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July2011 Vol.48 Issue:      3 (Supp.) Table of Contents
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Could P300 Predict Remission in Patients with Schizophrenia?

Eman Elsheshtawy1, Wafaa Elbahaey1, Ashraf Ahmed Zaher2, Mohamed Saad2


Department of Psychiatry1, Neurology2, Mansoura University; Egypt



Background: Schizophrenia is nowadays viewed as a general cognitive disorder characterized by relatively stable cognitive impairments. Event-related potentials offer an approach for eliciting neurophysiological correlates of cognitive functioning. The P300 event-related brain potential (ERP) is an index of endogenous cognitive processes. Objective: This study sought to determine whether P300 can indicate the change in cognitive functions in schizophrenic patients and to evaluate its value in predicting remission. Methods: We studied 93 schizophrenic patients and 30 controls over 2 years. The age, gender, marital status, level of education and occupation were analyzed. Patients were assessed by the following scales: scales for assessment of positive and negative symptoms (SAPS and SANS) of schizophrenia and Wechsler Memory scale (WMS). Neurophysiological assessment with Event-related potentials (P300) was done for patients and control groups. Patients were maintained on antipsychotics whether typical or atypical, followed regularly twice per month over 6 months and they were reassessed with the same tools of assessment. Results: A total of 93 patients were studied; they were 60 males and 33 females with a mean age of 22.56±7.07 years. There was a significant difference between patients and control as regard all P300 variables. Treatment with antipsychotics led to variable degree of improvement in most cognitive scales. P300 amplitude was the only P300 variable which showed improvement with antipsychotics. On doing regression analysis, significant correlation (R²=0.599, F=55.05) was found between P300 amplitude and positive symptoms (SAPS). Conclusion: P300 is a useful tool for assessing cognitive functions and predicting remission in schizophrenic patients. [Egypt J Neurol Psychiat Neurosurg.  2011; 48(3): 241-246]


Key Words: Schizophrenia, Event related potential, P300, Cognition.


Correspondence to Ashraf Ahmed Zaher, Lecturer of neurology, Faculty of medicine, University of Mansoura, Egypt.

Tel.: +20122816432      E-mail



Schizophrenia is nowadays viewed as a general cognitive disorder characterized by relatively stable cognitive impairments1 that represents a prominent and very disabling aspect of the disorder; in only 20-30% of patients performance on neuropsychological assessment is entirely within the normal range2.

Event-related potentials offer an approach for eliciting neurophysiological correlates of cognitive functioning. The P300 event-related brain potential (ERP) is an index of endogenous cognitive processes typically elicited by infrequent sensory stimuli that are either novel or task relevant. It is so named because of its appearance as a large vertex-positive component with a peak latency of approximately 300 msec after stimulus presentation. The obligate evoked potential response to the stimulus reflects a variety of cognitive processes elicited by a change in the sensory environment. These include directed attention, the contextual updating of working memory, and the attribution of salience to a deviant stimulus3. Indeed, it


is just these properties that make the P300 a valuable tool for assessing cognitive function. Because P300 latency is an index of the processing time required before response generation, it is a sensitive temporal measure of the neural activity underlying the processes of attention allocation and immediate memory. In addition, P300 latency is negatively correlated with mental function in normal subjects, with shorter latencies associated with superior cognitive performance4. The neuropsychological tests that are best correlated with P300 latency are those that assess how rapidly subjects can allocate and maintain attentional resources. This association is also supported by results indicating that P300 latency increases as cognitive capability decreases from dementing illness5. Thus P300 latency is directly associated with cognitive capability in both normal and patient populations.

The current study aimed to explore the value of using P300 as a tool for assessing cognitive impairment in schizophrenic patients and whether or not it could predict remission.





