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Editorial                                                                                                                                              Open Access

## Early-Onset Psychosis and Child and Adolescent Schizophrenia

Sune Bo* & Ulrik Helt Haahr

Psychiatric Research Unit, Region Zealand, Denmark

*Corresponding Author:

subh@regionsjaelland.dk

'Our lives disconnect and reconnect, we move on, and later we may again touch one another, again bounce away. This is the felt shape of a human life, neither simply linear nor wholly disjunctive nor endlessly bifurcating, but rather this bouncey-castle sequence of bumpings-into and tumblings-apart.'

- Salman Rushdie, The Ground Beneath Her Feet

We are excited  to  introduce  this  special  issue  of SJCAPP  about  early-onset  psychosis  (EOP)  and schizophrenia  in  children  and  adolescents.  Several years ago, an editorial in Nature described schizophrenia as 'the worst disease affecting mankind' (1). We know that approximately 1% of the  world's  population  is  directly  affected  by  this debilitating psychiatric disorder at some point during their  lives  (2).  Every  year,  more  than  5,000  new articles about schizophrenia spectrum disorders and psychosis are  added  to  PubMed  (3).  Schizophrenia remains  one  of  the  most  mysterious  and  severe mental disorders. It has a complex and heterogenic symptomatology that causes enormous suffering to patients and their relatives, and it is generally considered a costly burden on society, although its true financial cost is somewhat difficult to estimate (4,5). In the Diagnostic and Statistical Manual of Mental Disorders,  Fifth  Edition (DSM-5),  schizophrenia  is defined  as:  '…a  disorder  that  lasts  for  at  least  6 months and includes at least one month of activephase symptoms (i.e., two [or more] of the following: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms)' (6). The DSM-5 further states that 'no single symptom is pathognomonic of schizophrenia' (6). Across different diagnostic systems, there seems to exist a general understanding that schizophrenia is a  heterogeneous  syndrome  composed  of  various symptoms with different pathogeneses and etiologies. However, there is also consensus that the phenotypic characteristics include positive symptoms (e.g., hallucinations, delusional thoughts), negative  symptoms  (e.g.,  apathy,  lack  of  emotions, poor or absent social functioning), bizarre behavior, and  a  range  of  cognitive  dysfunctions,  including disorganized  thoughts,  difficulty  concentrating  and completing  tasks,  reduced  memory,  and  deficits  in the processing of information. These symptoms have been found in cross-cultural studies conducted by the World Health Organization  since  the  International Pilot Study in Schizophrenia was initiated during the 1960s; this study proved that schizophrenia and its related symptomatology are found worldwide, although the course and outcomes of the illness may vary (7).

Schizophrenia affects more than just mental health. Patients who are diagnosed with schizophrenia die 12 to  15  years  earlier  than the  average  population (8), and current studies have indicated that the mortality difference continues to increase, mainly as a result of suicide. The incidence rates for schizophrenia peak around the age of 22 years (9), but one third of the individuals  who  will  develop  the  disorder  do  so before they are 18 years old (10). Schizophrenia that appears in children and adolescents is accepted to be clinically  and biologically coherent with adult-onset schizophrenia  (AOS).  However,  there  are  some differences. Patients with early-onset schizophrenia (EOS) display a more severe clinical prognosis and a greater neurodegenerative trajectory, and they seem to be less responsive to treatment as compared with patients  with  AOS.  Schizophrenia  that  emerges  in patients before they are 18 years old is divided into two groups: 1) EOS, with an onset between the ages of 13 and 17 years and prevalence rates of 1 to 2 per 1,000  population;  and  2)  very  EOS,  which  begins before the age of 13 years and which has a prevalence that is estimated at 1 per 10,000 population (11). The modern construct of EOS differs significantly from that used during much of the twentieth century. Until the early 1970s, children who  would  now  be diagnosed  within  the  autism  spectrum  would  have been diagnosed with schizophrenia, and widespread uncertainty existed regarding the validity of a schizophrenia diagnosis in children and adolescents (12). With the introduction of the DSM-III and the International Statistical Classification of Diseases and Related Health Problems, 9th Revision, the specific criteria  that  were  used  to  define  childhood  and adolescent  schizophrenia  were  removed:  the  same criteria have since been used to diagnose schizophrenia  in  children,  adolescents,  and  adults. With the alignment of the defining criteria, prospective studies have demonstrated good validity of the diagnosis for children and adolescents; youths who are diagnosed with schizophrenia display high stability with regard to the phenotypical expression of  the  disorder  into  adulthood  (13).  Studies  of neuropsychological functions and brain structure in people  with  schizophrenia  have  shown  the  same degenerative patterns, regardless of the patient's age at the onset of the disorder (14).

