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July2005 Vol.42 Issue:      2 Table of Contents
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Event Related Potentials and Cognitive Functions in Egyptian Euthemic Bipolar Patients

Samia Abd Al-Rahman1, Mostafa R. Raslan1, Ann Ali Abd Alkader2, Noha Sabry1, Mona Mohammed Nada2, Maha Emad Al-Din1
Departments of Psychiatry1, Clinical Neurophysiology Unit2, Cairo University

ABSTRACT

Few studies have attempted to investigate cognitive and neurophysiological states in bipolar patients during periods of remission. This study was done to test the hypothesis that euthymic bipolar patients have persistent cognitive and neurophysiological impairment. 20 euthymic bipolar patients as diagnosed according to DSM-IV criteria of diagnosis were compared with 20 controls as regards cognitive functions and evoked related potential. The following tools were applied: Hamilton Rating Scale for Depression, Young Mania Scale, WAIS and WCST, in addition to measuring event related potential (P300 latency and amplitude). Our results revealed a generalized rather than selective impairment, in addition to impairment in executive functions, along with impairment in word fluency, which would suggest prefrontal pathology in bipolar patients. The number of episodes, the longer duration of illness and the positive family history of psychiatric disorders were found to be important risk factors of such impairments. Patients showed also prolonged P300 latency and reduction in amplitude which was correlated with some of the neurocognitive subtests and with the number of episodes. We conclude that there is some degree of neurocognitive and neurophysiological impairment in euthymic bipolar patients. This needs further investigations.

(Egypt J. Neurol. Psychiat. Neurosurg., 2005, 42(2): 377-390).

 





INTRODUCTION

 

Patients with bipolar disorder cycle pass through episodes of mania, depression and euthymia,    demonstrating dramatic fluctuations in energy, social behavior, mood and cognitive functioning. The apparent link between these associated changes suggests an important role for the study of this disorder in charting a map of the relationship between mood, cognition and electrophysiological brain functioning.

To date, little is known about the nature of cognitive deficits observed in patients with bipolar disorder or about how these deficits might relate to clinical symptoms and neurobiological substrate of the disorder. In contrast to large amount of work devoted to cognitive changes accompanying depression, only few studies have precise nature of impairment in patients with mania.1 A possible explanation of this imbalance may be the practical difficulties of using standard neuropsychological procedure to assess mania, the nature of the illness may prevent patients with mania from being reliable subjects, especially in tests of cognitive functioning.2

Kraepelin distinguished manic depression from schizophrenia on its relapsing and remitting course. Patients with affective illness, unlike those with dementia precox, were thought to have remission without cognitive impairment. Recent investigations of patients in the euthymic phase of bipolar disorder, however, have challenged this view. Many patients continue to experience psychological and social difficulties, and while the extent of which neuropsychological impairment remains is less clear, most studies reported at least some degree of residual dysfunction in one or more tasks administered.1

On the other hand, in contrast to the extensive literature on reduced amplitude and increased latency of P300  in schizophrenia, there are relatively few studies that used evoked potential in affective disorders. Several studies reported some abnormalities in P300 amplitude and latency from midline vertex position in large percentage of patients with bipolar disorder3, while Souza et al found an increase of P300 latency when recorded from midline sites in bipolar subjects.4 Such changes were viewed by some researchers as being state dependent.5,6

The aim of our work is to test that  bipolar patients have persistent cognitive impairment during periods of remission, and to assess the presence of correlation between P300 and neurocognitive tests.

 

SUBJECTS AND METHODS

 

Twenty euthymic bipolar patients were recruited from the psychiatric outpatients clinic in Kasr El-Aini Hospital, according to randomized basis on consecutive referral procedure, in addition to 20 control subjects with no past history or family history of psychiatric illness.

Inclusion criteria: (1) Patients confirming to DSM-IV criteria of bipolar I disorder in the euthymic7 (examined by two senior psychiatrists, and after period of remission of at least 6 months). (2) Both sexes are included. (3) Age:  20-40 years.  (4) A minimum 5 years of illness from the first recognized episode.

Exclusion criteria: (1) History of physical disease  that  may share  in cognitive disturbance e.g. hypertension and diabetes. (2) Mental retardation. (3) History of substance abuse. (4) History of head trauma with concussion. (5) Clinical epilepsy. (6) History of treatment with electroconvulsive therapy (ECT) in the last six months. (7) Higher scores than "8" (a level representing clinically significant depressive symptoms) on  the  Hamilton  Rating  Scale  for Depression (HRSD). (8) Higher scores than "8" on the Young Mania Scale (YMS). (9) For the control group, past history or family history (in first degree relatives) of psychiatric illness.