We prospectively studied 93 consecutive patients with schizophrenia recruited from those attending the Psychiatric Outpatient Clinic (OPC) of Mansoura University Hospital, Mansoura, Egypt, over 2 years. Patients and their families were informed about the nature of the study, and gave written consents to be involved in it. The work has been approved by the ethics committee of Mansoura University. 

The patients studied were diagnosed according to the criteria described by DSM–ΙV TR (American Psychiatric Association, 2000). The Inclusion criteria were: Educated to at least the level of preparatory school, duration of illness less than one year, not receiving treatment or if they had received, a drug free period was 2 weeks or more. The following subtypes were included: paranoid, undifferentiated and disorganized. We excluded the catatonic subtype because of expected uncooperativeness and the residual subtype as they are expected not to be seen in the 1st year of illness. The other exclusion criteria were: Patients in acute state, because of the expected uncooperativeness, deficit in hearing or vision, co morbidity with other psychiatric disorders, neurological disorders or major medical conditions e.g. diabetes, hypertension, cardiac, hepatic or renal troubles, as these conditions may affect P300. A control group of 30 apparently healthy subjects free from any clinical neuropsychiatric problems and have no past history of neurologic or psychiatric disorders was included. They were matched for age, gender, marital status, level of education and occupation with the patients group.

All patients were subjected to: Clinical psychiatric examination, Physical examination and thorough neurological examination, Psychometric study including: Scales for assessment of positive and negative symptoms of schizophrenia (SAPS, SANS) 6, 7 and Wechsler Memory scale 8. Neurophysiological assessment with Event-related potentials (P300) was done for patients and control groups, the apparatus used was Key-Point (Dantec), with Two Channels. It was done at the Department of Neurology, Mansoura University Hospital, Mansoura, Egypt and was applied only for 65 patients because of technical problems.

Patients group were followed up regularly twice per month over 6 months to adjust the dose of antipsychotics. Patients were blindly given medications whether typical or atypical antipsychotics. Typical antipsychotics were mainly Haloperidol and Chlorpromazine with adjuvant anticholinergic drugs in most patients. Atypical antipsychotics in the form of Resperidone, Olanzapine or Clozapine, taking into consideration the maximum effective dose of the used drug and medications were continued for 6 months, after that, patients were reassessed using the same tools of assessment used before. However, P300 was applied only for 50 patients as the remaining refused to do it.


Statistical Analysis:

The data were coded and entered into a computer using Statistical Package for Social Sciences (SPSS), version 15.0 (Chicago, IL, USA). The mean, standard deviation and chi-square for percent were used to summarize the data. Student's t-test was used to ascertain the significance of differences between mean values of two continuous variables and Pearson product moment correlation coefficient was calculated to assess the correlation between different continuous variable. Stepwise regression analysis was also done. The level of P<0.05 was considered as the cut-off value of significance.




We studied a total of 93 patients, 60 males and 33 females with a mean age of 22.56±7.07 years and 30 controls over a period of 2 years. The Sociodemographic characteristics of the participants are shown in Table (1). The patients group and the control group were matched for age, gender, marital status, level of education and occupation.

A statistically significant increase of P300 latency, decrease of P300 amplitude and increase of reaction time were detected in patients group when compared with the control group (Table 2).

When comparing patients before and after treatment with typical and a typical antipsychotics as regard P300 parameters, we found a statistically significant increase in the P300 amplitude while P300 latency and reaction time showed non-significant difference as observed in Table (3).

Treatment with antipsychotics led to variable degrees of improvement more manifest with atypical antipsychotics (41 patients). While the use of typical antipsychotics (52 patients) didn’t affect the negative symptoms in all schizophrenic subtypes and may even worsen it which is manifest in the undifferentiated and disorganized subtypes (Table 4).

Table (5) shows the results of regression analysis, significant R² was found between P300 amplitude and positive symptoms only (SAPS).

Table 1.  Sociodemographic characteristics of patients and control group.



