Positive And Negative Syndrome Scale Positive Symptom Scores Research Articles

In Vivo Reactive Astrocyte Imaging in Patients With Schizophrenia Using Fluorine 18–Labeled THK5351

ImportanceIn vivo imaging studies of reactive astrocytes are crucial for understanding the pathophysiology of schizophrenia because astrocytes play a critical role in glutamate imbalance and neuroinflammation.ObjectiveTo investigate in vivo reactive astrocytes in patients with schizophrenia associated with positive symptoms using monoamine oxidase B (MAO-B)–binding fluorine 18 ([18F])–labeled THK5351 positron emission tomography (PET).Design, Setting, and ParticipantsIn this case-control study, data were collected from October 1, 2021, to January 31, 2023, from the internet advertisement for the healthy control group and from the outpatient clinics of Seoul National University Hospital in Seoul, South Korea, for the schizophrenia group. Participants included patients with schizophrenia and age- and sex-matched healthy control individuals.Main Outcomes and MeasuresStandardized uptake value ratios (SUVrs) of [18F]THK5351 in the anterior cingulate cortex (ACC) and hippocampus as primary regions of interest (ROIs), with other limbic regions as secondary ROIs, and the correlation between altered SUVrs and Positive and Negative Syndrome Scale (PANSS) positive symptom scores.ResultsA total of 68 participants (mean [SD] age, 32.0 [7.0] years; 41 men [60.3%]) included 33 patients with schizophrenia (mean [SD] age, 32.3 [6.3] years; 22 men [66.7%]) and 35 healthy controls (mean [SD] age, 31.8 [7.6] years; 19 men [54.3%]) who underwent [18F]THK5351 PET scanning. Patients with schizophrenia showed significantly higher SUVrs in the bilateral ACC (left, F = 5.767 [false discovery rate (FDR)–corrected P = .04]; right, F = 5.977 [FDR-corrected P = .04]) and left hippocampus (F = 4.834 [FDR-corrected P = .04]) than healthy controls. Trend-level group differences between the groups in the SUVrs were found in the secondary ROIs (eg, right parahippocampal gyrus, F = 3.387 [P = .07]). There were positive correlations between the SUVrs in the bilateral ACC and the PANSS positive symptom scores (left, r = 0.423 [FDR-corrected P = .03]; right, r = 0.406 [FDR-corrected P = .03]) in patients with schizophrenia.Conclusions and RelevanceThis case-control study provides novel in vivo imaging evidence of reactive astrocyte involvement in the pathophysiology of schizophrenia. Reactive astrocytes in the ACC may be a future target for the treatment of symptoms of schizophrenia, especially positive symptoms.

Sex-differential association of suicide attempts with thyroid dysfunction in first-episode and drug-naïve young major depressive disorder patients with comorbid anxiety

This study aimed to explore sex differences in the relationship between thyroid function indicators and suicide attempts in first-episode and drug-naïve young major depressive disorder (MDD) patients with comorbid anxiety (MDA). A total of 917 MDD patients (aged 18–35 years) were recruited. The Hamilton depression rating scale (HAMD-17), Hamilton anxiety rating scale (HAMA), positive and negative syndrome scale (PANSS) positive subscale and clinical global impression of severity scale (CGI-S) were used. 467 patients were classified as MDA. The prevalence of suicide attempts was 31.3% in MDA patients, which was significantly higher than that (7.3%) in MDD patients without anxiety. Compared with MDA patients without suicide attempts, MDA patients with suicide attempts were older, had a later age of onset, higher HAMD-17, HAMA, and PANSS positive symptom subscale scores, as well as higher TSH, TgAb and TPOAb levels. For male patients, TSH and TPOAb levels were independently associated with suicide attempts. For female patients, HAMA, PANSS positive symptom scores, CGI-S score and TPOAb levels were independently associated with suicide attempts. Our results suggest that the indicators of thyroid function which can predict suicide attempts in male and female MDA patients have sex differences.

