A comparative study of temperamental, behavioral, and cognitive changes in thalassemia major, thalassemia minor, and normal population.

BACKGROUND: Temperament in children and adolescents acts as a trait marker which can predict behavioral abnormalities. There was no systemic study in India which has compared the temperamental, behavioral and cognitive changes associated with this hemoglobinopathy among thalassemia major (TM) group.
MATERIALS AND METHODS: The specific objectives of this study were to find the clinicodemographic profile of individuals and parents, the behavioral, temperamental profile of children of beta TM and correlation of temperamental profile with number of blood transfusions, cognitive profile of children having beta TM, minor and age-matched control children and adolescents.
RESULTS: Child and adolescents having TM have more temperamental and behavioral problems (P < 0.001) and have more psychopathology in comparison to Tm group. Descriptive statistics of the groups and group comparison (ANOVA) shows statistically significant difference in Temperament Measurement Schedule (TMS) total, CPMS total, TMT A, TMT B, and Children's Depression Rating Scale (CDRS) scales (P = 0.000). Descriptive statistics and group comparison (Chi-square test) show significance in number of blood transfusions not with other parameters (P < 0.001). Comparison between TM (Case) and Tm (Control) (t-test) shows significance with only TMS total and CPMS scales, not in other scales. The correlation matrix showed significant correlation in-between all the parameters (blood transfusion, TMS, CPMS, TMT A, TMT B, and CDRS). DISCUSSION: Those who have been diagnosed as TM have more behavioral and cognitive problems than their comparators. Youngsters receiving more blood transfusions due to their ailments scored higher in childhood depression rating scale.
CONCLUSION: The temperamental, behavioural and cognitive profile are key determinants of both internalizing and externalizing symptoms and management plan can be guided accordingly as reflected in this study. Copyright:

INTRODUCTION

Thalassemia is a chronic medical condition which incapacitates academic achievement as well as day-to-day life of the children and adolescents. It is an inherited blood disorder in which the body makes an abnormal form of hemoglobin.[1] There are three main types of thalassemia (and four subtypes), namely beta thalassemia, which includes the subtypes major and intermedia; alpha thalassemia, which include the subtypes hemoglobin H and hydrops fetalis and thalassemia minor.[2] Thalassemia major (TM) is the most severe form of beta thalassemia. It develops when beta globin genes are missing. In the severe form, TM (both β and Eβ thalassemia) requires frequent blood transfusion due to severe anemia and could not be able to function properly due to their illnesses and for attending day care centers to receive blood transfusions. This form of thalassemia is usually so severe that it requires regular blood transfusions.[34] It involves lifelong therapeutic regime, with repeated blood transfusions. With improved life expectancy, due to improved medical management, psychosocial aspects of thalassemia are gaining importance.[56]

MATERIALS AND METHODS

The study is an attempt to enrich the present knowledge and understanding of behavioral and emotional problems and the cognitive profile of children and adolescents suffering from Beta TM. All parameters had been compared with age- and sex-matched beta thalassemia trait patients and normal controls (excluded by high performance liquid chromatography, HPLC). The research work had been conducted in a peripheral tertiary care medical college for 3 months, and data preparation and statistical analysis had been done in a month. It was a single observational study with 50 samples in each group included in the study by stratified random sampling of children and adolescents attending day care centers of thalassemia control unit taking only odd numbers. Those who were 6–18 years old of both sexes and who can identify alphabets and numbers and not having any visual or hearing disability had been included in the study. Where HPLC could not be done or written informed consent could not be obtained were excluded from the study. The approval from institutional ethical committee had been taken, and the following tests had been administered.

