Neuropsychological functioning of children and adolescents (6-16) born with Congenital Adrenal Hyperplasia (CAH)

Cognitive functioning in CAH
A disturbed hormone balance as a result of Congenital Adrenal Hyperplasia (CAH)
may influence cognitive development in children living with this syndrome.
Different studies investigated the influence of hormones and neonatal salt loss
on brain development by comparing patients with CAH with healthy controls.
The first study investigating intelligence and cognitive functioning in CAH
patients was published by McGuire et al. (1975). No differences were found
between IQ of the CAH patients and healthy controls.
More recent studies focused on more differences within the cognitive profile,
trying to find support for a more male like cognitive profile in CAH girls.
This assumption was supported by Helleday et al. (1994). They found higher
differences between performal IQ and verbal IQ in favor of performal in CAH
girls compared to controls. Other studies also took different forms of CAH into
account: the salt wasting versus simple virilised type. Johannson et al. (2006)
found lower IQ scores in the salt wasting type, however other studies could not
support this (Malouf et al. 2006).
Other recent studies focused on different cognitive outcomes in CAH patients
prenatally treated with dexamethasone versus no prenatal treatment. There seems
to be a slight positive short term effect of dexa on cognitive functioning in
affected patients, however there seems to be a negative effect in non affected
prenatally treated persons (Maryniak et al. 2012; Meyer-Bahlburg et al. 2012).
In addition, prenatal dexamethasone treatment could influence the verbal
working memory (Hirvikoski, 2007).

Results on cognitive functioning in CAH are mixed. Differences in IQ and
cognitive functioning seem to be more related to details of treatment and
disease course than to general CAH as such. In future research all these
factors should be taken into account.

Quality of life/psychological functioning in CAH
In this pilot study, besides cognition, we also want to investigate quality of
life and psychological functioning in children and adolescents with CAH. From
limited previous results we know that CAH children experience more difficulties
developing relationships, have a disturbed self-concept and body image and
patients with CAH choose jobs where they don*t have to work with people more
often, compared to healthy controls.
Results of studies on quality of life in CAH are mixed (Johannsen et al. 2006;
Reisch et al. 2011). Han et al. (2013) investigated the association between
quality of life and different other factors like medicine treatment with
corticosteroids, disease control and health factors like metabolism (obese,
insulin resistance). They conclude that treatment with strong corticosteroids
is associated with worse metabolism and a disturbed quality of life. The
causality of this relationship isn*t clear and needs further investigation.

Social cognition in CAH
Structural imaging reveals reductions in amygdale volume in both CAH boys and
girls relative to healthy controls (Merke et al. 2003). fMRI research also
reveals a difference in amygdale function during emotional processing between
CAH patients and healthy controls. Ernst et al. (2007) discover that patients
show heightened responsivity to negative material in areas associated with face
processing (fusiform gyrus), the precuneus, temporal areas and the striatum).
Another interesting finding is that recognition memory is worse for negative
but not neutral scenes and faces in CAH adolescents (Maheu et al. 2008; Mazzone
et al. 2011). fMRI data of emotional memory processing reveals aberrant
activity in limbic circuitry in CAH including the amygdale, the hippocampus and
the anterior cingulate cortex.
The amygdala is an important structure involved in social cognition (Adolphs,
2010). According to different imaging studies the amygdala plays an important
role interpretating thoughts, beliefs and desires of others. A construct also
known as *Theory of Mind* (Shaw et al. 2003; Stone et al. 2005).
It should be relevant for society to combine above-mentioned research to find
out if CAH patients differ from healthy controls in social cognition.

Objective of this pilot study is to investigate differences in
neuropsychological functioning between CAH patients and healthy controls.
Differences in neuropsychological functioning may influence the quality of life
and daily functioning of children with CAH. Thats why we want to map out all
these different factors that can influence neuropsychological functioning in
CAH children and adolescents.

Questions that can be answered:

1) Is there a significant difference in psychological functioning at the age of
6-16 years between CAH patients and healthy controls? Which factors may be
associated?
2) Is there a significant difference in cognitive functioning at the age of
6-16 years between CAH patients and healthy controls? Which factors may be
associated?
3) In de second question we also want to take social cognition into account.

Clinicians need more knowledge about neuropsychological functioning in CAH
patients so that they can intervene more suitable to problems especially
experienced in CAH. Simultaneously the advice that's provided to children,
teachers and parents will contain more quality.

Method(s)
The incidence rate of CAH in Holland is 15-20 new patients a year. In the
period 1997-2007 there will be a maximum of 100 patients in the range from 6
till 16 years old.
For this pilot only children treated in the Radboud UMC hospital in Nijmegen
will be recruited. Therefore our amount of participants will be considerable
less.

We will only recruit children and adolescents still under treatment for CAH in
the Radboudumc. The attending endocrinologist will contact patients to give
them a description of the study. The study will be an extension of the already
existing care and clinical appointments. Children and their parents get the
chance to gain more information about the child*s functioning. The doctor will
use application forms and afterwards the researcher will contact the child and
their caregivers to give further information about the study.

Caregivers, or children older than the age of 12, will sign an informed
consent. Healthy controls will be matched on age and gender and are siblings of
children with CAH. They will also be recruited via the doctor of children with
CAH.

This study will consist of one visit where children and adolescents will
perform some neuropsychological tests. Children older than the age of 11 will
also fill in some questionnaires, this will be done digitally in a internet
programme. One of the caregivers will also fill in some questionnaires
digitally at home.

When we know the research results the children and their caregivers will
receive them written by mail. If there are uncertainties or questions parents
can contact the researcher by phone.

The whole study will consist of one visit. This visit will occupy a maximum of
approximately three hours for the child. We will ask the parents if they can
fill in some questionnaires digitally. There will be no further risks connected
to this study. Parents will conceive a rapport with study results of their
child. This offers them an overview of the neuropsychological functioning of
their child.