Decreased serum NCAM is positively correlated with hippocampal volumes and negatively correlated with positive symptoms in first-episode schizophrenia patients

BackgroundNeural cell adhesion molecule (NCAM) plays an important role in neurodevelopmental processes and regulates hippocampal plasticity. This study investigated the relationship between the serum NCAM concentrations and hippocampal volume and psychotic symptoms in first-episode drug naïve schizophrenia (FES) patients. MethodsForty-four FES patients and forty-four healthy controls (HC) were recruited in this study. Serum concentrations of NCAM were measured by ELISA. Psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). Brain structural images were obtained using a 3T MRI Scanner and obtained T1 images were processed in order to determine hippocampal grey matter volumes. ResultsSchizophrenia patients revealed significantly decreased serum NCAM concentrations (p = 0.017), which were positively correlated with the left (r = 0.523, p < 0.001) and right (r = 0.449, p = 0.041) hippocampal volumes, but negatively correlated with the PANSS positive symptom scores (r = −0.522 p = 0.001). However, no such correlations existed in the HC group. ConclusionsThis is the first time to report that decreased serum NCAM concentrations were associated with hippocampal volumes and symptom severity in FES patients. Our data indicate that the low NCAM is possible neuropathology that is associated with the decreased hippocampus in FES patients.

Sex differences in the association between symptoms and superoxide dismutase in patients with never-treated first-episode schizophrenia

Objectives Considering the sex differences and oxidative stress in the pathophysiological mechanism of schizophrenia (SCZ), we explored the sex differences in clinical characteristics and superoxide dismutase (SOD) activity as well as their relationship in never-treated first-episode (NTFE) patients with SCZ in the Han Chinese population, which has not been reported yet. Methods Total SOD and manganese SOD (MnSOD) activities were examined in 165 NTFE patients with SCZ (male/female = 98/67) and 133 healthy controls (male/female =70/63). Psychopathological symptoms were evaluated by a five-factor model of the Positive and Negative Syndrome Scale (PANSS). Results SCZ patients had higher plasma total SOD activity than healthy controls (p < .01). In healthy controls, the total SOD activity was significantly higher in males than that in females (p < .001), but not in patients group (p > .05). Further, Multiple regression analysis revealed that in male patients, the PANSS depressive factor was independently positively correlated with MnSOD or total SOD activity (both p < .01), while in female patients, the MnSOD activity was positively related to the PANSS positive symptom score (p < .05). Conclusions Our findings indicate sex differences in the relationship between SOD activities and psychopathological symptoms in the early stage of SCZ.

Sex difference in association of symptoms and white matter deficits in first-episode and drug-naive schizophrenia

Accumulating evidence shows that disruption of white matter (WM) may be involved in the pathophysiology of schizophrenia, even at the onset of psychosis. However, very few studies have explored sex difference in its association with psychopathology in schizophrenia. This study aims to compare sex differences in clinical features and WM abnormalities in first-episode and drug-naive (FEDN) schizophrenia among Han Chinese inpatients. The WM fractional anisotropy (FA) values of the whole-brain were determined using voxel-based diffusion tensor imaging (DTI) in 39 (16 males and 23 females) FEDN patients with schizophrenia and 30 healthy controls (13 males and 17 females) matched for gender, age, and education. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).Our results showed that compared with the controls, the patients showed widespread areas of lower FA, including corpus callosum, brainstem, internal capsule, cingulate, and cerebellum (all adjusted p < 0.01). Further, male patients showed lower FA values in left cingulate (F = 4.92, p = 0.033), but higher scores on the PANSS total, positive, and general psychopathology subscale scores (all p < 0.01) than female patients. Multivariate regression analysis showed that for male patients, FA values in right corpus callosum were positively associated with the PANSS total (beta = 0.785, t = 3.76, p = 0.002) and the negative symptom scores (beta = 0.494, t = 2.20, p = 0.044), while for female patients, FA values in left cingulate were negatively associated with the PANSS positive symptom score (beta = −0.717, t = −2.25, p = 0.041). Our findings indicate sex difference in white matter disconnectivity and its association with psychopathological symptoms in an early course of schizophrenia onset.

