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The Fear-of-Harm Phenotype
A Potential Path to the Genes
Investigators have found that the Fear-of-Harm phenotype (FOH) describes the group of children with a more severe form of pediatric bipolar disorder as exhibited by higher frequency and severity of manic and depressive symptoms, greater rates of hospitalization and greater likelihood of school performance difficulties. Further analysis of this trait has resulted in a highly refined and more complete definition of the behavioral syndrome associated with it. In addition, the high heritability of the FOH trait makes the phenotype a good candidate for a meaningful and replicable genetic study.
In order to arrive at the more refined list of behaviors particular to this phenotype, investigators conducted a dimensional analysis of the Child Bipolar Questionnaire (CBQ) to determine those behavioral dimensions that are most closely associated with FOH. That analysis produced the results listed below.
Of the ten CBQ dimensions, four of them: Territorial Aggression, Anxiety, Harm to Self/Others and PPSO, can predict with 96% accuracy the presence of FOH. A screening algorithm of the CBQ can easily identify which children fit the FOH phenotype. The ease of use and accessibility of the CBQ makes the identification of the large number of subjects needed for a genome-wide scan an attainable goal.
The expectation is that, when we identify the causative genes for bipolar disorder, we will be able to point to a network of signaling pathways in the brain that regulate specific behaviors associated with the condition. Once researchers are able to isolate the genes involved and understand their functions, the development of more targeted treatments becomes a real possibility. This has been a one of JBRF’s primary goals.
A quarter-century ago, a diagnosis of leukemia meant a child had less than a 50 percent chance of survival. Since then, research has identified many types of leukemia and has developed a battery of specialized treatments leading to a cure rate of nearly 90 percent. Many in the field of bipolar disorder research are hoping their work will follow a similar path.
What Else Can the Phenotype Do?
The discovery of a clearly defined subtype of the illness has enabled investigators to hypothesize about the underlying biology. Its symptoms of the four CBQ dimensions that play such a primary role (Territorial Aggression, Anxiety, Harm to Self/Others and PPSO) focused the attention of investigators on specific brain areas and neurobiological systems. As they learn more about the interaction of these structures and systems, the pathway that modulates basic survival systems: arousal, sleep, energy use, appetite, fear, reward and territorial aggression appears to be the likely target. This knowledge is leading to ideas for novel potential treatments and the possibility that the dissociation of body temperature and sleep rhythms may be a biomarker for this form of the illness.
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What it Looks Like In the Child
The combined insights from of all of these studies allows investigators to describe with a high level of detail the profile of a child who fits the FOH phenotype. It has been found that these children experience early age of onset, severe manic and depressive symptoms, early and frequent psychiatric hospitalizations, significant social impairment and school problems.
In addition to the commonly accepted symptoms of mania and depression, a child with FOH can be easily traumatized, is emotionally over-sensitive to criticism, rejection, disappointment and loss, and often misperceives the actions of others as threatening. They have an over-reactive and rapidly retaliatory response to real or imagined threats (however this is typically defensive to limit setting or perceived threat/deprivation which distinguishes it from other forms of aggressive behaviors). Given their overly-sensitive interpretation of threat, the retaliatory behavior is a frequent and problematic issue.
Often, poor modulation of appetitive and acquisitive impulses result in excessive cravings for sweets with periodic binges, as well as hoarding of food and possessions. When stressed, children with this behavioral phenotype also have a tendency to drift off readily into daydreaming states that may progress to mild hallucinations. During regular sleeping hours, the child may have difficulty getting to sleep, staying asleep and rousing to wakefulness. Dysregulation of their sleep architecture causes parasomnias (arousal disorders of sleep) such as night terrors and bed-wetting.
Other behavioral attributes include anxiety, fear of germs, fear of others, fear of intruders, nightmares of pursuit, and fascination with and fear of gore and horrific imagery.
Clearly this phenotype identifies a group of children who are suffering in a way that truly imperils their lives, derails their development and poses a threat to others around them. We hope that the delineation of the phenotype, along with availability of the CBQ, will pave the way for better and earlier identification of these severely ill children. Earlier identification could, in turn, lead to timely and appropriate treatment interventions that would diminish the cumulative effects of the illness. As our research continues, we hope that those treatment choices will become more effective.
For more information on these subjects, please read the following publications (linked below):
Fear of harm, a possible phenotype of pediatric bipolar disorder
Context and Summary of JBRF Sponsored Research
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About Juvenile-Onset
Bipolar Disorder
According to JBRF Sponsored Research
Approach and Definition
The Core Phenotype
The Fear of Harm Phenotype
Symptoms of the Fear of Harm Phenotype
The 6 CBQ Dimensions of Behavior
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Suggested Links
Suggested Readings
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