ERP-Lab 台大醫院精神部 神經生理研究室

Sensory gating deficits in the attenuated psychosis syndrome

Imperial College of London研究團隊發表於Schizophrenia Research (Impact Factor: 4.43). 12/2014; 161(2-3).之文章

ABSTRACT Background: Individuals with an “Attenuated Psychosis Syndrome” (APS) have a 20–40% chance of developing a psychotic disorder within two years; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether P50 gating deficits could help to discriminate individuals with APS and also those who are particularly likely to make a transition to psychosis. Method: 36 cases meeting PACE (Personal Assessment and Crisis Evaluation) criteria for the APS, all free of anti-psychotics, and 60 controls performed an auditory conditioning–testing experiment while their electroenceph-alogram was recorded. The P50 ratio and its C–T difference were compared between groups. Subjects received follow-up for up to 2 years to determine their clinical outcome. （繼續閱讀…）

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2014年，MMN大老芬蘭籍的Risto Näätänen與日本的Yabe發表於International Journal of psychophysiology: official journal of the International Organization of Psychophysiology(IF=3.05)之文章Mismatch negativity (MMN) deficiency: A break-through biomarker in predicting psychosis onset.

Highlights

•The MMN deficit is one of the most robust findings in schizophrenia.

•Schizophrenia patients have deficits in the duration MMN in the early course.

•Alterations in the MMN at risk-mental state may predict conversion to psychosis.

An important break-through has very recently taken place here in the prediction of conversion to psychosis when the MMN in particular to change in tone duration was recorded in clinically at risk-mental state (ARMS) individuals. Attenuations in the MMN in these patients may be very useful in helping clinicians determine who are most likely to develop a psychotic disorder, as we will review in the present article.

再來看看Näätänen與UCSD的中生代ERP專家Gregory A. Light於2013發表在PNAS之Commentary文章

Mismatch negativity is a breakthrough biomarker for understanding and treating psychotic disorders （繼續閱讀…）

Meta-analysis of Cognitive Deficits in Ultra-high Risk to Psychosis and First-Episode Psychosis: Do the Cognitive Deficits Progress Over, or After, the Onset of Psychosis? 2013 Schizophrenia Bulletin  。這一篇   Emre Bora and Robin M. Murray 刊登於 Schizophr Bull 2014 40: 744-755文章的 重要結論

1. Cognitive deficits are already established before the prodromal phases of psychosis
2. These data support the neurodevelopmental model rather than neurodegenerative and related staging models of schizophrenia.

下一篇International Journal of  Psychophysiology比較typically developing (TD)與children purportedly at risk of schizophrenia(ASz) （繼續閱讀…）

Auditory ERP components before and after transition to a first psychotic episode   荷蘭研究團隊的文章Biological Psychology, In Press, Uncorrected Proof, Available online 30 April 2011

1. 比較15Converter/ 23 Non-Converter與17 Control
2. (ERP) from prior to until shortly after a first psychotic episode in subjects at Ultra High Risk (UHR) for psychosis. N1, N2, N2b, P2 and P3 amplitudes were assessed using an auditory active oddball paradigm
3. ► N1 amplitudes show significant reductions from before until after psychotic onset.
4. ► P3 amplitudes are reduced before, but do not show changes after psychotic onset.
5. ► In UHR subjects, a differential breakdown occurs in processes that regulate the inflow of information from the environment before and after psychotic onset.

張文和教授的老朋友John Davis研究團隊之作品Proton Magnetic Resonance Spectroscopy and Illness Stage in Schizophrenia—A Systematic Review and Meta-Analysis 2011, Biological Psychiatry ; 69(5)Pages 495-503Stefan Brugger, John M. Davis, Stefan Leucht, James M. Stone

Results Significant reductions in NAA levels were found in frontal lobe, temporal lobe, and thalamus in both patient groups (effect size > .3; p < .01). In individuals at high risk of schizophrenia (of whom approximately 20% would be expected to undergo transition to psychosis), significant NAA reductions were present in thalamus (effect size = .78; p < .05), with reductions at trend level only in temporal lobe (effect size = .32; p < .1), and no reductions in frontal lobe (effect size = .05; p = .5).

