Models of mild cognitive deficits in risk assessment in early psychosis.

BACKGROUND: Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations. METHODS: A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed. RESULTS: Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively. CONCLUSIONS: The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.

Effects of polygenic risk of schizophrenia on interhemispheric callosal white matter integrity and frontotemporal functional connectivity in first-episode schizophrenia.

BACKGROUND: Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. METHODS: Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. RESULTS: Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)-left inferior temporal gyrus (ITG), right IFG-left ITG, right IFG-left middle frontal gyrus (MFG), and right IFG-right MFG in the FES group. CONCLUSION: Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.

Serum angioneurin levels following electroconvulsive therapy for mood disorders.

OBJECTIVES: The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted "angioneurins") that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD. METHODS: A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no-ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor-2, nerve growth factor (NGF), and insulin-like growth factor-1 levels in blood samples were performed at baseline and week 8. RESULTS: Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p = 0.002). No significant changes in angioneurin levels were observed in the no-ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction. CONCLUSIONS: This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.

Integrating Amorphous Molybdenum Sulfide Nanosheets with a Co9S8@Ni3S2 Array as an Efficient Electrocatalyst for Overall Water Splitting.

It is highly challenging to design low-cost, efficient electrocatalysts for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Herein, a hierarchical heterostructure was constructed on three-dimensional (3D) Ni foam, which contains Ni3S2 nanorods decorated with both Co9S8 and amorphous MoSx nanosheets and Ni3S2 nanowires decorated with amorphous MoSx nanosheets, namely, MoSx@Co9S8@Ni3S2/NF. The synergistic effects from the strong interactions of the heterointerface and unique hierarchical heterostructure endow the MoSx@Co9S8@Ni3S2/NF with abundant active sites and effective mass and electron transport pathways, resulting in excellent activity toward both HER and OER in 1 M KOH. It only gives a low overpotential of 76.5 mV to achieve 10 mA cm-2 for HER and a low overpotential of 310 mV to achieve 100 mA cm-2 for OER. Based on the superior catalytic activity of MoSx@Co9S8@Ni3S2/NF for OER and HER, we demonstrated the activity of overall water splitting using MoSx@Co9S8@Ni3S2/NF as both the anode and cathode. It shows a higher catalytic activity for overall water splitting with a low cell voltage of 1.52 V at 10 mA cm-2 than commercial Pt/C/NF||IrO2/NF (1.61 V) and superior stability. This work provides a platform for the design and preparation of efficient electrocatalysts with various hierarchical heterostructures.

Further evidence that antipsychotic medication does not prevent long-term psychosis in higher-risk individuals.

OBJECTIVE: Although existing guidelines have discouraged use of antipsychotics for general clinical high-risk (CHR) individuals, it is unclear if antipsychotics can prevent psychosis in higher-risk population. We aimed to study the comparative real-world effectiveness of antipsychotic treatments for preventing psychosis in higher-risk CHR individuals. METHODS: A total of 300 CHR individuals were identified using the structured interview for prodromal syndromes (SIPS) and followed the participants for 3 years. In total, 228(76.0%) individuals completed baseline assessments using the NAPLS-2 risk calculator (NAPLS-2-RC), and 210(92.1%) completed the follow-up. The sample was further stratified according to risk level. "Higher-risk" was defined based on the NAPLS-2-RC risk score (≥ 20%) and SIPS positive symptom total scores (≥ 10). The main outcome was conversion to psychosis and poor functional outcomes, defined as a global assessment of function (GAF) score lower than 60 at follow-up. RESULTS: In higher-risk CHR individuals, we found no significant difference in the rate of conversion to psychosis or poor functional outcomes between the antipsychotic and no-antipsychotic groups. Low-risk individuals treated with antipsychotic drugs were more likely exhibit poor functional outcomes compared with the no-antipsychotics group(NAPLS-2-RC estimated risk: χ2 = 8.330, p = 0.004; Positive symptom severity: χ2 = 12.997, p < 0.001). No significant effective factors were identified for prevention of the conversion to psychosis; conversely, CHR individuals who were treated with high dose antipsychotics (olanzapine, aripiprazole) showed a significantly increased risk of poor functional outcomes. CONCLUSIONS: In CHR individuals, antipsychotic treatment should be provided with caution because of the risk of poor functional outcomes. Further, antipsychotic treatment does not appear to prevent onset of psychosis in real-world settings.