The control subjects were recruited to be matched with patients in age, sex and education. Two patients were medication free, while the rest were asked to stop psychotropic medication two weeks before psychometric and neurophysio-logical assessment. During period of this study, the exclusion criteria led to exclusion of four patients, two of them had history of substance abuse, one patient had uncontrolled hypertension and one patient had a score 10 points on HRSD.

Subjects' consents to participate were first obtained after explaining the purpose of the study, from the patients and control subjects. Both groups were subjected to the following assessment procedure: )l) Psychiatric examination, using semi-structural interview derived from Kasr El-Eini Sheet, including sociodemographic data, family history and pattern of illness. (2) Full medical examination. (3) Hamilton Rating Scale for Depression (HRSD)8. Subjects scoring higher than eight points (a level representing clinically significant depressive symptoms) on the HRSD were excluded from the study. (4) Young Mania Rating Scale. The items in this scale cover the full spectrum of pure manic features9 Patients having scores more than eight points were excluded from this study. (5) Wechsler Adult Intelligence Scale (WAIS) (Arabic version): used to assess intellectual abilities of adults, as well as providing scores on a variety of cognitive tasks covering a range of skills, it is thus differently sensitive to dysfunction of various areas of the brain10 (6) Wisconsin Card Sorting Test (WCST): which can be considered a measure of executive functions, requiring the ability to develop and maintain an appropriate problem-solving strategy across changing stimulus conditions, in order to achieve a future goal11. Unlike other measures of abstract reasoning, the WCST provides objective scores, not only of overall success, but also for specific sources of difficulty on the task (e.g., inefficient initial conceptualization, failure to maintain cognitive set. and perseveration). The WCST proceeds through a number of shifts in set (i.e., sorting principle) among the three sorting categories (color, form, and number). The following items are provided after scoring the WCST: (1) Number of categories completed: scores can range from a minimum of 0 to a maximum of 6 (2) Trials to complete first category: which gives  an  indication  of  the  initial conceptualization before a shift of set is also required. (3) Percent of preservative errors: which reflects the "density" of perseverative errors in relation to overall test performance. (4) Failure to maintain a set: which occurs when the client makes five or more consecutive correct matches but then makes an error before successfully completing the category, and (5) Percent of conceptual level responses: which reflects insight into the correct sorting principles (6) Auditory Event Related Potential (ERP): P300 latency and P300 amplitude: P300 was assessed in all subjects using 4 Channel Nihon Kodhen  apparatus. Electrodes were placed at six sites on the scalp frontal [FZ], central [CZ], parietal [PZ], left temporal [T3] and right temporal [T4]  positions) according to the international 10-20 system. An odd ball paradigm was used, with frequent tones (frequency 1 kHz, rise and fall time 10 ms, stimulation are 0.5Hz) and rare tones (frequency 2 KHz), occurring at 20% random level. Intensity of the stimulus was 70 dB. The subject had to count the infrequent  tones,  and  samples  were included only if errors did not exceed 10%. Analysis time was 1 second, including 200 ms prestimulus delay time. The P300 latency w as concluded to the highest peak between 290 and 750 ms; with maximal distribution in the parietal area, while the amplitude was calculated between this peak and  average  voltage  of the  200 ms prestimulus baseline. The response to target tones was used in this analysis.

Statistical analysis: The data were entered on the IBM compatible computer using Statistical Package for Social Sciences (SPSS), version 6.0. The mean and standard deviation were used as suitable statistical parameters  to  summarize  the  data. Frequency tables, using the percent age, were used to describe the data.

The studied groups were subdivided into bipolar group and control group. Studying the difference between those two groups, the following tests of significance were used: (1) Pearson Chi-square test (X2): used to statistically test the differences between qualitative data. (2) Student's t-test: used to statistically test the difference between quantitative data. Correlations measure the degree of relationship between two or more characteristics of a population.12

 

RESULTS

 

Subjects of the patients and control groups were matched, as regards age, gender and education. The control  group  showed  similar  age distribution to the patients' one, ranging from  20-40  years.  As  for  gender distribution, females to males ratio was 2:1 in both patients and control groups.

45% of the patients have no family history of psychiatric disorders. The same percentage (45%) was found in those with family history of bipolar disorder and only 5% of the patients has family history of major depressive disorder and another 5% have history of schizoaffective schizophrenia. 60% of patients had never been admitted to mental hospital.

The differences in the following subtests of WAIS were statistically highly significant (P>0.00l): Digit span, arithmetic, picture arrangement, picture completion, verbal IQ, Full scale IQ and deterioration index. However, the differences were statistically significant in  information (p=0.002), comprehension (p=0.037), similarities (p=0.007), block design (p=0.04), object assembly (p=0.013), digit symbol (P=0.00l) and performance IQ (p=0.001). The only subtest that shows no statistically significant difference is the vocabulary one (p=0.059) (Table 1(.

