Prognostic subgroups for remission, response, and treatment continuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial.

OBJECTIVE: Identify moderators of treatment outcome from antipsychotic pharmacotherapy in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial. Specifically, we used logistic regression and receiver operating characteristic (ROC) analysis to explore the association between baseline characteristics and treatment outcomes in the CATIE trial. METHOD: This is a secondary analysis of the CATIE trial in which 1,460 adults with a DSM-IV diagnosis of schizophrenia were randomly assigned to olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone treatment for up to 18 months or until discontinuation between January 2001 and December 2004. Logistic regression was used to examine baseline characteristics associated with remission, response, and treatment continuation at 3 and 6 months of treatment. ROC analyses identified subgroups associated with similar likelihood of treatment outcome. Remission was defined by scores of selected items on psychoticism, disorganization, and negative symptoms. Response was defined as a 50% or greater improvement on the Positive and Negative Syndrome Scale. RESULTS: The most consistent predictors of poor outcome on all variables were low scores on neurocognitive tests (in particular verbal memory) (OR = 1.13-1.49, P< .05); previous reported side effects (OR = 0.49-0.69, P < .05); negative attitude to medication (OR = 1.03-1.10, P < .05); comorbid depression (OR = 0.47-0.51, P < .05); psychosocial factors such as unemployment (OR = 0.74-0.75, P <.05), homelessness (OR = 0.54, P <.05), and living alone (OR = 1.58-1.94, P < .01); and random assignment to a medication other than olanzapine (OR = 1.54-2.04, P < .01). ROC analysis demonstrated prognostic subgroups with large differences in response likelihood. CONCLUSION: Baseline characteristics in schizophrenia are informative regarding clinically important treatment outcomes with respect to antipsychotic pharmacotherapy. Further research should examine whether interventions that target improvement of patients' deficits in neuropsychological function and attitude toward medication as well as decreasing patients' social isolation can improve treatment outcomes with antipsychotic treatment in schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00014001.

DSM-5 and the 'Psychosis Risk Syndrome': The DSM-5 proposal is better than DSM-IV.

The American Psychiatric Association is considering the inclusion of the psychosis risk syndrome as a new diagnosis for DSM-5. The main evidence supporting inclusion is: (1) the patients meet criteria for having a current illness, (2) the patients are at high risk for becoming more severely ill, (3) no DSM-IV diagnosis accurately captures their current symptoms or future risk, (4) the diagnosis is reliable and valid, at least in the research setting, and (5) codification in DSM-5 will promote treatment and prevention research of sufficient quantity and quality to permit the development of treatment guidelines. Field trials are needed to determine whether the proposed diagnostic criteria can be used with reliability in actual clinical practice.

Development of the 40Hz steady state auditory evoked magnetic field from ages 5 to 52.

OBJECTIVE: Adults exhibit strong auditory 40 Hz magnetic steady state responses (SSR). Although EEG measured SSR has been studied in children, the developmental course of the magnetic SSR is unknown. METHODS: Sixty-nine healthy subjects ranging in age from 5 to 52 years participated in a magnetoencephalographic (MEG) study. Stimuli were monaural 500 ms duration click trains with a 25 ms inter-click interval. Contralateral magnetic responses for both hemispheres were recorded with a 37-channel MEG system. Responses were averaged and examined using wavelet-based time-frequency analysis. Source analyses were also conducted on a subset of the data. RESULTS: Gamma power from 200 to 500 ms post-stimulus onset was computed and was significantly related to subject age in both hemispheres. Hemispheric asymmetry was observed for the anterior-posterior SSR source locations, suggestive of asymmetry similar to that previously described for the SSR and other auditory evoked magnetic field components. CONCLUSIONS: The 40 Hz power findings are generally consistent with previous EEG studies of steady state responses in children showing age-related changes in the 40 Hz SSR. SIGNIFICANCE: Age-related changes in the strength of the magnetic 40 Hz SSR may continue to develop well beyond early childhood, which should be taken into consideration in planning future studies using adolescents and young adults.

Alterations in tonotopy and auditory cerebral asymmetry in schizophrenia.

BACKGROUND: Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiologic imaging research has documented a structure-function disassociation in the auditory system in schizophrenia. This study examines whether the most fundamental level of auditory cortical organization, tonotopy, is altered in schizophrenia. METHODS: The tonotopic organization for five tone frequencies in 19 patients with schizophrenia and 22 comparison subjects was evaluated using magnetoencephalography. Auditory evoked magnetic field dipole locations were examined for the N100m component for each frequency. RESULTS: The expected linear relationship between depth and frequency was found in the comparison subjects but not in the schizophrenia group (p <.004). In addition, normal anterior-posterior asymmetry of the N100m was found to be reduced at all five stimulation frequencies employed in the study (p <.04). No relationships between clinical symptom ratings and either tonotopy or asymmetry were observed. CONCLUSIONS: This finding suggests that the tonotopic organization of the auditory cortex in schizophrenia is disturbed and may help explain the relatively poor behavioral performance of schizophrenia patients on simple frequency discrimination tasks. Alterations in fundamental sensory organization may underlie or interact with higher order cognitive mechanisms to produce changes in cognitive task performance.