Conversion to psychosis in adolescents and adults: similar proportions, different predictors.

BACKGROUND: Age effects may be important for improving models for the prediction of conversion to psychosis for individuals in the clinical high risk (CHR) state. This study aimed to explore whether adolescent CHR individuals (ages 9-17 years) differ significantly from adult CHR individuals (ages 18-45 years) in terms of conversion rates and predictors. METHOD: Consecutive CHR individuals (N = 517) were assessed for demographic and clinical characteristics and followed up for 3 years. Individuals with CHR were classified as adolescent (n = 244) or adult (n = 273) groups. Age-specific prediction models of psychosis were generated separately using Cox regression. RESULTS: Similar conversion rates were found between age groups; 52 out of 216 (24.1%) adolescent CHR individuals and 55 out of 219 (25.1%) CHR adults converted to psychosis. The conversion outcome was best predicted by negative symptoms compared to other clinical variables in CHR adolescents (χ2 = 7.410, p = 0.006). In contrast, positive symptoms better predicted conversion in CHR adults (χ2 = 6.585, p = 0.01). CONCLUSIONS: Adolescent and adult CHR individuals may require a different approach to early identification and prediction. These results can inform the development of more precise prediction models based on age-specific approaches.

Calculating individualized risk components using a mobile app-based risk calculator for clinical high risk of psychosis: findings from ShangHai At Risk for Psychosis (SHARP) program.

BACKGROUND: Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program. METHOD: In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC. RESULTS: The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal. CONCLUSIONS: The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention.

Individualized risk components guiding antipsychotic delivery in patients with a clinical high risk of psychosis: application of a risk calculator.

BACKGROUND: Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics. METHODS: Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher). RESULTS: In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment. CONCLUSIONS: Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use.

Subtypes of Clinical High Risk for Psychosis that Predict Antipsychotic Effectiveness in Long-Term Remission.

INTRODUCTION: In a previous report, we used canonical correlation analysis to classify individuals with clinical high risk (CHR) of psychosis into the 3 subtypes: subtype-1, characterized by extensive negative symptoms and cognitive deficits, appeared to have the highest risk for conversion to psychosis; subtype-2, characterized by thought and behavioral disorganization, with moderate cognitive impairment; subtype-3, characterized by the mildest symptoms and cognitive deficits. The present study attempted to identify these subtypes' response to antipsychotic (AP) treatment. METHODS: A total of 289 individuals with CHR were identified and followed up for 2 years. Individuals with CHR were classified by subtype. Use of APs was examined at 2-month, 1-year, and 2-year follow-up interviews that inquired after the subjects' medication history since the first visit. The main outcome was remission, determined according to global assessment of function (GAF) score (i. e., functional outcome) and SIPS positive symptom score (symptomatic outcome) at the follow-up points. RESULTS: Among the 289 individuals with CHR included in the current analysis, 223 (77.2%) were treated using APs for at least 2 weeks during the follow-up period. Individuals with CHR tended to show significant improvement in both symptoms and function after 2 years, but subtypes exhibited significantly different trajectories. Subtype status can predict AP treatment outcome in terms of remission. The likelihood of remission differed significantly among the subtype groups. The remission rates for individuals with subtypes 1-3 treated using AP were 13.5%, 36.1%, and 67.0%, respectively. DISCUSSION: These subtypes may be of clinical value in AP treatment decision-making in the CHR population.

When to initiate antipsychotic treatment for psychotic symptoms: At the premorbid phase or first episode of psychosis?

