Investigation of Sensory Gating Processes in First-Episode Schizophrenia Patients and Their Healthy Siblings with Event-Related Potentials (ERPs) ERDIL ARSOY ADVISOR: PROF. MUGE DEVRIM UCOK Master Thesis in Neuroscience Istanbul University, Institute for Experimental and Medical Research - 2017
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Investigation of Sensory Gating Processes in First-Episode Schizophrenia Patients and Their Healthy Siblings with Event-Related Potentials (ERPs)
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Investigation of Sensory Gating Processes in First-Episode Schizophrenia Patients and Their Healthy Siblings with Event-Related Potentials (ERPs)
ERDIL ARSOY
ADVISOR: PROF. MUGE DEVRIM UCOK
Master Thesis in Neuroscience
Istanbul University, Institute for Experimental and Medical Research - 2017
Index
1. Objective
2. General Information
3. Method
4. Results
5. Discussion & Conclusion
6. References
Objective
Attain significances in sensory gating processes among first-episode
schizophrenia patient, sibling and control groups
Evaluation of P50, N100 and P200 potentials via different methods
Enhance the number of healthy sibling and control groups in previous
TUBITAK Project (Devrim-Ucok et al 2008)
Symptoms are mostly manifest themselves as:
o hallucinations, delusions, disorganized speech and decreases in DLAs
o insidious beginning
o slow and gradually increasing symptoms
Life-time prevalence % 0.3 – 0.7
Possibly start at late-adolescence in men and adulthood in women (APA 2013)
General InformationSchizophrenia
Keshavan & Schooler (1992) stated five clinical features for FES:
i. Decrease in social skills
ii. Onset of behavioral symptoms
iii. Onset of positive and negative symptoms
iv. First treatment
v. First hospitalization
General InformationFirst-Episode Schizophrenia
CNS’s ability of inhibit incoming irrevelant stimuli
and facilitate important ones
Standart measure of sensory gating is P50
P50 sensory gating is evaluated via paired-click
paradigm (PCP)
o S1 conditioning stimulus; S2 test stimulus
o S2/S1 ratio/S1-S2 difference
o Decreased ratio/high difference = successful gating
(Turetsky et al 2008)
Paired-Click Paradigm
General InformationSensory Gating
Abnormal P50 gating with PCP in schizophrenia is:
Potential endophenotype
«Fixed trait» associated with genetic features
Hereditable
Predispositional on unaffected siblings
General InformationP50 Gating Paradigm
(Lijffijt et al 2009)
Gating ratio and difference may measure brain stem, hippocampus and cerebral cx gating
S1 stimulus may be a neural response of synaptic activation of auditory cortex
interneural GABA oscillation
inhibition of S2 stimulus response
General InformationP50 Gating Paradigm
Some of medication studies state that:
• Patients with typical antipsychotic and non-medicated patients shows similar gating processes
(Boutros et al 2004)
• However, patients who were treated with atypical antipsychotics show improvement in gating
processes (Nagamoto et al 1999)
Therefore recent studies:
• Designed with early phase of illness as FES and prodromal
• Thus long-term impairments caused by cronicity can be eliminated (Devrim-Ucok et al 2008).
General InformationP50 Gating Paradigm
ERP indentified between 70-110 ms
Band-pass filter of 10-55 Hz
Patterson et al (2009) found:
• S1 and S2 peaks are similar in bipolar I disorder
patients but not in schizophrenia spectrum
disorder patients
• Therefore, P85 may not be an endophenotype for
schizophrenia but for bipolar I disorder
(Patterson et al 2009)
General InformationP85 Gating Paradigm
Represent higher cognitive functions and
further levels of information processes
Recent studies found that:
o Ultra-high risk patients show unsufficient gating
by comparison with healthy controls (Brockhaus-
Dumke et al 2008)
o More reliable than P50 (Rentzsch et al 2008)
o Hereditable (Anokhin et al 2006)(Lijffijt et al 2009)
General InformationN100/P200 Gating Paradigm
1. Latency
o 40-80 ms (Boutros et al 2004); 25-75 ms; 40-75
ms (Patterson et al 2008); 40-90 ms (Nagamoto
et al 1999); 40-85 ms (Clementz & Blumenfeld
2001)
2. P30/N40
o P30 15-40 ms, Pa, possible artifact (?)
(Nagamoto et al 1999)
o N40 25-60 ms, Nb (van Tricht et al 2012)(Rentzsch et al 2008)
General InformationMethodological Differences
Several methods are used in attempt to measure sensory gating:
3. Average
o S2/S1 ratio & S1-S2 difference
o Difference may be more reliable (Smith et al 1994)
o Difference and ratio might be interrelated (Peters et al 2014)
4. Amplitude
o Peak to peak (PP) standart measure of P50 and P85
o Baseline to peak (BP) standart measure of N100 and P200
o BP might be more reliable than PP with S2/S1 ratio measure (Rentzsch et al 2008)