|Year : 2012 | Volume
| Issue : 1 | Page : 40-44
Cognitive functions in euthymic adolescents with juvenile bipolar disorder
Lamis El Ray, Aref Khoweiled, Hoda Abdou, Shreen Abd El-Mawella, Mai Abdel Samie
Department of Psychiatry, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||22-Feb-2010|
|Date of Acceptance||24-Mar-2011|
|Date of Web Publication||6-Jun-2014|
Lamis El Ray
Department of Psychiatry, Faculty of Medicine, Cairo University, Cairo
Source of Support: None, Conflict of Interest: None
Bipolar disorder in adolescents is often referred to as juvenile bipolar disorder. A peak in the prevalence of bipolar disorder has been documented between the ages of 15 and 19 years. Wide-ranging neuropsychological deficits have been found in many studies of juvenile bipolar disorder. Persistent neuropsychological deficits present in the euthymic state suggest that such deficits could be vulnerability trait markers of the illness.
To identify and assess cognitive functioning in euthymic adolescents diagnosed with bipolar disorder.
Participants and methods
A case–control cross sectional study, in which 30 euthymic bipolar adolescents were recruited from the psychiatric adolescent clinic of Kasr al Ainy and compared with 30 healthy controls.
The Hamilton Rating Scale of Depression, the Young Mania Rating Scale, the letter cancellation test, the digit span and digit symbol/coding tests, the Bender gestalt test and the Wisconsin card sorting test were used.
Cases had significantly higher mean scores than controls in the letter cancellation test and its omission errors as well as in the perseverative errors of the Wisconsin card sorting test, and lower mean scores in the digit span, digit symbol coding and the Bender gestalt tests. There was a significant positive correlation between the number of omission errors on the letter cancellation test and both of the number of manic episodes and the age of onset of the illness.
There are neuropsychological deficits in the areas of sustained attention, set shifting, processing speed and visual and auditory short-term memory in euthymic bipolar adolescent patients, type I. There is a significant correlation between the number of manic episodes as well as age of illness onset and sustained attention.
Keywords: euthymia, juvenile bipolar disorder, neuropsychological deficits
|How to cite this article:|
El Ray L, Khoweiled A, Abdou H, El-Mawella SA, Samie MA. Cognitive functions in euthymic adolescents with juvenile bipolar disorder. Egypt J Psychiatr 2012;33:40-4
|How to cite this URL:|
El Ray L, Khoweiled A, Abdou H, El-Mawella SA, Samie MA. Cognitive functions in euthymic adolescents with juvenile bipolar disorder. Egypt J Psychiatr [serial online] 2012 [cited 2022 Aug 13];33:40-4. Available from: http://new.ejpsy.eg.net/text.asp?2012/33/1/40/133929
| Introduction|| |
Bipolar disorder in adolescents is often referred to as juvenile bipolar disorder (Cahill et al., 2009). It is a disabling condition characterized by extreme affective and behavioural dysregulation, aggression, severe irritability and a chronic course (Biederman, 2003). In clinical trials, euthymia in bipolar disorder is conventionally defined as scores below a certain threshold, but not zero, on the Young Mania Rating Scale and the Hamilton Rating Scale for Depression (HRSD) (Pizzagalli et al., 2008). During euthymia, bipolar patients exhibit minimal symptoms by definition, although a persistent vulnerability for mood dysregulation is always present. This persistent vulnerability has been hypothesized to result from over-reactive emotional (i.e. anterior limbic) brain networks (Phillips et al., 2003). If correct, this hypothesis suggests that, even during euthymia, dysfunction within the anterior limbic network persists, leaving patients at risk for mood and cognitive disturbances (Strakowski et al., 2004). Wide-ranging deficits have been found in many studies of juvenile bipolar disorder (Olvera et al., 2005; Bearden et al., 2007). Persistent neuropsychological deficits present in the euthymic state of bipolar affective disorder, particularly impairment in sustained attention, suggest that such deficits could be vulnerability trait markers of the illness (Thompson et al., 2005).
| Aim|| |
The aim of this work is to identify and assess the cognitive impairment of euthymic adolescents diagnosed with bipolar disorder on neuropsychological measures of sustained attention, short-term memory, processing speed and set shifting after exclusion of other comorbid psychiatric disorders.