OBJECTIVE: Antipsychotic drugs are widely used for treating patients with first episode of psychosis, targeting threshold psychotic symptoms. The clinical high risk of psychosis is characterized as subthreshold psychotic symptoms and it is unclear whether they can also benefit from antipsychotic drugs treatment. This study attempted to determine whether initiating antipsychotic drugs treatment in the clinical high risk of psychosis phase was superior to initiating antipsychotic drugs treatment in the first episode of psychosis phase, after the 2-year symptomatic and functional outcomes. METHOD: Drawing on 517 individuals with clinical high risk of psychosis from the ShangHai At Risk for Psychosis program, we identified 105 patients who converted to first episode of psychosis within the following 2 years. Patients who initiated antipsychotic drugs while at clinical high risk of psychosis (CHR_AP; n = 70) were compared with those who initiated antipsychotic drugs during a first episode of psychosis (FEP_AP; n = 35). Summary scores on positive symptoms and the global function scores at baseline and at 2 months, 1 year and 2 years of follow-up were analyzed to evaluate outcomes. RESULTS: The CHR_AP and FEP_AP groups were not different in the severity of positive symptoms and functioning at baseline. However, the CHR_AP group exhibited significantly more serious negative symptoms and total symptoms than the FEP_AP group. Both groups exhibited a significant reduction in positive symptoms and function (p < 0.001). Repeated-measures analysis of variance revealed group by time interaction for symptomatic (F = 3.196, df = 3, p = 0.024) and functional scores (F = 7.306, df = 3, p < 0.001). The FEP_AP group showed higher remission rates than the CHR_AP group (χ2 = 22.270, p < 0.001). Compared to initiating antipsychotic drug treatments in the clinical high risk of psychosis state, initiating antipsychotic drugs treatments in the first episode of psychosis state predicted remission in a regression model for FEP_AP (odds ratio = 5.567, 95% confidence interval = [1.783, 17.383], p = 0.003). CONCLUSION: For clinical high risk of psychosis, antipsychotic drugs might be not the first choice in terms of long-term remission, which is more reasonable to use at the first episode of psychosis phase.

An Open-label Trial of Adjuvant High-frequency Left Prefrontal Repetitive Transcranial Magnetic Stimulation for Treating Suicidal Ideation in Adolescents and Adults With Depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) offers promise for the treatment of depression, yet its potential impact on suicidal ideation (SI), particularly in adolescents, has not been well studied. This study aimed to investigate the efficacy of add-on rTMS for reducing SI in a large clinical sample experiencing an acute phase of depression. METHODS: This study included 146 patients with a score of ≥14 on the 17-item Hamilton Rating Scale for Depression (HAMD). Among them, 97 had a HAMD-SI (3-item) score of 1 or greater and were pooled into the analysis. Symptoms of depression and SI were measured using the HAMD total score and HAMD-SI score. Comparisons of clinical improvement for both SI and rates of remission were made between adolescent (n = 29) and adult patients (n = 68), as well as between high-frequency (HF) rTMS on the left dorsolateral prefrontal cortex (DLPFC) (80 trains, 30 pulses per train, 12 s intertrain interval, 2400 pulses per session) and low-frequency (LF) rTMS on the right DLPFC protocol (2 trains, 700 pulses per train, 1 s intertrain-interval, 1400 pulses per session), power (intensity) level of 120% of motor threshold (MT), and 5 sessions per week for 2 weeks. RESULTS: Add-on rTMS treatment showed significant clinical improvement in SI, and was also well tolerated, with no adverse events reported. The SI improvements and remission rates were more significant in adolescents treated with the HF left DLPFC rTMS protocol, compared with adults treated with the LF right DLPFC rTMS protocol (remission rates: adolescent with LF right DLPFC, 50%; adolescent with HF left DLPFC, 94%; adult with LF right DLPFC, 65%; adult with HF left DLPFC, 57%). A positive association between improvement in the HAMD total score and HAMD-SI score was found in adults, but not in adolescents. CONCLUSIONS: Add-on rTMS treatment for SI associated with depression is promising with respect to safety and feasibility. Our preliminary evidence supports an extension of the application of rTMS to adolescent patients with SI during the acute phase of depression, in addition to its use in adult treatment-resistant depression.

Poor functional recovery is better predicted than conversion in studies of outcomes of clinical high risk of psychosis: insight from SHARP.

BACKGROUND: Few of the previous studies of clinical high risk of psychosis (CHR) have explored whether outcomes other than conversion, such as poor functioning or treatment responses, are better predicted when using risk calculators. To answer this question, we compared the predictive accuracy between the outcome of conversion and poor functioning by using the NAPLS-2 risk calculator. METHODS: Three hundred CHR individuals were identified using the Chinese version of the Structured Interview for Prodromal Symptoms. Of these, 228 (76.0%) completed neurocognitive assessments at baseline and 199 (66.3%) had at least a 1-year follow-up assessment. The latter group was used in the NAPLS-2 risk calculator. RESULTS: We divided the sample into two broad categories based on different outcome definitions, conversion (n = 46) v. non-conversion (n = 153) or recovery (n = 138) v. poor functioning (n = 61). Interestingly, the NAPLS-2 risk calculator showed moderate discrimination of subsequent conversion to psychosis in this sample with an area under the receiver operating characteristic curve (AUC) of 0.631 (p = 0.007). However, for discriminating poor functioning, the AUC of the model increased to 0.754 (p < 0.001). CONCLUSIONS: Our results suggest that the current risk calculator was a better fit for predicting a poor functional outcome and treatment response than it was in the prediction of conversion to psychosis.