As for WC ST, as demonstrated in table (1), patients show higher scores on total administration, total errors, perseverative responses and perseverative errors. On the other hand, they have fewer score on total correct, non-perseverative errors, number of category completed and conceptual level response. The differences between the two groups were statistically highly significant in the following scores of the WCST: total administration,  perseverative  responses, perseverative errors and category completed. Differences were statistically significant on total correct (p=0.02), total errors (p=0.003) and conceptual level (p=0.001).

As shown in table (2), patients with positive family history of psychiatric disorders had less scores than the patients with negative family history in the following subtests: Information, Comprehension, Digit Span, Arithmetic, Vocabulary, Picture Arrangement, Picture  Completion and Block Design. They also had less verbal IQ, Performance IQ and Full scale IQ but less deterioration index. However, these differences did not reach a  statistically significant level. The same table (2) shows that patients with positive family history of psychiatric disorders had less total correct, non-perseverative errors, category completed and failure to maintain a set and more total administration, total errors, perseverative  responses,  perseverative errors and trial to complete first category than patients with negative family history.

Patients of bipolar group with duration of illness more than 10 years have fewer scores on the following subtests of WAIS (Table 3): Comprehension, Digit Span, Arithmetic,  Similarities,  Picture Completion and Block Design. They also show higher deterioration index. These differences did not reach a statistically significant level. Patients with duration of illness > 10 years had lower scores on total correct, non-perseverative error category completed and conceptual level and higher scores on total  errors,  perseverative responses and perseverative errors than patients with duration of illness <= 10 years. These differences did not reach a statistically significant level. As for ERP, patients with duration of illness > 10 years had  prolonged  latency  and  smaller amplitude of P300 than patients with duration of illness <= 10 years. These differences did not reach a statistically significant level (Table 3).

There was a statistically significant positive correlation between the number of episodes and the P300 latency (P= 0.04), while there was no significant correlation with P300 amplitude (Table 4). The same table reveals that there was negative correlation between P300 latency and scores on the following tests: information, comprehension, digit span, similarities, picture completion, block design and verbal IQ. A positive correlation was found between P300 latency and deterioration index. A positive correlation was found as well between the P300 amplitude and the scores of the following tests:  arithmetic, vocabulary, picture arrangement, object assembly, digit symbol and performance IQ. However none of these correlations reach a statistically significant level (Figs. 1 and 2)

Table (5) reveals a positive correlation between  P300  latency  and  total administration, total errors, perseverative responses, perseverative errors and trials to complete  first  category  and  negative correlation  with  total  correct,  non-perseverative errors, category completed, failure to maintain a set and conceptual level. On the other hand, P300 amplitude shows  positive  correlation  with  total correct, non- perseverative errors, category completed, failure to maintain a set and conceptual level and negative correlation with total administration, total errors, perseverative  responses,  perseverative errors  and  failures  to  complete first category. None of these correlations was statistically significant (Table 5).

The same correlations were repeated, but with patients with positive family history of bipolar disorder (Table 5). This revealed a positive correlation between P300 latency and  total  administration,  total  errors, perseverative  responses,  perseverative errors and trials to complete first category and negative correlation with total correct, non-perseverative errors, category completed, failure to maintain a set and conceptual level. On the other hand, P300 amplitude was positively correlated with total correct, non-perseverative errors. Category completed, failure to maintain a set and conceptual level and negative correlation with total administration, total errors, perseverative responses, perseverative errors and trials to complete first category. None of these correlations were statistically significant.


 

 

Table 1. Comparison between subjects and controls as regards WAIS, WCST and ERP Results.

 

 

Bipolar

(n= 20)

Control

(n= 30)

 

t

 

p

Mean

SD

Mean

SD

WAIS

 

Information

6.4

2.6

9.2

2.5

-3.33

.002*

Comprehension

12.7

3.45

14.6

1.87

-2.16

0.037*

Digit span

6.15

20.33

10.7

2.9

-5.69

<0.001**

Arithmetic

7.05

2.3

10

2.4

-3.95

<0.001**

Similarities

8.75

3.3

11.35

2.34

-2.86

0.007*

Vocabulary

7.55

2.6

9.05

2.25

-1.94

0.0059

Picture arrangement

5.9

2.02

9.05

3.08

-3.81

<0.001**

Picture completion

8.3

2.6

11.5

1.76

-4.53

<0.001**

Block design

7.2

2.8

9.4

3.51

-2.126

0.04*

Object assembly

8.85

3.29

11.1

2.04

-0.59

0.013*

Digit symbol

7.4

1.81

10.75

3.83

-3.52

0.01*

Verbal IQ

89.55

12.78

107.9

9.95

-5.06

<0.001**

Performance IQ

86.55

13.13

105.1

17.65

-3.76

0.001*

Full scale IQ

87.3

12.95

106.2

9.52

-5.25

<0.001**

DI

15.2

10.73

-3.7

18.19

4

<0.001**

WCST

 

