Decreased white matter FA values in the left inferior frontal gyrus is a possible intermediate phenotype of schizophrenia: evidences from a novel group strategy.

Intermediate phenotype could be used to investigate genetic susceptibility. However, genetic and environmental heterogeneity may interfere with identification of intermediate phenotypes. In this study, we minimized these interferences by using a novel group strategy. A total of 22 drug-naive and first-episode schizophrenia (FES) patients, along with 22 of their kin healthy siblings (HS), 22 non-kin healthy siblings (nHS) of other schizophrenia patients and 22 healthy controls (HC), were recruited. Brain imaging was acquired from the participants. Voxel-based analysis was used to investigate differences in white matter integrity derived from diffusion tensor imaging among the four groups. Two cognitive tests related to our findings were selected to confirm the related phenotypic changes. All of the FES, HS, and nHS groups showed decreased fractional anisotropy (FA) values in the left inferior frontal gyrus (IFG) compared with the HC group (p < 0.05, FDR corrected). The scores of Hopkins Verbal learning Test-Revised and Animal Naming in FES patients were significantly lower than in participants belonging to the other three groups (p < 0.05). Significant correlation between Animal Naming scores and FA values in the left IFG was found in FES patients (r = 0.53, p = 0.01). Moreover, FES patients also showed decreased FA values in the left medial frontal gyrus, left inferior temporal gyrus, left parahippocampal gyrus, left posterior cingulate, and right middle temporal gyrus compared with HC (p < 0.05, FDR corrected). Decreased FA values in the left IFG is a possible intermediate phenotype of schizophrenia, and this finding supports the hypothesis that disrupted connectivity of white matter may be the key substrate of schizophrenia.

[Relationship of daytime fatigue and hyperarousal in patients with primary insomnia].

OBJECTIVE: To study the relationship between daytime fatigue and hyperarousal in patients with primary insomnia. METHODS: One hundred and sixty eighty patients with primary insomnia as research group and 149 healthy people as control group were recruited during November 2013 to December 2014 in the psychiatry department of the Third Affiliated Hospital, Sun Yat-sen University. The Hyperarousal Scale (HAS), Pre-Sleep Arousal Scale (PSAS), Fatigue scale-14 (FS-14) and a visual analogue scale (VAS) were used to evaluate the symptom of hyperarousal trait, pre-sleep arousal, daytime fatigue and self reported sleep quality respectively. RESULTS: The participants in research group had more severe symptoms of hyperarousal trait [(41.9±9.7) vs (27.6±7.0)], pre-sleep arousal [(42.0±7.3) vs (22.1±4.7)], daytime fatigue [(9.2±3.1) vs (3.0±0.7)] than those in control group. According the multiple linear regressions, the daytime fatigue in research group was positively related not only to sleep quality, but also to hyperarousal trait and pre-sleep arousal. CONCLUSION: Hyperarousal is an important factor which could affect the daytime fatigue in patients with primary insomnia and should be given more attention to.

[Levels and evaluations of physical activity using 5-A counseling model in patients with stable schizophrenia].

OBJECTIVE: To explore the levels and evaluations of physical activity (PA) using 5-A counseling model in patients with stable schizophrenia. METHODS: A total of 258 patients with stable schizophrenia during February-August in 2014 were selected as research group while 214 healthy subjects as control group. A self-formulated questionnaire was used to assess the PA levels of participants. And a 5-A counseling model (assess, advise, agree, assist and arrange) was used to evaluate the experiences and qualities of PA counseling. RESULTS: There were significantly fewer people physically active in research group than those in control group (20.1% vs 35.9%). According to the results of PA counseling experience in research group, only 29.5% patients received PA counseling. And the strategies of "advising on personal benefits and principles of intensified PA" were most frequently used while other strategies seldom used. CONCLUSION: Most patients with stable schizophrenia are physically inactive and they should receive more PA counseling.

