Positive And Negative Syndrome Scale Subscales Research Articles

Mapping the Positive and Negative Syndrome Scale scores to EQ-5D-5L and SF-6D utility scores in patients with schizophrenia

ObjectiveThe current study aims to map the Positive and Negative Syndrome Scale (PANSS) onto the five-level EuroQol five-dimensional (EQ-5D-5L) and Short Form six-dimensional (SF-6D) utility scores for patients with schizophrenia.MethodsA total of 239 participants with schizophrenia spectrum disorder were recruited from a tertiary psychiatric hospital in Singapore. Ordinary least squares (OLS), censored least absolute deviations and Tobit regression methods were employed to estimate utility scores from the EQ-5D-5L and SF-6D. Model selection of the 18 regression models (three regression methods × six model specifications) was primarily determined by the smallest mean absolute error and mean square error, and the largest R2 and adjusted R2.ResultsThe mean age of the sample was 39.7 years (SD = 10.3). The mean EQ-5D-5L and SF-6D utility scores were 0.81 and 0.68, respectively. The EQ-5D-5L utility scores were best predicted by the OLS regression model consisting of three PANSS subscales, i.e. positive, negative and general psychopathology symptoms, and covariates including age and gender. The SF-6D was best predicted by OLS regression model consisting of five PANSS subscales, i.e. positive, negative, excitement, depression and cognitive subscales.ConclusionThe current study provides important evidence to clinicians and researchers on mapping algorithms for converting PANSS scores into utility scores that can be easily applicable for cost–utility analysis when EQ-5D-5L and SF-6D data are not available for patients with schizophrenia spectrum disorder in Singapore.

Specificity proteins 1 and 4 in peripheral blood mononuclear cells in postmenopausal women with schizophrenia: a 24-week double-blind, randomized, parallel, placebo-controlled trial

Accumulating evidence suggests that Specificity Protein 1 (SP1) and 4 (SP4) transcription factors are involved in the pathophysiology of schizophrenia. The therapeutic use of selective oestrogen modulators such as raloxifene added to antipsychotic drugs in the treatment of postmenopausal women with schizophrenia has been investigated in a few clinical trials, which reported an improvement in negative, positive, and general psychopathological symptoms. We aimed to investigate the possible association between peripheral SP protein levels and symptom improvement in postmenopausal women with schizophrenia treated with adjuvant raloxifene. In a subgroup of 14 postmenopausal women with schizophrenia from a 24-week, randomized, parallel, double-blind, placebo-controlled clinical trial (NCT015736370), we investigated changes in SP1 and SP4 protein levels in peripheral blood mononuclear cells. Participants were randomized to either 60mg/day adjunctive raloxifene or placebo. Psychopathological symptoms were assessed at baseline and at week 24 with the Positive and Negative Syndrome Scale (PANSS). The expression of SP proteins was evaluated by immunoblot, and changes in PANSS scores and protein levels were compared at baseline and after 24 weeks of treatment. An improvement in symptoms was observed in the intervention group, but not in placebo group. Post-treatment protein levels of SP4, but not SP1, correlated with improvements in general and total PANSS subscales in the raloxifene intervention group. A reduction in SP4 levels was found after raloxifene treatment. These results suggest that SP4 may be involved in raloxifene symptom improvement in postmenopausal women and could be a potential candidate for future studies investigating blood-based biomarkers for raloxifene effectiveness.

Aldosterone and aldosterone/cortisol ratio is higher in serum of long-term compared to first episode schizophrenia patients: A pilot study

We have previously shown that patients with severe depressive episode exhibit higher aldosterone concentrations compared to those with moderate depressive episode. The present study was undertaken to test the hypothesis that circulating concentration of aldosterone reflect the clinical state in patients with schizophrenia. The sample consisted of 36 hospitalized patients (25 men, 11 women) with the first episode or long-term course of schizophrenia. The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS). Samples for measurement of serum aldosterone were obtained immediately after awakening. The results showed that serum aldosterone concentrations were lower in patients with the first episode compared to those in patients with long-term course of schizophrenia. Importantly, lower aldosterone concentrations observed in patients with the first episode were associated with more severe clinical symptoms as indicated by all subscales of PANSS. Serum cortisol concentrations did not differ between the groups, while the aldosterone/cortisol ratio showed similar pattern as aldosterone concentrations. The present pilot study suggests that circulating aldosterone in patients with schizophrenia may reflect the severity of clinical symptoms but in an opposite direction than in patients with major depressive disorder.