| Participants and methods|| |
A total of 30 adolescents diagnosed with bipolar disorder type I participated in this research. All the patients were selected from the Kasr Al Aini adolescent outpatient psychiatric clinic. Both male and female patients were included. They were between the ages of 13 and 19 years, met the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for bipolar disorder type I and were euthymic during application of the psychometric tools, which was defined in our study as scores of 7 or below on both the 17-item HRSD and the Young Mania Rating Scale. All patients with comorbid psychiatric disorder, a history of attention deficit hyperactivity disorder before the onset of the disorder, intelligence quotient less than 90, any neurological deficit or chronic illness, a history of significant head trauma, electroconvulsive therapy in the past 6 months or those who were illiterate were excluded. The control group was selected to match the patients’ group for age, sex and educational level. All control participants had no past history of psychiatric or neurological disorders or family history of psychiatric disorders. The diagnosis of bipolar disorder type I as well as the exclusion of psychiatric co morbidities and history of attention deficit hyperactivity disorder starting before the onset of the bipolar disorder was established by interviewing the patients and at least one of their parents using the Kiddie Schedule for Affective Disorders and Schizophrenia in school-aged children (K-SADS-PL) (Kaufman et al., 1997). A written informed consent was obtained from parents for their minor adolescents and from the participants themselves if they were aged 18 years or older.
A specially designed semistructural interview derived from the Kasr Al Aini psychiatric sheet was used to cover demographic data, personal data, past history and family history.
The Kiddie Schedule for Affective Disorders and Schizophrenia in school-aged children (Kaufman et al., 1997)
The K-SADS-PL is a semistructured diagnostic interview designed to assess current and past episodes of psychopathology in children and adolescents according to DSM-III-R and DSM-IV criteria. Probes and objective criteria are provided to rate individual symptoms. The K-SADS-PL is administered by interviewing the parent(s), the child and finally achieving summary ratings that include all sources of information (parent, child, school). When administering the instrument to preadolescents, the parent interview should be conducted first. In working with adolescents, the interview should be conducted first with them, followed by the parent, which was followed in our research. The majority of the items in K-SADS-PL are scored using a 0–3-point rating scale. Score of 0 indicate that no information is available; a score of 1 suggests that the symptom is not present; a score of 2 indicates subthreshold levels of symptomatology; and a score of 3 represents threshold criterion. The remaining items are rated on a 0–2-point rating scale, in which 0 implies no information; 1 implies that the symptom is not present; and 2 implies that the symptom is present.
Hamilton Rating Scale for Depression (Hamilton, 1960)
The HRSD is the most widely used clinician-administered depression assessment scale. We have used the 17-item version, where a score of 0–7 is accepted to be within the normal range or in clinical remission. It has been used to ensure the euthymic state of cases after interviewing them using the K-SADS-PL.
Young Mania Rating Scale (Young et al., 1978)
It is a clinician-rated scale used to rate the severity of manic symptoms. The items rated are elevated mood, increased motor activity, sexual interest, sleep, irritability, speech and language, content of thought, disruptive or aggressive behaviour, appearance and insight. Scoring of each item is between 0 and 4 points. The cases had to score 7 or less to be considered euthymic and thus to be included in the study.
Letter cancellation test (Diller et al., 1974)
It is a measure of sustained attention (Ronald et al., 2000). It has been applied in its Arabic version, where participants were asked to cancel two fixed Arabic letters whenever they found them amidst 19 rows of Arabic letters, as fast as they could. The time in seconds taken by each participant to complete this task was calculated. Whenever any of the letters to be cancelled was missed, this was considered an omission error. We used the Arabic version by El Kholi (1985).
Digit span (Meleka and Ismail, 1996, 1999)
It is one of the subtests of both the adult and the child Wechsler Intelligence Scale used to measure auditory short-term memory. The candidate was asked to repeat a dictated series of digits forward and another backward, with two trials each time. The final score was calculated by adding the score of the forward series to that of the backward series.
Digit symbol coding (Meleka and Ismail, 1996, 1999)
It is one of the subtests of the Wechsler Intelligence Scale used to measure processing speed (Doyle et al., 2005). In the Arabic version of the Wechsler Intelligence Scale for children that was applied with participants below 16 years, the participants had to transcribe a digit symbol code as quickly as possible for a duration of 2 min, whereas in the adult version, used when participants were 16 years or above, participants had to transcribe the digit symbol code as quickly as possible for a duration of 90 s. The number of correct transcriptions completed by the participant in the given time was counted to yield the final score.
Bender gestalt test (Bender, 1938)
It is a measure of visual short-term memory and visual motor maturity (McCarthy et al., 2002). It was formulated by Lauretta Bender, a child neuropsychiatrist. The version used in our study comprises six figures on six separate cards. The cards were shown one after the other to each participant, who was instructed to draw each figure carefully, bearing in mind that he would be asked to recall the six figures after about 2 min. Scoring was carried out according to a standardized scoring system, where each recalled figure would receive a score between 0 and 5 points according to the accuracy of the details recalled.