Association between forkhead-box P2 gene polymorphism and clinical symptoms in chronic schizophrenia in a Chinese population

The forkhead-box P2 (FOXP2) gene polymorphism has been reported to be involved in the susceptibility to schizophrenia; however, few studies have investigated the association between FOXP2 gene polymorphism and clinical symptoms in schizophrenia. This study investigated whether the FOXP2 gene was associated with the development and symptoms of schizophrenia in relatively genetically homogeneous Chinese population. The FOXP2 rs10447760 polymorphism was genotyped in 1069 schizophrenia inpatients and 410 healthy controls using a case-control design. The patients' psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). We found no significant differences in the genotype and allele distributions between the patient and control groups. Interestingly, we found significant differences in PANSS total, positive symptom, and general psychopathology scores between genotypic subgroups in patients, with the higher score in patients with CC genotype than those with CT genotype (all p<0.05). After adjusting demographic and clinical variables, the difference still remained significant for the PANSS positive symptom score and general psychopathology (both p<0.05). Our findings suggest that the FOXP2 rs10447760 polymorphism may not contribute to the development of schizophrenia, but may contribute to the clinical symptoms of schizophrenia among Han Chinese.

111. Efficacy and Safety of MIN-101: A New Drug for the Treatment of Negative Symptoms in Schizophrenia. A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial

Background: To compare the efficacy, safety, and tolerability of MIN-101, a compound with high affinities for sigma 2 and 5-HT2A receptors, to placebo in treating negative symptoms, in stabilized patients with schizophrenia. Methods: This multi-national Phase 2b trial enrolled 244 patients diagnosed with schizophrenia who were symptomatically stable for ≥3 months prior to entering the trial and had scores ≥20 on the three factors negative subscale of the Positive and Negative Syndrome Scale (PANSS). Patients were randomized to monotherapy with MIN 101 32 mg/day, MIN-101 64 mg/day or placebo in a 1:1:1 ratio. The primary endpoint was the PANSS negative symptom score based on the five factors (pentagonal) model. Secondary outcomes were the three factors PANSS negative symptom subscale score, the PANSS total score, the PANSS positive symptom score, the Clinical Global Impression (CGI), the Brief Negative Symptoms Scale (BNSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Safety parameters included treatment-emergent adverse events (TEAE), clinical laboratory, vital signs, electrocardiograms, Sheehan-suicidality tracking scale (S-STS), and the Abnormal Involuntary Movement Scale (AIMS). The Mixed-Effect Model Repeated Measure (MMRM) was used for analyzing the efficacy data. Results: The three treatment groups were balanced on all demographic and illness-related baseline characteristics. Statistically significant reduction in the primary endpoint score was demonstrated for MIN-101 32 mg and 64 mg compared to placebo (P ≤ .022, ES 0.45 and ≤ .003, ES 0.58, respectively). This was supported by similar effects on most of the secondary measurements including: the PANSS three factors negative symptoms subscale, PANSS total score, CGI, BACS, CDSS, and PSP. There were no statistically significant differences in PANSS positive subscale scores between MIN 101 and placebo. No weight gain or clinically significant changes in vital sings, prolactin levels, routine laboratory values, metabolic indices and extrapyramidal symptom scores (EPS) were observed. One patient on 64 mg MIN-101 was discontinued from the trial based on a-priori established QT interval prolongation criteria and a second one following an episode of syncope. Conclusion: MIN-101 at dosages of 32 and 64 mg/day demonstrated statistically significant efficacy of medium ES in reducing negative symptoms and good tolerability in stable schizophrenia patients. Since positive symptoms and EPS did not change, the improvement in negative symptoms was not secondary to improvement in positive symptoms or EPS, suggesting that MIN-101 might be the first specific treatment to have a direct effect on negative symptoms.

