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22q11.2 Deletion Syndrome and Schizophrenia in Children and Adolescents
these different factors may lead an individual to confusions between
Figure 1: Stress-vulnerability Model of Positive
internal representations (internal mental events or images) and bottom-up
Symptom Formation
percepts (perception originating from the exterior), thus providing the
hallucinatory experience. For example, research with schizophrenic Precipitant
patients
34
and hallucination-prone college students
35
illustrates how
negative emotional content exacerbates self-monitoring deficits;
specifically, hallucination-prone individuals are more likely to attribute self-
generated negative contents to external agents. Some authors argue that
such external misattributions, when applied to ego-dystonic negative
Emotional and Anomalous Cognitive dysfunctions
metacognitive experiences/ associated with
content or intrusive thoughts, may underlie some forms of verbal auditory
factors arousal psychosis
hallucinations.
36
The neuroanatomical underpinnings of such
misattributions, including the amygdala at the emotional level and the
anterior cingulate cortex
18,37
and superior temporal gyrus
38
at the
monitoring level, also correspond to vulnerability sites in the cerebral
Search
for
structure associated with 22q11DS. To date, two studies have found
meaning
altered amygdala volume in children with 22q11DS,
39,40
and one
longitudinal follow-up observed a greater decrease in amygdala volumes in
youths with the deletion.
39
Two other studies found grey matter reduction
in the cingulate gyrus,
41
specifically in the anterior portion.
42
Other
Elaboration/selection
of explanation of
investigations have reported abnormal maturation patterns in the superior
delusional beliefs
temporal gyrus in youngsters with 22q11DS,
39
and recent preliminary data
suggest that a decrease in superior temporal cortical thickness is specifically
Inspired by Freeman et al., 2002.
19
associated with auditory hallucinations in this syndrome.
43
Neuroimaging
studies performed to date have demonstrated cerebral alterations that
potentially disturb self-monitoring mechanisms in youths with 22q11DS, Precipitants may also indirectly exercise their influence through their
and clinical studies have highlighted hallucination-proneness in these relationships with emotions (states and personality) and metacognitions
youngsters. Future studies may further describe the interaction between (beliefs about the self and others), as well as with cognitive deficits
cerebral alteration, self-monitoring dysfunctions, emotional disorders and related to psychosis (executive dysfunctions, attention deficits, self-
the unfolding of hallucinations in children and adolescents with 22q11DS. monitoring dysfunctions). We have already reviewed how some
cognitive deficits may participate in the unfolding of perceptual
The Unfolding of Positive Symptoms of Psychosis in aberrations such as hallucinations. Freeman and colleagues show how
Youths with 22q11DS – A Multifactorial Account emotional factors, particularly anxiety and depression, contribute to the
With respect to the wealth of schizophrenic-like cognitive deficits
44,45
and process of positive symptom formation. Experts in schizophrenia
neuroanatomical alterations,
46
as well as identified genetic factors prodrome research observe that clinically relevant anxiety symptoms
putting individuals with 22q11DS at increased risk of psychosis,
47
it seems often precede the onset of positive symptoms.
49,50
Specifically, anxiety
clear that only a multifactorial framework can account for psychosis- is thought to exert a decisive influence in the selection of an
proneness in this syndrome. Here, a stress-vulnerability model inspired by explanation leading to delusional beliefs.
19
As shown in research on
a cognitive account of persecutory delusion formation
19
allows us to start anxiety disorders, the cognitive component of anxiety orientates the
putting together the pieces of the puzzle collected to date in 22q11DS. individual to entertain thoughts about danger and to anticipate
Such a model may assist us beyond the iterative collection of evidence threats.
51
In other words, worry themes express the anticipation of
linking 22q11DS to schizophrenia at the descriptive level. It can also danger, which constitutes the principal component reflected in
provide further meaning of what it is to be prone to psychosis as a persecutory delusions. Anxiety may also influence beliefs about the self
youngster with 22q11DS. Figure 1 shows an adapted diagram of the and others (metacognitive beliefs). In certain cases, worry itself may
stress-vulnerability model, while Figure 2 attempts to tailor the become the object of belief: ‘I sometime worry so much that I feel as if
framework to include the evidence collected to date concerning I am going crazy’. This type of anxiety, referred to as ‘metaworry’, is
psychosis-proneness in 22q11DS. found to be more prevalent in those at high risk of schizophrenia and
in schizophrenic individuals.
52
Anxiety may also influence other
In their cognitive account of persecutory delusion formation, Freeman and delusional beliefs; if we consider the case of ideas of reference,
colleagues conceptualise the precipitant (starting point) of psychotic increased anxiety and threat anticipation may transform reference
symptom unfolding as a stress-vulnerability interaction between genetic, beliefs such as ‘people pay particular attention to me’ into more hostile
biological, psychological and environmental factors that can directly lead to elaborations such as ‘people looking at me are out to get me’. In this
an aberrant perceptual experience and/or to states of heightened arousal multifactorial model, Freeman and colleagues thus articulate the
(see Figure 1). The first central nod of this model is to suggest, following precipitant–emotion–cognitive dysfunction triad that contributes
Maher (1974), that delusional beliefs represent the individual’s attempt to to the formation of positive schizotypic manifestations.
elaborate an explanation concerning aberrant perceptions and/or
abnormally high arousal states.
48
It is also recognised that precipitants may In 22q11DS research, much attention has been paid to the genetic and
not always lead to aberrant experiences (extreme environmental stressors, cerebral precipitant factors yielding increased risk of psychosis in this
for example), and still constrain individuals to explain the precipitant/event. syndrome. Recent longitudinal research has reported interactions
EUROPEAN PSYCHIATRIC REVIEW 53
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