Trail Making A and B[7]

Children's Depression Rating Scale (CDRS)[8]

Childhood Psychopathology Measurement Schedule (CPMS)[9]

Temperament Measurement Schedule (TMS).[10]

Trail Making A and B (TMT A and TMT B) where 25 circles distributed over a sheet of paper. In Part A, the circles were numbered 1–25, and the patients are asked to draw lines to connect the numbers in ascending order whereas in Part B, the circles include both the numbers (1–13) and letters (A-L). The individuals were asked to connect the circles as early as possible, without lifting the pen or pencil from the paper. This measures the cognitive deficit of the child if any if it takes more than 78 seconds to complete TMT A and 273 seconds to complete TMT B.[7] The CPMS (Childhood Psychopathology Measurement Scale) has dimensional scoring system and it comprises 75 questions scored as 2, 1, and 0 (often and very much true, sometimes true and not true, respectively) whereas TMS has 5 headings (H) and various subheadings (h). They are Activity level (h4), Rhythmicity (h4), Approach withdrawal (h5), Adaptability (h5), and Mood (h5). Scoring done in a 5 point Likert scale (1–5).[10]

RESULTS AND DISCUSSION

The data analysis and interpretation had been done by descriptive as well as by inferential statistical methods with the help of SPSS version 25 @ IBM (BM Corp., Armonk, NY).[11] The questionnaire had been applied by the researchers themselves with the help of residents in the department to the individuals and the reliable informants or legal guardians preferably mother.

The descriptive statistics of group (ANOVA) shows there is no difference in age in three groups, which signifies that the sampling has been distributed equally [Table 1]. All the other five variables, for example, TMS total score, CPMS total score, TMT A score, TMT B score, and CDRS score vary significantly (P < 0.000). TMS total score is higher in TM group (mean = 65.20, standard deviation [SD] = 12.56) in comparison to thalassemia minor (mean = 26.44, SD = 3.72) and in normal group (mean = 27.04, SD = 3.26). Similarly, CPMS total score is significantly higher in TM group (mean = 81.14, SD = 50.21) than the thalassemia minor (mean = 25.43, SD = 13.87) and the age-matched normal children group (mean = 7.68, SD = 4.03). The time taken to complete TMT A (in seconds) by youngsters having TM (Mean = 114.96, SD = 47.56) is significantly higher than the thalassemia minor (mean = 55.94, SD = 24.96) and normal (mean = 42.94, SD = 18.21), and this statistically significant difference also persists while giving TMT B tasks to them. Due to chronic nature of illness, as expected, the depression as measured in CDRS-revised scale among TM is significant than in other groups.

Table 1

Descriptive statistics of the groups and group comparison (ANOVA)

Category	Cases (Thal Major; n=50)	Control (Thal Minor; n=50)	Normal (n=50)	F	P significance
Age	Mean=11.93	Mean=13.08	Mean=12.86	1.790	0.170
	SD=3.18	SD=3.72	SD=2.69
TMS TOT	Mean=65.20	Mean=26.44	Mean=27.04	421.79	0.000**
	SD=12.56	SD=3.72	SD=3.26
CPMS TOT	Mean=81.14	Mean=25.43	Mean=7.68	80.22	0.000**
	SD=50.21	SD=13.87	SD=4.03
TMT A	Mean=114.96	Mean=55.94	Mean=42.94	9.722	0.000**
	SD=47.56	SD=24.96	SD=18.21
TMT B	Mean=167.14	Mean=110.18	Mean=89.36	38.59	0.000**
	SD=51.91	SD=50.94	SD=31.80
CDRS	Mean=34.34	Mean=30.60	Mean=28.10	15.04	0.000**
	SD=7.21	SD=5.29	SD=4.32

SD – Standard deviation; TMS TOT – Temperament Measurement Schedule total; CPMS TOT – Childhood Psychopathology Measurement Schedule total; TMT A – Trail Making Test A; TMT B – Trail Making Test B; CDRS – Children’s Depression Rating Scale

While assessing demographic variables and number of blood transfusions as a variable, there is no statistical significant difference found in gender, religion, residence type, family type, income, and education among the groups, which again signifies that the sample population is uniform in distribution and unbiased. However, number of blood transfusions has emerged up one of the significant predictors, and the difference is significant in TM group which for obvious reason required more blood transfusions [Table 2].

