Psychiatric Rating Scale Positive Symptoms Research Articles

Anti-inflammatory Combination Therapy for the Treatment of Schizophrenia

Despite adequate antipsychotic treatment, most people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. The current study was designed to examine the efficacy and safety of adjunctive anti-inflammatory combination therapy for these illness manifestations. Thirty-nine people with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, schizophrenia or schizoaffective disorder were entered into a 12-week double-blind, 2-arm, triple-dummy, placebo-controlled, randomized clinical trial: 19 were randomized to anti-inflammatory combination therapy and 20 were randomized to placebo. The Brief Psychiatric Rating Scale positive symptom item total score was used to assess positive symptom change, the Scale for the Assessment of Negative Symptoms total score was used to assess negative symptom change, the Calgary Depression Scale total score was used to assess depressive symptom change, and the MATRICS Consensus Cognitive Battery was used to assess neuropsychological test performance. There was a significant time effect for Brief Psychiatric Rating Scale positive symptom item score (t226 = -2.66, P = 0.008), but the treatment (t54=1.52, P = 0.13) and treatment × time (t223 = 0.47, P = 0.64) effects were not significant. There were no significant time (t144 = 0.53, P = 0.72), treatment (t58=0.48, P = 0.63), or treatment × time (t143 = -0.20, P = 0.84) effects for the Scale for the Assessment of Negative Symptoms total score; or for any of the other symptom measures. There were no significant group differences in the change in the MATRICS Consensus Cognitive Battery composite score over the course of the study (F1,26=2.20, P = 0.15). The study results suggest that there is no significant benefit of combined anti-inflammatory treatment for persistent positive symptoms or negative symptoms or cognitive impairments (clinicaltrials.gov trial number: NCT01514682).

Progressive reduction of visual P300 amplitude in patients with first-episode schizophrenia: an ERP study.

To understand the underlying dynamic neurophysiological changes over the course of schizophrenia, it is important to study subjects longitudinally from the early stage of the illness. We previously reported that visual P300 was already impaired in patients with first-episode schizophrenia (FESZ). This study demonstrates how the visual P300, as well as earlier components P1, N1, and N200, changed at the 1-year follow-up after their initial measurement. Visual ERPs were recorded with the same experimental paradigm and acquisition protocol at both time points in FESZ (n = 18) and healthy comparison subjects (n = 24). Participants silently counted infrequent target stimuli ("x") amid standard stimuli ("y") presented on the screen while the 64-channel electroencephalogram was recorded. FESZ showed smaller visual P300, N200, P1 (trend level) amplitude and delayed P300 and N1 latency at both time points; however, only P300 showed progressive amplitude reduction over the course of the illness at 1-year follow-up. P300 latency did not change over time in either group. FESZ showed significantly reduced Spatial Span total score at both time points, and there was a significant negative correlation between P300 peak amplitude and the Brief Psychiatric Rating Scale positive symptom score at baseline. These data show progressive P300 amplitude reduction in response to visual stimuli in the early stage of schizophrenia. These visual P300 findings support the concept of progression of schizophrenia, suggesting the usefulness of the visual P300 as a biological marker of progression.

Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine

The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, have been used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia. Preclinical studies indicate that some ketamine effects may be mediated through increased glutamate release. In this study, we tested the hypothesis that lamotrigine, a drug reported to inhibit glutamate release, will reduce the neuropsychiatric effects of ketamine in humans. Healthy subjects (n = 16) completed 4 test days involving the administration of lamotrigine, 300 mg by mouth, or placebo 2 hours prior to administration of ketamine (0.26 mg/kg by intravenous bolus and 0.65 mg/kg per hour by intravenous infusion) or placebo in a randomized order under double-blind conditions. Behavioral and cognitive assessments were performed at baseline and after administration of the medications. Lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001); positive symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale positive symptoms subscale (P<.001); negative symptoms as assessed by the Brief Psychiatric Rating Scale negative symptoms subscale (P<.05); and learning and memory impairment as assessed by the Hopkins Verbal Learning Test (P<.05). However, lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05). Glutamate release-inhibiting drugs may reduce the hyperglutamatergic consequences of NMDA receptor dysfunction implicated in the pathophysiologic processes of neuropsychiatric illnesses such as schizophrenia. Further study is needed.

Blacks, Schizophrenia, and Neuroleptic Treatment-Reply

<h3>In Reply.—</h3> Dr McLeod-Bryant raises interesting and important questions. Of the 53 participants in our study, 26 were white, 26 were black, and one was Oriental (and was omitted from the following analyses). With regard to completers and dropouts, there were fewer dropouts among blacks (nine of 35) than whites (13 of 39); and there were fewer "non-Research Diagnostic Criteria" diagnoses (ie, Research Diagnostic Criteria exclusions for substance abuse or atypical features) among blacks (11 of 33) than whites (23 of 41), a difference that neared significance (×2 = 3.82, P =.051). Blacks and whites did not significantly differ with regard to schizoaffective diagnoses (seven of 26 whites and six of 26 blacks), dystonic reactions, tardive dyskinesia, need for treatmentfor parkinsonian side effects, or achievement of 40% or greater improvement in Brief Psychiatric Rating Scale positive symptoms(hallucinatory behavior + unusual