الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 114 |  |  |
| | | from | 114 | | |
Abstract
For decades, the negative impact of childhood adversity and maltreatment has been limited to the immediate harm and injuries. Recently, child maltreatment was connected with many long-term consequences in childhood, adolescents and adulthood among which are psychiatric symptoms and disorders.The present study aimed to determine the association between psychiatric consequences and different types of child maltreatment among adolescents between 12-18 years, explore the role of OXTR gene polymorphism (rs2254298) in moderating the relation between different types of child maltreatment and psychiatric consequences and to examine the relation between childhood abuse and global DNA methylation.
A case-control study was carried out on 90 children aged between 12- 18 years divided equally into two groups; cases suffering from psychiatric illness and attending child and adolescent psychiatric outpatient clinics at Al-Hadara University Hospital in Alexandria, Egypt and controls recruited from different outpatient clinics at Alexandria University Hospitals. Children with congenital developmental anomalies, neurological diseases or malignancies were excluded from the study. Moreover, cases with psychiatric disorders that lead to severe cognitive impairment and psychotic disorders were also excluded.Informed consent was obtained from caregivers or guardians of the study participants after explaining the nature and objectives of the procedure. At the same time, oral assent was obtained from the adolescents themselves for their own participation. All children in the present study participated on a voluntarily basis and were not paid for their participation. In addition, all participants were interviewed during their first visit to the psychiatric clinic before receiving any pharmacotherapy or psychotherapy. In addition, parents were asked about the onset of the psychiatric symptoms to be sure that all disturbances had occurred after the exposure to child maltreatment.Self-reported information on demographics including age, sex, biosocial data, parental consanguinity, education level and school performance were obtained. In addition, they were asked about psychological insult during childhood; as death of one or both parents or separation of parents. Guardians were also interviewed and asked about history of present illness; symptoms and its onset. They were also asked about the medical history of their children; for any previous diseases, injuries and operative procedures with special emphasis on repeated injuries, its causes and mechanism.Psychiatric evaluation was done by the psychiatric residents who assessed the children according to K-SADS-PL for diagnosis of psychiatric disorders. It is a semi-structured interview that diagnose recent and previous episodes of psychopathology according to DSM-IV-TR.Assessment of the severity of five classes of maltreatment including; emotional, physical and sexual abuse, and emotional and physical neglect, was done using the Arabic version CTQ-SF. Additional information was collected to determine age of onset, duration of maltreatment and its frequency.
Moreover, two psychometric assessment tests were used; all subjects were requested to complete the Arabic version of Kovac’s Children’s Depression Inventory (ACDI). This is a self-reported questionnaire and one of the broadly used screening tool for evaluating the presence and severity of depression in children and adolescents.
At the same time, the parents were given the Arabic version of CBCL to fill in or administered by an interviewer for those who cannot read. CBCL is designed to obtain standardized parent’s or other primary caregiver’s report of children’s problems and competencies.
In the present work, (2 ml) of whole blood was collected in EDTA tubes from all research participants who completed the previous assessment and gave informed consent. Upon collection, blood samples were immediately kept in refrigerator 4-8 °C for less than two weeks before DNA extraction. DNA extraction from whole blood was performed using QIAamp blood DNA isolation kit. DNA was stored at −20 °C prior to further analysis.
The OXTR gene polymorphism (rs2254298) was genotyped for individual alleles using a Taq Man SNP rs2254298 assay from Applied Biosystems with TaqMan universal master Mix II and the analysis of the data was done depending on real time PCR instrument.
Global DNA methylation in blood samples of research participants was determined by measuring 5-methylcytosine (5-mC) using MethylFlash methylated DNA quantification colorimetric kit.
Results of the present work were as follows:
No statistically significant difference was observed between the cases and controls regarding age and sex. On the other hand, a statistically significant difference between cases and controls was noted regarding level of education and school performance that were significantly lower in cases of psychiatric illness.
Regarding study participants’ habits, more than one quarter of the studied cases were smokers which was significantly higher than the controls.
There is a non-significant difference between cases and controls regarding consanguinity. However, more than half of the controls living with parents having positive consanguinity.
