Saccadic eye movements in different dimensions of schizophrenia and in clinical high-risk state for psychosis.

BACKGROUND: Oculomotor dysfunction is one of the most replicated findings in schizophrenia. However the association between saccadic abnormalities and particular clinical syndromes remains unclear. The assessment of saccadic movements in schizophrenia patients as well as in clinical high-risk state for psychosis individuals (CHR) as a part of schizophrenia continuum may be useful in validation of saccadic movements as a possible biomarker. METHODS: The study included 156 patients who met the ICD-10 criteria for schizophrenia: 42 individuals at clinical high-risk-state for psychosis and 61 healthy controls. The schizophrenia patients had three subgroups based on the sum of the global SAPS and SANS scores: (1) patients with predominantly negative symptoms (NS, n = 62); (2) patients with predominantly positive symptoms (PS, n = 54) (3) patients with predominantly disorganization symptoms (DS, n = 40). CHR subjects were characterized by the presence of one of the groups of criteria: (1) Ultra High Risk criteria, (2) Basic Symptoms criteria or (3) negative symptoms and formal thought disorders. Horizontal eye movements were recorded by using videonystagmograph. We measured peak velocity, latency and accuracy in prosaccade, antisaccade and predictive saccade tasks as well as error rates in the antisaccade task. RESULTS: Schizophrenia patients performed worse than controls in predictive, reflexive and antisaccade tasks. Oculomotor parameters of NS were different from the other groups of patients. Latencies of predictive and reflexive saccades were significantly longer than in controls only in the NS group. The accuracy of predictive saccades was also different from controls only in the NS schizophrenia group. More prominent loss of accuracy of reflexive saccades was found in the DS group and it significantly differed from the one in other groups. Participants from DS group made more errors in antisaccade task compared to NS and PS groups. CHR subjects performed worse than controls as measured by the accuracy of reflexive saccades and antisaccades. CONCLUSIONS: The study confirms the existence of different relations between the symptom dimensions of schizophrenia and saccades tasks performances. Saccadic abnormalities were revealed in the clinical (schizophrenia) and pre-clinical (clinical high risk) populations that provide further evidence for assessing saccadic abnormalities as a possible neurobiological marker for schizophrenia.

Intact Mismatch Negativity Responses in Clinical High Risk for Psychosis and First-Episode Psychosis: Evidence From Source-Reconstructed Event-Related Fields and Time-Frequency Data.

BACKGROUND: This study examined whether mismatch negativity (MMN) responses are impaired in participants at clinical high risk for psychosis (CHR-P) and patients with first-episode psychosis (FEP) and whether MMN deficits predict clinical outcomes in CHR-Ps. METHODS: Magnetoencephalography data were collected during a duration-deviant MMN paradigm for a group of 116 CHR-P participants, 33 FEP patients (15 antipsychotic-naïve), clinical high risk negative group (n = 38) with substance abuse and affective disorder, and 49 healthy control participants. Analysis of group differences of source-reconstructed event-related fields as well as time-frequency and intertrial phase coherence focused on the bilateral Heschl's gyri and bilateral superior temporal gyri. RESULTS: Significant magnetic MMN responses were found across participants in the bilateral Heschl's gyri and bilateral superior temporal gyri. However, MMN amplitude as well as time-frequency and intertrial phase coherence responses were intact in CHR-P participants and FEP patients compared with healthy control participants. Furthermore, MMN deficits were not related to persistent attenuated psychotic symptoms or transitions to psychosis in CHR-P participants. CONCLUSIONS: Our data suggest that magnetic MMN responses in magnetoencephalography data are not impaired in early-stage psychosis and may not predict clinical outcomes in CHR-P participants.

40-Hz Auditory Steady-State Responses Characterize Circuit Dysfunctions and Predict Clinical Outcomes in Clinical High-Risk for Psychosis Participants: A Magnetoencephalography Study.

BACKGROUND: This study aimed to examine whether 40-Hz auditory steady-state responses (ASSRs) are impaired in participants at clinical high-risk for psychosis (CHR-P) and predict clinical outcomes. METHODS: Magnetoencephalography data were collected during a 40-Hz ASSR paradigm for a group of 116 CHR-P participants, 33 patients with first-episode psychosis (15 antipsychotic-naïve), a psychosis risk-negative group (n = 38), and 49 healthy control subjects. Analysis of group differences of 40-Hz intertrial phase coherence and 40-Hz amplitude focused on right Heschl's gyrus, superior temporal gyrus, hippocampus, and thalamus after establishing significant activations during 40-Hz ASSR stimulation. Linear regression and linear discriminant analyses were used to predict clinical outcomes in CHR-P participants, including transition to psychosis and persistence of attenuated psychotic symptoms (APSs). RESULTS: CHR-P participants and patients with first-episode psychosis were impaired in 40-Hz amplitude in the right thalamus and hippocampus. In addition, patients with first-episode psychosis were impaired in 40-Hz amplitude in the right Heschl's gyrus, and CHR-P participants in 40-Hz intertrial phase coherence in the right Heschl's gyrus. The 40-Hz ASSR deficits were pronounced in CHR-P participants who later transitioned to psychosis (n = 13) or showed persistent APSs (n = 34). Importantly, both APS persistence and transition to psychosis were predicted by 40-Hz ASSR impairments, with ASSR activity in the right hippocampus, superior temporal gyrus, and middle temporal gyrus correctly classifying 69.2% individuals with nonpersistent APSs and 73.5% individuals with persistent APSs (area under the curve = 0.842), and right thalamus 40-Hz activity correctly classifying 76.9% transitioned and 53.6% nontransitioned CHR-P participants (area under the curve = 0.695). CONCLUSIONS: Our data indicate that deficits in gamma-band entrainment in the primary auditory cortex and subcortical areas constitute a potential biomarker for predicting clinical outcomes in CHR-P participants.