The profile of cognitive impairments in chronic ketamine users

The aim of this study was to examine the cognitive function in chronic ketamine users. Factors correlated to cognition impairments were analyzed. Sixty-three chronic ketamine users and 65 healthy subjects were recruited. Cognitive function was assessed by using immediate/delayed visual reproduction (IVR/DVR) tasks, immediate/delayed logical memory (ILM/DLM) tasks, Stroop test, Wisconsin card sorting test (WCST), and continuous performance test (CPT). Psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Ketamine users performed worse than controls on the IVR, ILM, DLM, Stroop and auditory CPT tests. IVR and DVR, color-naming and color-interference-reading scores were positively correlated with education level. In ketamine users ILM scores were negatively correlated with the negative subscale of PANSS. DLM score was positively correlated with average dose of ketamine use. Word-reading score was positively correlated with education level, and negatively correlated with duration of ketamine use. False hits in auditory CPT was positively correlated with duration of ketamine use. Number of trials to complete the first category and perseverative errors on WCST were positively correlated with the duration between the test and last ketamine use. Chronic ketamine users had cognitive impairments across multiple domains.

Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia

BackgroundKetamine has been used to probe the biology of psychosis and cognitive dysfunction in humans. High levels of ketamine abuse are associated with persisting psychosis (KPP) in a minority of users. However, relatively little is known about cognitive function among KPP patients and whether the cognitive impairments associated with KPP resemble those of schizophrenia (SZ). MethodsWe recruited 149 treatment-seeking patients, including nonpsychotic ketamine users (KNP, n=51), KPP (n=23), and SZ (n=75) patients. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychopathology and the Cogstate Brief Battery to assess cognitive function including psychomotor processing speed, attention, working memory, verbal and visual learning and memory, spatial problem solving, and social-emotional cognition. ResultsKetamine-dependent patients had an extensive history of ketamine use (average duration=7.1±4.2years, average consumption=3.8±2.7g per day). Although KPP patients used relatively less average ketamine daily dose than KNP patients, KPP patients exhibited significantly greater total PANSS score and subscale scores, while these scores in KPP and SZ patients did not differ significantly. After adjusting for demographic characteristics and antipsychotic dose, KPP and SZ patients showed impairments in spatial problem solving and verbal memory compared to KNP patients, but KPP and SZ patients did not significantly differ from each other. ConclusionThese data suggest that the symptom profile and cognitive impairments associated with persisting psychosis due to chronic heavy ketamine abuse resemble those of schizophrenia, while KNP patients showed significantly less severe symptom profile and cognitive impairment than KPP and SZ.

Genetic Variants Within Molecular Targets of Antipsychotic Treatment: Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features.

Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk. Exploratory analyses were performed on (1) symptom clusters response (as measured by PANSS subscales); (2) age of onset; (3) family history; and (4) suicide history. Associations evidenced in the primary analyses did not survive to the FDR correction. Concerning SCZ risk, we partially confirmed the associations among COMT and MAPK1 genetic variants and SCZ. Finally, our exploratory analysis suggested that CHRNA7 and HTR2A genes may modulate both positive and negative symptoms responses, while PLA2G4A and SIGMAR1 may modulate respectively positive and negative symptoms responses. Moreover, GSK3B, HTR2A, PLA2G4A, and S100B variants may determine an anticipation of SCZ age of onset. Our results did not support a primary role for the genes investigated in AP response as a whole. However, our exploratory findings suggested that these genes may be involved in symptom clusters response.

Therapeutic effect of adjunctive N-acetyl cysteine (NAC) on symptoms of chronic schizophrenia: A double-blind, randomized clinical trial

