Thierry d'Amato

Executive/attentional performance and measures of schizotypy in patients with schizophrenia and in their nonpsychotic first-degree relatives

Previous studies of executive/attentional functions have found impairments in nonpsychotic first-degree relatives of patients with schizophrenia. The aims of this study were: (1) to replicate these findings by three laboratory measures of attention/information processing - a continuous performance test (DS-CPT), a forced-choice span of apprehension task (SPAN), and a digit symbol substitution test (DSST), and by a series of neuropsychological tests sensitive to prefrontal cortical damage - Trail Making A and B, verbal fluency (VFT), Stroop Color and Word Test (Stroop), and Wisconsin Card Sorting Test (WCST); (2) to investigate whether such executive/attentional deficits are associated with schizotypal traits assessed using the social anhedonia, physical anhedonia, perceptual aberration and magical ideation scales (Chapman, L.J., Chapman, J.P., Raulin, M.L. 1976. Scales for physical and social anhedonia. J. Abnorm. Psychol. 85, 374-382; Chapman, L.J., Chapman, J.P., Raulin, M.L., 1978. Body-image aberration in schizophrenia. J. Abnorm. Psychol. 87, 399-407; Eckblad, M., Chapman, L.J., 1983. Magical ideation as an indicator of schizotypy. J. Consult. Clin. Psychol. 51, 215-225). In both patient and relative groups, performance was significantly poorer on the DSST, VFT and Trail B, and the reaction time on the SPAN was significantly longer. These neuropsychological impairments were present as much in siblings as in parents of schizophrenic patients; age did not appear to cancel differences between the relative and control groups. In the relative group, the four scores of schizotypy were at an intermediate level between those of patient and control groups, and the social anhedonia and perceptual aberration scores tended to be significantly different between the relative and the control groups. Only two significant correlations were found between the neuropsychological performance and the measures of schizotypy.

Neural correlates of action attribution in schizophrenia

Patients with first-rank symptoms (FRS) of schizophrenia do not experience all of their actions and personal states as their own. FRS may be associated with an impaired ability to correctly attribute an action to its origin. In the present study, we examined regional cerebral blood flow (rCBF) with positron emission tomography during an action-attribution task in a group of patients with FRS. We used a device previously used with healthy subjects that allows the experimenter to modulate the subjects degree of movement control (and thus action attribution) of a virtual hand presented on a screen. In healthy subjects, the activity of the right angular gyrus and the insula cortex appeared to be modulated by the subjects degree of movement control of the virtual hand. In the present study, the schizophrenic patients did not show this pattern. We found an aberrant relationship between the subjects degree of control of the movements and rCBF in the right angular gyrus and no modulation in the insular cortex. The implications of these results for understanding pathological conditions such as schizophrenia are discussed.

Saccadic eye movements in schizophrenic patients

The nature of saccadic abnormalities in schizophrenia was investigated in three different paradigms: (1) the visually guided saccade; (2) the antisaccade; and (3) the remembered saccade paradigm. Subjects comprised 14 schizophrenic patients and 14 normal volunteers. Deficits in the schizophrenic group were observed in the antisaccade and remembered saccade tasks, both of which were characterized by increased latency and reduced gain. Moreover, in the antisaccade task, schizophrenic patients showed an increased number of errors compared with control subjects. Saccadic abnormalities in the patients were correlated with impaired performance on the Wisconsin Card Sorting Test. These data suggest that schizophrenic patients have difficulty in inhibiting reflexive saccades and in producing voluntary saccades. The implications of these findings for a prefrontal cortex dysfunction involved in oculomotor control in schizophrenia are discussed.

Impaired social cognition in mild Alzheimer disease

Abnormal decoding of social information has been associated with the conversion from prodromal Alzheimers disease (AD) to dementia. Since the distributed neural networks involved in face processing are differentially affected in prodromal and dementia states of AD and in Fronto-Temporal Dementia (FTD), we hypothezed a differential impairment in face processing in these populations. Facial expression, gender and gaze direction decoding abilities were examined in patients with probable amnesic Mild Cognitive Impairment (aMCI, N = 10) fulfilling criteria for prodromal AD, in patients with mild and moderate AD (N = 10) as well as in FTD patients (N = 10) and in a group of age- and sex-matched healthy comparison subjects (N = 10). Gender recognition was preserved in all groups. Compared to controls, patients with mild or moderate AD were impaired in expression recognition and FTD patients were impaired in expression and gaze direction determination, whereas MCI patients were not impaired at all.

Alteration of event related potentials in siblings discordant for schizophrenia

This study was aimed at confirming that auditory event related potential (ERP) abnormalities are indicators of vulnerability to schizophrenia. Auditory ERP performances were assessed at Fz, Cz, and Pz, with an oddball paradigm, in 21 clinically stable patients with schizophrenia, 21 of their healthy biological full siblings and 21 control subjects. The evoked response did not differ between the three groups on N200 waves. Compared to controls, patients with schizophrenia exhibited reduced amplitudes of N100 and P300, and prolonged latency of P300, while their siblings showed prolonged latency of P200 and P300. Among the patients with schizophrenia, ERP abnormalities did not correlate with age, clinical state, duration of illness or antipsychotic treatments. Although other conditions also accounted for alterations of the same type, ERP abnormalities may represent a neurobiological marker of the genetic vulnerability to schizophrenia, independent of phenotypic expression.

