sensory(gang in psychiatry(€¦ · • eye(movementdisorders • sensory(gang (• p50 • p300...
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Sensory ga+ng in psychiatry
Rikus Knegtering 2015
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• Eye movement disorders • Sensory Ga+ng • P 50 • P 300 • Prepulse Inhibi+on, startle reflex • Clinical correlated • Importance for understanding psychopharmcology
Turetsky et al Schizophrenia Bulle+n vol. 33 no. 1 pp. 69–94, 2007 PoQer et al Schizophrenia Bulle+n vol. 32 no. 4 pp. 692–700, 2006
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Gladde oogvolgbewegingen
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Date of download: 3/8/2015 Copyright © 2015 American Medical Association. All rights reserved.
From: Dependence of Impaired Eye Tracking on Deficient Velocity Discrimination in Schizophrenia
Arch Gen Psychiatry. 1999;56(2):155-161. doi:10.1001/archpsyc.56.2.155
Sample tracings of smooth pursuit eye movements of a schizophrenic patient (top) and a normal control (middle) following a 0.4-Hz sine wave (bottom, dashed line). Note that the normal control record is smooth except for a blink at about 12 seconds into the record. The record of the schizophrenic patient shows a very irregular pattern, suggestive of low gain pursuit with frequent saccadic eye movements.
Figure Legend:
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Cri+cal Flicker fusion Frequency (threshold) CFFFt
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Jozarni Dlabač-‐de Lange MD., Marc Kuipers, Mike Vervoort MD., Gerben Duisterwinkel MD., Sjoerd Sytema MSc. PhD. Henderikus Knegtering MD. PhD. (2010). Schizophrenia can be diagnosed in the blink of an eye; it lowers the cri+cal flicker fusion frequency threshold.
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Jozarni Dlabač-‐de Lange MD., Marc Kuipers, Mike Vervoort MD., Gerben Duisterwinkel MD., Sjoerd Sytema MSc. PhD. Henderikus Knegtering MD. PhD. (2010). Schizophrenia can be diagnosed in the blink of an eye; it lowers the cri+cal flicker fusion frequency threshold.
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Cogni+ve deficits in schizophrenia 2
Sensory deficits
Sensory ga+ng deficits
AQen+on deficits
Reac+on +me deficits
(Working) memory deficits
Higher informa+on processing deficits (interpreta+on)
Hallucina+ons, delusions, desorganized thinking, nega+ve symptoms
Kitchen et al.Adv Ther. 2012 Feb;29(2):148-‐62
Metabolic? Connec+vity? Func+onal? Deficit
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P 300
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P 300
• P300, soms ook P3 of P3b genoemd, is een posi+eve elektrische golf in het EEG die op ongeveer 300 ms na een s+mulus optreedt.
• Event Related Poten+al (ERP)
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P 300
• P300 is het duidelijkst waarneembaar boven de pariëtale (achterste) loca+es op de schedel
• Na aanbieding van infrequent voorkomende en onverwachte signalen die een bepaalde reac+e van de proefpersoon vragen. Men krijgt bijvoorbeeld lage (500 Hz) en hoge tonen (1000 Hz) te horen die onvoorspelbaar zijn, maar met een ongelijke frequen+e van respec+evelijk 80% en 20% voorkomen. Dit wordt ook wel een oddballtaak genoemd.
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P300
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Controles N=36
Pa+enten Schiz N=52
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Wat weerspiegelt P300?
• P300: reflec+e van een mechanisme in de hersenen dat geac+veerd wordt als een relevante gebeurtenis bewust wordt verwerkt of herkend.
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Sensory ga+ng I Cocktail party effect.
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Prepulse Inhibi+on (PPI)
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Prepulse Inhibi+on
• Modellen van schizofrenie: • Amfetamine of fencyclidine. • Deze stoffen blijken inderdaad in staat ppi, p50-‐ga+ng, te verstoren
(Ellenbroek & Cools 2002).
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Prepulse Inhibi+on
• Een aantal nieuwere diermodellen richt zich vooral op de lange termijn consequen+es van vroege stressvolle factoren, zoals vroege hippocampale laesies en maternale depriva+e.
• In beide modellen blijken de ppi verminderd. Bovendien blijkt dat deze verstoring pas na de puberteit optreedt, terwijl de manipula+e reeds op hele jonge leemijd (tweede week na de geboorte) plaatsvindt.
Ellebroek en Cools Tijdschrim voor psychiatrie 44 (2002) 11
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Roken en schizofrenie
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Prepulse Inhibi+on (PPI), = startle respons
A weak sound preceding the loud acous+c s+mulus inhibits the startle reflex; this is called pre-‐pulse inhibi6on. Prepulse inhibi+on (PPI) is the decrease of startle amplitude by a prepulse presented shortly before the startle s+mulus that does not elicit a startle response itself. Pre-‐pulse inhibi+on (PPI) is impaired in schizophrenic pa+ents.