BackgroundSchizophrenia is one of the most disabling psychiatric syndromes with the prevalence of 1% in the general population. Despite availability of various antipsychotics, negative symptoms and cognitive impairment are difficult to treat. In addition antipsychotic monotherapy is not effective in most of these patients. Current evidence indicates the roles of glutamatergic system in this disorder. N-acetyl cysteine (NAC) also increases extracellular glutamate. This study was conducted to evaluate the clinical effects of oral NAC as an add-on to maintenance medication for the treatment of chronic schizophrenia. Materials and methodsThis 12-week, double-blind, randomized, placebo-controlled, clinical trial was performed to determine the effectiveness of 1200mg N-acetyl cysteine as an adjunctive treatment with conventional antipsychotic medications in 84 patients with chronic schizophrenia. The subjects were evaluated with the Positive and Negative Syndrome Scale (PANSS), Mini-Mental State Examination (MMSE), and a standard neuropsychological screening test. Data were analyzed with SPSS-16 software. ResultsNAC-treated patients showed significantly improvement in the positive (F=5.47, P=0.02) and negative (F=0.20, df=1) PANSS subscale. Also the general and total PANSS score of NAC group declined over times whilst it was increased for placebo group. Regarding cognitive functions, improvement was observed in some explored areas, such as attention, short-term and working memory, executive functioning and speed of processing. There was no significant difference between the 2 groups in the frequency of adverse effects. ConclusionThe present study detected improvement in positive, negative, general and total psychopathology symptoms as well as cognitive performance with NAC treatment. It is also well-tolerated, safe and easy-to-use agent as an effective therapeutic strategy to improve outcome in schizophrenia treatment.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Tocilizumab, An Interleukin-6 Receptor Antibody, For Residual Symptoms in Schizophrenia.

Evidence from preclinical, epidemiological, and human studies indicates that inflammation, and in particular elevated interleukin-6 (IL-6) activity, may be related to clinical manifestations and pathophysiology of schizophrenia. Furthermore, studies in preclinical models suggest that decreasing IL-6 activity may mitigate or reverse some of these deficits. The purpose of this trial was to test whether an IL-6 receptor antibody, tocilizumab, would improve residual positive and negative symptoms and cognitive deficits in schizophrenia. We randomized 36 clinically stable, moderately symptomatic (i.e., Positive and Negative Syndrome Scale (PANSS) >60) individuals with schizophrenia to 3 monthly infusions of 8 mg/kg tocilizumab or placebo (normal saline). The primary outcome was effect at week 12 on the PANSS Total Score. Effects on the MATRICS, other PANSS subscales, Clinical Global Impression, and Global Assessment of Functioning were secondary outcomes. There were no observed treatment effects on any behavioral outcome measure. Baseline C-reactive protein (CRP) or cytokine levels did not predict treatment outcome, nor were there correlations between changes in these inflammatory markers and the measured outcomes. As expected, IL-6 and IL-8 increased, while CRP decreased, in the tocilizumab group compared with the placebo group. This study did not reveal any evidence that an IL-6 receptor antibody affects behavioral outcomes in schizophrenia. One potential explanation is the lack of capacity of this agent to penetrate the central nervous system. Additional trials of medications aimed at targeting cytokine overactivity that act directly on brain function and/or treatment in early-stage psychosis populations are needed.

Adolescents at ultra-high risk of psychosis in Italian neuropsychiatry services: prevalence, psychopathology and transition rate.

Studies in adolescents on ultra-high risk (UHR) and basic symptoms (BS) criteria for psychosis prediction are scarce. In Italy, early interventions in psychosis are less widespread than in other European countries. In the present study, we (1) assessed the clinical relevance of a UHR diagnosis [according to the comprehensive assessment of at-risk mental states (CAARMS) criteria] to promote the implementation of specific services for UHR adolescents into the Italian health care system; (2) described severity of positive, negative, general, and basic symptoms in UHR adolescents compared to adolescents with first-episode psychosis (FEP) and non-UHR adolescents (i.e., individuals who did not meet CAARMS criteria for UHR or FEP); and (3) investigated the predictive validity of UHR criteria in relation to BS criteria. Seventy-nine adolescents (aged 13-18years) were assessed with the CAARMS, the positive and negative syndrome scale (PANSS), and the schizophrenia proneness instrument, child and youth version (SPI-CY). Both UHR (n=25) and FEP (n=11) had significantly higher PANSS subscale scores compared to non-UHR (n=43). UHR had significantly lower PANSS-positive symptom scores than FEP, but similar global functioning and PANSS-negative symptoms and general psychopathology scores. Compared to non-UHR, both FEP and UHR had more severe thought and perception BS disturbances, and significantly more often met BS criteria. After 12months, 2 of 20 (10%) UHR had transitioned to psychosis. They also met both BS criteria. Given the uncertain outcome of UHR adolescents, future research is needed to determine whether the combined assessment of BS with UHR symptoms can improve the accuracy of psychosis prediction in adolescence.

The effect of adjunctive telmisartan treatment on psychopathology and cognition in patients with schizophrenia.