Systematic review and meta-analysis of the efficacy and safety of minocycline in schizophrenia.

Our aim was to perform an updated systematic review and meta-analysis on the efficacy and safety of adjunctive minocycline as a treatment of schizophrenia. We conducted a PubMed/Scopus database search from inception to 3 February 2016 for randomized, placebo-controlled trials (RCTs), open non-randomized studies, and case reports/series evaluating minocycline in patients with schizophrenia. Random-effects meta-analysis of positive, negative, depressive, and cognitive symptom rating scales, discontinuation and adverse effects rates calculating standardized mean difference (SMD), and risk ratios±95% confidence intervals (CI 95%) were calculated. Six RCTs were eligible (minocycline n=215, placebo n=198) that demonstrated minocycline's superiority versus placebo for reducing endpoint Positive and Negative Syndrome Scale (PANSS) total scores (SMD=-0.59; CI 95%=[1.15, -0.03]; p=0.04), negative (SMD=-0.76; CI 95%=[-1.21, -0.31]; p=0.001); general subscale scores (SMD=-0.44; CI 95%=[-0.88, -0.00]; p=0.05), Clinical Global Impressions scores (SMD=-0.50; CI 95%=[-0.78, -0.22]; p<0.001); and executive functioning (SMD=0.22; CI 95%=[0.01, 0.44]; p=0.04). Endpoint PANSS positive symptom scores (p=0.13), depression rating scale scores (p=0.43), attention (p=0.47), memory (p=0.52), and motor speed processing (p=0.50) did not significantly differ from placebo, before execution of a trim-and-fill procedure. Minocycline did not differ compared to placebo on all-cause discontinuation (p=0.56), discontinuation due to inefficacy (p=0.99), and intolerability (p=0.51), and due to death (p=0.32). Data from one open-label study (N=22) and three case series (N=6) were consistent with the metaanalytic results. Minocycline appears to be an effective adjunctive treatment option in schizophrenia, improving multiple relevant disease dimensions. Moreover, minocycline has an acceptable safety and tolerability profile. However, more methodologically sound and larger RCTs remain necessary to confirm and extend these results.

Effect of Adjunctive Raloxifene Therapy on Severity of Refractory Schizophrenia in Women

A substantial proportion of women with schizophrenia experience debilitating treatment-refractory symptoms. The efficacy of estrogen in modulating brain function in schizophrenia has to be balanced against excess exposure of peripheral tissue. Raloxifene hydrochloride is a selective estrogen receptor modulator (mixed estrogen agonist/antagonist) with potential psychoprotective effects and fewer estrogenic adverse effects. To determine whether adjunctive raloxifene therapy reduces illness severity in women with refractory schizophrenia. This 12-week, double-blind, placebo-controlled, randomized clinical trial with fortnightly assessments was performed at an urban tertiary referral center and a regional center from January 1, 2006, to December 31, 2014. Participants included 56 women with schizophrenia or schizoaffective disorder and marked symptom severity despite substantial and stable antipsychotic doses. Data were analyzed using intention to treat as the basis. Adjunctive raloxifene hydrochloride, 120 mg/d, or placebo for 12 weeks. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score. Clinical response (defined as a ≥20% decrease in PANSS total score from baseline) and change in PANSS subscale scores, mood, cognition, reproductive hormone levels, and adverse events were also assessed. Of the 56 participants (mean [SD] age, 53 [7.7] years; age range, 40-70 years; mean [SD] duration of psychotic illness, 24 [11] years), 26 were randomized to raloxifene and 30 were randomized to placebo. Raloxifene produced a greater reduction in the PANSS total score relative to placebo (β = -6.37; 95% CI, -11.64 to -1.10; P = .02) and resulted in an increased probability of a clinical response (hazard ratio, 5.79; 95% CI, 1.46 to 22.97; P = .01). A significant reduction was found in the PANSS general symptom scores for the raloxifene compared with the placebo (β = -3.72; 95% CI, -6.83 to -0.61; P = .02) groups. For patients who completed the full 12-week trial, there was not a statistically significant treatment effect on PANSS positive symptom scores (β for change in raloxifene vs placebo, -1.92; 95% CI, -3.83 to 0.00; P = .05). Change in mood, cognition, and reproductive hormone levels and the rate of adverse events did not differ between groups. Raloxifene hydrochloride, 120 mg/d, reduces illness severity and increases the probability of a clinical response in women with refractory schizophrenia. This large trial of raloxifene in this patient population offers a promising, well-tolerated agent that has potential application in clinical practice. clinicaltrials.gov Identifier: NCT00361543.

