Positive Symptom Items Research Articles

M23. ALTERATION OF REGIONAL CEREBRAL BLOOD FLOW MEASURED BY ARTERIAL SPIN LABELING IN PATIENTS WITH TREATMENT-RESISTANT SCHIZOPHRENIA

BackgroundApproximately 30% of patients with schizophrenia do not respond to antipsychotics, which is called treatment-resistant schizophrenia (TRS). A recent systematic review showed decreased regional cerebral blood flow (rCBF) in the cerebral cortex and increased rCBF in the putamen in patients with schizophrenia. However, to date, no study has examined rCBF using arterial spin labeling (ASL) in patients with TRS. Thus, we compared rCBF between patients with TRS and those with non-TRS to investigate neural basis of this condition.MethodsWe acquired whole-brain rCBF measurements using 1.5T magnetic resonance imaging (MRI) with pseudo-continuous ASL in those with TRS and non-TRS. TRS was defined as 1) a Clinical Global Impression Severity (CGI-S) score of ≧ 4 (moderate) and 2) a score of ≧ 4 (moderate) on two Positive and Negative Syndrome Scale (PANSS) positive symptom items after optimal antipsychotic treatment. Non-TRS was defined as 1) a CGI-S score of ≦3, 2) scores of ≦ 3 on all positive symptom items of the PANSS, and 3) no symptomatic relapse during the previous 3 months. Optimal antipsychotic treatment was defined as ≧ 6 consecutive weeks with ≧ 400 mg of chlorpromazine (CPZ) equivalent daily dose antipsychotic treatment. The rCBF maps were subsequently derived from the proton-density-weighted reference images. Group differences in rCBF between the two groups (non-TRS vs. TRS) were tested using two sample t-test with age, gender, and PANSS positive scores as covariates. Multiple comparisons were corrected using familywise error (FWE) method with a significance threshold of P <.05.ResultsA total of 32 participants were included (13 TRS [6 females, age= 41.2±9.8, PANSS=80.3±9.7] and 19 non-TRS [6 females, age= 40.6±11.9, PANSS=58.9±10.0]). rCBF in the cerebellum was increased in the TRS group compared with the non-TRS group. In addition, there are inverse correlation between rCBF in the cerebellum and PANSS positive score in the non-TRS group.DiscussionThese preliminary results suggest that perfusion in the cerebellum may be implicated in the pathophysiology of TRS. This study will continue to enroll participants (our target sample is 30/each group). To identify the abnormal rCBF in patients with TRS will facilitate elucidating the pathophysiology of TRS and pave a way of developing novel treatment of this difficult-to-treat population.

T212. LEVELS OF GLUTAMATERGIC NEUROMETABOLITES IN PATIENTS WITH SEVERE TREATMENT-RESISTANT SCHIZOPHRENIA: A PROTON MAGNETIC RESONANCE SPECTROSCOPY STUDY

BackgroundApproximately 30% of patients with schizophrenia do not respond to antipsychotics and are thus considered to have treatment-resistant schizophrenia (TRS). To date, only four studies have examined glutamatergic neurometabolite levels using proton magnetic resonance spectroscopy (1H-MRS) in patients with TRS, collectively suggesting that glutamatergic dysfunction may be implicated in the pathophysiology of TRS. Notably, the TRS patient population in these studies had mild to moderate illness severity, which is not entirely reflective of what is observed in clinical practice.MethodsIn this present work, we compared glutamate+glutamine (Glx) levels in the dorsal anterior cingulate cortex (dACC) and caudate among patients with TRS, patients with non-TRS, and healthy controls (HCs), using 3T 1H-MRS (PRESS, TE=35ms). TRS criteria were defined by severe positive symptoms (i.e. ≥5 on 2 Positive and Negative Syndrome Scale (PANSS) positive symptom items or ≥4 on 3 PANSS positive symptom items) despite standard antipsychotic treatment.ResultsA total of 95 participants were included (29 TRS patients [PANSS=111.2±20.4], 33 non-TRS patients [PANSS=49.8±13.7], and 33 HCs). dACC Glx levels were higher in the TRS group versus HCs (group effect: F[2,75]=4.74, p=0.011; TRS vs. HCs: p=0.012). No group differences were identified in the caudate. There were no associations between Glx levels in these regions and clinical severity in either patient group.DiscussionOur results confirm that higher dACC Glx might be related to the pathophysiology underlying TRS, by demonstrating this phenomenon in a TRS patient population reflective of clinical practice.

