Susan Lurie, MD; Gautam Rajendran, MD; Scot McKay, MD; Elise M. Sannar, MD Schizophrenia Spectrum and Other Psychotic Disorders in Children and Adolescents Susan Lurie, MD; Gautam Rajendran, MD; Scot McKay, MD; Elise M. Sannar, MD Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Colorado School of Medicine Denver Health Behavioral Health Services, Pediatric Mental Health Institute, Children’s Hospital Colorado Introduction adolescent psychiatrists are likely to encounter a here are multiple causes of psychosis, including number of patients with adolescent or even younger Tboth psychiatric and medical. Schizophrenia, the onset illness. Early-onset schizophrenia (EOS) refers main focus of this article, is one of the most no- to individuals who have developed the full illness table. Schizophrenia is believed to have occurred in before age 18, and childhood onset schizophre- mankind throughout history, and is generally associ- nia (COS; onset before age 12) is a subset of EOS. ated with significant morbidity. The World Health The diagnostic validity of schizophrenia in children younger than 6 has not been established, though a Organization ranks it among the most disabling and 7 economically catastrophic medical disorders, and few cases have been reported. one of the top 10 illnesses contributing to the global burden of disease.1 Schizophrenia occurs in approxi- Diagnostic Considerations mately 1% of the population worldwide. It affects DSM II, published in 1968, was the first manual men and women equally, but men tend to manifest to include disorders of childhood. The concept of 2 symptoms on average 5 years earlier than women. schizophrenia at that time was broad, and included The concept of schizophrenia and psychosis has children with developmental disabilities in addi- evolved for well over a century. There is general con- tion to those with psychotic symptoms. Since DSM sensus that schizophrenia is a neurodevelopmental III, published in 1980, the criteria for diagnosis of disorder; the final presentation of the illness is the schizophrenia in youth have been essentially the end state of a complex pathological neural develop- same as those for the diagnosis in adults. mental process that started years before the onset The DSM-5 chapter on “Schizophrenia Spectrum and 3 of the illness. Studies support a multidimensional Other Psychotic Disorders” includes schizophrenia, model, with the interaction of environmental and delusional disorder, brief psychotic disorder, schizo- genetic influences leading to a complex syndrome of phreniform disorder, schizoaffective disorder, sub- 3 insidious onset and varied presentation. stance/medication-induced psychotic disorder, psy- Schizophrenia was first identified as a discrete chotic disorder due to another medical condition, mental illness by Dr. Emile Kraepelin in 1887, who and schizotypal personality disorder. These disorders termed it dementia praecox.4 The Swiss psychiatrist, are all defined by symptoms in 1 or more of the fol- Eugene Bleuler, coined the term, “schizophrenia” lowing 5 domains: delusions, hallucinations, disor- in 1911; it is derived from the Greek roots, schizo ganized thinking or speech, grossly disorganized or (split) and phrene (mind), to describe the fragment- abnormal motor behavior (including catatonia), and ed thinking of people with the disorder. Bleuler was negative symptoms.8 Catatonia is conceptualized also the first to describe the symptoms of the illness differently in DSM-5. It is not a class in itself, but can as “positive” or “negative.”5 occur in association with a number of psychiatric Approximately one-third of first episodes of schizo- and medical conditions, including schizophrenia. The phrenia occur before age 19,6 hence child and cluster A personality disorders—schizotypal, para- 23 Schizophrenia Spectrum and Other Psychotic Disorders in Children and Adolescents noid, and schizoid—are considered to be related to ten times, this phase is not appreciated until reflect- psychotic disorders. ing back after the emergence of psychotic symptoms. The current diagnostic criteria for schizophrenia The acute phase is marked by the onset of prominent (DSM-5) requires the presence of 2 or more charac- positive symptoms and a significant deterioration in teristic symptoms (hallucinations, delusions, disorga- functioning. It may last several months, depending on nized speech, disorganized or catatonic behavior, and/ the onset of treatment and the response. The recu- or negative symptoms), a decline in social or occupa- perative/recovery phase occurs after the remission of tional functioning, and evidence of the disorder for at acute psychosis, and is usually a several-month period least 6 months. The subtypes (paranoid, disorganized, where