Atypical attentional filtering of visual information in youth with chromosome 22q11.2 deletion syndrome as indexed by event-related potentials.

BACKGROUND: Youth with chromosome 22q11.2 deletion syndrome (22q) face one of the highest genetic risk factors for the development of schizophrenia. Previous research suggests impairments in attentional control and potential interactions with elevated anxiety and reduced adaptive functioning may increase the risk for developing psychosis in this population. Here, we examined how variations in attentional control relate to the presence or severity of psychosis-proneness symptoms in these individuals. METHODS: To achieve this, we measured attentional control in youth (12-18 years) with 22q (N = 35) compared to a typically developing group (N = 45), using a flanker task (the Distractor Target task) while measuring neural activity with event-related potentials. RESULTS: Similar to previous findings observed in people with schizophrenia, greater attentional capture by, and reduced suppression of, non-target flanker stimuli characterized participants with 22q and was indexed by the N2pc (N2-posterior-contralateral) and PD (distractor positivity) components. Although we observed no relationships between these components and measures of psychosis-proneness in youth with 22q, these individuals endorsed a relatively low incidence of positive symptoms overall. CONCLUSIONS: Our results provide neural evidence of an attentional control impairment in youth with 22q that suggests these individuals experience sustained attentional focus on irrelevant information and reduced suppression of distracting stimuli in their environment. Impairments in attentional control might be a valid biomarker of the potential to develop attenuated positive symptoms or frank psychosis in high-risk individuals long before the age at which such symptoms typically arise. The evaluation of such a hypothesis, and the preventive potential for the putative biomarker, should be the focus of future studies.

Brain free water alterations in first-episode psychosis: a longitudinal analysis of diagnosis, course of illness, and medication effects.

BACKGROUND: Multiple lines of evidence suggest the presence of altered neuroimmune processes in patients with schizophrenia (Sz) and severe mood disorders. Recent studies using a novel free water diffusion tensor imaging (FW DTI) approach, proposed as a putative biomarker of neuroinflammation, atrophy, or edema, have shown significantly increased FW in patients with Sz. However no studies to date have investigated the longitudinal stability of FW alterations during the early course of psychosis, nor have studies focused separately on FE psychosis patients with Sz or bipolar disorder (BD) with psychotic features. METHODS: The current study included 188 participants who underwent diffusion magnetic resonance imaging scanning at baseline. Sixty-four participants underwent follow-up rescanning after 12 months. DTI-based alterations in patients were calculated using voxelwise tract-based spatial statistics and region of interest analyses. RESULTS: Patients with FE psychosis, both Sz and BD, exhibited increased FW at illness onset which remained unchanged over the 12-month follow-up period. Preliminary analyses suggested that antipsychotic medication exposure was associated with higher FW in gray matter that reached significance in the BD group. Higher FW in white matter correlated with negative symptom severity. CONCLUSIONS: Our results support the presence of elevated FW at the onset of psychosis in both Sz and BD, which remains stable during the early course of the illness, with no evidence of either progression or remission.

Disrupted GABAergic facilitation of working memory performance in people with schizophrenia.

OBJECTIVES: Gamma-Amiobutyric acid (GABA) is a primary inhibitory neurotransmitter that facilitates neural oscillations that coordinate neural activity between brain networks to facilitate cognition. The present magnetic resonance spectroscopy (MRS) study tests the hypothesis that GABAergic facilitation of working memory is disrupted in people with schizophrenia (PSZ). METHODS: 51 healthy participants and 40 PSZ from the UC Davis Early Psychosis Program performed an item and temporal order working memory (WM) task and underwent resting MRS to measure GABA and glutamate concentrations in dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) regions of interest. MRS was acquired on a 3 Tesla Siemens scanner and GABA and glutamate concentrations were referenced to creatine. Percent correct on the WM task indexed performance and correlation coefficients examined GABAergic or Glutamatergic facilitation of WM, with Fisher's Z transformation testing for group differences. RESULTS: There were no group differences in GABA or glutamate concentrations, but WM correlations were reversed between groups. In patients, higher DLPFC GABA was associated with worse rather than better WM performance. This pattern was not observed for glutamate or in the ACC. Although under-powered, there was no indication of medication effects. CONCLUSIONS AND RELEVANCE: Results cannot be explained by group differences in DLPFC GABA or glutamate concentrations but, instead, indicate that schizophrenia disrupts the GABAergic facilitation of WM seen in healthy individuals. Results appear to parallel post mortem findings in suggesting that schizophrenia alters the distribution of different classes of GABAergic interneurons rather than producing a general deficit across the total population of neurons.

Impact of schizophrenia on anterior and posterior hippocampus during memory for complex scenes.

OBJECTIVES: Hippocampal dysfunction has been proposed as a mechanism for memory deficits in schizophrenia. Available evidence suggests that the anterior and posterior hippocampus could be differentially affected. Accordingly, we used fMRI to test the hypothesis that activity in posterior hippocampus is disproportionately reduced in schizophrenia, particularly during spatial memory retrieval. METHODS: 26 healthy participants and 24 patients with schizophrenia from the UC Davis Early Psychosis Program were studied while fMRI was acquired on a 3 Tesla Siemens scanner. During encoding, participants were oriented to critical items through questions about item features (e.g., "Does the lamp have a square shade?") or spatial location (e.g., "Is the lamp on the table next to the couch?"). At test, participants determined whether scenes were changed or unchanged. fMRI analyses contrasted activation in a priori regions of interest (ROI) in anterior and posterior hippocampus during correct recognition of item changes and spatial changes. RESULTS: As predicted, patients with schizophrenia exhibited reduced activation in the posterior hippocampus during detection of spatial changes but not during detection of item changes. Unexpectedly, patients exhibited increased activation of anterior hippocampus during detection of item changes. Whole brain analyses revealed reduced fronto-parietal and striatal activation in patients for spatial but not for item change trials. CONCLUSIONS: Results suggest a gradient of hippocampal dysfunction in which posterior hippocampus - which is necessary for processing fine-grained spatial relationships - is underactive, and anterior hippocampus - which may process context more globally - is overactive.

Peak-to-peak measurement of P300 recorded at 0.3 Hz high pass filter settings in intraindividual diagnosis: complex vs. simple paradigms.

We compared effects of 0.3 Hz with 0.01 Hz settings of the high pass amplifier filter, and baseline-to-peak with peak-to-peak measurements of the P300 event-related potential. The key dependent variable of interest was intraindividual rate of accuracy in discrimination of oddball vs. frequent evoked P300 responses, in various paradigms. In Experiment 1 (a lab deception paradigm), we found that the combination of the 0.3 Hz filter setting and the peak-peak measurement of P300 correctly diagnosed oddball vs. frequent in 26 of 26 (100%) cases. This parameter combination outperformed all others. In a second, more field-like experiment (in that the participant knew that the experimenter was blind to ground truth), the peak-peak index again outperformed the base-peak index. It was also observed that the pre-stimulus EEG baseline variability exceeded that of the negative peak (NEG) following P300, i.e. the peak to which the peak-peak index refers P300 for computation. We also observed that the base-peak measurement of P300 is uncorrelated with NEG, and that NEG, seen only in 0.3 Hz channels, correlates highly (-0.67) with the duration of recovery of P300 to the pre-stimulus baseline EEG level as seen in the 0.01-Hz channel. However, in a final experiment using two simple visual and auditory oddball tasks, the base-peak measurement was as diagnostic as the peak-peak measurement.