The discrete developmental trajectories of schizophrenia  remain  obscure,  but  recent  research has enhanced our understanding of the disorder and of the underlying etiological factors (3,15,16). Geneenvironment studies have emphasized genetic factors that affect an individual's vulnerability to the development of schizophrenia, and twin studies have shown  that  the  syndrome  has  heritability  rates  of approximately 80%  (17,18). There has been a substantial effort from those supporting the medical disease model to demonstrate that schizophrenia has a  biological  origin.  This  stance  is  supported  by studies that have demonstrated a genetic predisposition for schizophrenia among family members,  twins,  adoptees,  and  offspring  of  twins (19). Other studies have shown that schizophrenia is associated  with  structural  brain  abnormalities  (20) and  with  biochemical  imbalances  that  are  mostly associated with the functioning of the dopaminergic system (21).

Epidemiological studies also indicate that environmental factors affect the rate of schizophrenia (8;22-24), including adverse experiences  in  childhood  (25).  Living  in  urbanized communities  raises  the  risk  of  schizophrenia  (26), and the tendency to develop schizophrenia is higher among  certain  ethnic  groups  as  compared  with native-born individuals (27).

With respect to long-term prognosis, longitudinal studies that have followed patients with schizophrenia for more than 25 years have suggested that approximately 35% of patients recover fully and that  another  35%  function  independently  and  are self-supporting,  with  some  possibility  of  residual symptoms  (28).  A  25-year  follow-up  study  that evaluated profoundly disabled patients with schizophrenia with an average of 16 years of schizophrenic symptoms and an average total disability  of  10  years  found  that  68%  of  these subjects  were free of  schizophrenic symptoms and that 45% were free of all psychiatric symptoms at 25 years (29).

Specifically, studies of EOS show that the disease displays  strong  associations  with  poor  premorbid functioning and a reduction in normative development (30), and this diminution seems to be more severe in patients with EOS as compared with AOS. In addition, studies have shown that, in about 20% of adolescents who have been diagnosed with schizophrenia, clear language and motor developmental  delays  are  present;  these  delays  are only found in about 10% of patients with AOS (31). Research has also reported a substantial difference in the premorbid intelligence quotients of patients with EOS  as  compared  with  those  with  AOS,  with patients with EOS scoring roughly 10 to 15 points lower (30). Patients with EOS generally have more negative symptoms, more severely incoherent thoughts, and a more profoundly disordered sense of self,  whereas  AOS  is  associated  with  more  severe positive symptomatology, such as paranoid delusions (32). As compared with the relatively high remission rates  for  patients  with  AOS,  only  12%  of  patients with EOS are in full remission at discharge. In several prospective  follow-up  studies,  patients  with  EOS have  displayed  a  chronically  disabling  course  of illness  and  severely  impaired  functioning  well  into adulthood (13,33).

Important EOS predictors of diminished functioning point to premorbid cognitive and social deficiencies (33), long periods of untreated psychosis, and a long first psychotic episode (34).

This special issue of SJCAPP addresses several of the  issues  just  described,  and  the  two  included commentaries  build  further  on  these  ideas.  In  the first commentary, Aggernæs connects the four articles included in this issue, and she describes the growing evidence of a shared genetic risk for autism, attention-deficit/hyperactivity disorder, and schizophrenia.  She  emphasizes  the  importance  of  the thorough assessment of the patient in addition to the need  for  intervention  during  the  first  psychotic episode  and  the  prodromal  phase.  Nordgaard  and colleagues also address this in their commentary, and they discuss the need for more specific instruments for  the  assessment  of  clinically  high-risk  patients. Patients who  experience their first episode of psychosis need to be treated early and optimally to decrease morbidity and to improve the outcomes of their  illnesses.  This  is  a  special  challenge  for  the treatment  of  children  due  to  the  associated  side effects of antipsychotic drugs. The article by Haapasalo-Peru and colleagues discusses the growing trend of prescribing antipsychotics to young people and calls for the development of nonpharmacological  treatment  modalities,  as  described in a recent review (35).

These  relatively  new  research  findings  related  to EOS and its devastating prognosis obligate researchers  to  continue  their  explorations  into  the ways in which the early forms of schizophrenia and psychosis emerge, how they develop in children and adolescents, and how they carry over into adulthood.

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