الفهرس 
NEUROBIOLOGY OF BIPOLAR AFFECTIVE DISORDEROnly 14 pages are availabe for public view
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Abstract
Bipolar affective disorder (BD) is a neuropsychiatric disorder characterized by extreme fluctuations mood shifts alternating between episodes of mania and depression (Craddock and Sklar, 2013). Depressive episodes are associated with sad mood, suicidality, impaired cognition, and anhedonia whereas Manic symptoms includedecreased sleep, high-risk actions, and impulsivity, (Barnett &Smoller, 2009).So, the estimated lifetime prevalence of BD is 1 to 3 percent worldwide (Pedersen et al., 2014). In 60% there is evidence of inherited of mood disorder fromfamily members referring a potentially large genetic contribution to the disorder(Senda et al.,2019).
Genetic factors in bipolar affective disorder tends to be familiar, about half the people with Bipolar affective disorder have family member with a mood disorder, such as depression. To person who has one parent with bipolar disorder has a 15 to 25 % chance of having the incidence. A person who has a non-identical twin with the disorder has a 25% chance of disorder, the same risk as if both parents have BD. A person who has an identical twin with Bipolar affective disorder has an even higher risk of developing the disorder about an eightfoldhigher risk than a non-identical twin (Goretti et al.,2017).
In 5 years, a prospective study in the Netherlands showed an increasing level of psychopathology in the bipolar offspring, especially for mood disorders. Important determinants for the development of mood disorders were familial loading with unipolar disorder and substance use disorder, low birth weight and stressful life events. It was found that the lifetime prevalence of Bipolar affective disorder had increased from 3% to 10%; of overall mood disorders from 27% to 40% and of overall psychopathology from 44% to 59% (Hillegers et al., 2005). According to a meta-analysis, the offspring of bipolar parents are 4.0 times more likely to suffer from a mood disorder and 2.7 times more likely to suffer from any mental disorder than the children of healthy parents (Singh et al., 2007).
• Rationale of the work:
It is generally held that the offspring of parents with Bipolar affective disorder are at risk for a spectrum of future psychiatric disorders. The degree of risk is an important question for both clinicians and parents. These risks involving conduct disorders, learning problems, neuropsychological deficits, and high rates of internalizing problems. Although the link between family functioning and children’s development remainedwell-established, there is a small research examining whether family factors play a role in helping children with behavior problems outgrow their difficulties. Even rarer are studies that examine factors which predict how well children with behavior problems develop emotionally, socially, and academically, over time. Since children with behavior problems are at risk for a host of negative outcomes. It is critical to identify factors that might increase risk among these children. Parents’ psychopathology is one aspect of family functioning that is thought to play an important role in children’s development (Breaux et al., 2013).
• Hypothesis:
The study was designed to test the hypothesis that offspring of parents with Bipolar affective disorder are at increased risk of developing a wide range of psychiatric disorders and accompanying dysfunction than offspring of healthy or non-BP parents.
• Aim of the work:
The aim of the study was to identify the risk factors that contributes to the development of psychiatric morbidity, to identify the nature of psychiatric morbidity that affects these children, to correlate the various risk factors in the children with various risk factors in the parents and, and to compare the pictures of psychopathology in offspring of parents with Bipolar affective disorder with control group.
• Subjects and Methods:
A sample of 200 participants was recruited and divided into:
Case group: consisting of 100 offspring of parents diagnosed with bipolar affective disorder (patients were selected from either new or follow up cases, who were attending the outpatient clinics, psychiatry department, Ain Shams University Hospitals).
Control group:100 offspring of parents with irrelevant psychiatric history.
Parents involved in this work were evaluated using the Structured Clinical Interview for DSM-IV (SCID) (First et al., 1996) to confirm diagnosis of Bipolar affective disorder in the case group and to exclude psychiatric morbidity in the control group. Arabic version was used (El Missiry et al., 2004). Answering the scale took from 35 to 45minutes.
After confirming the BD diagnosis, parents were interviewed about their current and past symptoms of Bipolar affective disorder I, II or irrelevant psychiatric disorder
All offspring were assessed by the Wechsler Intelligence Scale for Children (WISC) (Wechsler, 1991) to exclude mental subnormality. Arabic version was used (Ismail&Malika, 1999). Children were also evaluated by The Child Behavior Checklist (CBCL) (Achenbach &Edelbrock, 1983) to screen for psychopathology. Arabic version was used.
After that we assessed the child by the schedule for affective disorders and schizophrenia for School-Age Children–Present and Lifetime version [K-SADS-PL] (Kaufman et al.,1997) to screen bipolar and psychotic disorders.
Offspring of bipolar patients in this study (31 males and 69 females) were compared to the control group constituted of (44 males and 55 females) Offspring of parent’s irrelevant psychiatric disorder.