Wisconsin card sorting test
The purpose of this test is to assess the ability to form abstract concepts, to shift and maintain set and to utilize feedback. The test is considered a measure of executive function (Heaton et al., 1993) in that it requires strategic planning, organized searching, the ability to use environmental feedback to shift cognitive set, goal-oriented behaviour and the ability to modulate impulsive responding. The test can be used with individuals aged 5 to 89 years. The time required is about 15–30 min (Strauss et al., 2006).
The statistical methods
Statistical analysis was performed using the Statistical Package of Social Science, version 16 (SPSS-V16, IBM, Chicago, IL, USA). Descriptive analysis was performed using frequency tests, pie and bar charts. The student’s unpaired t-test was used to compare quantitative data between two groups and the analysis of variance and the post-hoc tests were used to compare quantitative data between more than two groups. The correlation between different quantitative data was assessed using the Pearson correlation test. Finally, the χ2-test with Yates correction was used for the analysis of categorical data. The level of significance was set at P less than 0.05.
| Results|| |
53.3% of the cases were women and 46.7% were men. The mean age of the cases was 18.03. The case and control groups were matched in terms of age, sex and educational level (P=1, 1, 0.6, respectively) [Table 1], [Table 2], [Table 3] and [Table 4].
|Table 4: Correlation between clinical data and neuropsychological test scores|
Click here to view
There were no statistically significant differences between cases with positive and negative intake of any of the classes of psychotropic drugs used by the cases at the time of assessment as regards the mean scores of the neuropsychological tests.
| Discussion|| |
Our study aimed at assessing the performance of euthymic adolescent patients with bipolar disorder on neuropsychological measures of sustained attention, short-term memory, processing speed and set shifting. The comparison between the neuropsychological test scores of our cases and controls revealed that the euthymic patients showed poorer performance than controls in the letter cancellation test, which is a measure of sustained attention, with a highly significant statistical difference between the mean scores of both groups on this test. This is consistent with findings in the study conducted by Kolur et al. (2006) and where euthymic bipolar patients showed poorer performance than healthy controls on tests of sustained attention. However, this finding is not concordant with the study by DelBello et al. (2004), where no statistically significant difference was found between the performance of euthymic bipolar patients and healthy controls in tests of sustained attention, but this may be due to the small sample size in their study (10 cases and a matched control group).
The euthymic patients in our study also showed poorer performance than controls on the digit span test, which is a measure of auditory short-term memory, with a highly significant difference between the mean scores of both groups in this test. This finding is consistent with the findings by Gruber et al. (2007), where euthymic bipolar patients showed an impaired auditory short-term memory in comparison with healthy controls. However, this finding was in contrast to a recent study by Langenecker et al. (2010), where euthymic patients showed no impairment in auditory memory ability, although the sample size in the latter was larger.
Moreover, the patients in our study showed poorer performance than controls in the Bender gestalt test, which is a measure of visual short-term memory, also with a statistically significant difference between both groups. This is concordant with the study by Langenecker et al. (2010) but is inconsistent with the study by Pavuluri et al. (2006), where there was no difference between euthymic patients and controls as regards visual short-term memory.
In addition, the cases and controls in our study showed a statistically significant difference between their mean scores on the digit symbol coding test, where cases showed a poorer performance, revealing impairment in mental processing speed. This finding is consistent with the findings obtained in a study conducted by Langenecker et al. (2010).
Regarding the performance on the Wisconsin card sorting test, the patients in our study committed more perseverative errors than controls, with a statistically significant difference, which revealed a deficit in set shifting ability in cases. This finding is in agreement with the findings in the study by Trivedi et al. (2007), where euthymic patients committed more perseverative errors than healthy controls on the Wisconsin card sorting test, also with a statistically significant difference between both groups.
As for the correlation between the clinical variables and the mean neuropsychological scores of the patients in our study, the number of manic episodes was positively correlated to the mean number of omission errors in the letter cancellation test, which is statistically significant (i.e. the number of manic episodes was negatively correlated to the sustained attention function of the euthymic patients in our study).This is consistent with the findings in the study by Clark et al. (2002), where sustained attention performance suffered with increasing burden of manic episodes.
In our study, the age of illness onset, like the number of manic episodes, was positively correlated to the mean number of omission errors on the letter cancellation test, which is consistent with the finding obtained by Martinez Aran et al. (2004b), where the age of onset of illness was also positively correlated to a score on a measure of sustained attention (i.e. those with a later onset of illness performed more poorly on measures of sustained attention).