Levels of glutamatergic neurometabolites in patients with severe treatment-resistant schizophrenia: a proton magnetic resonance spectroscopy study.

Approximately 30% of patients with schizophrenia do not respond to antipsychotics and are thus considered to have treatment-resistant schizophrenia (TRS). To date, only four studies have examined glutamatergic neurometabolite levels using proton magnetic resonance spectroscopy (1H-MRS) in patients with TRS, collectively suggesting that glutamatergic dysfunction may be implicated in the pathophysiology of TRS. Notably, the TRS patient population in these studies had mild-to-moderate illness severity, which is not entirely reflective of what is observed in clinical practice. In this present work, we compared glutamate + glutamine (Glx) levels in the dorsal anterior cingulate cortex (dACC) and caudate among patients with TRS, patients with non-TRS, and healthy controls (HCs), using 3T 1H-MRS (PRESS, TE = 35 ms). TRS criteria were defined by severe positive symptoms (i.e., ≥5 on 2 Positive and Negative Syndrome Scale (PANSS)-positive symptom items or ≥4 on 3 PANSS-positive symptom items), despite standard antipsychotic treatment. A total of 95 participants were included (29 TRS patients [PANSS = 111.2 ± 20.4], 33 non-TRS patients [PANSS = 49.8 ± 13.7], and 33 HCs). dACC Glx levels were higher in the TRS group vs. HCs (group effect: F[2,75] = 4.74, p = 0.011; TRS vs. HCs: p = 0.012). No group differences were identified in the caudate. There were no associations between Glx levels and clinical severity in either patient group. Our results are suggestive of greater heterogeneity in TRS relative to non-TRS with respect to dACC Glx levels, necessitating further research to determine biological subtypes of TRS.

Clinical characteristics and related factors of somatization symptoms in outpatients with psychiatric disorders of the department of cardiology in general hospitals

Objective: To explore the clinical characteristics and related factors of somatization symptoms in outpatients with psychiatric disorders of the cardiology department in general hospital. Methods: Cross-sectional survey method was used in this study. From August 2017 to September 2018, 508 outpatients of our department with suspected mental disorders, who complained of physical discomfort and screened by the "Three Questions" method recommended by the Chinese Expert Consensus on Psychological Prescriptions of Cardiovascular Patients in 2014, were consecutively included. General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire (PHQ-9), Patient Health Questionnaire-15 (PHQ-15) and self-made general demographic questionnaire (including age, sex, marital status, educational level, occupation, duration of disease, clinical diagnosis and the process of medical treatment for the main somatic symptoms in recent one year) were used to investigate these patients, under the assistance of unified training psychological consultants. The detection rate of anxiety and depression, the degree and distribution of somatization symptoms in outpatients with mental disorders were analyzed, and the related factors affecting the occurrence of somatization symptoms were screened by multivariate logistic regression. Results: The selected patients were (51.3±10.1) years old, of which 37.8% (192/508) were males and 62.2% (316/508) were females. The total detection rate of anxiety/depression was 86.8% (441/508), and the detection rate of somatization symptoms was 93.1% (473/508). The number of positive symptom items in PHQ-15 was 8.0±2.7, and the detection rate of anxiety/depression was 78.6% (372/473) in patients with somatization symptoms. There were significant differences in the proportion of women, the average number of outpatient visits and hospitalizations in the past one year, GAD-7 score and PHQ-9 score among the patients with mild, moderate and severe somatization symptoms (all P<0.05). PHQ-15 score was positively correlated with GAD-7 score (r=0.524 5, P<0.001) and PHQ-9 score (r=0.574 9, P<0.001) in patients with somatization symptoms. Stepwise logistic regression analysis showed that total scores of PHQ-9 (OR=8.020, 95%CI 3.470-18.930, P<0.001) and GAD-7 (OR=6.526, 95%CI 2.903-13.045, P<0.001) and female (OR=4.440, 95%CI 1.059-9.073, P=0.011) were related factors of somatizations. Conclusions: The incidence of somatization symptoms is high in patients with psychological disorders in outpatients of cardiology department in general hospital. Anxiety, depression and gender are the main related risk factors of somatization symptoms in this patient cohort. Degree of anxiety and depression increased in proportion to the severity of somatization symptoms. Anxiety, depression and female is related to somatization symptoms.

