Helene Adami

Evoked gamma band synchronization and the liability for schizophrenia.

OBJECTIVE Electroencephalographic (EEG) synchronization in the gamma band is thought to represent a neuronal mechanism by which the brain integrates information processed in different cortical areas to build a coherent internal representation. Previous studies have reported abnormal gamma range ( approximately 40 Hz) synchronization in schizophrenic patients. We tested a group of first-degree relatives of schizophrenic probands who have schizophrenia spectrum personality symptoms, and a group of schizophrenic patients, to examine whether individuals with increased liability for schizophrenia have reduced gamma synchronization. METHOD A steady-state auditory evoked potential paradigm was used to evaluate the brains capacity to sustain 20, 30, and 40 Hz EEG synchronization in 11 relatives, 24 schizophrenic patients (11 on conventional, 13 on new generation antipsychotic medications), and 17 normal controls. RESULTS Relatives with schizophrenic spectrum personality symptoms had reduced power at 40 Hz synchronization compared to normal controls (p=0.022). Previous findings of reduced steady-state gamma band synchronization in schizophrenic patients were not directly replicated in this study. Patients as a group did not significantly differ from controls, but patients taking new generation antipsychotics had significantly enhanced 40 Hz synchronization compared to patients taking conventional antipsychotics (p<0.001). There were no group differences in 20 or 30 Hz synchronization. CONCLUSIONS Gamma band synchronization was found to be reduced in first-degree relatives with schizophrenia spectrum personality symptoms. Patients on new generation antipsychotic medications may exhibit enhanced gamma band synchronization.

Smooth pursuit eye movements to extra-retinal motion signals: deficits in patients with schizophrenia

In order to understand mechanisms underlying the smooth pursuit abnormality(ies) in schizophrenia, new methods, which independently evaluated predictive smooth pursuit responses to extra-retinal motion signals, were developed and tested. The study compared responses to only extra-retinal motion signals in normal volunteers (n = 25), and individuals with a chronic (n = 21) and a recent onset (n = 18) schizophrenia. Subject groups with chronic schizophrenia and recent onset schizophrenia had significantly poorer predictive pursuit than normal subjects in response to only extra-retinal motion signals. The poor predictive pursuit was evident even at low target velocity when the closed-loop pursuit gain was normal in patients with schizophrenia. Ten of the 18 recent onset patients were drug-free at the time of testing and had no or minimum previous exposure to anti-psychotic medications. Re-analyses of the data showed that on most measures of predictive pursuit, drug-free patients were not significantly different from patients who received anti-psychotic drug treatment. Both patient groups had significantly poorer predictive pursuit than normal subjects. These results suggest that a deficit in processing extra-retinal motion may underlie the abnormal smooth pursuit response in schizophrenia. At low target velocities, patients with schizophrenia were able to compensate for the low extra-retinal gain by increasing the gain of response to the retinal slip velocity. This indicates that patients were able to process retinal slip velocity and generate smooth pursuit eye movements, but experienced a specific deficit in processing and/or integrating extra-retinal motion information for the smooth pursuit response.

Components of the smooth pursuit function in deficit and nondeficit schizophrenia

The diagnosis of schizophrenia likely encompasses a heterogeneous group of disorders, complicating the search for its causes. Studies of deficit schizophrenia represent an attempt to reduce this heterogeneity by identifying biologically distinct subgroups. Supplementing clinical phenotypes with biological markers of risk (e.g., eye-tracking and sensory-gating deficits) have also been used to reduce disease heterogeneity. In this study, we examined smooth pursuit eye movements in healthy controls (n = 37), and deficit (n = 18) and nondeficit (n = 32) patients with schizophrenia to determine what aspects of abnormal smooth pursuit are associated with the two patient groups, and which, if any, specifically mark the deficit phenotype. A small sample of relatives of deficit (n = 12) and nondeficit (n = 35) patients was also examined. Positive symptoms were equally present in deficit and nondeficit patients. Subtle, psychotic-like positive traits were also equally present in the relatives of both deficit and nondeficit probands, whereas negative symptoms were significantly more prevalent among the relatives of deficit probands. Deficits in predictive pursuit were present in both patient groups and both groups of relatives. Deficit patients showed significantly lower initiation acceleration. A similar pattern of results was seen in our pilot sample of relatives of deficit patients. These findings suggest that predictive smooth pursuit abnormality is associated with positive symptoms in schizophrenia, and that initiation abnormalities may be associated with the deficit syndrome.

