Background
Schizophrenia is a psychiatric disorder that affects a relatively small portion of the population, approximately 20 million people worldwide [
1], but its manifestation can be incredibly debilitating. If we were better able to predict who might manifest as schizophrenic in adolescence or adulthood, then intervention strategies could be applied to try to prevent or delay the onset of the disorder. The long-held premise that schizophrenia occurs after a period of normal mental development [
2] has been challenged recently. For instance, adolescent psychotic patients were often treated in pediatric services for various psychosomatic symptoms before receiving a psychiatric consultation as adolescents [
3]. As the direct relationship between “duration of untreated psychosis” and “poor prognosis” has been elucidated, early intervention is crucial [
4,
5].
In order to identify children who will eventually develop schizophrenia we will rely on observations of the prodromal phase of the illness. Nearly 90 years after Mayer-Gross first proposed the prodrome concept [
6], attention to this concept is increasing once more. The prodrome may be defined as the group of symptoms that indicates the continuous transition to a disorder [
7,
8]. Huber identified poor social functioning and cognitive problems as the basic symptoms in the prodrome of schizophrenia [
9]. The prodrome period can also be described as the time between the first onset of unusual behavior or noticeable symptoms to the first signs of psychosis [
10].
Despite few reports on children’s prodromal symptoms, it has been pointed out that the age of onset, when prodromal symptoms first appear for schizophrenia, is at least 11 years [
11]. It is logical to presume that schizophrenia may start to develop, in the form of prodromal signs, even earlier in childhood as it is considered a neurodevelopmental disorder. Research has linked its occurrence to pregnancy and birth complications, perinatal viral exposure, and winter birth, to name a few [
12‐
16].
Studies show extensive brain volume changes from the first psychotic episode of schizophrenia [
17]; such changes may even occur during the transition to psychosis [
18‐
22]. The occurrence of major anatomical changes early during the clinically identifiable course of the disease highlights the need for the identification of early prodromal signs. Psychotic-like experiences, which are reported by 15% of adolescents [
23], predicted the onset of subsequent psychosis at a high rate [
11]. Around 35% of patients who met the Structured Interview for Prodrome Syndromes criteria (e.g., unusual thought content, suspicion/paranoia, perceptual anomalies, grandiosity, and disorganized communication) experienced full psychosis onset within two and a half years [
24]. A systematic review of studies attempting to create prognostic models identified a conversion to psychosis rate of 27% on average [
25], while another systematic review focusing on ages below 18 reported the 2-year conversion to psychosis rate at a maximum of 21% [
26].
Schizophrenia is a psychiatric disorder in particular need of early intervention strategies, which necessitates a valid way to assess who is at risk of developing it. Clinical tools for identifying psychosis risk groups have been developed, mainly in English- and German-speaking countries [
27‐
31]. For example, the Prodromal Questionnaire [
30], the Bonn Scale for the Assessment of Basic Symptoms [
27], and the Comprehensive Assessment of At-Risk Mental States have all been developed [
32]. However, objective biomarkers for psychotic risk group screening have not yet been identified, and current clinical risk identification often relies on the subjective judgement of symptoms by clinicians. For this reason, the accuracy of risk identification inevitably varies. Additionally, prodromal state research and intervention trials have often not included children; meaning that methods for identifying at-risk children have not yet been developed, as previous studies have assumed that prodromal psychopathology does not exist in childhood.
Tor et al. studied the neuropsychological profile of at-risk for psychosis children and adolescents (aged 10–17) [
33]. They found this group showed lower general performance in intelligence, executive functioning, and attention compared to healthy controls. A systematic review in 2017 also found that clinically high-risk children and adolescents show lower general intelligence [
26]. Retrospective epidemiological studies as far back as the 1970’s have looked for predictive characteristics in childhood, but could not find much with the sensitivity of the tests of the day [
34‐
37]. As a result, studies of childhood prodromal signs of schizophrenia have been largely neglected in the modern literature.
Prospective studies, such as long-term longitudinal research on genetically high-risk children whose mothers had schizophrenia [
38] and birth cohort studies [
39‐
41] have also been conducted. These studies indicated that common characteristics of at-risk groups in early childhood (6–8 years) include isolated tendencies, poor social functioning, delayed motor and language development, among others, none of which are unique to schizophrenia. One prospective study conducted by Bolhuis et al. analyzed child behavior at 3 and 6 years old and found that behavioral problems associated with anxiety, depression, and aggression were predictive of psychotic-like experiences at age 10 [
42].
The age group 6–8 years is an often neglected time of childhood to be studied. Kolvin et al. reported a biphasic distribution of the age of onset of mental disorders, with developmental disabilities becoming apparent before age 5 and schizophrenia-related disabilities occurring after age 9 [
43,
44]. Cognitive abnormalities generally only appear after age 10 [
37]. The 6–8 year old group is therefore important to investigate prodromal symptoms of schizophrenia.
To date, none of the early signs reported in studies are specific to schizophrenia, but identifying a specific pattern of characteristics could be useful to predict later development of schizophrenia and identify at-risk children. Therefore, we designed a retrospective clinical epidemiological study of patients with schizophrenia using the Child Behavior Checklist (CBCL) to assess possible behavioral alterations in children (6–8 years old) that could be used to develop a pediatric screening system.
We consider the CBCL to be effective for extracting early characteristics that may be prodromal of schizophrenia as it has been used extensively in the literature to predict psychiatric disorders meeting DSM criteria [
42,
45,
46].
A systematic review of the models that aim at predicting the transition to psychosis were broadly found to have poor methodology and reporting of results [
25]. Thus, there is a need for better prediction tools, especially those that can be utilized with children. This study aimed to develop a risk-predicting algorithm for identifying children that would benefit from early intervention strategies to reduce the risk of psychosis. The present study is also novel in examining the possibility of extending the prodromal concept to childhood.
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