Insula shows abnormal task-evoked and resting-state activity in first-episode drug-naïve generalized anxiety disorder.

BACKGROUND: Interoception is associated with neural activity in the insula of healthy humans. On the basis of the somatic symptoms in generalized anxiety disorder (GAD), especially abnormal heartbeat perception, we hypothesized that abnormal activity in the insula was associated with interoceptive awareness in patients with GAD. METHODS: We investigated the psychological correlates of interoceptive awareness in a sample of 34 patients with first-onset, drug-naïve GAD and 30 healthy controls (HCs). Furthermore, we compared blood oxygenation level-dependent responses between the two groups during a heartbeat perception task to assess task-evoked activity and its relationship with psychological measures. We also examined between-group differences in insular subregions resting-state functional connectivity (rsFC), and its relationship with anxiety severity. RESULTS: Patients with GAD had significantly higher body perception scores than HCs. They also exhibited greater task-evoked activity in the left anterior insula, left posterior insula, and right anterior insula during interoceptive awareness than HCs. Left anterior insula activity was positively correlated with body awareness in patients with GAD, and rsFC between the left anterior insula and left medial prefrontal gyrus was negatively correlated with somatic anxiety severity. CONCLUSIONS: Investigating a sample of first-episode, drug-naïve patients, our study demonstrated abnormal interoceptive awareness in patients with GAD and that this was related to abnormal anterior insular activity during both rest and task. These results shed new light on the psychological and neural substrates of somatic symptoms in GAD, and they may serve to establish abnormal interoceptive awareness as a neural and psychological marker of GAD.

Real-world effectiveness of antipsychotic treatment in psychosis prevention in a 3-year cohort of 517 individuals at clinical high risk from the SHARP (ShangHai At Risk for Psychosis).

OBJECTIVE: Antipsychotics are widely used for treating psychosis, but it is unclear whether they can also prevent psychosis. This study attempted a longitudinal evaluation of antipsychotics under real-world conditions in China to evaluate their effect on the rate of conversion to psychosis in individuals with a clinical high risk (CHR) of psychosis. METHOD: A total of 517 CHR individuals were recruited between 2011 and 2016 and followed up for 3 years. Among these, 450 (87.0%) individuals completed follow-up, 108 (24.0%) showed conversion to psychosis and 309 (68.7%) received antipsychotics. The main outcome was conversion to psychosis. The sample was further stratified according to the severity of positive symptoms. RESULTS: Patients who did not receive antipsychotics showed a lower conversion rate than those who did (17.7% vs 26.9%; odds ratio [OR] = 0.660, 95% confidence interval [CI] = [0.442, 0.985], p = 0.035). In mild CHR cases, antipsychotic treatment was more likely to be associated with conversion to psychosis, compared with the no-antipsychotics group, with no such difference observed in severe CHR cases. Among those who received antipsychotics, monotherapy or low-dose treatment was associated with lower conversion rates. Our results did not favor any specific type of antipsychotics and suggested that a very small subgroup of CHR individuals with severe positive and general symptoms but mild negative symptoms may benefit from antipsychotic treatment. CONCLUSIONS: Administration of antipsychotics to CHR patients is potentially harmful with no preventive benefits. We do not recommend antipsychotic treatment for CHR individuals, which is practiced widely in China, and strongly advise caution if these drugs are used.

Clinical subtypes that predict conversion to psychosis: A canonical correlation analysis study from the ShangHai At Risk for Psychosis program.