Tardive dyskinesia in children treated with atypical antipsychotic medications

Recent years have witnessed increased antipsychotic treatment of children despite limited long‐term safety data in children. In this study, motor side effects associated with the use of antipsychotic drugs in children were examined in a sample of pediatric psychiatric patients. Child and adolescent psychiatric patients receiving antipsychotics (most were on atypicals) for 6 months or longer (n = 118) were compared with antipsychotic‐naïve patients (n = 80) with similar age, sex ratio, and diagnoses. Only 19% of patients on antipsychotics had ever experienced psychotic symptoms. Eleven children (9%) on antipsychotics exhibited dyskinesia, when compared with 0 in the naïve group (P = 0.003, Fishers exact test). Nine of 62 African–American children (15%) on antipsychotics exhibited dyskinesia, when compared with only 4% (2 of 52) of European–American children (P = 0.003, Fishers exact test). Children treated with antipsychotic drugs might experience a significant risk of dyskinesia even when treated only with atypical antipsychotics. Ethnicity might also be a risk factor for dyskinesia in children. Side‐effect profile of the atypical antipsychotic drugs in children may be much different than that in adults.

Ethnicity and the course of tardive dyskinesia in outpatients presenting to the motor disorders clinic at the Maryland psychiatric research center.

Background: Although newly emergent tardive dyskinesia (TD) is less of a concern, about one-fourth to one-third of patients on or previously on chronic first-generation antipsychotic agents have TD. The long-term course and outcome, as well as their predictors, are unknown. Earlier studies identify ethnicity as one of the risk factors for the development of TD, and case reports have noted a preponderance of African-American males in cohorts of patients with tardive dystonia. The current study examines the anatomic distribution and course of TD in a cohort of schizophrenia patients of European and African descent with TD who were referred to the Motor Disorders Clinic (MDC). Methods: We evaluated data collected on 1149 TD patients who were given a focused neurologic examination for movement disorders. Movements were evaluated with the MPRC Scale for Involuntary Movements (IMS). All patients met RDC-TD criteria for diagnosis of persistent TD. One to 10-year follow-up data on 528 patients were evaluated to examine the course of TD following recommendations made to referring primary clinicians. Suggested interventions to referring primary clinicians included dose reduction of first-generation antipsychotic medication, or switching to a second-generation antipsychotic. Results: Initial evaluation included 701 European American (EA) patients and 448 African-American (AA) patients. AA patients had a significantly higher proportion of males [χ2(1) = 7.50, P < 0.05]. EA subjects had a higher mean age than AA patients 42.8 ± 11.2 and 39.8 ± 10.4, respectively [F(1,1147) = 22.27, P < 0.05]. Mean neuroleptic exposure (chlorpromazine equivalents) was similar in both groups after controlling for differences in age. Follow-up data analyzed in 528 patients (329 EA and 199AA) showed a significant ethnicity by TD interaction [F(1,504) = 4.26, P < 0.05]. Examination of body distribution of dyskinetic movements showed an effect of ethnicity. Subsequent analyses suggest EA patients experienced more improvement in TD over the course of follow up [F(1,319) = 22.39, P < 0.05] compared with AAs [F(1,189) = 1.58, P > 0.05]. These findings were unchanged when age, change in antipsychotic drug dose, and duration of follow-up were covaried. Conclusion: Reports from earlier studies note ethnicity (African descent) as a risk factor in the development of TD. Our study findings suggest ethnicity might be an important factor in predicting a poor course of TD.

Recruitment of non-patient volunteers with schizophrenia spectrum personality symptoms

Authors aimed to evaluate the yield and effectiveness of recruiting community schizophrenia spectrum personality (SSP) subjects via targeted newspaper advertisements listing SSP traits. Eight newspaper advertisements listing SSP traits were placed in regional newspapers over a 3-year period. Respondents (n = 209) were screened thoroughly via telephone, and eligible subjects were invited for face-to-face clinical interviews. One hundred and one subjects (48% of the respondents) were screened out over the phone and another 30% were no-shows or refused. Of the 46 subjects who were interviewed, a majority (24 subjects; 52%) met this studys criteria for SSP. These subjects experienced significant psychotic-like symptoms, as ascertained by a self-rating scale, and showed a downward drift in their socio-economic status. One can successfully recruit SSP subjects, with high yield, using targeted telephone advertisements combined with thorough telephone screening.