This study examined the effect of adjunctive telmisartan on psychopathology and cognition in olanzapine- or clozapine-treated patients with schizophrenia. In a 12-week randomized, double-blind, placebo-controlled study, patients diagnosed with schizophrenia or schizoaffective disorder received either telmisartan (80mg once per day) or placebo. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS), and a neuropsychological battery was used to assess cognitive performance. Assessments for psychopathology and cognition were conducted at baseline and week 12. Fifty-four subjects were randomized, and 43 completed the study (22 in the telmisartan group, 21 in the placebo group). After 12-weeks of treatment, the telmisartan group had a significant decrease in PANSS total score compared withthe placebo group (mean±SD: - 4.1±8.1 vs. 0.4±7.5, P=0.038, SCohen's d=0.57). There were no significant differences between the two groups in change from baseline to week 12 in PANSS subscale scores, SANS total score, or any cognitive measures (P>0.100). The present study suggests that adjunctive treatment with telmisartan may improve schizophrenia symptoms. Future trials with larger sample sizes and longer treatment durations are warranted.

Item Response Theory to Quantify Longitudinal Placebo and Paliperidone Effects on PANSS Scores in Schizophrenia.

As biomarkers are lacking, multi‐item questionnaire‐based tools like the Positive and Negative Syndrome Scale (PANSS) are used to quantify disease severity in schizophrenia. Analyzing composite PANSS scores as continuous data discards information and violates the numerical nature of the scale. Here a longitudinal analysis based on Item Response Theory is presented using PANSS data from phase III clinical trials. Latent disease severity variables were derived from item‐level data on the positive, negative, and general PANSS subscales each. On all subscales, the time course of placebo responses were best described with Weibull models, and dose‐independent functions with exponential models to describe the onset of the full effect were used to describe paliperidone's effect. Placebo and drug effect were most pronounced on the positive subscale. The final model successfully describes the time course of treatment effects on the individual PANSS item‐levels, on all PANSS subscale levels, and on the total score level.

P50 suppression deficits and psychopathology in Han Chinese patients with schizophrenia.

Numerous studies have reported P50 gating deficits in schizophrenia, though with mixed results. Moreover, few studies have explored the association between P50 gating deficits and psychopathology in Chinese patients with schizophrenia. In the present study, we investigated the P50 auditory sensory gating patterns and their correlations with clinical symptoms in a large sample of Han Chinese patients with schizophrenia. We assessed P50 sensory gating with a 64-channel electroencephalography system in 133 patients with schizophrenia and 148 healthy controls. The schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS). Patients with schizophrenia had a significantly higher P50 gating ratio (p<0.001), longer S1 latency (p<0.05), lower S1 amplitude (p<0.01), and lower P50 difference (p<0.001) than did controls. No significant correlations were found between the P50 gating measures and the PANSS total score or subscale scores in patients with schizophrenia. These findings suggest that the P50 sensory gating deficits identified in Chinese patients with schizophrenia may not be involved in the psychopathology of the illness.

Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation

Aripiprazole lauroxil (AL), a new long-acting injectable antipsychotic, demonstrated safety and efficacy in treating acute exacerbation symptoms of schizophrenia in a 12-week placebo-controlled trial of two doses of AL (441mg and 882mg) administered every 4weeks. We performed a post hoc analysis of this trial to evaluate the efficacy of AL in the subgroup of patients with severe psychotic symptoms, defined as those with baseline Positive and Negative Syndrome Scale (PANSS) Total score above the median score of 92 (n=309). Change from baseline to Day 85 in PANSS Total score; Positive, Negative, and General Psychopathology subscale scores; and overall response rate were assessed. Statistically significant and clinically meaningful improvements in PANSS Total score were demonstrated with AL 441mg and AL 882mg, with placebo-adjusted differences of −14.7 (p<0.0001) and −16.6 (p<0.0001), respectively. Significant and clinically meaningful findings with both doses of AL were also demonstrated for the PANSS subscales and responder rates. Overall responder rates at Day 85 were significantly greater for AL 441mg (49%; p<0.001) and 882 mg (61%; p<0.001) groups vs. placebo (18%). Common adverse events (>5%) were schizophrenia, akathisia, headache, insomnia, and anxiety. AL demonstrated robust efficacy in treatment of the subgroup of patients experiencing severe psychotic symptoms. Both doses (441mg and 882mg) were effective, with numerically greater improvement in symptoms and proportion of responders favoring the higher dose arm. Both doses had a side effect profile consistent with the known safety profile of aripiprazole.