Total administration

125.95

9.16

103.85

18.81

4.72

<0.001**

Total correct

55.23

17.84

71.6

12.21

-3.38

0.02*

Total errors

46.59

17.51

30.11

15.7

3.13

0.003**

Preservative  responses

45.21

25.2

16.3

8.34

4.87

<0.001**

Non–preservative errors

11.18

7.12

12.73

9.33

-.58

.561

Preservative errors

33.9

17.63

13.05

8.27

4.78

<0.001**

Category completed

2.9

1.77

5.35

1.59

-4.58

<0.001**

TCFC

23.95

42.56

9.8

28.63

1.23

.225

FMS

1.55

1.95

0.7

0.8

1.79

.081

conceptual level

38.08

19.96

61.27

20.21

-3.64

001*

ERP

 

P300 latency

469.73

663.51

374.31

95.45

-.637

.528

P300 amplitude

4.72

3.14

6.43

3.9

-1.52

.136

 

*              = Significant <0.05                                               **           = Highly significant < 0.001

IQ            = Intelligence Quotient                          DI          = Deterioration index

TCFC = Trial to complete first category           FMS = Failure to maintain a set


Table 2. Results of the subtest of WAIS, WCST and ERP in Bipolar patients with positive and negative family history of psychiatric disorders.

 

 

+ve family history

(n= 11)

-ve family history

(n= 9)

 

t

 

p

Mean

SD

Mean

SD

WAIS

 

Information

6.44

2.69

2.81

-0.008

-0.008

0.99

Comprehension

12.66

4.71

2.19

-0.03

-0.03

0.97

Digit span

5.88

1.36

2.5

-0.5

-0.5

0.61

Arithmetic

6.66

2.91

1.74

-0.66

-0.66

0.51

Similarities

8.77

3.56

3.25

0.03

0.03

0.97

Vocabulary

7.44

2.74

2.61

-0.16

-0.16

0.87

Picture arrangement

5.33

2.5

1.5

-1.14

-1.14

0.26

Picture completion

8.22

3.41

1.91

-0.11

-0.11

0.9

Block design

7

3.12

2.73

-0.34

-0.34

0.73

Object assembly

8.66

2.44

3.97

-0.21

-0.21

0.82

Digit symbol

7.55

1.94

1.79

0.33

0.33

0.73

Verbal IQ

88

12.11

13.75

-0.48

-0.48

0.63

Performance IQ

84.33

15.23

11.58

-0.67

-0.67

0.51

Full scale IQ

86.11

14.28

12.37

-0.36

-0.36

0.72

DI

16.88

13.59

8.15

0.62

0.62

0.53

WCST

 

Total administration

128

0

124

12.36

0.9

0.38

Total correct

54.12

19.48

54.14

17.31

-024

0.8

Total errors

47.54

15.62

45.8

19.64

0.21

0.83

Preservative  responses

50.62

19.3

40.79

29.33

0.86

0.4

Non–preservative errors

9.76

7.7

12.35

6.75

-0.8

0.43

Preservative errors

37.68

15.24

30.8

19.53

0.86

0.4

Category completed

2.55

1.58

3.18

1.94

-0.77

0.44

TCFC

26.44

46.23

21.9

41.42

0.23

0.82

FMS

1.11

1.96

1.9

1.97

-0.9

0.37

conceptual level

34.66

18.49

40.88

21.55

0.68

0.5

ERP

 

P300 latency

386.88

123.16

358.95

46.86

0.64

0.53

P300 amplitude

4.14

2.95

5.19

3.35

-0.73

0.47

* = Significant <0.05            +ve : positive             - ve: negative

IQ = Intelligence Quotient                               DI =Deterioration index

TCFC =trial to complete first category            FMS =failure to maintain a set


Fig. (1): Comparison of P300 latency in the bipolar and control groups.

 

 

 

 

Fig. (2): Comparison of P300 amplitude in the bipolar and control groups.


Table 3. Correlation between duration of illness and scores on WAIS, WCST and ERP.