Comparison of first‐episode and chronic patients diagnosed with schizophrenia: symptoms and childhood trauma

There has been considerable interest in identifying and addressing the specific needs of early-episode patients diagnosed with schizophrenia in the hope that by addressing such needs early, chronic disabilities can be avoided. One hundred twenty-eight early-episode and 571 chronic patients were compared on socio-demographic characteristics, clinical symptoms and history of childhood trauma. Symptoms were measured with the Positive and Negative Syndrome Scale (PANSS), and trauma with the short version of the Childhood Trauma Questionnaire. First-episode patients scored 9.3% higher than chronic patients on the PANSS positive symptom scale and 16.3% lower on the negative symptom scale. More first episode patients reported childhood sexual abuse (P = 0.033); however, fewer reported childhood emotional neglect (P = 0.01). Childhood trauma was associated with positive symptoms, specifically with hallucinations in first-episode patients (r = 0.174; P = 0.049). Moreover, fewer parents of first episode patients were living alone (P = 0.008). On multiple logistic regression, the first-episode patients were younger (odds ratio = 0.92), had higher PANSS positive symptom scores (odds ratio 1.04) and lower negative symptom scores (odds ratio 0.948 recalculate). More positive symptoms, fewer negative symptoms, less isolated parents and greater risk of childhood sexual abuse might warrant attention in first episode schizophrenia and perhaps should be a focus for the development of targeted interventions.

Cross-sectional assessment of the factors associated with occupational functioning in patients with schizophrenia

BackgroundStudies from other countries indicate that occupational skills training can improve the social functioning and the quality of life of patients with schizophrenia but there is little research about the relationship of occupational skills and the functional status of patients in China.AimUse a translated Chinese version of the Comprehensive Occupational Therapy Evaluation scale to evaluate occupational functining in inpatients and recently discharged patients with schizophrenia and assess the relationship of occupational functioning to demographic, clinical and cognitive measures.MethodsThirty-five inpatiens and 29 recently discharged outpatients with schizophrenia were evaluated by trained clinicals using the COTE, the Positive and Negative Syndrome Scale (PANSS) and a neuropsychological battery that included the Wisconsin Card Sorting Test (WCST), the Continuous Perfomance Test (CPT), the digit symbol-coding subtest from the Wechsler Adult Intelligence Scale (WAIS), and Trail Making Test Parts A and B (TMT-A, TMT-B).ResultsThe total score on the COTE and the three COTE dimensional scores (evaluating general behavior, interpersonal communication and task behavior) were all strongly correlated with the PANSS total score and the PANSS positive symptom, negative symptom and general pathology subscale scores (ranked correlation coefficients range from 0.40 to 0.90). The correlationship of the COTE measures was significantly greater with the PANSS negative symptom score than with the PANSS positive symptom score. The COTE scores were also significantly correlated with the Continuous Performance Test measures, the WAIS digit symbol-coding test scores and some, but not all, of the measures derived from the TMT-A, the TMT-B, and the WCST. Mutiple regression analyses found that the four COTE measures of occupational functioning were most strongly associated with either the PANSS total score or the PANSS negative symptom score and secondarily associated with time to complete TMT-B, the CPT measure on number of omissions, and the respondent's years of education.ConclusionOccupational functioning measures of inpatients and recently discharged outpatients with schizophrenia are closely related to the severity of psychiatric symptoms and, to a lesser extent, with cognitive functioning measures and duration of education.