Effects of repeated amphetamine administration on antisaccades in schizophrenia spectrum personality

Repeated amphetamine administration is used to examine the responsivity of cerebral dopaminergic systems. Schizophrenia spectrum personality (SSP) provides a unique opportunity to study the pathophysiology of schizophrenia because of shared neurobiology without the confounding factors of acute psychosis and psychotropic exposure. Previously we noted that on repeated amphetamine administration, dyskinesia and SSP symptoms were less likely to worsen in SSP than in healthy volunteers. In the current study, we report the effects of repeated amphetamine on antisaccade task performance. Eleven SSP and seven healthy subjects were given placebo once and amphetamine (30 mg) twice, in randomized double-blind fashion at least 1 week apart. Antisaccade eye measurements (error rate and latency) were recorded over 30 trials in each direction. Analysis of error rate showed no significant main effects of the drug. There was a significant group by field by drug interaction effect on the antisaccade latency. The SSP group showed a significant reduction in antisaccade latency for right field targets whereas no significant effects were noted in healthy control subjects. Findings from this preliminary study suggest SSP may be more receptive to the beneficial effects of repeated amphetamine on cognition than healthy controls.

Nonverbal delayed recognition in the relatives of schizophrenia patients with or without schizophrenia spectrum.

BACKGROUND There is increased interest in the study of cognitive deficits as possible endophenotypic markers for schizophrenia. The main goal of this study was to determine how familiality and schizophrenia spectrum personality symptomatology are related to performance of auditory and visuospatial delayed recognition memory tasks. METHODS The study sample consisted of 162 subjects divided into five groups. The groups included 39 patients with a DSM-IV diagnosis of schizophrenia or schizophreniform disorder; first-degree relatives of schizophrenia patients, 22 with and 31 without schizophrenia spectrum personality traits; and healthy control subjects with no family history of psychosis, 22 with and 48 without schizophrenia spectrum traits. Auditory and visuospatial delayed recognition memory performance was assessed. RESULTS Significant differences were observed between patients and healthy control subjects in both auditory [F(1,79) = 7.358 p = .008] and visual [F(1,47) = 34.67, p < .001] delayed recognition tasks. When comparing the four non-patient groups, auditory and visuospatial discriminability decreased as a function of familiality of schizophrenia (p < .05). Deficits were more pronounced in relatives with schizophrenia spectrum traits [auditory d = .7114; visual d = 1.0199]. CONCLUSIONS A biological relationship to schizophrenia increases the likelihood of impaired delayed recognition memory. Likewise, poorer performance is associated with schizophrenia spectrum phenotype only when combined with familiality.

Use of telephone screens improves efficiency of healthy subject recruitment

Previous reports have indicated that a high percentage of those responding to advertisements for healthy controls for psychiatric research have personal or family histories of illness which would exclude them from such studies. We reviewed 1757 telephone screen interviews conducted over 14 years to determine: (1) the effectiveness of a screen for excluding unhealthy volunteers, (2) whether the reasons for exclusion changed over time, and (3) the final yield of healthy participants for psychiatric research after taking account of exclusions from telephone screens, no-shows and exclusions identified by direct interviews. Volunteers for psychiatric research, solicited by 43 newspaper advertisements in the Baltimore metropolitan area from 1989-2002, were initially screened by telephone and scheduled for in-person interviews if no exclusions were identified at the initial screen. More than half of the telephone respondents had major medical illnesses, substance abuse problems, depression, an Axis I disorder (not depression), a relative with a psychotic disorder or were otherwise deemed not eligible for face-to-face interview. Of the telephone respondents scheduled for direct interviews, 29% did not show up. However, the respondents who completed the direct interviews had a high likelihood of inclusion as non-ill controls for psychiatric research studies. Since Axis I and II interviews and family history take approximately 4-5 h per subject, the telephone screen is a cost-effective initial step in identifying healthy controls for psychiatric research.