ZNF804A rs1344706 is associated with cortical thickness, surface area, and cortical volume of the unmedicated first episode schizophrenia and healthy controls.

The effects of ZNF804A rs1344706, a prominent susceptibility gene for schizophrenia, on gray matter (GM) structure in unmedicated schizophrenia (SZ) patients are still unknown, although several previous studies investigated the effects in medicated SZ patients and healthy controls (HC). Analyzing cortical thickness, surface area, and GM volume simultaneously may provide a more precise and complete picture of the effects. We genotyped 59 unmedicated first episode SZ patients and 60 healthy controls for the ZNF804A single nucleotide polymorphism (SNP) rs1344706, and examined between-group differences in cortical thickness, surface area, and cortical volume using a full-factorial 2 × 2 analysis of variance (ANOVA). We found the risk allele (T) in ZNF804A rs1344706, compared to the non-risk allele (G), was associated with thinner cortex in the bilateral precuneus, left precentral gyrus, and several other regions, associated with a smaller cortical surface area in the left superior parietal, precuneus cortex and left superior frontal, and associated with a lower cortical volume in the left superior frontal, left precentral, and right precuneus in SZ patients. In contrast, in the controls, the T allele was associated with the increased cortical measurements compared to the G allele in the same regions as those mentioned above. ZNF804A rs1344706 has significant, but different, effects on cortical thickness, surface area, and cortical volume in multiple regions of the brain cortex. Our findings suggest that ZNF804A rs1344706 may aggravate the risk for schizophrenia by exerting its effects on cortical thickness, surface area, and cortical volume in these brain regions.

Cost-effectiveness analysis of psychosocial intervention for early stage schizophrenia in China: a randomized, one-year study.

BACKGROUND: A combination of psychosocial interventions and medications has been highly recommended as a successful treatment package for schizophrenia. Its cost-effectiveness has not been fully explored yet. The aim of the present analysis was to evaluate the cost-effectiveness of antipsychotics combined with psychosocial treatment and treatment as usual for patients with early-stage schizophrenia. METHOD: Patients with schizophrenia (N = 1, 268) were assigned to the combination of medication and psychosocial intervention or treatment as usual for up to 12 months. Cost analysis included direct medical costs, direct nonmedical costs and indirect costs. Quality-adjusted life year (QALY) ratings were assessed with Short- Form 6D. RESULTS: Average monthly psychosocial intervention costs for combined treatment were higher than treatment as usual (p = 0.005), but no significant differences were found in direct costs, indirect costs, and total costs between two groups (all p-values ≥ 0.556). Combined treatment was associated with significant higher QALY ratings than treatment as usual (p = 0.039). Compared with treatment as usual, combined treatment resulted in a gain of 0.031 QALY ratings at an additional cost of US$ 56.4, yielding an incremental cost-effectiveness ratio of US$ 1819.4 per QALY gained. CONCLUSIONS: Despite some limitations, our results supported that medication combined with psychosocial treatment was more cost-effective than treatment as usual for patients with early-stage schizophrenia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00654576.

Distinguishing schizophrenia and bipolar disorder through a Multiclass Classification model based on multimodal neuroimaging data.

This study aimed to identify neural biomarkers for schizophrenia (SZ) and bipolar disorder (BP) by analyzing multimodal neuroimaging. Utilizing data from structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI), multiclass classification models were created for SZ, BP, and healthy controls (HC). A total of 113 participants (BP: 31, SZ: 39, and HC: 43) were recruited under strict enrollment control, from which 272, 200, and 1875 features were extracted from sMRI, DTI, and rs-fMRI data, respectively. A support vector machine (SVM) with recursive feature elimination (RFE) was employed to build the models using a one-against-one approach and leave-one-out cross-validation, achieving a classification accuracy of 70.8%. The most discriminative features were primarily from rs-fMRI, along with significant findings in sMRI and DTI. Key biomarkers identified included the increased thickness of the left cuneus cortex and decreased regional functional connectivity strength (rFCS) in the left supramarginal gyrus as shared indicators for BP and SZ. Additionally, decreased fractional anisotropy in the left superior fronto-occipital fasciculus was suggested as specific to BP, while decreased rFCS in the left inferior parietal area might serve as a specific biomarker for SZ. These findings underscore the potential of multimodal neuroimaging in distinguishing between BP and SZ and contribute to the understanding of their neural underpinnings.