Cross-sectional assessment of the factors associated with occupational functioning in patients with schizophrenia.

Studies from other countries indicate that occupational skills training can improve the social functioning and the quality of life of patients with schizophrenia but there is little research about the relationship of occupational skills and the functional status of patients in China. Use a translated Chinese version of the Comprehensive Occupational Therapy Evaluation scale to evaluate occupational functining in inpatients and recently discharged patients with schizophrenia and assess the relationship of occupational functioning to demographic, clinical and cognitive measures. Thirty-five inpatiens and 29 recently discharged outpatients with schizophrenia were evaluated by trained clinicals using the COTE, the Positive and Negative Syndrome Scale (PANSS) and a neuropsychological battery that included the Wisconsin Card Sorting Test (WCST), the Continuous Perfomance Test (CPT), the digit symbol-coding subtest from the Wechsler Adult Intelligence Scale (WAIS), and Trail Making Test Parts A and B (TMT-A, TMT-B). The total score on the COTE and the three COTE dimensional scores (evaluating general behavior, interpersonal communication and task behavior) were all strongly correlated with the PANSS total score and the PANSS positive symptom, negative symptom and general pathology subscale scores (ranked correlation coefficients range from 0.40 to 0.90). The correlationship of the COTE measures was significantly greater with the PANSS negative symptom score than with the PANSS positive symptom score. The COTE scores were also significantly correlated with the Continuous Performance Test measures, the WAIS digit symbol-coding test scores and some, but not all, of the measures derived from the TMT-A, the TMT-B, and the WCST. Mutiple regression analyses found that the four COTE measures of occupational functioning were most strongly associated with either the PANSS total score or the PANSS negative symptom score and secondarily associated with time to complete TMT-B, the CPT measure on number of omissions, and the respondent's years of education. Occupational functioning measures of inpatients and recently discharged outpatients with schizophrenia are closely related to the severity of psychiatric symptoms and, to a lesser extent, with cognitive functioning measures and duration of education.

Superoxide dismutase and cytokines in chronic patients with schizophrenia: association with psychopathology and response to antipsychotics

Both schizophrenia and oxidative stress have been associated with immune system abnormalities in interleukin-2 and -6 (IL-2; IL-6) and increases in superoxide dismutase (SOD) activity. These abnormalities may improve during antipsychotic drug treatment that reduces symptoms in schizophrenic patients. Subjects included 30 healthy controls (HC) and 78 schizophrenic (SCH) in-patients who were randomly assigned to 12 weeks of double-blind treatment with risperidone 6 mg/day or haloperidol 20 mg/day. Ratings using the Positive and Negative Syndrome Scale (PANSS) were correlated with blood SOD and serum IL-2 levels. SCH patients who were medication-free for 2 weeks had greater SOD, IL-2, and IL-6 levels than HC. At baseline, these SOD elevations were associated with higher PANSS total scores and the IL-2 elevations with lower PANSS positive symptom scores. The SOD and IL-2 levels in the SCH were also positively correlated. After treatment, PANSS positive symptoms and both SOD and IL-2 showed a significant decrease, but IL-6 showed no change. The SOD and IL-2 reductions were correlated with the reductions in PANSS total score, and SOD reductions also correlated with positive subscore reductions. Females showed these associations more strongly than males. Our results suggest that the dysregulation in the cytokine system and oxidative stress in patients with schizophrenia is implicated in clinical symptoms and is improved at least partially with antipsychotic treatment. The stronger associations in females deserve further study and confirmation.