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Prepulse Inhibi+on (PPI), = startle respons
A weak sound preceding the loud acous+c s+mulus inhibits the startle reflex; this is called pre-‐pulse inhibi6on. Prepulse inhibi+on (PPI) is the decrease of startle amplitude by a prepulse presented shortly before the startle s+mulus that does not elicit a startle response itself. Pre-‐pulse inhibi+on (PPI) is impaired in schizophrenic pa+ents.
control pa+ent
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Prepulse Inhibi+on (PPI)
Swerdlow NR et al Arch Gen Psych. December, 2006;63:1325-‐1335
pa+ent
A significant rela+onship between PPI and the Global Assessment of Func+oning (GAF) scale—GAF scores were higher in pa+ents with the highest PPI.
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Prepulse Inhibi+on (PPI)
Swerdlow NR et al Arch Gen Psych. December, 2006;63:1325-‐1335
pa+ent
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Prepulse Inhibi+on (PPI)
Swerdlow NR et al Arch Gen Psych. December, 2006;63:1325-‐1335
pa+ent
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Sensory ga+ng II
• The Cocktail Party Effect illustrates how the brain inhibits input from environmental s+muli, while s+ll processing sensory input from the aQended s+mulus.
• The cocktail party effect demonstrates sensory ga+ng in hearing, but the other senses also go through the same process protec+ng primary cor+cal areas from being overwhelmed.
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Paired-‐click paradigm 1 klik waargenomen
1 klik waargenomen
2 klik waargenomen door control 2 klikken door mensen met schizofrenie
P50 NC laag
P50 NC Hoog
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Sensory ga6ng deficits and mental illness
• Nico6ne and sensory ga6ng • Nico+ne aids selec+ve aQen+on. • Nico+ne can correct sensory ga+ng deficits for individuals with schizophrenia, but the effects only last about thirty minutes amer nico+ne intake.
• The same self-‐medica+on may be present among those with aQen+on-‐deficit/hyperac+vity disorder.
• Adler, L. E., Oliency, A., Waldo, M., Harris, j. G., Griffith, J., Stevens, K., Flach, K., Nagamoto, H., Bickford, P., Leonard, S., Freedman, R. (1998). Schizophrenia, Sensory Ga+ng, and Nico+nic Receptors. Schizophrenia Bulle+n, 24(2):189-‐202.
• Perry, W., Minassian, A., Lopex, B., Lincoln, A. (2007). Sensorimotor Ga+ng Deficits in Adults with Au+sm. Society of Biological Psychiatry, 61: 482-‐496.
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P 50 Sensory Ga+ng Abnormali+es in Schizophrenia
• Posi+ve and perhaps the nega+ve symptoms of schizophrenia are a result of sensory overload and/or an impairment in the response to sensory input within the central nervous system?
• Sensory ga+ng abnormali+es have also been hypothesized to be associated with various cogni+ve impairments?
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P 50 Sensory Ga+ng Abnormali+es in Schizophrenia
• Pharmacological studies: importance of the cholinergic system in regula+ng the diminished response to repeated s+muli, through s+mula+on of the a-‐7 nico+nic receptor.
• In pa+ents with schizophrenia, nico+ne can transiently reverse the P50 sensory ga+ng deficits.
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P 50 Sensory Ga+ng Abnormali+es in Schizophrenia
• A marker of the gene for the a-‐7 nico+nic receptor has been linked to schizophrenia and P50 abnormali+es (Freedman et al 1997-‐2001).
• Polymorphisms in the promotor region of the gene for the a-‐7 nico+nic receptor may be related to abnormal sensory ga+ng (Leonard et al 2002).
• Sensory ga+ng abnormality in schizophrenia has been evidence that family members of people with schizophrenia also have deficits in P50 sensory ga+ng inhibi+on
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S1 S1 S2 S2
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Sensory Ga+ng, P50 Clinical correlates
• Correla+ons are suggested between P50 abnormali+es in schizophrenia – Sustained aQen+on (CPT) – Processing speed (digit symbol)
• Possible associa+on with severity of symptoms (posi+ve and nega+ve) in schizophrenia, but many studies could not confirm an associa+on
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Sensory Ga+ng, P 50, Psychopharmacology I
• First and second genera+on an+psycho+cs seems not to influence sensory ga+ng expressed as a reverse P50 T/C ra+o differences in schizophrenia
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Sensory Ga+ng, P 50, Psychopharmacology II
• Clozapine and nico+ne may reverse P50 T/C ra+o differences in schizophrenia
• Nico+ne lowers P50 T/C ra+o through diminished S2 amplitude, which is thought to reflect enhanced sensory ga+ng through ac+va+on of the a7 nico+nic receptor.
PoQer et al Schizophrenia Bulle+n vol. 32 no. 4 pp. 692–700, 2006
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Conclusies • Veel mensen die voldoen aan DSM criteria van schizofrenie (en deels ook hun verwanten) hebben een veranderde verwerking van sensorische input en motorisch output wat o.a. blijkt uit
• Afwijkingen in gladde oogbewegingen maar ook andere aspecten van motoriek (+jdschrim psychiatrie febr 2015)
• PPI • P50, P300 • En vele andere testen (o.a. mismatch nega+vity, CFFF) • Wat betekent dit voor het dagelijks bestaan?