Minor Physical Anomalies
Background
Recent decades have witnessed a burgeoning
interest in signs of physical trauma and early maldevelopment associated
with schizophrenia. This interest has been promoted by important
findings relating schizophrenia to a series of factors associated
with the fetal life of individuals who will later develop schizophrenia:
e.g. season of birth patterns, influenza epidemics and major stressful
events during gestation (i.e. during the mother’s pregnancy),
climate patterns overlapping gestation, birth in urban environments,
and – not the least – early developmental abnormalities
observable in the brain tissues/structures and more grossly in the
remainder of the body.
The most frequently studied maldevelopmental
phenomenon in schizophrenia is Minor Physical Anomalies (MPAs).
MPAs are very minor structural deviations found in many areas of
the body. For practical reasons, MPAs are typically studied in the
visible surfaces in the head, eyes, mouth, ears, hands and feet.
Examples of specific MPAs are abnormal hair whorls, wide-set eyes,
high or steepled palate in the mouth, adherent ear lobes, curved
fifth fingers, and a large gap between the first and second toes.
While such MPAs are in themselves quite benign and common in the
general population, their existence signals the occurrence of maldevelopment
in the fetus at a time during which the brain also experiences major
development (i.e. the first and perhaps early second trimesters
of pregnancy). Further, both the brain and most of the MPAs arise
out of the cellular differentiation of the ectoderm, thus having
a common general origin. Researchers have thus reasoned that a large
number of MPAs in the body in general might well indicate parallel
maldevelopment in the brain and would thus be found in individuals
with an increased risk for psychopathology that is based on early
neural maldevelopment.
The empirical findings regarding MPAs in
schizophrenia are impressively consistent. At least 12 different
studies have found MPAs to be significantly increased in frequency
in patients with schizophrenia, as compared with controls. To our
knowledge, only one study has failed to find such a difference.
Nevertheless, MPAs are quite frequent in the general population,
and almost all individuals have at least one of the 41 different
MPAs we have included in our investigations. The differentiation
of patients with schizophrenia from mentally well comparison persons
is thus more a question of the total amount of MPAs rather than
the existence of any one particular MPA. Using a quantitative approach,
we found that fully 60% of the patients with schizophrenia have
an increased level of MPAs (> 6 MPAs) that characterizes only
5% of the normal population. Use of an optimal combination of specific
MPAs (identified through logistic regression analysis) correctly
identifies study group membership for 73% of the patients and 85%
of the comparison subjects. The specific MPAs contributing to this
discrimination are found in the hands, eyes and mouth. Researchers
in Ireland have found similar or even stronger discrimination.
In spite of the notable empirical success
in studying MPAs in schizophrenia, the origin of MPAs in schizophrenia
remains unknown, as is the particular association MPAs have with
this disease. Genetic factors associated with both MPAs and schizophrenia
may play a role, and the mentally healthy siblings of relatives
with schizophrenia also show increased rates of MPAs, suggesting
a possible genetic link. Nevertheless, several studies done by our
group show that MPAs occur in patients who have been exposed to
somatic complications during early pregnancy. No systematic relationship
has been found in our studies between high rates of MPAs and the
subsequent neurological or neuropsychological disorders found in
patients with schizophrenia or their healthy siblings. Furthermore,
increased levels of MPAs are clearly not found only in schizophrenia,
but rather also in samples of patients with attention deficit disorder,
autism, cerebral palsy, epilepsy, fetal alcohol syndrome, mental
retardation, hyperactivity etc. Questions thus remain regarding
not only the origins and consequences of MPAs in schizophrenia per
se, but also – more specifically – the relationship between
externally visible MPAs and the structural anatomy and functioning
of the brain in schizophrenia. These questions represent the focus
for current research in HUBIN.
Investigation in
HUBIN
The purpose of investigating MPAs in HUBIN
is to determine the extent and particular nature of MPAs in the
various subject groups, for investigation in relationship to group
differences and in relationship to other characteristics of the
subjects, notably brain structure. The method chosen for use has
been partially developed by our research group (Ismail et al. 1998)
and represents both the classical 18 items from the Waldrop Scale
(Waldrop and Halverson 1971) plus 23 additional items chosen from
the pediatric literature. The extended examination for MPAs takes
less than 15 min and requires very minimal removal of clothing (only
shoes and stockings). Our examiners have obtained an acceptable
level of interscorer agreement (intraclass correlation +0.84). We
are currently in the process of producing a graphical manual illustrating
different degrees and scores for the specific MPAs, in order to
facilitate inter-scorer reliability both within and across different
studies. We have also recently initiated international collaboration
with leading researchers from Dublin (Doctors A. Lane and B. Kelly)
in investigation of external physiological characteristics’
relationship to brain structure (volume and size) measured independently
by HUBIN researchers (Doctors I. Agartz and K. Henriksson).
Relevant References:
Waldrop MF & Halverson CF. Minor physical anomalies and hyperactive
behavior in young children. In: Hellmuth J, ed. Exceptional Infant.
New York: Brunner/Mazel, 1971:343-381.
Ismail
B, Cantor-Graae E, McNeil TF. Minor physical anomalies in schizophrenic
patients and their siblings. American Journal of Psychiatry 1998;155:1695-1702.
B, Cantor-Graae E, McNeil TF. Problems with the Waldrop Scale. American
Journal of Psychiatry 2000;157:3.
Ismail
B, Cantor-Graae E, McNeil TF. Minor physical anomalies in schizophrenia:
cognitive, neurological and other clinical correlates. Journal of
Psychiatric Research 2000;34:45-56.
McNeil
TF, Cantor-Graae E, Ismail B. Obstetric complications and congenital
malformation in schizophrenia. Brain Research Reviews 2000;31:166-178.
McNeil
TF, Cantor-Graae E, Weinberger DR. Relationship of obstetric complications
and differences in size of brain structures in monozygotic twin
pairs discordant for schizophrenia. American Journal of Psychiatry
2000;157:203-212.
Cantor-Graae
E, McNeil TF, Torrey EF, Quinn P, Bowler A, Sjöström K,
Rawlings R. Link between pregnancy complications and minor physical
anomalies in monozygotic twins discordant for schizophrenia. American
Journal of Psychiatry 1994;151:1188-1193.
Cantor-Graae
E, Ismail B, McNeil TF. Neonatal head circumference and related
indices of disturbed fetal maldevelopment in schizophrenic patients.
Schizophrenia Research 1998;32:191-199.
Project leader: Tom
McNeil
Co-workers: Ingrid Agartz, Karin Henriksson,
Abbie Lane, Brendan Kelly, Roger Hult
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