The relationship between obesity and neurocognitive function in Chinese patients with schizophrenia.

BACKGROUND: Studies have reported that up to 60% of individuals with schizophrenia are overweight or obese. This study explored the relationship between obesity and cognitive performance in Chinese patients with schizophrenia. METHODS: Outpatients with schizophrenia aged 18-50 years were recruited from 10 study sites across China. Demographic and clinical information was collected. A neuropsychological battery including tests of attention, processing speed, learning/memory, and executive functioning was used to assess cognitive function, and these 4 individual domains were transformed into a neurocognitive composite z score. In addition, height and weight were measured to calculate body mass index (BMI). Patients were categorized into 4 groups (underweight, normal weight, overweight and obese) based on BMI cutoff values for Asian populations recommended by the World Health Organization. RESULTS: A total number of 896 patients were enrolled into the study. Fifty-four percent of participants were overweight or obese. A higher BMI was significantly associated with lower scores on the Wechsler Memory Scale-Revised (WMS-R) Visual Reproduction subscale, the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol subscale, and the composite z score (p's ≤ 0.024). Obese patients with schizophrenia had significantly lower scores than normal weight patients on the Trail Making Test B, the WMS-R Visual Reproduction subscale, the WAIS Digit Symbol subscale, and the composite z score (p's ≤ 0.004). CONCLUSIONS: Our study suggests that, in addition to its well established risk for various cardiometabolic conditions, obesity is also associated with decreased cognitive function in Chinese patients with schizophrenia. Future studies should explore if weight loss and management can improve cognitive function in obese patients who suffer from schizophrenia.

[A study of cerebral cortex in untreated first-episode schizophrenics].

OBJECTIVE: To detect the changes of cortical thickness and cortical surface area in untreated patients of first-episode schizophrenia. METHODS: Fifty-seven untreated patients of first-episode schizophrenia (SCZ) hospitalized from September 2009 to March 2012 at Department of Psychiatry, Third Affiliated Hospital, SUN Yat-sen University and 57 healthy controls (HC) recruited by advertising during the same period underwent a high resolution three-dimensional magnetic resonance imaging of brain structures. And cortical-surface based technique was used to analyze the cortical thickness and cortical surface area. The general linear model (GLM) was employed to detect the differences of cortical thickness and cortical surface area between two groups. RESULTS: were corrected for multiple comparisons by the Monte Carlo simulation method. RESULTS: As compared with HC, the cortical thickness of left superior frontal, left caudal middle cingulate, left lateral occipital, right superior frontal, right superior temporal and right fusiform regions in SCZ decreased by 6.0%, 7.2%, 8.2%, 5.2%, 7.1% and 6.0% respectively. And the largest reductions occurred in left lateral occipital regions. Cortical surface area of each brain regions in SCZ had no significant difference with HC. CONCLUSION: Cortical thickness reductions exist in multiple brain regions in schizophrenia. It may be the neuropathological mechanisms of schizophrenia.

Calcium Involved in the Enrichment of γ-Aminobutyric Acid (GABA) in Broccoli Sprouts under Fructose Treatment.