In our study, no statistically significant correlation was found between the duration of illness and any of the neuropsychological test scores, which was concordant with a study assessing the same neuropsychological functions in euthymic bipolar patients (Kolur et al., 2006).
As regards the number of depressive episodes, no significant correlation was found between the number of depressive episodes and any of the neuropsychological scores in our study, which is in agreement with the findings obtained in the study conducted by Martinez Aran et al. (2004b), where no significant correlation was found between the number of depressive episodes and scores on measures of verbal memory and sustained attention.
Moreover, no significant correlation was found between the number of hospitalizations and any of the neuropsychological scores in our study, which is similar to the findings obtained by Cavanagh et al. (2002), where no significant relationship was found between the total number of hospitalizations and executive function, psychomotor speed and visual recognition. It is also concordant with the finding obtained by Clark et al. (2002), where no significant relationship was found between the total number of hospital admissions and measures of sustained attention, set shifting, verbal memory and speed of information processing. Moreover, this similarity was present despite the fact that these two studies included patients of an older age group than those in our study, with more number of hospitalizations.
As for the intake of psychotropic medication, no statistically significant difference was found between cases with positive and negative intake of typical antipsychotics, atypical antipsychotics, antiepileptics, anticholinergic drugs and antidepressants as regards neuropsychological test scores, which are consistent with the finding in the study by Kolur et al. (2006). Moreover, there was no statistically significant difference between cases with positive and negative intake of lithium as regards neuropsychological test scores, which is similar to the finding in the study conducted by Martinez Aran et al. (2004a) and also by Kolur et al. (2006).
| Limitations|| |
Our study was cross sectional, whereas longitudinal studies can track the decline in neuropsychological function with illness progression better and can also track the impact of medication on cognition more accurately.
Our study was not drug free; although no significant relationship was found between psychotropic drug intake and neuropsychological test scores in our study and similar others, yet, the effect of psychotropic drugs on cognition cannot be excluded. However, for euthymia to be established, being drug free is quite a remote possibility; moreover, it gives rise to ethical issues.
| References|| |
|1.||Bearden CE, Glahn DC, Caetano S, Olvera RL, Fonseca M, Najt P, et al. Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder. Bipolar Disord. 2007;9(Suppl 1):145–159 |
|2.||Bender L Visual motor gestalt and its clinical use. 1938 New York American Orthopsychiatry Association |
|3.||Biederman J. Pediatric bipolar disorder coming of age. Biol Psychiatry. 2003;53:931–934 |
|4.||Cahill CM, Walter G, Malhi GS. Neurocognition in bipolar disorder and juvenile bipolar disorder. J Can Acad Child and Adolesc Psychiatry. 2009;18:221–230 |
|5.||Cavanagh JT, Van Beck M, Muir W, Blackwood DH. Case-control study of neurocognitive function in euthymic patients with bipolar disorder: an association with mania. Br J Psychiatry. 2002;180:320–326 |
|6.||Clark L, Iversen SD, Goodwin GM. Sustained attention deficit in bipolar disorder. Br J Psychiatry. 2002;180:313–319 |
|7.||DelBello MP, Zimmerman ME, Mills NP, Getz GE, Strakowski SM. Magnetic resonance imaging analysis of amygdala and other subcortical brain regions in adolescents with bipolar disorder. Bipolar Disord. 2004;6:43–52 |
|8.||Diller L, Ben Yishay Y, Gerstman LJ, Goodkin R, Gordon W, Weinberg J Studies in cognition and rehabilitation in hemiplegia. 1974 New York New York University Medical Center Institute of Rehabilitation Medicine |
|9.||Doyle AE, Wilens TE, Kwon A, Seidman LJ, Faraone SV, Fried R, et al. Neuropsychological functioning in youth with bipolar disorder. Biol Psychiatry. 2005;58:540–548 |
|10.||El Kholi SW 1985 Attention in psychiatric patients. A psychometric study. MA Thesis, Faculty of Arts |