 

 

Duration of

(illness > 10 n= 7)

Duration of

(illness < 10 n= 13)

 

t

 

p

Mean

SD

Mean

SD

WAIS

 

Information

6.71

2.62

6.3

2.81

0.31

0.75

Comprehension

11.28

4.42

13.46

2.69

-1.37

0.18

Digit span

5.85

2.34

6.3

1.93

-0.46

0.64

Arithmetic

6.85

2.67

7.15

2.19

-0.26

0.79

Similarities

7.71

4.07

9.3

2.83

-1.02

0.31

Vocabulary

7.85

3.13

7.38

2.39

0.37

0.71

Picture arrangement

6.14

2.47

5.76

1.83

0.38

0.7

Picture completion

8

3.05

8.46

2.47

-0.36

0.71

Block design

6

2.51

7.92

2.87

-1.48

0.15

Object assembly

9.71

2.43

8.38

3.68

0.85

0.4

Digit symbol

7.85

1.77

7.15

1.86

0.81

0.42

Verbal IQ

90.71

15.6

88.92

11.65

0.29

0.77

Performance IQ

90.14

15.21

84.61

12.07

0.89

0.38

Full scale IQ

89.42

13.98

86.15

12.79

0.52

0.6

DI

16.71

10.38

14.38

11.25

0.45

0.65

WCST

 

Total administration

124.84

11.37

128

0

-0.72

0.47

Total correct

55.02

19.22

55.62

16.4

-0.07

0.94

Total errors

47.24

17.85

45.37

18.18

0.22

0.82

Preservative  responses

47.47

25.86

41.01

25.33

0.53

0.59

Non–preservative errors

10.15

7.96

13.11

5.2

-0.88

0.39

Preservative errors

34.83

17.59

32.18

18.98

0.31

0.75

Category completed

2.61

1.89

3.42

1.51

-0.97

0.34

TCFC

34.84

49.82

3.7

5.15

1.62

0.12

FMS

1.69

1.88

1.28

2.21

0.43

0.67

conceptual level

37.73

20.5

38.72

20.51

-0.1

0.91

ERP

 

P300 latency

374.45

63.68

374.05

144.01

0.009

0.99

P300 amplitude

3.89

3.58

5.16

2.93

-0.85

0.4

 

* = Significant <0.05


Table 4. Correlation of P300 latency and amplitude with number of episodes and with WAIS results.

 

 

P300 latency

P300 amplitude

t

p

t

p

WAIS

 

 

 

 

 

0.46

0.041

0.063

0.792

Information

-0.1

0.77

-0.19

0.61

Comprehension

-0.11

0.76

-0.32

0.38

Digit span

-0.36

0.32

-0.34

0.35

Arithmetic

0.12

0.75

0.28

0.45

Similarities

-0.29

0.44

-0.4

0.27

Vocabulary

0.16

0.66

0.22

0.56

Picture arrangement

0.27

0.47

0.34

0.36

Picture completion

-0.45

0.22

-0.6

0.08

Block design

-0.18

0.64

-0.28

0.45

Object assembly

0.23

0.53

0.03

0.92

Digit symbol

0.21

0.57

0.18

0.63

Verbal IQ

-0.03

0.92

-0.08

0.83

Performance IQ

0.23

0.54

0.06

0.86

Full scale IQ

0.04

0.9

-0.06

0.86

DI

0.35

0.35

0.28

0.45

* = Significant <0.05

 

Table 5. Correlation of p300 latency and amplitude with scores on WCST.

 

 

P300 latency

P300 amplitude

t

p

t

p

WCST

 

Total administration

0.198

0.403

-0.298

0.734

Total correct

-0.169

0.477

0.184

0.438

Total errors

0.263

0.263

-0.099

0.679

Preservative  responses

0.206

0.206

-0.053

0.823

Non–preservative errors

-0.105

0.661

0.032

0.982

Preservative errors

0.289

0.216

-0.152

0.524

Category completed

-0.335

0.148

0.068

0.774

TCFC

0.147

0.537

-0.0965

0.692

FMS

-0.039

0.87

0.101

0.672

conceptual level

-0.179

0.451

0.187

0.431

WCST (FH+)**

 

Total administration

0.17

0.65

-0.39

0.29

Total correct

-0.15

0.69

0.16

0.66

Total errors

0.22

0.55

-0.13

0.73

Perseverative responses

0.24

0.53

-0.11

0.77

Non- perseverative errors

-0.17

0.65

0.19

0.61

Perserverative errors

0.32

0.4

-0.15

0.69

Category completed

-0.26

0.49

0.02

0.94

TCFC

0.04

0.9

-0.008

0.98

FMS

-0.15

0.69

0.07

0.84

Conceptual

-0.18

0.64

0.18

0.63

* = Significant <0.05

** WCST (FH+): scores on WCST in group of patients with positive family history

 

Fig. (3): P300 recorded from a bipolar patient showing prolonged latency and small amplitude.

