temporal gyrus, and left insular cortex. Increased FDs in the MDD group, relative to HCs, were located in the superior frontal gyrus. In contrast, decreased FDs were located in the left superior temporal gyrus and left superior frontal gyrus. Conclusion: Although the group differences in GI and FD values obtained did not withstand family-wise error (FWE) correction, the results show a consistent trend of alterations in left-hemisphere CCC in first-episode, drug-naive patients diagnosed with MDD. These findings support the hypothesis that there is a pattern of subtle neocortical aberrations in early-stage MDD.

Unstructured Group Support Enhances Compliance to Pharmacological Treatment by Improving Social Cognition in Patients with Bipolar Disorder: A Pilot fMRI Study.

Objective: Unstructured group support (UGS) has been shown to improve the prognosis of patients with bipolar disorder (BP). However, objective evidence is needed to support implementation of UGS intervention. This study aimed to investigate the effectiveness of UGS intervention and the associated alterations in the objective indexes, mainly global function connectivity density (gFCD), in BP patients. Methods: Remitted BP patients were enrolled and randomly assigned into a UGS group (received UGS intervention for 26 weekly UGS sessions, and a sham group (received sham intervention). The effects of UGS on adherence to the prescribed medications, social cognition, and quality of life were examined and compared between these 2 groups. Magnetic resonance imaging (MRI) was performed to determine the functional index and gFCD values, as an objective measurement of functional alterations in the brain. Results: The compliance rate was significantly greater in the UGS group than in the sham group at the 2-year follow-up, after 26 weekly intervention sessions. The proportion of patients with increased levels of compliance to pharmacological treatment, improved social cognition, and improved quality of life were significantly higher in the UGS group than in the sham group. Furthermore, consistent with these subjective measurements, the fMRI study revealed that gFCD values significantly increased in the regions of the brain that are related to social cognition, in patients with UGS intervention. Conclusion: UGS improves the compliance to pharmacological treatment, quality of life, and social cognition of remitted BP patients. Notably, these findings offer the first objective evidence that UGS enhances gFCD in BP patients. Thus, UGS implementation can help improve the psychiatric care for BP patients.