Dopamine serotonin stabilizer RP5063: A randomized, double-blind, placebo-controlled multicenter trial of safety and efficacy in exacerbation of schizophrenia or schizoaffective disorder

The study objectives were to evaluate the efficacy, safety, tolerability, and pharmacokinetics of RP5063 versus placebo. The study was conducted in adults with acute exacerbation of schizophrenia or schizoaffective disorder. This 28-day, multicenter, placebo-controlled, double-blind study randomized 234 subjects to RP5063 15, 30, or 50mg; aripiprazole; or placebo (3:3:3:1:2) once daily. The aripiprazole arm was included solely to show assay sensitivity and was not powered to show efficacy. The primary endpoint was change from baseline to Day 28/EOT (End-of-Treatment) in Positive and Negative Syndrome Scale (PANSS) total score; secondary endpoints included PANSS subscales, improvement ≥1 point on the Clinical Global Impressions-Severity (CGI-S), depression and cognition scales.The primary analysis of PANSS Total showed improvement by a mean (SE) of −20.23 (2.65),−15.42 (2.04), and −19.21 (2.39) in the RP5063 15, 30, and 50mg arms, versus −11.41 (3.45) in the placebo arm. The difference between treatment and placebo reached statistical significance for the 15mg (p=0.021) and 50mg (p=0.016) arms.Improvement with RP5063 was also seen for multiple secondary efficacy outcomes. Discontinuation for any reason was much lower for RP5063 (14%, 25%, 12%) versus placebo (26%) and aripiprazole (35%). The most common treatment-emergent adverse events (TEAE) in the RP5063 groups were insomnia and agitation. There were no significant changes in body weight, electrocardiogram, or incidence of orthostatic hypotension; there was a decrease in blood glucose, lipid profiles, and prolactin levels.In conclusion, the novel dopamine serotonin stabilizer, RP5063 is an efficacious and well-tolerated treatment for acute exacerbation of schizophrenia or schizoaffective disorder.

Impact of alcohol and substabce use by patients with schizophrenia on burden, quality of life, anxiety and depression levels of primary caregivers

Aim: Alcohol and substance use are the most common comorbidities among patients with schizophrenia, with significantly higher levels of burden reported among primary caregivers. In this study, we aimed to assess the impact of alcohol and substance use on caregivers, and the effects of the severity of disease symptoms and certain attributes of patients and their primary caregivers on the burden, depressive symptoms, quality of life, and anxiety levels of caregivers. Methods: We recruited 100 patients with schizophrenia according to DSM-IV TR from inpatient clinics of Bakirkoy Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery and their primary caregivers from September 2010 to March 2011. The severity of patient symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). All caregivers completed the Sociodemographic and Clinical data form, The Zarit Burden Scale, Beck Depression Inventory, State-Trait Anxiety Inventory, and WHO Quality of life-BREF. Results: The ages of caregivers and patients were 23–68 and 20–65 years, respectively. The primary caregiver was the patient’s mother in 53% of cases. We found levels of burden that were significantly higher for caregivers of patients with alcohol or substance use, and these were positively correlated with the positive psychotic subscale of PANSS. Caregivers of patients without alcohol and substance use had significantly higher scores for psychological and social relationship domains of WHOQOL-BREF. Discussion: Alcohol and substance use disorder which causing more complicated and severe needs of schizophrenia patients is associated with increased level of caregiver burden, depression and anxiety levels and decreased quality of life. Our findings suggest that there is a significant relationship between caregiver burden and alcohol and substance use by patients with schizophrenia.

Music-evoked emotions in schizophrenia

Background/objectivesPrevious studies have reported that people with schizophrenia have impaired musical abilities. Here we developed a simple music-based assay to assess patient's ability to associate a minor chord with sadness. We further characterize correlations between impaired musical responses and psychiatric symptoms. MethodWe exposed participants sequentially to two sets of sound stimuli, first a C-major progression and chord, and second a C-minor progression and chord. Participants were asked which stimulus they associated with sadness, the first set, the second set, or neither. The severity of psychiatric symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Study participants were 29 patients diagnosed with schizophrenia and 29 healthy volunteers matched in age, gender and musical background. Result37.9% (95% confidence interval [CI]:19.1–56.7) of patients with schizophrenia associated the minor chord set as sad, compared with 97.9% (95%CI: 89.5–103.6) of controls. Four patients were diagnosed with treatment-resistant schizophrenia, and all four failed to associate the minor chord with sadness. Patients who did not recognize minor chords as sad had significantly higher scores on all PANSS subscales. ConclusionsA simple test allows music-evoked emotions to be assessed in schizophrenia patient, and may show potential relationships between music-evoked emotions and psychiatric symptoms.