 

 


DISCUSSION

 

Recent investigations of patients in the euthymic phase of bipolar disorder found that many patients continue to experience psychological and social difficulties, and while the extent of which neuropsychological impairment remains is less clear, most studies report at least some degree of residual dysfunction in one or more tasks administered.1

In this study we selected patients in the age group 20- 40 years to eliminate the effect of ageing on cognitive functions.13 The male to female ratio in the patients group was 1:2. This is not consistent with Sadock and Sadock, who reported that bipolar disorder has the prevalence that is equal for men and women.14 However, this could be explained by the fact that the majority of patients of the Kasr El-Aini outpatient clinic, are females due to the morning working hours of the clinic giving more chance to the housewives to attend. The small number of the sample could be another contributing factor.

In this study 50% of the patients had family history of mood disorder (45% bipolar disorder and 5% major depressive disorder). This is consistent with Sadock and Sadock who supported our finding.(14) This result may direct our attention to the possibility of presence of genetic factor, which may need further studies to explain this point. In selecting our sample, we selected Kasr El-Aini Hospital representing a big university hospital covering almost all areas in Egypt, providing a greater chance to find euthymic patients coming for follow up.

There was significant difference between patients and the control groups as regard most of the subtests of WAIS, verbal IQ, performance IQ, full scale as well as DI (Table 3). These differences were significant between euthymic patients group and control group in spite of being matched for sex, age and education. This led us to a finding that the cognitive impairment in bipolar patients is rather generalized than selective, and it affects most of the cognitive domains and causes global impairment of intellectual abilities. This finding does not agree with Bearden et al, who reported that bipolar affective disorder is not associated with general cognitive impairment, and it is associated with selective impairment in attention, speed information processing, learning and memory.15

The results of our study showed that patients performed significantly worse than controls on WCST. This is consistent with Morice, and McGrath et al, who also found significant impairment in WCST in bipolar patients.16,17 The psychological functions tested by WCST, including the ability to shift cognitive set, is believed to be subserved by the prefrontal cortex especially the left dorsolateral cortex.18

On the other hand, P300 latency provides an indication of the duration of the process involved in stimulus discrimination, while its amplitude, influenced by the number of variables, provides an index of the intensity of the energetic activation or arousal involved.19 So, P300 components are considered to be related to cognitive functions such as attention and information processing20. They also reflect the state of function of attention control and memory, both necessary for final evaluation of the stimulus21. The results of ERP in our study showed an increase in the latency of P300 and reduction of its amplitude in bipolar patients compared to control subjects (Fig. 3). These suggest a definite cognitive impairment in euthymic bipolar patients. The ERP results in our study agree with Souza et al.4, who found that P300 latency was prolonged at all sites in bipolar patients, compared to controls. However, the difference did not reach statistical significance, which could be explained by the fact that patients in our sample were euthymic and symptom free. Many studies have postulated a relationship between  P300  results  and  clinical presentation, while others postulated that  P300  latency  and  amplitude abnormalities found in bipolar patients are neither due to clinical state nor to medication effects.3

The final results of these scales indicate a generalized rather than selective impairment with variable degrees in almost all domains of cognitive spheres. The results of disturbance in attention and memory should be considered in the context of distributed functions, not as individual processes. At the same time, memory functions, especially the  short  term memory, depend  on  attention  and concentration and are governed by proper stimulus and its relevant response in one side and duration of information processing on the other side.

One of the greatest impairment in euthymic patients was in attention and concentration (55%). This was associated with decrease in P300 amplitude, which reflects the stimulant and  relevant response,  and increase in P300 latency which indicates the duration  of  information  processing19. Although P300 is considered state dependent, yet our results indicate that there is still some elements of disturbance even in euthymic  states.(6) P300  responses  are reflected on the motor sphere, whether in praxis or in verbal fluency, which may reflect a possible coordinating system in the brain that may be affected in bipolar patients as reported by many studies. Soares and Mann found a smaller cerebellum  in  bipolar  patients23 while Blumberg  reported  heightened activity in fronto-cortico-subcortical neural system that includes caudate nucleus.24

All these comments may indicate that cortical and subcortical disturbance in circuits of the brain share in various aspects of cognition in systemic state. This may be biochemical at the very beginning (i.e. the onset of the illness) but in remission it may acquire a usual activity of these circuits, explaining the persistence of cognitive impairment in euthymic patients.