Conclusions  These data suggest that schizophrenia is associated with loss of neuronal integrity in frontal and temporal cortices and in the thalamus and suggest that these changes in the frontal and temporal lobe might occur in the transition between the at-risk phase and the first episode.

另一篇Early Recognition and Disease Prediction in the At-Risk Mental States for Psychosis Using Neurocognitive Pattern Classification.  Schizophr Bull published 16 May 2011, 10.1093/schbul/sbr037

http://schizophreniabulletin.oxfordjournals.org/cgi/content/abstract/sbr037v1?papetoc

Different ARMS and their clinical outcomes may be reliably identified on an individual basis by evaluating neurocognitive test batteries using multivariate pattern recognition. These patterns may have the potential to substantially improve the early recognition of psychosis.

包含美國八個大醫學中心的聯合研究，NAPLS官方網站

莊明哲教授與Kristin S. Cadenhead都是NAPLS的成員之一，

就anatomy上，Progressive Gray Matter Reduction of the Superior Temporal Gyrus During Transition to Psychosis Arch Gen Psychiatry   2009;66(4):366-376

支持P50與MMN有關係之文獻研究：

Gjini, K., Arfken, C., Boutros, N.N., 2010. Relationships between sensory “gating out” and sensory “gating in” of auditory evoked potentials in schizophrenia: a pilot study. Schizophr. Res. 121, 139-145.【注意這一篇：Boutrous不知是否為了讓他的研究有道理，提出了奇特的gating in[MMN]–gating out[P50/N100/P200]說法】When including all subjects (N=24) a negative correlation was found between the P50 gating and the amplitude of the MMN. In healthy subjects this correlation was significantly stronger compared to schizophrenia patients. （繼續閱讀…）

Test–retest reliability was moderate to high for P50, N100, and P200 latencies, amplitudes, and difference scores, low to moderate for N100 and P200 gating ratios, but low for P50 ratio ( [Rentzsch et al., 2008] and [Fuerst et al., 2007]).

Evidence of abnormalities in mid-latency auditory evoked responses (MLAER) in cognitive subtypes of patients with schizophrenia 澳洲Assen Jablensky團隊 2011刊登於Psychiatry Research之文章: abnormal pathophysiologic mechanisms (P50/N100/P200) underlying the electrophysiological brain responses to auditory stimulation are associated with the pervasive cognitive deficits, which characterize the pervasive cognitive deficits of schizophrenia

Cognitive abilities and 50- and 100-msec paired-click processes in schizophrenia.Smith AK, Edgar JC, Huang M, Lu BY, Thoma RJ, Hanlon FM, McHaffie G, Jones AP, Paz RD, Miller GA, Cañive JM.Am J Psychiatry. 2010 Oct;167(10):1264-75. 這一篇不但作了P50/N100也作了M50/M100

¹H-MR spectroscopy in ultra-high risk and first episode stages of schizophrenia JPR (September 2011) 45(9) 1135-1139
德國研究團隊 Using proton magnetic resonance spectroscopy biochemical characteristics in early stages of schizophrenia were examined. N-acetylaspartate, choline and creatine were measured in hippocampus, anterior cingulate gyrus (ACC) and medial prefrontal cortex (mPFC) of 24 first episode and 30 ultra-high risk patients. Careful LCModel analyses revealed no differences between the patient groups and 31healthy controls, casting doubt upon the idea of metabolic changes in early stages of psychosis.

Altered Relationship Between Hippocampal Glutamate Levels and Striatal Dopamine Function in Subjects at Ultra High Risk of Psychosis Biological Psychiatry 2010;68(7)Pages 599-602