All data gathered were recorded, tabulated, and transferred on Statistical Package for Social Science (SPSS) version 16. Many statistical methods were used for analysis of data. The study resulted in the following: The general characteristics of the studied participants showed no statistically significant difference between both groups for age (P-value >0.05), while for gender distribution, study group included more females than the control group. Most of study group were the 2nd child and at low level of living, and these differences are statistically significant (P-value <0.05).
The general characteristics of the studied parents showed older mother’s age as well as father’s age of the study group, and these differences are statistically significant (P-value <0.05). No statistically significant difference between both groups for marital status (P-value >0.05).
Most of the parents (84%) were mothers and (61%) of the parents with bipolar have type 2. They all had disease duration with mean (±SD) 9.9±3. Also, in control sample most of the parents (80%) were mothers.
On examining the cognitive functions of the patients, we found that, study group had higher degrees of IQ in Wechsler Intelligence Scale for Children (WISC), (Wechsler, 1991) by Arabic version (Ismail & Malika, 1999). In classes: below average, low average, average and high average, while control group had higher degrees of IQ in classes: superior and very superior. These differences are statistically significant (P-value <0.05).
On evaluating predictive factors, we found by using The Child Behavior Checklist (CBCL) (Achenbach & Edelbrock, 1983). Arabic version by ( El – Defrawi, 1997 ) showed no statistically significant difference between both groups for anxious and withdrawn (P-value >0.05), while theses statistically significant differences between both groups (P-value <0.05) are observed as 43% of the sample were diagnosed as Social problems, while among Aggressiveness was the most prevailing diagnosis with 82%, followed by attention problems with 67%, generalized anxiety disorder with 33%, while Rule Breaking Problems with 31%. And, as regarding somatic complaints all the control group was normal while 17% of the study group were borderline.
The study used the K-SADS-PL (Kaufman et al., 1997) to assess current and past episodes of psychopathology among the studied participants according to DSM-IV criteria.
-ADHD & Disruptive disorders: 58% of the sample was diagnosed as ADHD, and 23% as oppositional defiant disorder.
-Mood and anxiety disorders: 19% of the sample were diagnosed as generalized anxiety disorder, while among depression was the most prevailing diagnosis with 9%, followed by Social phobias with 6%, while separation anxiety disorder, Dysthymia and Suicidal tendencies each with 2%, 1% of the sample were had Manic attack and OCD. On comparing the BD offspring suffering from ADHD, Binary logistic regression showed only child’s age and PerformanceIQ to be statistically significant predictors of ADHD among the studied participants (P-value >0.05), where younger age and lower PerformanceIQ were more among ADHD cases.
On evaluating the predictive factors, the study findings found that anxiety among the studied participants was a significant predictor withverbal IQ age and total IQ (P-value >0.05), where lower verbal IQ and lower total IQ were more among ADHD cases by Linear logistic regression analysis.Although this study has many limitations, yet some findings could be concluded with some precautions:
We proved our hypothesis that Offspring of parents with Bipolar affective disorder are at risk for a spectrum of psychopathology.
Offspring of BD probands are at significantly higher risk of developing a broad range of affective and non-affective psychopathology when compared to control offspring. It is likely that higher prevalence of psychopathology in this group represents the complex interrelationship between genetic loading and psychosocial factors. Psychopathology was more common among the lower Performance IQ rather than study group. Prospective studies with larger samples are needed to confirm and expand these results.
Among the sample, ADHD and Oppositional defiant disorder (ODD) were more among the study group. ADHD was the commonest diagnosis, while mood and anxiety disorders were less common.
History of disruptive behavior disorders, as well as presence of parental BP, is associated with elevated risk of bipolar spectrum disorders among offspring.
Children of bipolar parents had an elevated risk for developing bipolar and other psychiatric disorders. The study of children of bipolar parents who are at high risk for developing Bipolar affective disorder themselves is essential to identify potential prodromal manifestations of the disorder and to eventually establish targeted early intervention strategies. Longitudinal studies to confirm the prodromal manifestations of Bipolar affective disorder and risk factors associated with the development of specific diagnoses in children are needed.
The present study supports that ADHD and oppositional defiant problems are an important and promising area of continued research in children at risk for developing affective disorders.
Our findings prove that additional research related to bipolar offspring is needed to enhance understanding of differences between BP-I and BP-II.
Offspring of parents with Bipolar affective disorder are at elevated risk for suicidal ideation as compared with offspring of controls. Suicide risk assessment in this population should attend to specific risk factors identified.
These findings give us a clue that results corroborate preceding studies that children and adolescents with parents with severe psychopathology are at high risk for developing mental disorders. So Public policies and standard protocols of action directed to this population are urgently needed, especially for offspring of parents that are hospitalized in psychiatric in-patient units or outpatients.