the patient still experiences significant impair- catatonic, residual, and undifferentiated) have been ment. Negative symptoms predominate, though some eliminated. positive symptoms may persist. A number of patients have significant depression. In the residual phase, Attenuated psychosis syndrome (APS) has been most patients continue to be somewhat impaired due included in the appendix of DSM-5 as a condition for to the negative symptoms. Though they may improve further study. Symptoms are psychosis-like, but below significantly, they may never return to their premor- the threshold for a full psychotic disorder. Preventive bid level of cognitive functioning.11 Some individuals strategies, including psychotherapy and antipsychotic remain chronically symptomatic, despite treatment, medication, typically target this early phase. Though and never really enter the residual phase. there is general agreement among researchers about the existence and importance of this syndrome, there Differential Diagnosis is debate about whether it should be in the main body of DSM-5. Concerns include the fact that it can- When an individual presents to a medical setting with not be reliably diagnosed in community settings, and acute psychosis, etiologies other than psychiatric that the majority of individuals diagnosed with APS causes need to be considered. These include medi- do not go on to develop schizophrenia or full-blown cal conditions such as CNS infections, delirium, neo- psychosis.9 There is the risk that they may be exposed plasms, endocrine disorders, and genetic syndromes, to unnecessary and potentially harmful interven- including 22q11.2 deletion syndrome. In addition, tions.10 multiple drugs of abuse (cannabis, LSD, mushrooms, and dextromethorphan) and prescriptions medica- In the EOS research literature, the terms clinical high tions (steroids, anticholinergics, antihistamines, and risk (CHR) and at risk mental state are both used to stimulants) can cause psychotic symptoms. Acute psy- refer to what was formerly known as the prodrome. chosis due to toxic exposure usually resolves in days Their criteria are overlapping, but not synonymous. to weeks, after the offending agent is removed. When These terms are preferred over prodrome as not all drug use occurs before the onset of schizophrenia, it individuals at risk will eventually develop the full ill- can be difficult to determine whether the psychosis is ness. APS was a compromise set of criteria between an independent drug effect, or due to the unmasking both sets of research criteria, and input from less- of the underlying illness in a vulnerable individual.12 biased individuals outside the field. There are also multiple psychiatric conditions, other Course of Illness than schizophrenia, that can cause psychotic symp- toms. Both bipolar mood disorder and major de- Schizophrenia is unique among psychiatric disorders pressive disorder can present with florid psychosis, in that distinct phases are recognized. Not all individu- including hallucinations and delusions.13,14 Youth with als with schizophrenia pass through all of the phases. certain psychiatric disorders, including post-traumatic In the clinical high-risk phase, there is usually some stress disorder (PTSD), conduct disorder, and/or degree of social or cognitive deterioration before the depression, tend to report high rates of psychotic onset of psychotic symptoms. These changes may be symptoms.15 Children who have been abused are associated with depression, anxiety, and other behav- particularly likely to report psychotic symptoms, and ioral problems, as well as substance use, making the it is frequently difficult to differentiate trauma-related diagnosis of schizophrenia in the early phase difficult. symptoms from other causes of psychosis.16 Individu- The onset of symptoms may be acute or insidious. Of- 24 Susan Lurie, MD; Gautam Rajendran, MD; Scot McKay, MD; Elise M. Sannar, MD als with severe obsessive compulsive disorder and Risk and Protective Factors poor insight can also appear psychotic. The majority Genetic vulnerabilities and environmental risk factors of children and adolescents who report psychotic likely interact to trigger psychosis in adolescence and symptoms will not go on to be diagnosed with schizo- young adulthood. Environmental risk factors associat- phrenia. ed with schizophrenia include living in an urban area, immigration, famine, prenatal and perinatal factors, Etiology/Pathophysiology and advanced paternal age.30 High family expressed emotion and cannabis use have also been implicat- Neuroimaging Studies ed.31 Preventing or treating perinatal complications Volumetric studies of gray matter in youth at risk (such as hypoxia, infection, and malnutrition),