The Shine-Through Masking Paradigm Is a Potential Endophenotype of Schizophrenia

BACKGROUND: To understand the genetics of schizophrenia, a hunt for so-called intermediate phenotypes or endophenotypes is ongoing. Visual masking has been proposed to be such an endophenotype. However, no systematic study has been conducted yet to prove this claim. Here, we present the first study showing that masking meets the most important criteria for an endophenotype. METHODOLOGY/PRINCIPAL FINDINGS: We tested 62 schizophrenic patients, 39 non-affected first-degree relatives, and 38 healthy controls in the shine-through masking paradigm and, in addition, in the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST). Most importantly, masking performance of relatives was significantly in between the one of patients and controls in the shine-through paradigm. Moreover, deficits were stable throughout one year. Using receiver operating characteristics (ROC) methods, we show that the shine-through paradigm distinguishes with high sensitivity and specificity between schizophrenic patients, first-order relatives and healthy controls. CONCLUSIONS/SIGNIFICANCE: The shine-through paradigm is a potential endophenotype

GEE results of shine-through, CPT-DS, and WCST.

<p>Dependent variables were SOA (stimulus onset asynchrony), d', and total number of errors, respectively. Bars indicate performance of schizophrenic patients (schiz), non-affected first-order relatives (rel), and healthy controls (con). Error bars indicate standard errors. Schizophrenic patients perform worse than controls in all tests. The difference between relatives and healthy controls is only significant in the shine-through paradigm; * <i>p</i><0.01, ** <i>p</i><0.001, *** <i>p</i><0.0001.</p

Effect sizes (ES) and confidence intervals (CI) of the comparisons between relatives and patients, relatives and controls, and patients and controls.

<p>The SOA of the shine-through test is log-transformed. ES =  Mean difference adjusted by age, gender, and education (GEE). Partial eta-squared values are estimated by the general linear model.</p

ROC (receiver operating characteristics) curves for the shine-through paradigm, the CPT-DS, and WCST.

<p>(A) ROC curves for schizophrenic patients and healthy controls. The x-axis indicates the error of the second kind (100%-specificity). The y-axis indicates sensitivity. The area under the curve (AUC) shows the discriminative power between the two groups. The diagonal from (0,0) to (100,100) with AUC = 0.5 indicates a total lack of discriminative power. AUC values are given in the text. All tests discriminate well between schizophrenic patients and healthy controls with the shine-through paradigm showing the significantly best discrimination. (B) ROC curves for non-affected first-order relatives of schizophrenic patients and healthy controls. All ROC curves are more attenuated than the ones comparing patients and controls (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014268#pone-0014268-g003" target="_blank">figure 3 A</a>). Again, the shine-through paradigm yields the highest discriminative power.</p

Procedure.

<p>(A) For each observer, we determined the individual vernier duration (VD) for which 75% correct responses were reached. (B) In the next step, the vernier was presented with the individual VD of each observer. The vernier offset was fixed at 1.15′. This vernier was followed by a blank screen (ISI) and a grating comprised of 25 aligned verniers, (SOA = VD + ISI).</p

Demographic data.

<p>Gender, age (ys), education (ys), duration of illness (ys), SANS (Scale for the Assessment of Negative Symptoms), SAPS (Scale for the Assessment of Positive Symptoms), and vernier duration (VD). There are more males in the schizophrenia group. Controls are better educated than patients and relatives. The VD of schizophrenic patients is nearly twice that of relatives and controls. Indicated are means and standard deviations.</p

Performance in the shine-through paradigm for 18 schizophrenic patients and 20 controls at three occasions.

<p>Session II took place about 6 months after session I and session III about 6 months after session II. Schizophrenic patients show a weak (but statistically non significant) improvement with time. Error bars show standard errors.</p