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HPPD Project Tidbits

David S. Kozin

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"The importance of GABA–5-HT interactions and the role of these interactions in the pathophysiology of altered perception, psychosis, dissociative states, and anxiety. Gamma-aminobutyric acid deficits resulting in excess serotonergic activation, multiple sites in the brain where this can occur (protocol suggested), could be the measure that predisposes the production or exacerbation of perceptual alterations,

and this same mechanism studied in other contexts might apply to HPPD, DPD, DR, and other disorders where GABA deficits have been described (Anxiety, etc). Recent studies (cite DS) lend support to the notion that dysfunction within a network involving several neurotransmitters might underlie the pathophysiology of psychosis and dissociative- like perceptual states."

This is incorporated with are interested in using PPI as an operational measure of sensorimotor gating with HPPD and control participants. A number of neurological and psychopathological disorders that have known dysfunction in brain substrates that regulate PPI also have evidence of impaired cognitive, motor or sensorimotor inhibition. We intend on determining if the HPPD population has impaired senorimotor gating, which will help demonstrate the neurological basis for HPPD.

PPI occurs when a relatively weak sensory event (the prepulse) is presented 30–500 ms before a strong startle-inducing stimulus, and this reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different sensory modalities (acoustic, visual, or cutaneous). Our objective is to examine if visual persisting perception disorder influences on PPI related to the underlying construct of sensori- (prepulse) motor gating (startle reflex; measured with electromygraphy). We can compare our results with past PPI studies with other psychopathological and neurological disorders, which form a group of related gating disorders. Lastly, we will note any effects correlated with different medications that individuals may be taking that could influence PPI in individuals with HPPD. Notably, others (Pouretemad et al. 1998) reported PPI deficits in individuals with “non-epileptic seizures”, which may constitute a variant of Temperal Lobe Epilepsy. This latter observation suggests that psychosis per se is not a requirement for deficient PPI in seizure disorder patients. Study findings of PPI deficits in non-psychotic individuals for reduced PPI in non-psychotic patients with bipolar affective disorder will be reduced with JH’s differential diagnosis.

In humans, Abduljawad et al. (1997) assessed the effects of clonidine and diazepam on startle and PPI in normal male volunteers. Subjects were tested in a within-subject design in which they received oral doses of placebo, 10 mg diazepam, and 0.2 mg clonidine in a balanced double-blind protocol. EMG recordings from the right eye were obtained during each drug’s peak plasma level for maximal CNS effect. Both drugs dramatically reduced the magnitude of startle responses, neither drug significantly altered PPI calculated as a percent score.

Hallucinogenic serotonin agonists, such as 2,5-dimethoxy-4-iodoamphetamine (DOI), disrupt PPI in rats (Geyer et al. 2001), psilocybin, however, does not appear to disrupt PPI in rats reliably, perhaps because it is less selective as a serotonin agonist relative to DOI. As discussed in Geyer et al. 2001, this 5-HT1A agonists increase PPI in mice despite the fact that they decrease PPI in rats. Thus, the 5-HT1A agonist actions of psilocybin, which are not shared by DOI, may be responsible for the increased PPI observed in human subjects by Gouzoulis-Mayfrank et al. (1998). PPI’s unique actions will help support information related to the neurobiological pathways and receptor sites potentially implicated in the cause of the disorder.

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