Pre-pulse inhibition
Disorders that have PPI in common
Thus, as reviewed in some detail in Braff et al. (2001), studies prior to 2001 demonstrated that PPI deficits are also evident in patients with schizotypal personality disorder, Obsessive Compulsive Disorder (OCD), Tourette’s Syndrome, and Huntington’s Disorder, and under some experimental conditions PTSD. This group of disorders has been suggested to reflect a family of disorders which can be characterized as having deficits in the gating of motor (Huntington’s, Tourette’s), sensory (schizophrenia), and/or cognitive information (OCD). (R5)
PPI is lowered in OCD
OCD patients had significantly less PPI across all three PP intensities compared with controls. Exploratory analyses indicated that OCD patients with a history of tics had lower levels of PPI. Our results demonstrate that unmedicated OCD patients have impaired sensorimotor gating as measured by PPI.
This indicates that PPI deficits are present in OCD patients and are not the result of medication effects. Our findings also suggest that OCD patients with a history of tics may have greater impairment in sensorimotor gating than the general OCD population. (R6)
We found a trend for disruption of sensorimotor gating in Sapap3-KOs using the translational measure prepulse inhibition (PPI); however, there was significant heterogeneity in both PPI and compulsive grooming in KOs.
Disruption of PPI was significantly correlated with a more severe compulsive phenotype. In addition, PPI disruption and compulsive grooming severity were associated with reduced dopamine D1 and D2/3 receptor density in the nucleus accumbens core (NAcC).
Compulsive grooming progressively worsened in Sapap3-KOs tested longitudinally, but PPI disruption was first detected in high-grooming KOs at 7 months of age. (R7)
PPI in schizophrenia may depend on the state of the patient
A longitudinal study on patients with schizophrenia reported that PPI deficits in medicated patients were observed in acute illness, but not in an improved clinical state, which suggests that PPI deficits may be state dependent (R8)
Typical antipsychotics may plower PPI, while Lamotrigine and lithium may increase PPI in Bipolar Disorder
Female patients on typical antipsychotics had significantly lower PPI than those without such medication. PPI was significantly positively correlated with lamotrigine dosage in male patients and lithium dosage in female patients. These findings may suggest that lamotrigine and lithium ameliorate the PPI deficits if sufficient dosage is prescribed. (R8)
PPI differs between phases of menstrual cycle
It is known that women present fluctuations in PPI across the menstrual cycle, with the lowest PPI in the mid-luteal phase when ovarian hormones (estrogen and progesterone) are maximal.
Thus, Gogos et al. examined PPI in euthymic patients with BD stratified by gender and reported sexually dimorphic differences: male patients showed reduced PPI, while female patients in the follicular phase had increased PPI compared to their healthy counterparts. (R8)
Theta-oscillation
These results suggest that PPI functions not only as sensory-motor gating but also as sensory-cognitive gating since theta oscillations are involved in control of cognitive processes. Absence of significant correlations between PPI of the startle reflex and of theta oscillations at all electrode locations indicates that the two processes may be controlled by different neural mechanisms. (R2)
Factors leading to impaired PPI
Vitamin D deficiency
Combined prenatal and chronic postnatal vitamin D deficiency in rats impairs prepulse inhibition of acoustic startle (R1)
Omega-3 deficiency
Diminished PPI has been consistently demonstrated in patients with a variety of neuropsychiatric disorders such as schizophrenia, schizotypal personality disorder, Huntington’s disease, obsessive compulsive disorder, Tourette’s syndrome, bipolar disorder and attention deficit disorder.
These patients are characterized by a general reduction of the ability to gate intrusive sensory, motor or cognitive information, leading to sensory flooding and cognitive fragmentation and, consequently, to a significant deficit in attention and information processing.
The experimental diets employed here were designed to provide for varying levels of DHA in the nervous system. It was hypothesized that PPI would vary with nervous system DHA content. (R3)
H2S overload
Restoring PPI
Clonidine
Structures relevant to PPI include the frontal dopaminergic pathways and striatum (Swerdlow et al., 2001). Pharmacological interventions that restore normal PPI typically have good predictive validity for efficacy in multiple neuropsychiatric disorders including TS.
PPI has a relevant noradrenergic component as disruptions to PPI can be restored with clonidine, an alpha-2 agonist, and a separable dopaminergic component (Swerdlow et al., 2006). In addition to the predictive validity, it has been suggested that PPI models may also have possible face validity for TS, perhaps modeling the sensory component or premonitory urge present in TS that cannot be filtered or gated (Swerdlow and Sutherland, 2005). (R4)