Previous studies with prepulse inhibition in panic disorder (PD) have suggested that the early stages of sensory information processing are abnormal in patients with PD. To further investigate sensory gating function in panic disorder we performed a case-control study in a sample of 28 patients with PD, compared to 28 normal subjects and 28 schizophrenic subjects evaluating auditory mid-latency evoked potential P50 in a double-click paradigm as a measure of sensory gating. PD subjects showed weaker sensory gating as evidenced by higher P50 ratios as compared to normal subjects (62.5% vs. 45.4%, p = 0.03) and higher S2 (test) amplitude (3.5 μV vs. 2.1 μV, p = 0.01). Schizophrenic subjects when compared to healthy controls showed higher P50 ratios as compared to normal subjects (79.2% vs. 45.4%, p < 0.01) and higher S2 amplitude (3.3 μV vs. 2.1 μV, p = 0.01), but were not statistically different from PD subjects (p > 0.1). The present study corroborates recent findings of sensory gating dysfunction in PD. Further studies are still necessary to better understand the pathophysiology of this neurophysiological dysfunction and its nature as a trait or a state marker.
Auditory brain evoked potentials and other neurophysiological examinations have been performed in panic disordered patients in order to understand its underlying pathophysiology. Panic disordered patients were found to exhibit significantly larger N1 amplitudes associated initially to abnormal temporal processing (Knott et al., 1991) and N3 latency abnormalities, correlated to pontine activation, probably through locus ceruleus ( Levy et al., 1996). These patients also showed enlarged prefrontal P300 in response to stimulus change, related to prefrontal-limbic pathways that could affect the processing of incoming information, supposedly disrupted in panic disorder (PD) ( Clark et al., 1996 and Turan et al., 2002) or even related to reticulothalamic structures plus septohippocampal limbic system ( Gordeev et al., 2003). A standard two-tone discrimination task study (oddball task) showed amplitudes that are also suggestive of alteration of early information processing in PD, specifically N1 and N2 amplitudes for target tones and the N1 amplitude for non-target tones were significantly larger in the PD patients ( Iwanami et al., 1997). Another odd-ball study replicated findings of an abnormal N2 in PD ( Wang et al., 2003). More recently, studies focusing sensory gating based in the pre-pulse inhibition (PPI) were carried out in PD. Panic disorder patients in remission exhibited normal startle reactivity, reduced habituation and significantly reduced pre-pulse inhibition (PPI) and these alterations were more pronounced in patients with high trait and state anxiety ( Ludewig et al., 2002). Increased startle response and decreased habituation were found in PD patients that were not under treatment and correlated significantly with higher cognitive dysfunction scores, but this was not the case for PPI ( Ludewig et al., 2005).
The suppression of the P50 component of the auditory event-related potential has been used as an index of sensory gating in neuropsychiatric research (Freedman et al., 1983 and Adler et al., 1998). The P50 wave is a small amplitude, positive wave occurring about 50 ms after an auditory stimulus. In the P50 suppression paradigm, when two stimuli are presented 500 ms apart, the amplitude of the second peak (S2), compared to the first (S1), is usually attenuated in healthy subjects (S2/S1 ratio <0.5), whereas in patients with schizophrenia, acute mania or post-traumatic stress disorder this suppression is impaired (S2/S1 ratio > 0.5) (Adler et al., 1998 and Ghisolfi et al., 2004). The hippocampus, as well as structures of brainstem and temporal cortex have been suggested as mediators of P50 suppression and it is generally assumed that impaired suppression due to an inhibitory deficit, which leads to an overflow of information and diminished capacity to filter out irrelevant stimuli (Adler et al., 1998). The neurochemical basis of P50 suppression is not yet completely understood, but cholinergic, GABAergic and monoaminergic systems have been proposed to modulate this phenomenon (Adler et al., 1998, Hershman et al., 1995 and Light et al., 1999) and more recently adenosine has been implicated in P50 dysfunction (Ghisolfi et al., 2002).
Despite the cumulative evidence for the involvement of auditory sensory processing and for disturbed sensory gating in PD, studies on P50 auditory gating are lacking, as far as we know. This work was designed to compare P50 auditory gating between PD patients and control healthy volunteers as well as schizophrenic patients as an additional control group.