|11.||Gruber S, Rathgeber K, Bräunig P, Gauggel S. Stability and course of neuropsychological deficits in manic and depressed bipolar patients compared to patients with major depression. J Affect Disord. 2007;104:61–71 |
|12.||Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62 |
|13.||Heaton RK, Chelune GJ, Talley JL, Kay GG, Curtiss G Wisconsin card sort test manual: revised and expanded. 1993 Odessa, FL Psychological Assessment Resources Inc. |
|14.||Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, et al. Schedule for affective disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36:980–988 |
|15.||Kolur US, Reddy YCJ, John JP, Kandavel T, Jain S. Sustained attention and executive functions in euthymic young people with bipolar disorder. Br J Psychiatry. 2006;189:453–458 |
|16.||Langenecker SA, Saunders EFH, Kade AM, Ransom MT, McInnis MG. Intermediate: cognitive phenotypes in bipolar disorder. J Affect Disorders. 2010;122:285–293 |
|17.||Martinez Aran A, Vieta E, Colom F, Torrent C, Sanchez Moreno J, Reinares M, et al. Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome. Bipolar Disord. 2004a;6:224–232 |
|18.||Martinez Aran A, Vieta E, Reinares M, Colom F, Torrent C, Sanchez Moreno J, et al. Cognitive function across manic or hypomanic, depressed and euthymic states in bipolar disorder. Am J Psychiatry. 2004b;161:262–270 |
|19.||McCarthy J, Rabinowitz D, Habib M, Goldman H, Miley D, Stefanyshyn HY, et al. Bender Gestalt Recall as a measure of short-term visual memory in children and adolescents with psychotic and other severe disorders. Percept Mot Skills. 2002;95(3 Pt 2):1233–1238 |
|20.||Meleka LK, Ismail ME Wechsler Intelligence Scale for children. 1996 Cairo El Nahda Egyptian Bookshop |
|21.||Meleka LK, Ismail ME Wechsler Intelligence Scale for children. 1999 Cairo El Nahda Egyptian Bookshop |
|22.||Olvera RL, Semrud Clikeman M, Pliszka SR, O’Donnell L. Neuropsychological deficits in adolescents with conduct disorder and comorbid bipolar disorder: a pilot study. Bipolar Disord. 2005;7:57–67 |
|23.||Pavuluri MN, Schenkel LS, Aryal S, Harral EM, Hill SK, Herbener ES, et al. Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients. Am J Psychiatry. 2006;163:286–293 |
|24.||Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biol Psychiatry. 2003;54:515–528 |
|25.||Pizzagalli DA, Goetz E, Ostacher M, Iosifescu DV, Perlis RH. Euthymic patients with bipolar disorder show decreased reward learning in a probabilistic reward task. Biol Psychiatry. 2008;64:162–168 |
|26.||Ronald TB, Patricia CD, Richard L. Neurocognitive functioning and magnetic resonance imaging in children with sickle cell disease. J Pediatric Psychol. 2000;25:503–513 |
|27.||Strakowski SM, Adler CM, Holland SK, Mills N, DelBello MP. A preliminary fMRI study of sustained attention in euthymic, unmedicated bipolar disorder. Neuropsychopharmacology. 2004;29:1734–1740 |
|28.||Strauss E, Sherman E, Spreen O. The compendium of neuropsychological tests. Administration, Norms and Commentary. 20063rd ed. Oxford University Press |
|29.||Thompson JM, Gallagher P, Hughes JH, Watson S, Gray JM, Ferrier IN, et al. Neurocognitive impairment in euthymic patients with bipolar affective disorder. Br J Psychiatry. 2005;186:32–40 |
|30.||Trivedi JK, Goel D, Sharma S, Singh AP, Sinha PK, Tandon R. Cognitive functions in stable schizophrenia and euthymic state of bipolar disorder. Indian J Med Res. 2007;126:433–439 |
|31.||Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429–435 |
[Table 1], [Table 2], [Table 3], [Table 4]
|This article has been cited by|
||Cognitive correlates of impulsive aggression in youth with pediatric bipolar disorder and bipolar offspring.
| ||Alessio Simonetti,Sherin Kurian,Johanna Saxena,Christopher D. Verrico,Jair C. Soares,Gabriele Sani,Kirti Saxena |
| ||Journal of Affective Disorders. 2021; |
|[Pubmed] | [DOI]|
||Cognitive Impairment in Euthymic Pediatric Bipolar Disorder: A Systematic Review and Meta-Analysis
| ||Liana R. Elias,Kamilla W. Miskowiak,Antônio M.O. Vale,Cristiano A. Köhler,Hanne L. Kjærstad,Brendon Stubbs,Lars V. Kessing,Eduard Vieta,Michael Maes,Benjamin I. Goldstein,André F. Carvalho |
| ||Journal of the American Academy of Child & Adolescent Psychiatry. 2017; |
|[Pubmed] | [DOI]|
||Cognitive functions and cognitive styles in young euthymic patients with bipolar I disorder
| ||Hala Fakhry,Soheir H. El Ghonemy,Afra Salem |
| ||Journal of Affective Disorders. 2013; 151(1): 369 |
|[Pubmed] | [DOI]|