Table 2

Descriptive statistics and group comparison (Chi-square test)

Category		Cases (Thal Major; n=50)	Control (Thal Minor; n=50)	Normal (n=50)	Chi Square Test	Significance (Two tailed)
Gender	Male	22 (44%)	22 (44%)	25 (50%)	0.483	0.785
	Female	28 (56%)	28 (56%)	25 (50%)
Religion	Hindu	22 (44%)	29 (58%)	29 (58%)	2.625	0.269
	Muslim	28 (56%)	21 (42%)	21 (42%)
Residence	Urban	14 (28%)	18 (36%)	17 (34%)	0.788	0.674
	Non Urban	36 (72%)	32 (64%)	33 (66%)
Family Type	Nuclear	18 (36%)	17 (34%)	17 (34%)	0.059	0.971
	Non nuclear	32 (64%)	33 (66%)	33 (66%)
Income	Above Rs 10,000 pm	10 (20%)	12 (24%)	13 (26%)	3.193	0.526
	Rs 5001-10,000	33 (66%)	33 (66%)	35 (70%)
	<Rs 5000	7 (14%)	5 (10%)	2 (4%)
Education	Upto 4th Std	12 (24%)	9 (18%)	5 (10%)	6.266	0.180
	5th-10th Std	31 (62%)	27 (54%)	35 (70%)
	Above 10th Std	7 (14%)	14 (28%)	10 (20%)
Blood Transfusion (BT) requirement)	No BT	0 (0%)	39 (78%)	50 (100%)	123.892	<0.001**
	1-3 BT/yr	23 (46%)	11 (22%)	0 (0%)
	4-6 BT/yr	25 (50%)	0 (0%)	0 (0%)
	7 or more BT/yr	2 (4%)	0 (0%)	0 (0%)

BT=No of blood transfusions required per year

The number of blood transfusions is directly related to total score in CDRS-revised item [Table 3]. Youngsters and those having thalassemia required more blood transfusions. Those received 1–3 blood transfusions per year had scored in mild to moderate depression (CDRS rev >35) and those who received 4–6 blood transfusions per year had scored in severe depression range (CDRS rev >40). TMS total and CPMS total scores have been found stastically significant in Thalassemia major and minor group not CDRS scores [Table 4].

Table 3

Blood transfusion and correlation with depression

Category	No Depression, CDRS (<17)	Mild to Moderate Depression, CDRS (17-34)	Severe Depression, CDRS (>34)	Pearson’s Chi Square test (df=6)	Significance (Two tailed)
No BT	73	14	2	45.874	<0.000**
2-3 BT/year	18	14	2
4-6 BT/year	9	6	10
>7 BT/year	2	0	0

CDRS – Children’s Depression Rating Scale; BT – Blood Transfusion required

Table 4

Comparison between thalassemia major (case) and thalassemia major (control) (t-test)

Variable	Category	Mean	SD	F	Significance
Age	Case (n=50)	11.93	3.18	1.299	0.257
	Control (n=50)	13.08	3.72
TMS Total	Case (n=50)	65.12	12.34	59.188	<0.001**
	Control (n=50)	26.44	3.02
CPMS Total	Case (n=50)	81.14	50.21	54.691	<0.001**
	Control (n=50)	25.20	13.83
CDRS	Case (n=50)	34.34	7.20	2.962	0.088
	Control (n=50)	30.60	5.29
TMT A	Case (n=50)	114.96	147.57	2.436	0.122
	Control (n=50)	55.94	24.96
TMT B	Case (n=50)	167.14	51.92	0.194	0.661
	Control (n=50)	110.18	50.94

TMS TOT – Temperament Measurement Schedule total; CPMS TOT – Childhood Psychopathology Measurement Schedule total; TMT A – Trail Making Test A; TMT B – Trail Making Test B; CDRS – Children’s Depression Rating Scale, SD- Standard deviation

The correlation matrix had shown that each individual items (no of blood transfusions, TMS total, CPMS total, CDRS, TMT A, and TMT B) are statistically significant [Table 5]. The youngsters with beta TM has significantly higher scores in temperamental, childhood psychopathology, childhood depression, and cognitive profile, and all these items including number of blood transfusions are significantly correlated with each other.

