The earlier the onset, the more boys are at risk
One outstanding sex
difference in neuropsychiatry is that diseases with early onset are more
prevalent in the male child. Some of
these diseases or disorders are more prevalent in males no matter whether their
onset is relatively early or relatively late in childhood: autism (consisting essentially of emotional
and verbal shutdown), hyperactivity (extreme agitation without psychosis),
Tourette's disease (bizarre tics including obscene utterances), character disorder (immorality and
destructiveness). Likewise, nearly all developmental language disorders
affect boys more than girls, and do so earlier in boys. These include language delay, developmental aphasia (severe and relatively
permanent failure to acquire language functions), stuttering, dyslexia (reading
impairment), and hyperlexia (excellent recital or reading out loud, but without understanding of what is being
read). There is one interesting
exception to this rule in the domain of language disorders, namely elective
mutism. For reasons which I shall
explain later, girls are more at risk
for this disorder. In a more subtle
vein, those neuropsychiatric disorders
which affect either sex approximately equally over the entire life span, are more prevalent in male children in their
early onset forms: obsessive-compulsive
disorder (uncontrollable thoughts or acts), schizophrenia (delusions and
hallucinations), mania (agitation, euphoria or extreme happiness,
grandiosity). Several psychiatric
disorders which afflict the female sex more prevalently tend to become manifest
at puberty or adolescence. These include
depression (extreme sadness with insomnia, loss of appetite, constipation),
anorexia nervosa (extreme repulsion for personal fatness with resultant
self-starving), phobia (unreasonable fear of specific objects), anxiety (fear
without an identifiable object).
Elective mutism, a female-preponderant disorder, can also be considered a form of internalizing
disorder: it is essentially a social
phobia, or anxiousness expressing itself
as a partial shutdown of social interaction limited to language. The elective mutist typically refuses to
speak to anybody with the occasional exception of a sister or one or both
parents. Jane Campion, the director of
the film “The Piano” presents a wonderfully effective portrait of an elective
mutist woman. Finally, some diseases such as schizophrenia or
tardive dyskinesia (abnormal movements) tend to occur around menopause in
women, whereas their onset is more often
in childhood in males.
There is an additional twist to this story: early onset variants of behavioral disorders
usually express themselves more severely than do the late (adult) onset
variants. Consequently, the male sex is not only more at risk for a
longer pathological trajectory, but also
for a more debilitating condition. Details
of these phenomena are presented in table 4.
Table 4
Examples
of neuropsychiatric disorders whose early onset forms are more severe than the
adult onset forms
Disorder
|
Reference
|
Female prevalent
disorders regardless of onset
|
|
Anorexia nervosa
|
Walford et al, 1991
|
Panic disorder
|
Maier et al, 1989
|
Generalized anxiety disorder
|
Scheibe et al, 1992
|
Bulimia
|
Witcher et al, 1992
|
Phobia
|
Holt et al, 1992
|
Male prevalent disorders
regardless of onset
|
|
Tourette’s disease
|
Hyde et al, 1993*
|
Autism
|
Garreau et al, 1984* Short et al, 1988*
|
Psychopathy
|
Offord et al, 1983*
|
Alcoholism
|
Lee et al, 1985*
|
Disorders which are
male-prevalent only in the early onset forms
|
|
Manic-depressive disease
|
Dwyer et al, 1987 Thompson et al, 1992*
|
Obssessive-compulsive disorder
|
Flor-Henry, 1990* Hanna, 1995*
|
Schizophrenia
|
Szymanski et al, 1995* Seeman, 1982*
|
Depression
|
Golden et al, 1985; Gasquet,
1994*
|
* These authors demonstrate that the early onset and more severe forms are more prevalent in
the male sex.
There are several lines of explanation of this
wide-reaching pattern of sex differences:
the human male could manifest early-onset forms of neuropsychiatric
disease because 1) he is more susceptible to brain damage related to difficult
prenatal or obstetric events relating to maternal health during pregnancy and
complications during childbirth; 2) there could be an adverse influence of
maternal immunity on the male fetus; 3)
the balance of his steroid hormones could affect his early brain development in
an unfavorable direction.
The early onset forms of schizophrenia (hebephrenia,
catatonia, etc.) are more chronic (long lasting bouts of incapacitation) and
are more devastating (requiring institutionalization) than the late onset
forms. The latter (often the paranoid
form) are typically less chronic (intermittent,
recurrent) and are less devastating (less frequently requiring prolonged
institutionalization). The
childhood-onset forms of schizophrenia are twice more frequent in the male
sex. On the other hand, schizophrenia
occurring at or just after the age of menopause is twice as frequent in
women. There is only one type of drug
class which has unequivocally been proven to alleviate the problems of
schizophrenics (delusions, hallucinations, agitation). These are neuroleptics (also known as major
tranquilizers). All neuroleptics are
effective against these specific symptoms exactly in proportion to their
ability to reduce the brain activity of one neurotransmitter, dopamine.