Patients (93)

Control (30)





Age   (Mean±SD)



21.3± 3.4














Marital status










21.5 %







Level of education


Primary, preparatory


Higher education


















Intermediate group

Skilled Labourers

Unskilled Labourers











 3.2 %


  5. 4 %

16.1  %

21.5  %

16.1 %

















Table 2. Comparison between patients and control group regarding P300 Parameters.


P300 Parameters


N= 65


N= 30

F test

Latency (msec) Mean ± S.D




Amplitude (µv) Mean ± S.D




Reaction time (msec) Mean ± S.D




                  *Significant P< 0.05   


Table 3. Comparison between patients before and after treatment with typical and atypical antipsychotics as regard P300 Parameters.


P300 Parameters

Typical antipsychotics


Atypical antipsychotics

N= 24











Latency (msec) Mean ± S.D


397.5± 44.7





Amplitude (µv) Mean ± S.D







Reaction time (msec) Mean ± S.D







* Significant P<0.05


Table 4. Comparison between patients before and after treatment with typical and atypical antipsychotics as regard Scales for assessment of positive and negative symptoms (SAPS, SANS) and Wechsler Memory scale.



Typical antipsychotics

Paranoid (14), undifferentiated (29), disorganized (9)

Atypical antipsychotics

Paranoid (9), undifferentiated (23),  disorganized  (9)
















39.6± 3










Memory Quotient














43.9 *








Memory Quotient






















Memory Quotient







* Significant P<0.05


Table 5. Regression analysis for P300.


Predictor (P300 amplitude)

Regression analysis

Cognitive measures





Memory scale

Before Treatment





After Treatment




Before Treatment





After Treatment




Before Treatment





After Treatment



* Significant P<0.05




Recent advances in brain imaging techniques (particularly the functional procedures) and detailed neuropsychological testing have led to a rapid rise in our understanding and view of schizophrenia. We learned much about the underlying functional and structural pathology of the disorder and its different presentations. Schizophrenia is nowadays viewed as a general cognitive disorder characterized by relatively stable cognitive impairments that represents a prominent and very disabling aspect of the disorder1.

In the present study, it was observed that the number of female patients was less than that of males (35% and 65% respectively). These results could be explained by the tendency of families to hide any psychiatric illness particularly in females for fear of stigma. Also, high social demands are placed on males which push their relatives to seek medical help that leads to increase in the percentage of male patients brought for treatment by parents as compared to female patients. As our study was carried during the first year of illness, the mean age was 22.56 years, secondary to this young age, most of the patients were single and still unemployed. This could be further explained by the delayed job opportunity available in our society.

Event-related potentials (P300) offer an approach for eliciting neurophysiological correlates of cognitive functioning. It depends mainly on expectancy (subjective probability), together with high degree of attention, so that, it has been proposed to assess attention and working memory. From our results, schizophrenic patients had a delayed P300 latency as compared to controls and the difference was statistically significant. This is in agreement with most studies using the same method to detect P300 (i.e. auditory Odd-ball paradigm)9,10. Latency is considered as an index of the processing time before response generation. Pallanti et al.11, considered latency as a measure of neural activity underlying the processes of attention allocation and immediate memory, which are already disturbed in schizophrenia leading to its prolongation, which reflects slowing of cognitive processing speed among schizophrenic patients.  Some studies did not confirm our results as Niwa et al.12. Blackwood et al.,13 related this controversy to the small number of subjects included in some of these studies or to the use of different methods by researchers.

We found a statistically significant decrease of P300 amplitude in patients when compared to controls. This finding is supported by the study of Groom et al.14, and this could be explained on the basis that amplitude is considered as an index to brain activity, that is required in the maintenance of working memory, and it is proportional to the amount of attentional resources. From a neurobiological perspective, reduced amplitude may reflect gray matter abnormalities shown on quantitative magnetic resonance imaging (MRI) studies15. Also, being apparent soon after or even prior to the onset of psychotic symptoms evidence that it may be prior to the first psychotic episode, P300 may be considered as a marker of the biological changes that initiate psychotic symptoms, rather than a marker of vulnerability16. P300 amplitude has therefore been a featured candidate for genetic research in the schizophrenia endophenotype17.

