اختلالات راهگاهی حسی در سندرم روان پریشی ضعیف

Background Individuals with an “Attenuated Psychosis Syndrome” (APS) have a 20–40% chance of developing a psychotic disorder within two years; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether P50 gating deficits could help to discriminate individuals with APS and also those who are particularly likely to make a transition to psychosis. Method 36 cases meeting PACE (Personal Assessment and Crisis Evaluation) criteria for the APS, all free of antipsychotics, and 60 controls performed an auditory conditioning–testing experiment while their electroencephalogram was recorded. The P50 ratio and its C–T difference were compared between groups. Subjects received follow-up for up to 2 years to determine their clinical outcome. Results The P50 ratio was significantly higher and C–T difference lower in the APS group compared to controls. Of the individuals with APS who completed the follow-up (n = 36), nine (25%) developed psychosis. P50 ratio and the C–T difference did not significantly differ between those individuals who developed psychosis and those who did not within the APS group. Conclusion P50 deficits appear to be associated with the pre-clinical phase of psychosis. However, due to the limitations of the study and its sample size, replication in an independent cohort is necessary, to clarify the role of P50 deficits in illness progression and whether this inexpensive and non-invasive EEG marker could be of clinical value in the prediction of psychosis outcomes amongst populations at risk.

The P50 auditory evoked potential has been used to reflect the brain's gating mechanism, which is the individual's ability to filter out repetitive or trivial stimuli in order to minimize information overload (Freedman et al., 1996). P50 auditory event-related potential (ERP) waves are generated by identical pairs of clicks 500 ms apart in what is commonly referred to as the conditioning–testing paradigm. The first stimulus (condition P50; C) activates or conditions the inhibition phenomenon, while the second (test P50; T) tests its strength. Normally, individuals exhibit more than a 70% reduction of the second wave relative to the first. This diminished T wave is thought to be the product of inhibitory neural circuitry by the C stimuli (Adler et al., 1982 and Freedman et al., 1997). Compared to controls, patients with schizophrenia show a relatively larger P50 response to the second stimulus in a paired-click auditory evoked response paradigm, resulting in only 20%–50% suppression (Freedman et al., 1983, Freedman et al., 1987, Nagamoto et al., 1989, Judd et al., 1992, Ward et al., 1996, Clementz et al., 1997, Clementz et al., 1998 and Shaikh et al., 2010). Unaffected first-degree biological relatives of schizophrenia patients also have poor P50 suppression, suggesting that this effect may be familial, indeed relating to the genetic liability for this illness (Siegel et al., 1984, Waldo et al., 1988, Waldo et al., 1995, Waldo et al., 2000, Stevens et al., 1996, Clementz et al., 1998 and Shaikh et al., 2010). Diminished P50 suppression has also been found in bipolar disorder patients with psychotic features and their unaffected relatives (Franks et al., 1983, Baker et al., 1990, Olincy and Martin, 2005, Schulze et al., 2007, Hall et al., 2008 and Sanchez-Morla et al., 2008). There is some controversy regarding whether or not the schizophrenia-related deficit represents a ‘gating’ phenomenon. Some studies have reported that the amplitude from the second stimulus is the same in patients and controls, while the amplitude and/or latency for the first stimulus is altered in patients, perhaps accounting for the decreased ratio (Jin and Potkin, 1996 and Jin et al., 1997). As such, the reduced P50 amplitude to the second of paired clicks (C, T) might be more reliably measured as the difference between P50 amplitudes (C–T) rather than its ratio (T/C) (Dalecki et al., 2011). Generally, the utility of P50 paired-click measures has been limited by their unestablished reliability, unknown effects of time differences in peak selection methodology and rater blinding, poor signal-to-noise ratio, sound intensity, seating position and long protocol (de Wilde et al., 2007a, de Wilde et al., 2007b and Dalecki et al., 2011). In spite of controversies surrounding the P50 ERP, reduced P50 ratio in schizophrenia has been confirmed meta-analytically (Bramon et al., 2004, de Wilde et al., 2007a and de Wilde et al., 2007b). Studies have shown that P50 gating is already impaired in the early stages of schizophrenia. Myles-Worsley et al. (2004) compared a genetically defined high-risk group and a clinically defined sample of at-risk adolescents and showed that P50 suppression was impaired in both groups. Yet, in the genetically high-risk group, P50 suppression abnormalities were found only in those with clinically defined prodromal symptoms. Cadenhead et al. (2005) showed that subjects at risk of developing a psychosis with a first-degree relative with schizophrenia had significantly lower levels of P50 suppression relative to control subjects. Furthermore Brockhaus-Dumke et al. (2008) found that P50 gating deficits are present in individuals at clinical high risk and amongst drug-naïve first-episode patients in comparison to control subjects. However, not all studies have shown P50 deficits in high risk individuals (Ziermans et al., 2012), first episode psychosis (de Wilde et al., 2007b and Bachmann et al., 2010) and established schizophrenia (Kathmann and Engel, 1990). Since the P50 wave has been shown to be both heritable (Young et al., 1996 and Hall et al., 2006) and possibly linked to liability for psychotic disorders, we expected to demonstrate and replicate P50 suppression in individuals with APS. Our first prediction was that P50 ratio would be increased and C–T amplitude difference smaller in the APS group relative to controls. As a preliminary analysis we also explored whether P50 suppression could be used to identify those individuals with APS who are likely to make a conversion to psychosis.