Facial Expression and Sex Recognition in Schizophrenia and Depression

Background: Impaired facial expression recognition in schizophrenia patients contributes to abnormal social functioning and may predict functional outcome in these patients. Facial expression processing involves individual neural networks that have been shown to malfunction in schizophrenia. Whether these patients have a selective deficit in facial expression recognition or a more global impairment in face processing remains controversial. Objective: To investigate whether patients with schizophrenia exhibit a selective impairment in facial emotional expression recognition, compared with patients with major depression and healthy control subjects. Methods: We studied performance in facial expression recognition and facial sex recognition paradigms, using original morphed faces, in a population with schizophrenia (n = 29) and compared their scores with those of depression patients (n = 20) and control subjects (n = 20). Results: Schizophrenia patients achieved lower scores than both other groups in the expression recognition task, particularly in fear and disgust recognition. Sex recognition was unimpaired. Conclusion: Facial expression recognition is impaired in schizophrenia, whereas sex recognition is preserved, which highly suggests an abnormal processing of changeable facial features in this disease. A dysfunction of the top-down retrograde modulation coming from limbic and paralimbic structures on visual areas is hypothesized.

Cannabis use correlates with schizotypal personality traits in healthy students

The literature suggests that cannabis use and schizotypal traits both constitute risk factors for the later development of schizophrenia. However, their interrelationships remain to be evaluated. The present study examined the association between cannabis use and schizotypal traits in 232 healthy students who ranged in age from 18 to 25 years. All the students had completed the Schizotypal Personality Questionnaire and four of the Chapman Psychosis Proneness Scales: the Magical Ideation Scale; the Perceptual Aberration Scale; the Revised Physical Anhedonia Scale; and the Revised Social Anhedonia Scale. Subjects were divided into three groups according to cannabis use typology: those who had never used cannabis, those who were past or occasional users, and those who were regular users. Higher scores on the Schizotypal Personality Questionnaire and the Magical Ideation Scale characterized the regular and past or occasional users compared with those who had never used cannabis. The co-occurrence of cannabis use and schizotypal traits appeared to be independent of anxiety and depression dimensions. These data suggest that cannabis use and schizotypal traits have to be jointly considered in further longitudinal studies of schizophrenia risk factors.

Effects of acute metabolic stress on the dopaminergic and pituitary–adrenal axis activity in patients with schizophrenia, their unaffected siblings and controls

A genetically mediated abnormal sensitivity to stress is thought to play a role in the onset, exacerbation and relapse of schizophrenia. In a double blind, placebo-controlled crossover study, peak increases in plasma ACTH (Delta ACTH) and homovanillic-acid, a dopamine metabolite, (Delta HVA) following exposure to a metabolic stressor(2DG) were studied in unaffected siblings of patients with schizophrenia (n=15), their patient relatives (n=15) and healthy controls (n=14). Siblings showed a stress response (both Delta ACTH and Delta HVA) that was significantly greater compared to controls and significantly less pronounced compared to patients. The results suggest that the genetic risk for schizophrenia may be characterized by an enhanced sensitivity to stress.

Auditory event-related potentials and clinical scores in unmedicated schizophrenic patients.

Event-related potentials (ERPs) have been widely examined in schizophrenic patients. However, although neuroleptic medication could be a potentially confounding variable, studies with unmedicated patients are relatively scarce. The present work was undertaken to determine whether ERP abnormalities persist in stabilized schizophrenic patients after drug withdrawal. In addition, ERP amplitudes and latencies were compared with clinical ratings (the Positive and Negative Syndrome Scale, PANSS) by means of Spearman rank order correlation coefficients. The P300 and N200 responses to rare tones and the P200 and N100 responses to frequent tones were recorded in 20 clinically stabilized drug-free schizophrenic patients and 19 age-matched control subjects during a two-tone discrimination task. Major findings were that the schizophrenic patients had reduced P300, N200 and N100 amplitudes and an increased P300 latency. The P300 amplitude was negatively correlated with age in patients. The P200 latency was negatively correlated with the PANSS positive syndrome score. The ERP abnormalities shown in this study appear to be enduring traits of the disorder as they persist in stabilized patients even after drug withdrawal.

Left temporo-limbic and orbital dysfunction in schizophrenia during odor familiarity and hedonicity judgments

Impairments of olfactory processing in patients with schizophrenia (SZ) have been reported in various olfactory tasks such as detection, discrimination, recognition memory, identification, and naming. The purpose of our study was to determine whether impairments in odor familiarity and hedonicity judgments observed in SZ patients during a previous behavioral study are associated with modifications of the activation patterns in olfactory areas. Twelve SZ patients, and 12 healthy comparison (HC) subjects, were tested using the H2(15)O-PET technique and 48 different odorants delivered during 8 scans. In addition to an odorless baseline condition, they had either to detect odor, or to judge odor familiarity or hedonicity, giving their responses by pressing a button. Regional cerebral blood flows during olfactory conditions were compared with those for baseline condition. Between-group analyses were then performed, and completed by regions of interest analyses. Both groups had equivalent ability for the detection of suprathreshold odorants, but patients found odors less familiar, and pleasant odors less pleasant than HC subjects. These behavioral results were related to functional abnormalities in temporo-limbic and orbital olfactory regions lateralized in the left hemisphere: the posterior part of the piriform cortex and orbital regions for familiarity judgments, the insular gyrus for hedonicity judgments, and the left inferior frontal gyrus and anterior piriform cortex/putamen region for the three olfactory tasks. They mainly resulted from a lack of activation during task conditions in the SZ patients. These data could explain olfactory disturbances and other clinical features of schizophrenia such as anhedonia.