A randomized trial of aripiprazole vs blonanserin for the treatment of acute schizophrenia and related disorders.

ObjectiveThere has been no direct comparison of aripiprazole and blonanserin for schizophrenia treatment. We conducted a 24-week, rater-masked, randomized trial of aripiprazole (6−30 mg/d) vs blonanserin (4−24 mg/d) in schizophrenia patients who were not taking any antipsychotic medication for more than 2 weeks before enrollment (UMIN000011194).MethodsThe primary outcome measure for efficacy was improvement of Positive and Negative Syndrome Scale (PANSS) total score at week 24. Secondary outcomes were PANSS subscale scores, 21-item Hamilton Rating Scale for Depression (HAMD-21) score, response rate, discontinuation rate, and individual adverse events.ResultsForty-four patients were recruited. The discontinuation rate was 86.4% in the aripiprazole group and 68.2% in the blonanserin treatment group. There was no significant difference in mean time to discontinuation between the groups. Although both treatment groups showed significant reductions in the PANSS total score, PANSS subscale scores, and HAMD-21 scores at week 24, the magnitudes of the changes did not differ between the groups. There were no significant differences in the incidences of adverse events including somnolence, extrapyramidal symptoms, prolactin-related adverse events, and weight change between the groups.ConclusionOur results suggest similar efficacy and safety profiles of aripiprazole and blonanserin in the patients with schizophrenia. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole and blonanserin in schizophrenia.

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.

Association between serum levels of bioavailable vitamin D and negative symptoms in first-episode psychosis

Total vitamin D levels had been commonly reported to be lowered in patients with chronic psychotic illnesses in countries from the higher latitudes. However, studies on patients with first episode psychosis (FEP) are limited. In this study we investigated serum concentrations of total and bioavailable vitamin D levels in FEP patients compared to healthy controls and the association between symptom severity and vitamin D components. A total of 31 FEP patients and 31 healthy controls were recruited from Institute of Mental Health, Singapore. FEP patients were identified using Structured Clinical Interview for DSM-IV Axis I disorders (SCID-1) and severity symptoms were assessed using the positive and negative syndrome scale (PANSS). Sera from participants were analyzed for total vitamin D, vitamin D-binding protein (DBP) and bioavailable vitamin D. Linear regressions were performed to examine the associations between serum total and bioavailable vitamin D and the PANSS subscales. Current study noted a significantly lower bioavailable vitamin D was in the FEP group and an association between bioavailable vitamin D and negative symptoms in FEP patients in a population with a consistent supply of sun exposure throughout the year.

Relationship between Erythrocyte Fatty Acid Composition and Psychopathology in the Vienna Omega-3 Study.

This study investigated the relationship between erythrocyte membrane fatty acid (FA) levels and the severity of symptoms of individuals at ultra-high risk (UHR) for psychosis. Subjects of the present study consisted of 80 neuroleptic-naïve UHR patients. Partial correlation coefficients were calculated between baseline erythrocyte membrane FA levels, measured by gas chromatography, and scores on the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning Scale, and Montgomery–Asberg Depression Rating Scale (MADRS) after controlling for age, sex, smoking and cannabis use. Subjects were divided into three groups according to the predominance of positive or negative symptoms based on PANSS subscale scores; membrane FA levels in the three groups were then compared. More severe negative symptoms measured by PANSS were negatively correlated with two saturated FAs (myristic and margaric acids), one ω-9 monounsaturated FA (MUFA; nervonic acid), and one ω-3 polyunsaturated FA (PUFA; docosapentaenoic acid), and were positively correlated with two ω-9 MUFAs (eicosenoic and erucic acids) and two ω-6 PUFAs (γ-linolenic and docosadienoic acids). More severe positive symptoms measured by PANSS were correlated only with nervonic acid. No associations were observed between FAs and MADRS scores. In subjects with predominant negative symptoms, the sum of the ω-9 MUFAs and the ω-6:ω-3 FA ratio were both significantly higher than in those with predominant positive symptoms, whereas the sum of ω-3 PUFAs was significantly lower. In conclusion, abnormalities in FA metabolism may contribute to the neurobiology of psychopathology in UHR individuals. In particular, membrane FA alterations may play a role in negative symptoms, which are primary psychopathological manifestations of schizophrenia-related disability.