OBJECTIVE: Since only 30% or fewer of individuals at clinical high risk convert to psychosis within 2 years, efforts are underway to refine risk identification strategies to increase their predictive power. The clinical high risk is a heterogeneous syndrome presenting with highly variable clinical symptoms and cognitive dysfunctions. This study investigated whether subtypes defined by baseline clinical and cognitive features improve the prediction of psychosis. METHOD: Four hundred clinical high-risk subjects from the ongoing ShangHai At Risk for Psychosis program were enrolled in a prospective cohort study. Canonical correlation analysis was applied to 289 clinical high-risk subjects with completed Structured Interview for Prodromal Syndromes and cognitive battery tests at baseline, and at least 1-year follow-up. Canonical variates were generated by canonical correlation analysis and then used for hierarchical cluster analysis to produce subtypes. Kaplan-Meier survival curves were constructed from the three subtypes to test their utility further in predicting psychosis. RESULTS: Canonical correlation analysis determined two linear combinations: (1) negative symptom and functional deterioration-related cognitive features, and (2) Positive symptoms and emotional disorganization-related cognitive features. Cluster analysis revealed three subtypes defined by distinct and relatively homogeneous patterns along two dimensions, comprising 14.2% (subtype 1, n = 41), 37.4% (subtype 2, n = 108) and 48.4% (subtype 3, n = 140) of the sample, and each with distinctive features of clinical and cognitive performance. Those with subtype 1, which is characterized by extensive negative symptoms and cognitive deficits, appear to have the highest risk for psychosis. The conversion risk for subtypes 1-3 are 39.0%, 11.1% and 18.6%, respectively. CONCLUSION: Our results define important subtypes within clinical high-risk syndromes that highlight clinical symptoms and cognitive features that transcend current diagnostic boundaries. The three different subtypes reflect significant differences in clinical and cognitive characteristics as well as in the risk of conversion to psychosis.

Antidepressant Effect of Adjunct Repetitive Transcranial Magnetic Stimulation in Inpatients 60 Years and Older.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is now an established, safe, and effective treatment for adults with depression. However, specific research in rTMS for use in elderly patients with acute depression is scarce. OBJECTIVE: The aim of the present study was to investigate the efficacy of add-on rTMS in a clinical sample of older adults experiencing an acute phase of depression. METHOD: This study examined 114 patients (54 elderly [aged ≥60] and 60 adults [aged 18-59]) with acute depression who were drug free at baseline. They were treated with at least 10 sessions of rTMS for 4 weeks along with 1 antidepressant. Symptoms of depression were measured using the Hamilton Rating Scale for Depression at baseline and after 2 and 4 weeks of treatment. Clinical improvement and rates of response and remission were compared across groups. RESULTS: Significant improvement was noted after 2 and 4 weeks of treatment in both adult and elderly groups. Higher remission rates were found in adult patients but with no differences in response. The stimulation intensity and course of illness were significant predictors of remission after 4 weeks of rTMS treatment in the elderly. CONCLUSIONS: The add-on rTMS treatment for elderly depression patients is promising with respect to safety and feasibility. This preliminary evidence supports the application of rTMS to this group during acute episodes.

Prediction of psychosis in prodrome: development and validation of a simple, personalized risk calculator.

BACKGROUND: This study aim to derive and validate a simple and well-performing risk calculator (RC) for predicting psychosis in individual patients at clinical high risk (CHR). METHODS: From the ongoing ShangHai-At-Risk-for-Psychosis (SHARP) program, 417 CHR cases were identified based on the Structured Interview for Prodromal Symptoms (SIPS), of whom 349 had at least 1-year follow-up assessment. Of these 349 cases, 83 converted to psychosis. Logistic regression was used to build a multivariate model to predict conversion. The area under the receiver operating characteristic (ROC) curve (AUC) was used to test the effectiveness of the SIPS-RC. Second, an independent sample of 100 CHR subjects was recruited based on an identical baseline and follow-up procedures to validate the performance of the SIPS-RC. RESULTS: Four predictors (each based on a subset of SIPS-based items) were used to construct the SIPS-RC: (1) functional decline; (2) positive symptoms (unusual thoughts, suspiciousness); (3) negative symptoms (social anhedonia, expression of emotion, ideational richness); and (4) general symptoms (dysphoric mood). The SIPS-RC showed moderate discrimination of subsequent transition to psychosis with an AUC of 0.744 (p < 0.001). A risk estimate of 25% or higher had around 75% accuracy for predicting psychosis. The personalized risk generated by the SIPS-RC provided a solid estimate of conversion outcomes in the independent validation sample, with an AUC of 0.804 [95% confidence interval (CI) 0.662-0.951]. CONCLUSION: The SIPS-RC, which is simple and easy to use, can perform in the same manner as the NAPLS-2 RC in the Chinese clinical population. Such a tool may be used by clinicians to counsel appropriately their patients about clinical monitor v. potential treatment options.