Reaction time in schizophrenic patients is significantly prolonged than in healthy control subjects. This was supported by the study of Krieger et al.18, who concluded that prolonged reaction time reflects of the more time needed by the patients to start and to execute movement. It seems that patients spend time for the decision to start movement, because of the necessity to translate percepts (auditory stimuli) into actions. Krieger et al.18, have stated that the primary effect of schizophrenia is on percept action translation which massively influences the ability of patient to act appropriately in the presence of environmental demands and that disturbance of this process occurred early in the course of the disorder.

Different authors have documented the presence of structural changes that caused abnormalities in P300 wave and found that multiple brain structures generate P300 like potentials including the hippocampus, parahippocampal gyrus. Thus, P300 abnormalities in schizophrenia could be a sign of disturbed neuronal migration during brain development. It may be a result of either microscopic abnormalities of the hippocampus in the form of disorganized neuronal architecture and reduced neuron size that have been frequently observed in schizophrenia19. Or alternatively, abnormal P300 may be secondary to macroscopic abnormalities of the hippocampus such as that have been revealed by some neuroimaging studies or other brain structures related to attention and working memory20. McCarley et al.,21 have reported that there is marked reduction of the left posterior superior temporal gyrus gray matter volume, a structure considered important for auditory associative memory.

As observed from the results of P300, significant improvement was seen in the amplitude of P300 while latency didn't show any improvement. This was seen in both groups of patients whether treated with typical or atypical antipsychotics. However, the improvement in amplitude still did not return to the level of normal controls. Duncan et al.22, suggested that improvement of P300 amplitude occur when intake of medications was associated with improved clinical status. Regarding the reaction time, there was apparent shortening of it from base line but this didn’t reach a significant level. This could be a beneficial effect due to medication. The shortening of time is seen to be more in patients treated with atypical antipsychotics than that in patients treated with typical antipsychotics. This was supported by the study of Krieger et al.18, who found that, patients who were medicated with atypical antipsychotics showed remarkable improvement.         

Schizophrenic patients of different clinical subtypes who received both typical and atypical antipsychotics showed significant improvement on the scale of positive symptoms. Negative symptoms were significantly improved in those patients who were maintained on atypical antipsychotics, while there was minimal effect of typical antipsychotics on negative symptoms, even may be worsening as seen is some patients. This could be explained by noting that positive symptoms are considered to be neuro-chemically mediated through dopamine excess and thus respond favorably to conventional antipsychotics which would support the dopamine hypothesis23. Negative symptoms are usually explained by decreased dopaminergic activity and serotonergic hyperactivity in the prefrontal cortex and so, they respond favorably to atypical antipsychotics which act at this site. Atypical antipsychotics are effective in reducing total symptoms score, as they act also on the limbic area, thus they are effective on positive symptoms. Another explanation of the apparent improvement in negative symptoms associated with atypical antipsychotic medications may be attributed to the reduction of cognitive impairment24. However, the disorganized group of patients showed improvement that doesn’t reach a significant degree which may be due to the marked distractibility which characterizes those patients together with lack of motivation and cooperation25. 

In our study, Wechsler memory scale showed variable degrees of improvement especially evident in the group of patients who were receiving atypical antipsychotics. This may be explained by the direct effects of these drugs, as its mechanism of action may be associated with block of 5HT²a receptors (the highest density of these receptors are in frontal cortex), a region relevant to working memory26. Beside this direct effect, these drugs are thought to improve alertness and distractibility together with increased motivation and cooperation in those patients which would be reflected in improving performance on the scale27.