Regarding the number of family members, a non-significant difference between cases and controls was observed regarding the number of family members where the majority of cases living in families consisting of five members.
Concerning the birth order of the participated child, a non-significant difference was also noted between cases and controls. However, the first child was the commonest (53.3%) to be affected in the cases group.
A significant difference was found between both groups regarding death of one or both parents and state of relationship of parents. Regarding cases, (44 children) had living parents; (35.6%) of these parents were divorced and only one child was adopted. On the contrary, (15.6%) and (13.3%) of the controls had dead fathers or mothers and divorced parents respectively.
Data of the parents were collected; a significant difference was noted between both groups in parent’s education where (20.5%) and (22.7%) of the cases belonged to fathers and mothers who did not continue their primary school education respectively.
A significant difference between cases and control groups was detected regarding the father’s occupation where (46.3%) of the children in the control group are living with their employed fathers with a fixed monthly salary. On the other hand, (52.3%) of children in the cases group belonged to manual worker fathers with a changed salary according to their work.
Regarding father’ habits, in the current work, (70.3%) and (6.8%) of the cases belonged to smoker fathers and drug abusing fathers respectively and it was not significantly different than that of the control group.
Concerning child maltreatment, assessment of the severity of different forms of child maltreatment was done using the Arabic version of CTQ-SF. A statistically significant difference was noted between the cases and controls as regard exposure to emotional abuse, physical abuse, sexual abuse and emotional neglect. However, a non-significant difference was noted between both groups regarding physical neglect. In addition to that a significant difference was found between both groups regarding exposure to previous injuries including non-accidental one.
Moreover, a significant difference was noted between the cases and controls regarding; the age of onset of child maltreatment, duration and frequency of exposure to maltreatment and witnessing domestic violence.
Three children (6.7%) of the cases group were forced by their parents to leave school at an age less than 13 years and start work for financial gain. On the other hand, only one child (2.2%) in the control group was forced to leave school and start work after death of his father.
The relation between the psychiatric illness and exposure to child maltreatment was done in the cases group. The commonest psychiatric disorders detected among maltreated cases were ADHD, depressive disorder and PTSD.
All subjects in the current study were requested to complete the Arabic version of Kovac’s children’s depression inventory (ACDI). It was found that the mean score for depression symptoms of the cases was significantly higher than the controls. In addition, a significant positive correlation between the depression scores assessed by ACDI and four types of child maltreatment; emotional, physical and sexual abuse and emotional neglect. On the other hand, no significant correlation was noted between the depression score and physical neglect.
To measure other psychometric problems of research participants, guardians were asked to fill in the Arabic version of CBCL. A significant difference was noticed between the cases and controls regarding the total scale, externalizing symptoms and internalizing symptoms scales. Moreover, a significant positive correlation was detected between CBCL total scale and four types of child maltreatment; emotional, physical and sexual abuse and emotional neglect. On the other hand, no significant correlation was detected between the CBCL total scale and physical neglect.
Regarding OXTR gene (rs2254298) polymorphism, the observed genotype frequencies were consistent with Hardy-Weinberg with and showed a non-significant difference between both groups. GG genotype represented the most frequent genotype among both cases and control groups followed by AG genotype. However, AA genotype represented the least frequent genotype in both groups.
Moreover, the mean score of depression symptoms (ACDI), total and externalizing scales (CBCL), in the cases group, was higher in AA genotype. A statistically significant difference was present between AA and AG genotypes and between AA and GG genotypes regarding depressive symptoms.
Furthermore, to judge gene-environmental interaction in the present work, Multivariate linear regression was done to examine the effect of OXTR gene SNP rs2254298 and its interaction with different forms of child maltreatment on the depressive symptoms (ACDI) and total scale (CBCL). However, no significant interaction between this SNP and child maltreatment was found in the prediction of both depression score (ACDI) and (CBCL) total scale.
Regarding epigenetic mechanisms, the present work showed global DNA hypomethylation in the cases with psychiatric illness than it in the control group. Also, a significant negative correlation was detected between the mean level of global DNA methylation and three types of child maltreatment; emotional and physical abuse and emotional neglect. On the other hand, no significant correlation was detected between the global DNA methylation and sexual abuse and physical neglect.