The effect of fructose on γ-aminobutyric acid (GABA) content and its metabolic pathway in broccoli sprouts was investigated. The results demonstrated that the fructose treatment not only significantly increased the fresh weight, GABA, and glutamate contents in sprouts, but also promoted the activity of glutamic acid decarboxylase (GAD) and the expressions of BoGAD1 and BoGAD2. Meanwhile, fructose treatment inhibited the stem length of broccoli sprouts and enhanced the abscisic acid (ABA) production in comparison with the control. Ca2+, CaM contents, and BoCaM2 expression in broccoli sprouts were also stimulated after fructose treatment. Exogenous fructose increased inositol trisphosphate (IP3) content and activated the activity of phosphatidylinositol-specific phospholipase C (PI-PLC) and the expression of BoPLC2, contributing to Ca2+ influx into the cells. These results suggested that Ca2+ played an essential role in GABA enrichment under fructose treatment, which may be associated with GAD and PI-PLC.

[Diffusion tensor imaging analyses of white matter in healthy siblings of schizophrenics].

OBJECTIVE: To explore the diffusion tensor imaging (DTI) features of white matter in healthy siblings of schizophrenics. METHODS: Twenty healthy siblings of schizophrenics and 45 healthy controls without a family history of mental disorder. They responded to advertised recruitment during December 2009 and March 2012. All participants underwent diffusion weighted magnetic resonance images with a single-shot echo planar imaging (EPI) sequence aligned to straight axial plane. The fractional anisotropy (FA) images of two groups underwent two-sample t-test with SPM5 software. RESULTS: The healthy siblings of schizophrenics demonstrated a significant decrease of regional white matter FA values in right anterior cingulated (MNI: x = 9, y = 43, z = 4; cluster = 106). CONCLUSION: Reduced white matter integrity in right anterior cingulated may be a risk actor of schizophrenia.

[Diffusion tensor imaging analyses of white matter at an early stage of first-episode schizophrenia].

OBJECTIVE: To explore the roles of diffusion tensor imaging (DTI) of white matter at an early stage of schizophrenia. METHODS: The participants were 20 first-episode, medication-naïve schizophrenics at an early stage (1 - 6 months) and 20 healthy controls adjusted in gender and age during December 2009 and October 2010. They underwent diffusion weighted magnetic resonance imaging with a single-shot echo planar imaging (EPI) sequence aligned to straight axial plane. The fractional anisotropy (FA) images of two groups underwent two-sample paired t-test with SPM5 software. RESULTS: The schizophrenics at an early stage demonstrated a significant decrease of regional white matter FA values in right anterior cingulated (MNI: x = 12, y = 24, z = -10; cluster = 145) and right middle occipital lobe (MNI: x = 36, y = -76, z = -2; cluster = 135). CONCLUSION: The altered white matter DTI in right anterior cingulated and middle occipital lobe may contribute to an early detection of schizophrenia.

[Diffusion tensor imaging findings in first-episode and chronic schizophrenics].

OBJECTIVE: To investigate the integrity of white matters in first-episode and chronic schizophrenics. METHODS: For this study, 39 first-episode and 38 chronic schizophrenics, 69 healthy controls (age, gender and years of received education no significantly different from those of the patients) underwent diffusion weighted images with a single-shot echo planar imaging (EPI) sequence aligned to the straight axial plane. The fractional anisotropy (FA) images of three groups underwent one-way ANOVA with the methods of voxel-based morphometric (VBM) analysis. RESULTS: (1) There were three brain regions where the FA values of white matter were different among three groups: right caudate nucleus (MNI: 20, 12, 14; cluster = 432 voxels; FA value: 0.36 ± 0.18 vs 0.35 ± 0.24 vs 0.38 ± 0.17), left insula (MNI: -32, 18, 2; cluster = 204 voxels; FA value: 0.35 ± 0.31 vs 0.33 ± 0.24 vs 0.36 ± 0.21) and right anterior cingulate (MNI: 16, 36, 12; cluster = 132 voxels; FA value: 0.35 ± 0.29 vs 0.34 ± 0.31 vs 0.37 ± 0.25). (2) The mean FA values of the three brain regions of two patients groups decreased versus those of healthy controls (P < 0.05). (3) The mean FA values of left insular region in chronic patients decreased versus those of the first-episode patients (P < 0.05). CONCLUSION: The reduced integrity of white matter may play an etiological role in schizophrenia and the changes are probably progressive.