On discussing the results of regression analysis, a relation was found between the P300 amplitude (dependent variable) and positive symptoms of schizophrenia from SAPS (R²= .599*) (independent variable). So that, P300 amplitude could be considered as an indicator of improvement of cognitive functions in schizophrenia which can lead to improvement in social functioning. This was supported by the study of Strik et al.28, who found that, there was a predictive value of the P300 amplitude on the clinical outcome in terms of social functioning of schizophrenic patients. On the contrary, Norman et al.29 have used symptoms as a dependent variable and found that, symptoms were more predictive of community functioning than were neurocognitive measures, and thus suggesting the importance of using symptom levels after optimal treatment as predictors of community functioning.



P300 is a useful tool which can be used for detection of cognitive impairment and also for prediction of remission in patients with schizophrenia.


[Disclosure: Authors report no conflict of interest]




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الملخص العربي

هل يمكن أن تتنبأ الموجة الموجبة  ..3 بالتحسن فى مرضى الفصام؟


أصبح من المعروف أن الخلل المعرفى من الصفات الهامة الملازمة للفصام. وقد أدى التقدم التكنولوجى الكبير فى استخدام أنواع الأشعة المختلفة والاختبارات المعرفية الدقيقة إلى المساعدة على توضيح مختلف التغيرات البيولوجية والكيميائية  والتشريحية والوظيفية التى تحدث فى المخ مصاحبة لمرض الفصام  والتى قد يكون لها علاقة بظهور هذا الخلل فى الوظائف المعرفية. وتهدف هذه الدراسة الى تحديد ما اذا كان اختبار الموجة الموجبة 300 يمكن ان يشير الى التغير فى الوظائف المعرفية والتنبؤ بسكون الحالة المرضية فى مرضى الفصام. تم إجراء هذه الدراسة على 93 مريضا بالفصام خلال العام الأول من المرض, و 30 من الأصحاء يمثلون المجموعة الضابطة. وقد أجريت الفحوصات التالية على مجموعة المرضى: فحص إكلينيكي للجهاز العصبى لإبعاد واستقصاء للأسباب العضوية للخلل المعرفى, فحص إكلينيكي نفسى كامل, مقياس الأعراض الموجبة والسالبة, مقياس وكسلر لاختبار الذاكرة واختبار الموجة الموجبة 300 والذى تم إجراؤه أيضا للمجموعة الضابطة وكان التقييم عن طريق دراسة كمون الموجة ومداها وزمن الاستجابة. وقد أجريت جميع هذه الفحوصات والاختبارات على المرضى مع ملاحظة كونهم لم يتناولوا أية أدوية نفسية علاجية, أو توقفوا عن تعاطى الأدوية لمدة لا تقل عن أسبوعين كاملين. وقمنا بتقسيم المرضى إلى مجموعتين مختلفتين من حيث نوع العلاج, فالمجموعة الأولى كانت تتناول مضادات الذهان الغير تقليدية, أما المجموعة الثانية من المرضى كانت تتناول مضادات الذهان التقليدية. وتمت متابعة المرضى على مدار ستة أشهر كاملة, وفى نهاية الستة أشهر تم إعادة تقييم المرضى بنفس الفحوصات السابقة. وأظهرت النتائج ان اختبار الموجة الموجبة 300  أوجد  فرقا ذو دلالة احصائية بين مجموعة المرضى الفصاميين والمجموعة الضابطة. أما الدراسة التتبعية فقد توصلنا منها إلى أن مضادات الذهان بمختلف أنواعها تؤدى إلى التحسن فى الوظائف المعرفية التى تم تقييمها بدرجات متفاوتة, وكان مدى الموجبة 300 هو المتغير الوحيد الذي أظهر تحسنا مع مضادات الذهان. نستنتج من هذه الدراسة ان اختبار الموجة الموجبة300 هو أداة مفيدة لتقييم الوظائف المعرفية والتنبؤ بسكون الحالة المرضية فى مرضى الفصام.

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