S131. PERCEPTUAL ABNORMALITIES AND RELIGIOSITY IN ULTRA HIGH-RISK FOR PSYCHOSIS (UHR) INDIVIDUALS IN A LATIN AMERICAN POPULATIONAL SAMPLE RESULTS FROM THE SAO PAULO SSAPP COHORT

BackgroundIn the last decades, the ultra-high risk for psychosis (UHR) status has been studied to prevent people from developing full-blown psychosis. To better understand this condition, and to better predict conversion, the relationship between UHR and several biological and environmental markers have been assessed. Nevertheless, most UHR studies come from developed countries, constituting a gap in the literature regarding culture-related environmental factors. This study aims to study religiosity, a peculiar cultural constituent of Latin-American societies, in populational samples of UHR individuals and controls from the city of Sao Paulo, Brazil.MethodsThese are partial results from the cohort project SSAPP (Subclinical Symptoms and Prodromal Psychosis).Over 2500 individuals aged between 18 and 30 years were asked to participate in the research in a household survey. The Prodromal Questionnaire was used, a screening instrument for UHR constituted of 92 yes-or-no items divided into 4 domains; positive, negative, disorganization, and general symptoms. Those with 18 points or more in the positive subscale were asked to come to the Institute of Psychiatry to undergo blood testing, neuropsychological evaluation, to complete several self-filling questionnaires, and to undergo a clinical interview with an experienced psychiatrist with the SIPS (Structured Interview for Prodromal Syndromes). Functioning was assessed with the Global Assessment of Functioning (GAF), and religiosity was evaluated with the DUREL (Duke religiosity Index), which measures organizational and non-organizational religious activity, and intrinsic religiosity.Total sample for this study was constituted of 60 UHR individuals and 91 controls.The scores on the 5 positive symptoms items in the SIPS, the three religiosity dimensions, and the GAF were correlated, in controls and in UHR individuals.All variables had a non-normal distribution (Kruskal-Wallis p<0.001), so Spearman’s test was used. Generalized linear model was used between the resulting significantly associated variables.SPSS 23 for Mac was used for the analysis.ResultsLevel of organizational and non-organizational religious activity did not differ between samples, but controls had significantly higher levels of intrinsic religiosity than UHR individuals (p=0.04).None of the religiosity measures were related to positive symptom items for controls. For UHR individuals, P4 (perceptual abnormalities) was positively related to organizational religiosity (p=0.001).GAF was not related to any P item in controls, but they inversely correlated to P4 (perceptual abnormalities, p=0.033) and P5 (disorganized communication, p=0.031) in UHR individuals. GAF was not correlated to religiosity, neither in UHR nor in controls.Generalized linear model using P4 as dependent variable and GAF and Organizational religiosity as independent variable showed that organizational religiosity determined P4 score rather than GAF.DiscussionResults indicate that a higher score on perceptual abnormalities was related to a higher attendance in churches/temples in UHR individuals in our sample. Our study sheds light to an important aspect of Latin American cultures, namely the relationship between exceptional experiences and religion in lay people. In developing countries with a lack of mental health services churches might act as important gatekeepers for UHR individuals. Since an expected inverted correlation between GAF and religiosity was not found, we might hypothesize that religion might have been used to cope with subclinical symptoms. Longitudinal data would be required to test this hypothesis.

Assessing the Sources of Unreliability (Rater, Subject, Time-Point) in a Failed Clinical Trial Using Items of the Positive and Negative Syndrome Scale (PANSS)

Considering the increasing attention to the study of failed clinical trials, the goal of this study was to identify the sources of unreliability in a failed clinical trial by assessing scores on the Positive and Negative Syndrome Scale (PANSS). This study is a substudy from a failed phase 2 double-blind, placebo-controlled trial of schizophrenia. Using the generalizability theory, this substudy assesses reliability on 3 conditions: raters, time points (PANSS evaluations, 1 week apart), subjects for 3 groups (placebo responders, placebo nonresponders, and treatment group). The placebo response rate was 40.07% (32/71). For all PANSS positive symptom items, the most variability was for raters (range, 33%-72%) for the placebo responders, 31% to 68% for the placebo nonresponders, and 29% to 60% for the treatment group. The variability of the interaction of rater and time point was the second source of unreliability, with an average of 12.28% compared to 12.00% for the placebo nonresponders and 10.00% for the treatment group. All items of the negative symptom subscale showed the most percent variability for raters, for all groups. For general psychopathology items (except preoccupation), raters accounted for the most variability in the scores for placebo responders with an average of 51.00% across items. A similar pattern was observed for the placebo nonresponders and for the treatment group; for the treatment group, the interaction between rater and time point accounted for the most variability for somatic concern and anxiety. Results confirm the efficacy of applying the generalizability theory to the estimation of reliability to identify a source of unreliability and provide evidence for the relationship between low reliability and failed trials. Findings can be used to guide data monitoring, rater training, and identification of PANSS items, which may require supplementary training.