[Comparison of white matter integrity of schizophrenic patients with and without impulsive behaviors by diffusion tensor magnetic resonance imaging].

OBJECTIVE: To compare the regional white matter integrity of schizophrenics with impulsive behaviors versus those without. METHODS: Seventeen patients with first-episode-schizophrenia impulsive behaviors and 24 patients with first-episode-schizophrenia non-impulsive behaviors underwent diffusion weighted magnetic resonance imaging with a single-shot echo planar imaging (EPI) sequence aligned to straight axial plane. The fractional anisotropy (FA) images of two groups received two-sample t-test with SPM5 software. RESULTS: The patients with impulsive behaviors demonstrated a significant decrement of white matter FA values in left precentral gyrus (MNI: x = -28.00, y = -28.72, z = -54.71; cluster = 79 voxels), left cerebellum anterior lobe (MNI: x = -22, y = -56, z = -28; cluster = 130 voxels) and left occipital lobe (MNI: x = -6, y = -72, z = 6; cluster = 54 voxels). CONCLUSION: The altered white matter integrity of left precentral gyrus, cerebellum anterior lobe and occipital lobe may be involved in the neural mechanism of impulsive behaviors in schizophrenia.

TCM nonpharmacological interventions for ankylosing spondylitis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Ankylosing spondylitis (AS) is a common infammatory rheumatic disease that affects the axial skeleton. Traditional Chinese medicine (TCM) nonpharmacological interventions are gaining an increasing popularity for AS. Nevertheless, the evidence of efficacy and safety of random controlled trials (RCTs) remains controversial. This study aims to evaluate the efficacy and acceptability of different TCM nonpharmacological therapies by systematic review and network meta-analysis. METHODS: According to the strategy, the authors will retrieve a total of 7 electronic databases by December 2020, including PubMed, the Cochrane Library, EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chongqing VIP, and Wan-fang databases After a series of screening, 2 researchers will use Aggregate Data Drug Information System and Stata software to analyze the data extracted from the randomized controlled trials of TCM nonpharmacological interventions for AS. The primary outcome will be the improvement of Pain intensity and functional status/disability and the secondary outcomes will include lobal improvement, health-related quality of life, satisfaction with treatment, and adverse events. Both classical meta-analysis and network meta-analysis will be implemented to investigate direct and indirect evidences on this topic. The quality of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation instrument. RESULTS: This study will provide a reliable evidence for the selection of TCM nonpharmacological therapies in the treatment of AS. CONCLUSION: This study will generate evidence for different TCM nonpharmacological therapies for AS and provide a decision-making reference for clinical research. ETHICS AND DISSEMINATION: This study does not require ethical approval. The results will be disseminated through a peer-reviewed publication. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/FHD2U.

Specific white matter connectomic changes in schizophrenia compared with psychotic bipolar disorder.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder with psychosis (BDP) can be clinically confusing. The specific connectomic changes in SZ compared with BDP may lead to a deeper comprehension of the pathophysiological core of SZ. Therefore, this study explored the common and distinct white matter (WM) structural connectomic alterations between these two diseases. METHOD: Diffusion tensor imaging data were collected from 19 drug-naïve patients with first episode SZ, 19 drug-naïve patients with BDP, and 19 healthy controls (HC). A graph theoretical approach was used to assess the brain WM network properties. RESULTS: Except for the clustering coefficients, no significant differences in the global parameters was found between SZ and BDP. Five brain regions, the right precentral, right post-cingulum, right insula, left superior occipital, and left inferior temporal gyri, showed specific differences in the nodal parameters in SZ compared with BDP and HC. Nine brain regions, the left rectus, left lingual, right inferior parietal, left superior temporal, right precentral, right postcentral, bilateral middle frontal, and right post-cingulum gyri, showed specific differences in the nodal parameters in BDP. Significant correlations between clinical symptoms and connectomic changes were detected in the right insula and left superior occipital gyrus in patients with SZ but in the left lingual gyrus in patients with BDP. CONCLUSIONS: Identifying shared and distinct WM structural networks between SZ and BDP may improve the understanding of the neuroanatomy of mental diseases. Specifically, the insula, the inferior temporal, superior temporal, and the lingual gyri may help to distinguish between SZ and BDP.