On the other hand, patients with family history of psychiatric disorder performed worse than patients with negative family history in most of the subtests of the neurocognitive tests used in our study. This could be explained by the  definite biological base of the patients with positive family history. This agrees with Winokur et al, who found that patients with positive family history predict more severe course of illness  in bipolar patients suggesting more cognitive impairment.25

In our study, patients with duration of illness more than 10 years had more impaired executive function as tested by WCST. This is consistent with Landro, et al., who found that executive functions are one of the least impaired cognitive functions in first episode mood disorder and first episode schizophrenia.26 The  authors  also  stated  that  poor performances of frontal lobe associated functions are more prominent in chronic patients.

Also, patients with duration of illness more than 10 years had less scores on digit span, arithmetic, similarities and block design on WAIS subtests. They also had higher deterioration index. The duration of illness also affected P300, as patients with duration of illness more than 10 years had prolonged latency and reduced amplitude of P300 than patients with duration less than 10 years. All these findings support the hypothesis of the influence of duration of illness on cognitive functioning of bipolar patients.

60% of the patients have never been admitted to a mental hospital, while 25% of the patients were admitted once. This considered disproportioned to the mean number of episodes which was 5.65+4.47. This  could  be  explained by  the unavailability of inpatients facilities in our hospitals for females, which contribute the major component of the sample (65%).

Significant correlation between number of hospitalization at mental hospital and performance on cognitive tasks was not found in our study. This could be explained by the small number of admissions in our sample. This is consistent with Rubinsztein et al., who failed to find any significant correlation between number of hospitalization and cognitive tests of memory, attention and executive functions.2 However Tham et al., found significant correlation between number of hospitalization and performances on executive functions.27

On the other hand, our results revealed negative correlation between the scores of these neurocognitive subsets and P300 latency, in addition to a positive correlation between P300 amplitude and these scores. This could be explained by the close relation between P300 wave and cognition. However none of these correlations reached a statistically significant level except for the negative correlation between P300 latency and praxis. Souza et al. also failed to find significant correlation of P300 latency or amplitude to any    cognitive tests in bipolar group and control subjects.4

As reported by Hodges, the areas responsible for praxis ideational are the inferior parietal and the prefrontal areas.28 These areas could be related to generation of P300. Halgren et al., suggest that deep recordings of temporal, frontal and parietal areas are supposed to contribute to surface potentials of P300.29

 

REFERENCES

 

1.      Murphy, FC and Sahakian, BJ (2001): Neuropsychology of bipolar disorder, Br. J Psychiatry, 178:120-127.

2.      Rubinsztien, JS, Michael, A and Paykel ES (2000): Cognitive impairment in remission in bipolar affective disorder. Psychological Medicine, 30: 1025-1036.

3.      Muir, WJ, Claris, DM and Blackwood DHR (1991): Long latency auditory event related potentials in schizophrenia and in bipolar affective disorder, Psychol Med, 21: 867-879.

4.      Souza, VB, Muir, WJ and Walker, MT (1995): Auditory P300  event related potentials and  neuropsychological performance in schizophrenia and bipolar affective disorder. Society of Biological Psychiatry, 37: 300-310.

5.      Ford JM, White P and Lim, K (1994): Schizophranics have fever and smaller P300. A single trial analysis. Biol Psychiatry, 35: 96-103.

6.      Rao, KM, Ananthnaranan, CC and Gangadhar, BN (1999): Smaller auditory amplitude in schizophrenia in remission. Neuropsychobiology, 23: 171-174.

7.      American Psychiatric Association (1994): Diagnostic and Statistical Manual of Mental Disorders, Forth  Edition. American Psychiatric Press. Washington DC.

8.      Hamilton M.  (1969):  Standardized assessment and recording of depressive symptoms. Psych Neurosurg., 72: 201-205.

9.      Young RC, Biggs J, Ziegler VE and Meyer, DA (1978): Rating scale for mania: reliability, validity and sensitivity. Br. Journal of Psychiatry, 133, 429-435.

10.    Melika, LK (1976): Wechsler- Bellevue Test for Adolescent and Adults (Arabic version), El Nahda Egyptian Press.

11.    Heaton R, Chetune, G, Kay, G and Curtiss, G (1993): Wisconsin Card Sorting Test Manual: Revised and  expanded. Odessa, FL: Psychological. Assessment Resources, Inc.

12.    Saunders, BD and Trapp, RG (1994): Basic and Clinical Biostatistics, 2nd edition Pbs Appeleton and lange, U.S.A.

13.    Fillit, HM, Bulter, RN, O'Connell AW and Albert MS (2002): Achieving and maintaining cognitive vitality with aging. Mayo Clin Proc. 77 (7): 681-696.

14.    Sadock, BJ and Sadock, VA (2000): Comprehensive textbook of psychiatry, 7th edition, New York: Lippincott Williams and Williams.