Use of NON-PARAMETRIC Item Response Theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS)

BackgroundNonparametric item response theory (IRT) was used to examine (a) the performance of the 30 Positive and Negative Syndrome Scale (PANSS) items and their options ((levels of severity), (b) the effectiveness of various subscales to discriminate among differences in symptom severity, and (c) the development of an abbreviated PANSS (Mini-PANSS) based on IRT and a method to link scores to the original PANSS.MethodsBaseline PANSS scores from 7,187 patients with Schizophrenia or Schizoaffective disorder who were enrolled between 1995 and 2005 in psychopharmacology trials were obtained. Option characteristic curves (OCCs) and Item Characteristic Curves (ICCs) were constructed to examine the probability of rating each of seven options within each of 30 PANSS items as a function of subscale severity, and summed-score linking was applied to items selected for the Mini-PANSS.ResultsThe majority of items forming the Positive and Negative subscales (i.e. 19 items) performed very well and discriminate better along symptom severity compared to the General Psychopathology subscale. Six of the seven Positive Symptom items, six of the seven Negative Symptom items, and seven out of the 16 General Psychopathology items were retained for inclusion in the Mini-PANSS. Summed score linking and linear interpolation was able to produce a translation table for comparing total subscale scores of the Mini-PANSS to total subscale scores on the original PANSS. Results show scores on the subscales of the Mini-PANSS can be linked to scores on the original PANSS subscales, with very little bias.ConclusionsThe study demonstrated the utility of non-parametric IRT in examining the item properties of the PANSS and to allow selection of items for an abbreviated PANSS scale. The comparisons between the 30-item PANSS and the Mini-PANSS revealed that the shorter version is comparable to the 30-item PANSS, but when applying IRT, the Mini-PANSS is also a good indicator of illness severity.

Time to Treatment Response in First-Episode Schizophrenia

Response patterns may differ between patients with first-episode and multiepisode schizophrenia. This analysis explored trial duration with first-episode patients and asked whether early limited improvement predicts ultimate lack of treatment response with first-episode patients as it does with multiepisode patients. One hundred twelve subjects (mean age = 23.3 years, SD = 5.1 years) who presented between November 1998 and October 2004 with a first episode of psychosis and had a DSM-IV diagnosis of schizophrenia or schizophreniform or schizoaffective disorder were randomly assigned to treatment with olanzapine or risperidone for 16 weeks. Treatment response, the primary outcome measure, was defined as a rating of mild or better on all of the positive symptom items on the Schedule for Affective Disorders and Schizophrenia Change Version With Psychosis and Disorganization Items. Response rates were calculated for each study week. A logistic regression analysis examined the association between percentage reduction in symptom severity scores from baseline values at weeks 2, 4, or 8 and response by week 16. The study was conducted at The Zucker Hillside Hospital, Glen Oaks, New York and the Bronx-Lebanon Hospital Center, Bronx, New York. The estimated cumulative response rate was 39.59% (95% CI, 29.77%-49.41%) by week 8 and 65.19% (95% CI, 55.11%-75.27%) by week 16. The confidence intervals for estimated response at weeks 10, 12, 14, and 16 were not distinct. Response rates increased approximately 5 to 6 percentage points each 2-week interval between week 10 and 16. Percentage reduction in symptom severity score at week 4 (but not 2 or 8) was associated (χ²₁ = 3.96; P < .05) with responder status at week 16 (odds ratio = 1.03; 95% CI, 1.00-1.05). However, receiver operating characteristic curves did not suggest any level of percentage symptom reduction that would be clinically useful as a predictor of response by week 16. Many first-episode patients respond between weeks 8 and 16 of treatment with a single antipsychotic medication. Limited early symptom improvement does not identify those first-episode patients who will not improve with a full 16-week trial with enough accuracy to be clinically useful. clinicaltrials.gov Identifier: NCT00000374.