Relationship between duration of untreated prodromal symptoms and symptomatic and functional recovery.

Our previous study has found that a long duration of untreated prodromal symptoms (DUPrS) does not increase the conversion risk to psychosis in individuals with attenuated psychosis syndrome (APS). However, whether a long DUPrS will lead to other poor outcomes remains unknown. The purpose of this study was to analyse the association between the DUPrS and outcomes (symptomatic and functional recovery) in APS population. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. Of total 391 individuals, 334 were followed up for 2 years to assess clinical outcome, 82 (24.6%) had shown conversion to psychosis, 79 (23.7%) met the criteria of poor functioning outcome, and 145 (43.4%) met the criteria of poor symptomatic outcome. A significant correlation between GAF scores and DUPrS was observed in the non-converter group, but not in the converters. Individuals with APS who had a longer DUPrS were correlated with poorer functional outcome. However, it was not correlated with poorer symptomatic outcome. While a longer DUPrS was not related to poor symptomatic outcome, it was significantly related to poor functional outcome. Our findings highlight the importance of reducing DUPrS to decrease future functional impairment in populations at risk for psychosis.

Frequency of narcissistic personality disorder in a counseling center population in China.

BACKGROUND: Narcissistic personality disorder (NPD) has never been applied in Chinese clinical practice, and the distribution of NPD in the clinical population of China is largely unknown. The current study uses two-stage clinic-based screening to investigate the frequency and clinical features of NPD in a Chinese help-seeking sample. METHODS: A total of 1402 consecutive outpatients ages 18-60 were recruited during their visit to the Shanghai Mental Health Center and screened with the Personality Diagnostic Questionnaire Fourth Edition Plus (PDQ-4+) and Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis II (SCID-II). The structured clinical interview was administered to estimate the rate of NPD and the frequency of each disorder criterion. RESULTS: The frequency estimate of NPD in the total sample was 4.0%. Among the 56 outpatients who met the criteria for NPD, there were more males than females, and many had a better educational background. The SCID-II interviews revealed high frequencies of diagnostic criterion 1 ("exaggerated sense of self-importance. NPD likely overlaps with Histrionic PD, Borderline PD, and Paranoid PD. This two stage screening method can enhance detection of Chinese NPD patients in clinical settings. CONCLUSIONS: Narcissism pathology is not rare in the Chinese psychiatric community when using the DSM-IV NPD criteria. Existing evidence suggests, at least indirectly, that there are important benefits of NPD diagnosis in psychiatric practice.

Duration of untreated prodromal symptoms in a Chinese sample at a high risk for psychosis: demographic, clinical, and outcome.

BACKGROUND: The duration of untreated psychosis (DUP) has been widely studied. However, for individuals with attenuated psychosis syndrome (APS), it is unclear whether the duration of untreated prodromal symptoms (DUPrS) also has a negative effect on the progression of psychosis. Our aim was to identify demographic and clinical factors contributing to the DUPrS in a large sample of individuals with APS, and to evaluate the association between DUPrS and the conversion to psychosis. METHOD: A sample of 391 individuals with APS, who were identified through a structured interview for prodromal syndromes, were included in this study, of whom a total of 334 patients had completed at least a 1-year clinical follow-up. A total of 57 individuals had converted to psychosis. RESULTS: The average DUPrS was 4.8 months for the whole sample. Individuals with a longer DUPrS were likely to be men, non-local residents, with abnormal thought symptoms, a higher severity level of negative symptoms, the lower severity level of general symptoms, and lower level of general function before the onset of attenuated positive symptoms. A DUPrS of less than 2 months, or more than 6 months, lowered the risk for conversion to psychosis. CONCLUSIONS: Our data suggested that the association between the DUPrS and outcome in individuals with APS were likely to be different, which is either long or short DUPrS was not related to future psychosis onset. Individuals with APS were more likely to have a group of features associated with a longer DUPrS.