15.    Bearden, CE, Hoffman, KM and Cannon, TD (2000): The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disorder, 3(3): 106 - 150.

16.    Morice, R (1990): Cognitive inflexibility in schizophrenia and mania. Br. J Psychiatry 157: 50-54.

17.    MeGrath, J, Scheldt, S and Weiham, J (1997): Perform on tests sensitive to impaired executive ability in schizophrenia, mania and well controls: acute and subacute phases. Schizophrenia Res, 26 (2): 127-37.

18.    Fuster, JM (1989): The Prefrontal Cortex (2nd ed). New York: Raven Press.

19.    Hansenne, M (2000): The P300 cognitive Event Related Potential: theoretical and Physiologic perspective. Neurophysiol Clin, 30:191-201.

20.    Higuchi S, Liu, Y and Yuasa, T (2000): Diurnal variation of the P300 component of human cognitive Event Related Potentials. Chronobiol. Int. 17 (5): 669-78.

21.    Loeches, M, Munoz, F, Molina, V and Pozo, MA (2001): The P300 component of evoked potentials in the evaluation of schizophrenia: new evidence and future vision. Rev Neurol, 32(3): 250-8.

22.    Blackwood, DH, Sharp, CW and Walker, MD (1996): Implication  of comorbidity of bipolar disorder: P300 and eye-tracking as biological markers of illness. Br J Psychiatry, 168 (30): 85 - 92.

23.    Soares, JC and Mann, JJ (1997): The anatomy of mood disorders-review of structural n euro imaging studies, Biological Psychiatry, 41: 86-106.

24.    Blumberg, HP, Stein, E and Martinez, D (2000): Increased anterior cingulate and caudate activity in bipolar mania. Biol Psychiatry. 48 (1): 1045-52.

25.    Winokur, G, Coryell, W and Akiskal HS (1994): Manic-depressive (boplar) disorder; the course in light of a prospective.

26.    Landro, NI, Orbeck, AL and Rund, BR (1993): Memory functioning in chronic and non-chronic  schizophrenic,  affectively disturbed patients and normal controls. SchizophrRes, 10: 85-92.

27.    Tham, A, Engelbrekson, K and Mathe, AA (1997): Impaired neuropsychological performance in euthymic patients with recurring  mood  disorders.  J  Clin Psychiatry, 58(1): 26-29.

28.    Hodges, JR (1996): Cognitive assessment for clinicians. Oxford University Press.

29.    Halgren E, Stapleton, JM and Altafullall (1986): Generators of the human scalps P3 (s). Liss, New York, PP: 269 -384.


 

الملخص العربى

 

دراسة الجهد المستثار والوظائف المعرفية لدى مرضى الاضطراب الوجدانى ثنائى القطب للمصريين

أثناء فترة اعتدال المزاج

 

تناول القليل من دراسات الحالات المعرفية والفسيوعصبية لدى  المرضى الاضطراب ثنائى القطب خلال فترة اعتدال المزاج. وقد تم تطبيق هذا البحث على عشرين مريضا من هؤلاء المرضى حيث تمت مقارنتهم بعينة ضابطة مكونة من عشرين فرد خاليين من الأمراض النفسية أو من التاريخ السابق أو العائلى للمرضى النفسيين وقد تم تشخيص  العينة المرضية وفقاً للمعايير المحددة فى دليل التشخيص الإحصائى الرابع للرابطة الأمريكية للطب النفسى وتم تطبيق اختبار هاملتون لقياس الاكتئاب واختبار يونج للهوس لتجنب وجود اعراض المزاج فى الحالات المختارة وقد تم أيضا استخدام اختبار وكسلر للذكاء  للبالغين واختبار  وسكونسن لترتيب  الكروت, كذلك  تم قياس الجهد المستثار ( طول وارتفاع الموجه ب 300) لأفراد المجموعتين. وقد اشارت  النتائج إلى وجود اضطراب عام فى الوظائف المعرفية والوظائف التنفيذية لدى عينة المرضى مما يرجح وجود خلل مرضى فى المنطقة قبل الجبهية بالمخ. وقد رجحت النتائج ان يمثل عدد النوبات والمدة المرضية والتاريخ العائلى الإيجابى للمرض عوامل خطورة لهذا الاضطراب . وقد وجد أن العينة المرضية يزيد عندها طول الموجة ب 300 ويقل ارتفاعها , كما تبين أن هناك علاقة بين هذه النتائج ووجود الاضطراب فى الوظائف المعرفية, كذلك وجدت علاقة أيضا مع عدد النوبات المرضية وهنا نستخلص وجود درجة ما من الاضطرابات المعرفية والفسيوعصبية لدى هؤلاء المرضى, مما يتطلب المزيد من الدراسات.



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