Estrogen has an antidopaminergic brain effect. It is an indirect dopamine antagonist. Testosterone, on the other hand, is an indirect dopamine agonist. It favors the synthesis of dopamine. Menopause comprises a gigantic drop in
estrogen, many times more significant
than the low point in the fertile woman's menstrual cycle. In men, the blood concentration of
testosterone undergoes a constant decline in adulthood through to senescence.
The girl is protected against schizophrenia by her estrogen until menopause at
which time she becomes more susceptible than the age-equivalent man, whose testosterone has descended low enough
to remove the risk factor which threatened him as a child.
This reasoning could apply to another male preponderant psychiatric disorder, though perhaps less clearly. Indeed,
the most effective medication for the specific symptoms of Tourette's
disease, a male prevalent disorder, is neuroleptic medication. As for hyperactivity and character
disorder, another neurotransmitter of
the brain could be involved,
noradrenalin. Noradrenalin has a
molecular structure identical to the hormone secreted by the adrenal gland
called adrenaline. It is commonly known
that adrenaline excites people when it is secreted in large doses into the
blood stream. The effects of
noradrenalin in the brain are more complex,
more subtle, and less
understood. The drugs most effective
against the specific symptoms of hyperactivity and turbulent forms of character
disorder are composites molecularly close to amphetamine (a central nervous
system stimulant) as well as to noradrenalin,
such as methylphenidate (Ritalin).
Logically, in light of the effectiveness of methylphenidate, one ought
not be surprised to find some sort of insufficiency of brain noradrenalin in
hyperactive or conduct-disordered boys,
and this has indeed been observed in several investigations. In accordance with this, one experimentally induced brain lesion
which produces hyperactivity in rats happens to be situated in a posterior part
of the brain surface (cortex) called the parietal lobe, but only when it is the right side of the
brain which is lesioned, not the
left. And it is the right sided lesion
of this brain area which produces a huge drop in brain noradrenalin, not the
left. One ought perhaps not be surprised
then that right sided cortical lesions result much more frequently in
psychomotor agitation or mania (psychomotor agitation with delusions of
grandeur or persecution and elated mood) in humans, than do left sided lesions.
A vignette on a case with Tourette’s disease
S1 is a case seen in a hospital neuropsychology service which came
to my attention recently. This 11 year
old boy of Haitian extraction was first seen because of learning disability in
a Quebec school. He had been to five
schools previously and was already in a special education class in a public
school. In school and at home he was
disobedient, disruptive, pig
headed, socially inept and
isolated, suspicious, anxious and very
nervous but not depressed. He was
believed to have an attention deficit by his teachers. He reached the clinical criteria for
hyperactivity and conduct disorder, but
his essential problem was immediately identified by the neuropsychologist: he manifested multiple changing tics, eye blinking,
shoulder shrugs, sniffing,
barking, swearing, trichotillomania
(hair twirling), and he would slap his
own head persistently when frustrated.
These are typical manifestations of Tourette’s disease, and the other behavioral disturbances noted
above are common co-morbidities.
Cognitive evaluation revealed preserved attention, borderline IQ and memory, normal visuospatial ability, but very poor executive abilities. Executive abilities are a constellation of
abilities associated with frontal lobe function which include planning, judgment,
mental flexibility, and the
like. Recommendations were made to
transfer him to a school specialized in behavior disorders, and to provide him with ongoing neurological
care and a very structured environment with regard to surveillance, rules,
emotional security, leisure
activities, and so on.
Why would many female-preponderant psychiatric
disorders often have an onset at puberty or adolescence ? One idea has been that the onset of these
disorders, though determined primarily by hereditary factors and by environmental
stress (family conflict or emotional disturbance due to life events), is helped along by high levels of
estrogen, which in turn favor the
build-up and metabolism of the neurotransmitter serotonin in the brain. Studies of animals and humans have shown
that serotonin influences appetite and sleep more than most other
neurotransmitters. Drugs effective
against depression, such as Prozac, influence the metabolism of serotonin more
than of any other known neurotransmitter.
Estrogen is an indirect serotonin agonist. The problem with this model is that it
predicts that depression ought to be caused by excess serotonin, and should be treatable with serotonin
antagonists. Well, it just so happens that things are the other
way around! Antidepressant medication
increases serotonin concentrations and activity in the brain. What seems more likely to me is that
estrogen puts serotonin neuron networks into high gear and at the same time
destabilizes and disturbs them, and
antidepressant medication such as Prozac somehow stabilizes serotonin metabolism. I review this notion three sections down.
Post Comment
No comments