Predicting Prognosis in Patients with First Episode Psychosis Using Mismatch Negativity : A 1 Year Follow-up Study

Moonyoung Jang; Minah Kim; Tak Hyung Lee; Jun Soo Kwon

doi:10.16946/kjsr.2017.20.1.15

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Jang, Kim, Lee, and Kwon: Predicting Prognosis in Patients with First Episode Psychosis Using Mismatch Negativity : A 1 Year Follow-up Study

Original Article

Korean J Schizophr Res 2017;20(1):15-22.

Published online: 17 January 2017

DOI: https://doi.org/10.16946/kjsr.2017.20.1.15

Predicting Prognosis in Patients with First Episode Psychosis Using Mismatch Negativity : A 1 Year Follow-up Study

Moonyoung Jang, MS¹, Minah Kim, MD², Tak Hyung Lee, MS³, Jun Soo Kwon, MD, PhD^2,³

¹ Seoul National University College of Medicine, Seoul, Korea

²Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea

³Department of Brain and Cognitive Science-World Class University Program, Seoul National University College of Natural Science, Seoul, Korea

Address for correspondence: Minah Kim, Department of Psychiatry, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: 02-3668-7666, Fax: 02-747-9063 E-mail: verte82@snu.ac.kr

Revised 31 March 201731 May 2017 Accepted 2 June 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives

It has been shown that early intervention is crucial for favorable outcome in patients with schizophrenia. However, development of biomarkers for predicting prognosis of psychotic disorder still requires more research. In this study, we aimed to investigate whether baseline mismatch negativity (MMN) predict prognosis in patients with first episode psychosis (FEP).

Methods :

Twenty-four patients with FEP and matched healthy controls (HCs) were examined with MMN at baseline, and their clinical status were re-assessed after 1 year. Repeated-measures analysis of variance was performed to compare baseline MMN between the two groups. Multiple regression analysis was used to identify factors predicting prognosis in FEP patients during the followup period.

Results

MMN amplitudes at baseline were significantly reduced in patients with FEP compared to healthy controls. In the multiple regression analysis, baseline MMN amplitude significantly predicted later improvement of performances on digit span and delayed recall of California Verbal Learning Test. However, baseline MMN did not predicted improvement of clinical symptoms.

Conclusion

These results indicate that MMN may be a possible predictor of improvement in cognitive functioning in patients with FEP. Future study with larger sample and longer followup period would be needed to confirm the findings of the current study.

Keywords: Event related potential, Mismatch negativity, First episode psychosis, Schizophrenia, Cognitive function, Prognosis

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Fig. 1.

A : The grand averaged Mismatch negativity waveforms at Fz and FCz electrode sites in patients with FEP and HC. B : Two-dimensional topographic maps of MMN across FEP and HC groups. Color bar with numbers indicates MMN amplitude (μV). FEP : first episode psychosis, HC : healthy controls.

Fig. 2.

Association between baseline MMN amplitude at FCz electrode site and improvement in performances of neurocognitive function tests. CVLT : California Verbal Learning Test.

Table 1.

Demographic, clinical, and neurocognitive characteristics of the patients with FEP and HCs at baseline

	FEP (N=24)		HC (N=24)		Statistical analysis∗
	Mean	SD	Mean	SD	χ² or T	p
Sex (Male/Female)	10/14		9/15		0.087	0.500
Handedness (Right/Left)	22/2		22/2		-	0.696
Age (years)	22.4	1.0	23.5	4.0	-0.813	0.420
IQ	98.0	2.8	118.2	13.4	-5.160	＜0.001^‡
Education (years)	13.3	0.4	14.6	1.6	-2.488	0.017^†
DUP (months)	5.7	0.8	-	-	-	-
PANSS
Total	69.1	14.0	-	-	-	-
Positive symptoms	17.3	4.6	-	-	-	-
Negative symptoms	17.3	4.6	-	-	-	-
General symptoms	34.5	7.1	-	-	-	-
NCFT measures
Working memory
Digit span	10.6	1.8	12.8	2.2	-3.844	＜0.001^‡
Attention
Trail Making Test, part A	29.0	9.1	22.3	7.4	2.8	0.008^†
Verbal memory
CVLT, immediate recall	8.2	3.2	12.9	2.2	-5.990	＜0.001^‡
CVLT, delayed recall	8.6	3	13.3	2.2	-6.092	＜0.001^‡

^∗ : Independent t test or Welch's t test if the variances were not equal, χ analysis or Fisher's exact test for categorical data,

^† : p ＜0.05,

^‡ p＜0.005. FEP : first episode psychosis, HCs : healthy controls, SD : Standard Deviation, IQ : Intelligent Quotient, DUP : Duration of Untreated Psychosis, PANSS : Positive and Negative Syndrome Scale, NCFT : neurocognitive function test, CVLT : California Verbal Learning Test

Table 2.

Follow-up characteristics and change in symptoms as well as neurocognitive functioning during the 1 year of followup period of the patients with FEP

	FEP (N=24)
	Mean	SD
Antipsychotics dose∗	21.0 4	47.56
Use of medication^†
Antipsychotics	24 (100)
Antidepressants	10 (41.7)
Mood stabilizers	4 (16.7)
Anxiolytics	19 (79.2)
Change in PANSS^‡
Total	22.4	17.6
Positive symptoms	7.1	5.0
Negative symptoms	4.5	5.9
General syptoms	10.8	9.3
Changes in NCFT^‡
Working memory
Digit span	0.6	1.6
Attention
Trail making test, part A	3.7	9.3
Verbal memory
CVLT, immediate recall	0.7	3.0
CVLT, delayed recall	0.9	3.1

^∗ : Mean olanzapine equivalent dose,

^† : Number (percent-age) of subjects who were prescribed each medication during the followup period,

^‡ : Which was calculated by sub-tracting scores at last followup point from scores at baseline. FEP : first episode psychosis, SD : Standard Deviation, PANSS : Positive and Negative Syndrome Scale, NCFT : Neurocognitive Function Test, CVLT : California Verbal Learning Test

Table 3.

Means and SD of MMN peak amplitudes and latencies in patients with FEP and HCs at surface electrodes

Electrode sites	FEP (N=24)		HC (N=24)		Statistical Analysis∗
Electrode sites	Mean	SD	Mean	SD	T	p
Amplitude (μV)
F3	-1.8	1.2	-2.3	1.3	1.207	0.234
Fz	-1.8	1.0	-2.8	1.3	2.770	0.008^†
F4	-1.9	1.0	-2.9	1.2	3.211	0.002^‡
FC3	-1.7	0.9	-1.9	1.1	0.948	0.348
FCz	-2.1	2.0	-2.8	1.2	1.529	0.133
FC4	-1.8	1.0	-2.7	1.1	3.162	0.003^‡
Latency (ms)
F3	181.7	31.7	183.3	25.9	-0.200	0.843
Fz	179.2	35.6	182.3	27.1	-0.351	0.727
F4	179.2	37.9	184.7	28.2	-0.566	0.574
FC3	212.9	201.3	176.0	32.9	0.884	0.381
FCz	175.5	29.9	184.5	25.4	-1.128	0.265
FC4	179.3	38.3	174.9	27.5	0.485	0.630

^∗ : Independent t test or Welch's t test if the variances were not equal,

^† : p＜0.05,

^‡ : p＜0.005. SD : standard deviations, MMN : mismatch negativity, FEP : first episode psychosis, HCs : healthy controls

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