Table 5

Correlation matrix

Variables	Blood Transfusions	TMS Total	CPMS Total	CDRS	TMT A	TMT B
Blood	CC=1.000	CC=0.748**	CC=0.755**	CC=0.382**	CC=0.589**	CC=8.524**
Transfusions	Sig	Sig=0.000	Sig=0.000	Sig=0.000	Sig=0.000	Sig=0.000
TMS Total	CC=0.748**	CC=1.000	CC=0.652**	CC=0.310**	CC=0.501**	CC=0.748**
	Sig=0.000	Sig	Sig=0.000	Sig=0.000	Sig=0.000	Sig=0.000
CPMS Total	CC=0.755**	CC=0.652**	CC=1.000	CC=0.430**	CC=0.631**	CC=0.755**
	Sig=0.000	Sig=0.000	Sig	Sig=0.000	Sig=0.000	Sig=0.000
CDRS	CC=0.382**	CC=0.310**	CC=0.430**	CC=1.000	CC=0.444**	CC=0.382**
	Sig=0.000	Sig=0.000	Sig=0.000	Sig	Sig=0.000	Sig=0.000
TMT A	CC=0.589**	CC=0.501**	CC=0.631**	CC=0.444**	CC=1.000	CC=0.589**
	Sig=0.000	Sig=0.000	Sig=0.000	Sig=0.000	Sig	Sig=0.000
TMT B	CC=0.524**	CC=0.486**	CC=0.590**	CC=0.424**	CC=0.939**	CC=1.000
	Sig=0.000	Sig=0.000	Sig=0.000	Sig=0.000	Sig=0.000	Sig

**Correlation significant at the 0.01 level (two-tailed). TMS TOT – Temperament Measurement Schedule total; CPMS TOT – Childhood Psychopathology Measurement Schedule total; TMT A – Trail Making Test A; TMT B – Trail Making Test B; CDRS – Children’s Depression Rating Scale; SIG – Significant; BL TRANSF – Blood transfusion; CC – Correlation coefficient

The cognitive deficits in beta TM group affect multiple domains and can be explained by hemosiderosis which offers following multiple blood transfusions. The time to complete the TMT A and TMT B tasks by TM group was significantly higher to age-matched control normal populations as well as those suffering from beta thalassemia minor. Moreover, there are higher number of omission, commission, and perseverative errors in TM group. Their attentional deficit contributes to poor memory, processing speeds, and executive tasks. The temperamental changes among children and adolescents having TM affect various domains including activity, rhythmicity, approach–withdrawal, adaptability, and mood symptoms. The psychosocial issues are extremely important to build up psychosocial support network. Interestingly, more literate and urban parents are more receptive to listen and accept advice of mental health professionals.[1213] The immediate impact of blood transfusions is a sense of well-being, but with subsequent transfusions, the youngsters have to attend day care center which results in absenteeism in the school and they are forced to play a sick role.[14]

The temperament of the adolescents suffering from beta TM and minor depends on many factors. The parental frustration and worry; repeated pain, anxiety, gastrointestinal symptoms; failure to thrive, discrimination in school by peer group, and sometimes teachers adding to the stigma are some common factors.[15] The improved treatment facilities with availability of chelation therapy and quick discharge protocol on the day of admission following blood transfusion is helpful to overcome the roadblocks of long admissions, waiting period, and worry for collecting blood subjected to availability.[16] The cognitive deficits in this group is also difficult to assess, and one of the simplest technique, the TMT A and TMT B, had been administered here which depends on age and education. The hemosiderin deposit in central nervous system can affect the cognition as well as childhood and adolescent depression and social discrimination.[1718]

Building up awareness and treating comorbidities are extremely helpful to improve quality of life of both the youngsters having thalassemia as well as their parents. Thus, the role of psychiatrists and other mental health professionals, pediatricians, school teachers, and psychosocial workers are extremely crucial for multisectorial intervention.[192021]

CONCLUSION

Although the study had generated significant information, there are certain limitations of the study. Although 50 sample size is quite significant as there had been no such studies being done comparing those variables in both TM and minor groups, more inclusion of the cases, control, and normal individuals could have improved the power of study. The study population is clinic based and not community based. Although CDRS scales are being applied in 6–14 years' group, some individuals having age in-between 14 and 18 years applied the same scale, and the scoring was compared with Hamilton's depression rating scale and Beck's depression inventory, and kappa value has been found above 0.8.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.