Lack of relationship between acoustic startle and cognitive variables in schizophrenia and control subjects

Hasenkamp, Wendy; Kelley, Mary E.; Egan, Glenn; Green, Amanda; Wilcox, Lisette; Boshoven, William; Lewison, Barbara; Duncan, Erica

doi:10.1016/j.psychres.2011.02.011

Cited by 19 publications

(14 citation statements)

References 52 publications

(62 reference statements)

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“…The mechanisms underlying the apparent different effects of chronic (i.e. life-long) and acute elevations of brain KYNA on gating (29), and implications for psychiatric diseases, where PPI disruptions are not always synonymous with cognitive deficits (62), are unclear and will need to be explored in future studies (see ref. 63 for further discussion).…”

Section: Discussionmentioning

confidence: 99%

Adaptive and Behavioral Changes in Kynurenine 3-Monooxygenase Knockout Mice: Relevance to Psychotic Disorders

Erhardt

Pocivavsek

Repici

et al. 2017

Biological Psychiatry

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BACKGROUND Kynurenine 3-monooxygenase (KMO) converts kynurenine to 3-hydroxykynurenine, and its inhibition shunts the kynurenine pathway - which is implicated as dysfunctional in various psychiatric disorders - towards enhanced synthesis of kynurenic acid (KYNA), an antagonist of both α7 nicotinic acetylcholine and NMDA receptors. Possibly as a result of reduced KMO activity, elevated central nervous system levels of KYNA have been found in patients with psychotic disorders, including schizophrenia (SZ). METHODS In the present study, we investigated adaptive – and possibly regulatory – changes in mice with a targeted deletion of Kmo (Kmo−/−) and characterized the KMO-deficient mice using six behavioral assays relevant for the study of SZ. RESULTS Genome-wide differential gene expression analyses in the cerebral cortex and cerebellum of these mice identified a network of SZ- and psychosis-related genes, with more pronounced alterations in cerebellar tissue. KYNA levels were also increased in these brain regions in Kmo−/− mice, with significantly higher levels in the cerebellum than in the cerebrum. Kmo−/− mice exhibited impairments in contextual memory and spent less time than controls interacting with an unfamiliar mouse in a social interaction paradigm. The mutant animals displayed increased anxiety-like behavior in the elevated plus maze and in a light-dark box. After a D-amphetamine challenge (5 mg/kg, i.p.), Kmo−/− mice showed potentiated horizontal activity in the open field paradigm. CONCLUSIONS Taken together, these results demonstrate that the elimination of Kmo in mice is associated with multiple gene and functional alterations that appear to duplicate aspects of the psychopathology of several neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Adaptive and Behavioral Changes in Kynurenine 3-Monooxygenase Knockout Mice: Relevance to Psychotic Disorders

Erhardt

Pocivavsek

Repici

et al. 2017

Biological Psychiatry

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“…In individuals with schizophrenia however, where PPI has been proposed as an endophenotype of the disease, some studies show relationships between sensorimotor inhibition deficits and impaired cognition (Butler, Jenkins, Sprock, & Braff, 1992; Rabin, Sacco, & George, 2009), while others do not (Hasenkamp et al, 2011; Kishi et al, 2012; Molina et al, in press; N. R. Swerdlow et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Prepulse Inhibition in HIV-Associated Neurocognitive Disorders

Minassian

Henry

Woods

et al. 2013

J Int Neuropsychol Soc

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Sensorimotor inhibition, or the ability to filter out excessive or irrelevant information, theoretically supports a variety of higher-level cognitive functions. Impaired inhibition may be associated with increased impulsive and risky behavior in everyday life. Individuals infected with HIV frequently show impairment on tests of neurocognitive function, but sensorimotor inhibition in this population has not been studied and may be a contributor to the profile of HIV-associated Neurocognitive Disorders (HAND). 37 HIV-infected individuals (15 with HAND) and 48 non-infected comparison subjects were assessed for prepulse inhibition (PPI), an eyeblink startle paradigm measuring sensorimotor gating. Although HIV status alone was not associated with PPI deficits, HIV-positive participants meeting criteria for HAND showed impaired PPI compared to cognitively intact HIV-positive subjects. In HIV-positive subjects, PPI was correlated with working memory but was not associated with antiretroviral therapy or illness factors. In conclusion, sensorimotor disinhibition in HIV accompanies deficits in higher-order cognitive functions, though the causal direction of this relationship requires investigation. Subsequent research on the role of sensorimotor gating on decision-making and risk behaviors in HIV may be indicated.

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“…This deficit has been linked with weak dopamine regulation by the frontal cortex (Arnsten, 2013). Although several paradigms of startle reflex have been used (Hasenkamp et al, 2011;Dominelli et al, 2014), one of the most classic for studying this deficient sensory gating in schizophrenia is the prepulse inhibition of the startle reflex (PPI) (Hasenkamp et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Stress induced by the socially evaluated cold-pressor test cause equivalent deficiencies of sensory gating in male subjects with schizophrenia and healthy controls

Rubio

López-Muñoz

Jurado‐Barba

et al. 2015

Psychiatry Research

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It is known that patients with schizophrenia show a deficiency in the prepulse inhibition reflex (PPI). These patients display abnormalities in autonomic nervous system and hypothalamic-pituitary-adrenal function and may have an altered sensitivity to stress. To date, no studies have been carried out to determine the effect of acute stress on the PPI. We investigated whether there was a differential response in reactivity to acute stress caused by the socially evaluated cold-pressor test (SECPT) in a sample of 58 chronic male patients with schizophrenia and 28 healthy control subjects. PPI, salivary cortisol and heart rate (HR) were measured. The patients were evaluated in two sessions (with and without the SECPT) 72 h apart and basal measurements were carried out and 30 min post-startle probe. We found an increase in salivary cortisol levels and the HR with SECPT condition in both groups and a significantly lower PPI% in patients with schizophrenia. The most relevant findings of this study are that the impairment of the PPI is increased by stress. Stress-induced increase in cortisol in both groups, mainly in healthy control group which allows us to hypothesize that at least such deterioration may be due to the hypercortisolemia caused by the SECPT.

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Lack of relationship between acoustic startle and cognitive variables in schizophrenia and control subjects

Cited by 19 publications

References 52 publications

Adaptive and Behavioral Changes in Kynurenine 3-Monooxygenase Knockout Mice: Relevance to Psychotic Disorders

Adaptive and Behavioral Changes in Kynurenine 3-Monooxygenase Knockout Mice: Relevance to Psychotic Disorders

Prepulse Inhibition in HIV-Associated Neurocognitive Disorders

Stress induced by the socially evaluated cold-pressor test cause equivalent deficiencies of sensory gating in male subjects with schizophrenia and healthy controls

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