The role of altered brain structural connectivity in resilience, vulnerability, and disease expression to schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is a highly heritable disorder associated with brain connectivity changes. Although the mechanism of disease expression and vulnerability of SCZ have been reported by previous studies, the mechanism of resilience to SCZ based on the brain structural connectivity is poorly understood. The goal of the present study was to identify the structural brain connectivity related with the resilience to SCZ, which is defined here as the capacity to avoid or delay the onset of SCZ in unaffected siblings of SCZ probands. METHOD: We collected diffusion tensor imaging (DTI) data of 49 medication-naive, first-episode SCZ (FE-SCZ) patients, 56 unaffected siblings of SCZ probands (SIB-SCZ), and 90 healthy controls. Then we used graph theoretical approach to calculate the topological properties of the brain structural network, including global, subnetwork, and regional parameters. Finally, we compared the parameters between the three groups, and identified the brain structural network related to the resilience, vulnerability and disease expression to SCZ. RESULTS: With respect to resilience, only the SIB-SCZ showed significantly increased connectivity in the subnetworks of the left cuneus-precuneus and left posterior cingulate gyrus-precuneus, and in brain areas of right supramarginal gyrus and right inferior temporal gyrus. With respect to vulnerability, both the FE-SCZ and SIB-SCZ had decreased cluster coefficients and local efficiency, and decreased nodal efficiency in the right medial superior frontal gyrus and right medial orbital superior frontal gyrus compared with the healthy controls. With respect to disease expression, only the FE-SCZ group showed decreased or increased global, subnetwork, and nodal connectivity in broader brain regions compared with the healthy controls. CONCLUSION: Difference in the topological properties of brain structural connectivity not only reflect the underlying mechanism of vulnerability but also that of resilience to schizophrenia. Alteration in the brain structural connectivity associating with resilience and disease expression may contribute to the onset of SCZ.

Factors related to duration of untreated psychosis of first episode schizophrenia spectrum disorder.

AIM: Duration of untreated psychosis (DUP) is associated with outcome and functioning. It is expected that scientists will find factors that modulate DUP, but thus far, research on this topic has shown inconsistent results. Furthermore, similar studies in China are insufficient. This study aims to explore social and clinical factors for DUP in South China and to learn the influence that family plays on DUP through their awareness of psychosis. METHODS: Participants included 216 patients with first episode schizophrenia spectrum disorder. The Nottingham Onset Schedule was used to assess DUP. The relationship between DUP and social and clinical characteristics were then analysed by correlation analysis, survival analysis and Cox regression analysis. The awareness of the patient's family for the cause of psychosis, the reason for treatment and the cause for delay of treatment were investigated using a questionnaire. RESULTS: The median DUP was 64.5 days. Insidious onset and being unemployed were found to be risk factors for a long DUP. The family attributed the main cause of psychosis to stress. The main cause for the delay of treatment was because families misjudged the patients' disease. More family members of long DUP patients compared to short DUP patients thought the causes were due to ideological problems or puberty, rather than to mental health. CONCLUSION: The results of this study indicated that some social or clinical characteristics influence DUP. The family's awareness plays an important role when seeking help. To reduce DUP, the public needs more knowledge of mental illness.

Up-regulated expression of oxytocin mRNA in peripheral blood lymphocytes from first-episode schizophrenia patients.