Elevated Plasma Dopamine Metabolites in Cannabis Psychosis

Back to table of contents Previous article Next article Letters to the EditorFull AccessElevated Plasma Dopamine Metabolites in Cannabis PsychosisMALCOLM B. BOWERS M.D.JOSHUA T. KANTROWITZ M.D.,MALCOLM B. BOWERS M.D.Search for more papers by this authorJOSHUA T. KANTROWITZ M.D.Search for more papers by this author,Published Online:1 Oct 2007https://doi.org/10.1176/appi.ajp.2007.07010217AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To The Editor: Cannabis has received increasing attention as a risk factor for the development of psychotic states (1) . There are relatively little data related to the biochemical profile in cannabis psychosis (2 , 3) . We report on five consecutive cases of first-admission psychosis associated with documented cannabis use. For comparison, we used a consecutive series of first-admission psychosis and a group of nonpsychotic inpatients treated during the same period. We collected plasma for homovanillic acid on the first morning after admission following an overnight fast. The first-admission cannabis psychosis group (N=5) had a mean age of 21.2 years. Urine tests were positive for cannabis subjects on admission. The comparison groups had urine samples negative for cannabinoids on admission. The first-episode psychosis group (N=15) had a mean age of 20.4 years, and the nonpsychotic group (N=17) had a mean age of 32.0 years. The psychosis groups did not significantly differ in age, race, sex, or level of psychosis. The degree of psychosis was rated as moderate on the four positive symptom items of the Brief Psychiatric Rating Scale.Plasma homovanillic acid was measured using gas chromatography mass spectrometry with deuterated internal standards. Homovanillic acid levels were compared using a Student’s t test. Plasma homovanillic acid values were as follows: cannabis psychosis group, 24.8 ng/ml (SD=2.9); first-episode group, 15.1 ng/ml (SD=3.1); and nonpsychotic group, 9.6 ng/ml (SD=2.1). Homovanillic acid values for the cannabis group were significantly higher relative to the first-episode group (p<0.001) and the nonpsychotic group (p<0.001). Homovanillic acid values for the first-episode group were significantly higher when compared with the nonpsychotic group (p<0.001). To our knowledge, this is the first report of elevated plasma homovanillic acid in cannabis-related psychosis, although we are aware of a report of elevated urinary homovanillic acid following cannabis administration to a volunteer population (2) . In this small case series of patients with first-episode psychosis associated with cannabis use, plasma homovanillic acid was significantly higher than values for each of the comparison groups. There are several possibilities for this result. First, plasma homovanillic acid is elevated in a number of newly admitted psychosis patients (4) , which was the case in our first-episode psychosis group. However, plasma homovanillic acid was even higher in the cannabis group. Second, acute cannabis administration can produce increased dopamine activity in animals and humans (2 , 3) . Third, individuals with cannabis psychosis may also have a genetic vulnerability that can lead to increased dopaminergic activity (1) . New Haven, Conn.The authors report no competing interests.This letter (doi: 10.1176/appi.ajp.2007.07010217) was accepted for publication in July 2007.Reprints are not available; however, Letters to the Editor can be downloaded at http://ajp.psychiatryonline.org.

The multidimensional measurement of the positive symptoms of psychosis

The measures most frequently used to assess psychotic symptoms fail to reflect important dimensions. The Psychotic Symptom Rating Scale (PSYRATS) aims to capture the multidimensional nature of auditory hallucinations and delusions. Individuals (N = 276) who had recently relapsed with positive symptoms completed the auditory hallucinations and delusions PSYRATS scales. These scores were compared with the relevant items from the SAPS and PANSS, and with measures of current mood. Total scores and distribution of items of the PSYRATS scales are presented and correlated with other measures. Positive symptom items from the SAPS and PANSS reflected the more objective aspects of PSYRATS ratings of auditory hallucinations and delusions (frequency and conviction) but were relatively poor at measuring distress. A major strength of the PSYRATS scales is the specific measurement of the distress dimension of symptoms, which is a key target of psychological intervention. It is advised that the PSYRATS should not be used as a total score alone, whilst further research is needed to clarify the best use of potential subscales.