Schizophrenia spectrum disorders are considered a heterogeneous group of conditions with a multifactorial etiopathogenesis. Current evidence suggests that the neurodevelopmental model best explains the pathogenesis of schizophrenia, and that the interaction of genetic background and multiple environmental risk factor exposures might cause disease pathogenesis. While early onset (before 13 years) appears to be quite rare, the rate of onset increases during adolescence, with a peak age ranging from 18 to 30 years [
1]. Although neurobiologically and phenomenologically continuous with its adult counterpart, childhood-onset schizophrenia represents a more severe disorder, with more prominent pre-psychotic developmental disorders, brain abnormalities, and genetic risk factors [
2].
In the last decades, multiple lines of evidence support the association between autoimmunity/inflammation and schizophrenia spectrum disorders [
3,
4]. Overlaps in clinical course, in addition to epidemiological and genetic associations, raised the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches [
5]. In more recent years, the focus of the research regarding the relationship between autoimmune diseases and schizophrenia has been narrowed to gastrointestinal (GI) disorders [
6]. In the context of the intricate interaction between the gut and the brain, the normal ecological balance of gut microorganisms plays an important role. Disorders in the composition and quantity of gut microorganisms, the so-called gut microbiota, have been reported to be associated with various central nervous system diseases [
7] and current evidence suggests that probiotic supplementation could improve mild and moderate depressive symptoms [
8]. On the other hand, a recently published systematic review found that there is a paucity of clinical studies to support the benefits of probiotic supplementation in patients with schizophrenia [
9]. At the turn of the twenty-first century, inflammatory bowel disease (IBD) has become a global disease with accelerating incidence in newly industrialized countries with a prevalence surpassing 0.3% [
10]. Ulcerative colitis (UC) is a form of IBD with diffuse inflammation of the rectal and colonic mucosa, manifesting with abdominal pain, diarrhea, bleeding, and weight loss. The pathogenesis of IBD, which is only partly understood, is thought to arise from dysregulation of the innate and adaptive immune systems, leading to an abnormal inflammatory response to commensal bacteria in genetically susceptible individuals [
11]. The incidence rate of UC may vary from 0.5 to 31.5 per 100,000 people each year, depending on the studied population; the majority of patients with UC are in the age group of 30–40 years at diagnosis, while pediatric IBD, so defined when the age at onset is < 19 years, covers approximately 5–25% of patients [
12]. UC displays a chronic clinical course, characterized by periods of exacerbation and remission, which may occur either spontaneously or in response to treatment [
12]. UC rarely exists in isolation but is rather part of a complex matrix of disorders arising in patients over time [
13]. Psychiatric comorbidity in IBD is well known, but to date the nature of the relationship between these two diseases has not been fully understood and is still a matter of debate. The most common psychiatric disorders in IBD are depression and anxiety, whereas data on other conditions, such as bipolar disorders and psychoses, are limited [
14,
15].
In the current paper we present the case of an adolescent patient with a severe form of early onset UC, refractory to conventional therapies, manifesting an early onset first-episode psychosis (FEP) during treatment with thalidomide.