Schizophrenia (SZ) is a severe neuropsychiatric disorder with significant social cognition impairment. Increasing evidence has suggested that neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are important mediators of complex social cognition and behavior associates with SZ. In the present study, forty-three first-episode schizophrenia (FES) patients and forty-seven healthy controls (HC) were included. The peripheral mRNA expression of OXT, OXT receptor (OXTR), AVP, AVP 1a receptor (AVPR1a) and CD38 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The FES patients have a relatively higher mRNA level of OXT and OXTR genes and lower expression of AVP and CD38 genes than HC. No difference was found for AVPR1a between FES patients and HC. As for the sex difference, the mRNA expression of OXT and OXTR showed no difference in both male and female FES patients compared to HC group. The AVP and CD38 genes in female FES patients showed decreased mRNA expression than female HC. Our findings support disrupted OXT and AVP systems in the FES patients.

Decreased Functional Connectivity of Insular Cortex in Drug Naïve First Episode Schizophrenia: In Relation to Symptom Severity.

BACKGROUND: This study was to examine the insular cortical functional connectivity in drug naïve patients with first episode schizophrenia and to explore the relationship between the connectivity and the severity of clinical symptoms. METHODS: Thirty-seven drug naïve patients with schizophrenia and 25 healthy controls were enrolled in this study. A seed-based approach was used to analyze the resting-state functional imaging data. Insular cortical connectivity maps were bilaterally extracted for group comparison and validated by voxel-based morphometry (VBM) analysis. Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). RESULTS: There were significant reductions in the right insular cortical connectivity with the Heschl's gyrus, anterior cingulate cortex (ACC), and caudate (p's<0.001) in the patient group compared with the healthy control (HC) group. Reduced right insular cortical connectivity with the Heschl's gyrus was further confirmed in the VBM analysis (FDR corrected p<0.05). Within the patient group, there was a significant positive relationship between the right insula-Heschl's connectivity and PANSS general psychopathology scores (r = 0.384, p = 0.019). CONCLUSION: Reduced insula-Heschl's functional connectivity is present in drug naïve patients with first episode schizophrenia, which might be related to the manifestation of clinical symptoms.

Time to lack of persistence with pharmacological treatment among patients with current depressive episodes: a natural study with 1-year follow-up.

INTRODUCTION: Medication nonadherence remains a big challenge for depressive patients. This study aims to assess and compare the medication persistence between unipolar depression (UD) and bipolar depression (BD). METHODS: A total of 146 UD and 187 BD patients were recruited at their first index prescription. Time to lack of persistence with pharmacological treatment (defined as a gap of at least 60 days without taking any medication) was calculated, and clinical characteristics were collected. Final diagnosis was made at the end of 1-year follow-up. RESULTS: A total of 101 (69.2%) UD and 126 (67.4%) BD patients discontinued the treatment, with a median duration of 36 days and 27 days, respectively. No significant difference was found between UD and BD in terms of time to lack of persistence with pharmacological treatment. The highest discontinuation rate (>40%) occurred in the first 3 months for both groups of patients. For UD patients, those with a higher risk of suicide (odds ratio [OR] =0.696, P=0.035) or comorbidity of any anxiety disorder (OR =0.159, P<0.001) were less likely to prematurely drop out (drop out within the first 3 months), while those with onset in the summer (OR =4.702, P=0.049) or autumn (OR =7.690, P=0.012) were more likely to prematurely drop out than those with onset in the spring (OR =0.159, P<0.001). For BD patients, being female (OR =2.250, P=0.012) and having a history of spontaneous remission or switch to hypomania (OR =2.470, P=0.004) were risk factors for premature drop out, while hospitalization (OR =0.304, P=0.023) and misdiagnosis as UD (OR =0.283, P<0.001) at the first index prescription were protective factors. LIMITATION: Conservative definition of nonadherence, low representativeness of sample. CONCLUSION: Treatment discontinuation was frequently seen in patients with UD or BD, especially in the first 3 months of treatment. In spite of the similar pattern of medication persistence, UD and BD differ from each other in predictors of premature drop out.