Early-Onset Psychosis and Child and Adolescent Schizophrenia

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Scandinavian Journal of Child and Adolescent Psychiatry and Psychology

Psychiatric Research Unit, Region Zealand

Ole Jakob Storebø

Subject: Medicine

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VOLUME 4 , ISSUE 1 (January 2016) > List of articles

Early-Onset Psychosis and Child and Adolescent Schizophrenia

Early-Onset Psychosis and Child and Adolescent Schizophrenia

Sune Bo * / Ulrik Helt Haahr

Citation Information : Scandinavian Journal of Child and Adolescent Psychiatry and Psychology. Volume 4, Issue 1, Pages 1-3, DOI: https://doi.org/10.21307/sjcapp-2016-001

License : (CC BY-SA 4.0)

Published Online: 30-November-2015

ARTICLE

ABSTRACT

“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 active-phase 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). Gene-environment 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 non-pharmacological 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.

Conflicts of interest

The authors declare no conflicts of interest.

References


  1. Where next with psychiatric illness? (Editorial) Nature 1988; 336(6195):95-96.
    [PUBMED] [CROSSREF]
  2. Remschmidt H. Schizophrenia in children and adolescents. Biol Child Psychiatry 2008;24(8):118-137.
    [CROSSREF]
  3. Tandon R, Keshavan MS Nasrallah HA. (2008). Schizophrenia, “just the facts”: what we know in 2008 part 1: overview. Schizophr Res 2008;100(1-3):4-19.
    [PUBMED] [CROSSREF]
  4. Mueser KT, McGurk SR. Schizophrenia. Lancet 2004;363(9426):2063-2072.
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  5. Rice DP, Kelman S, Miller LS. The economic burden of mental illness. Hosp Community Psychiatry 1992;43(12):1227-1232.
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  6. APA. Diagnostic and statistical manual of mental disorders: DSM-5. Arlington, VA: American Psychiatric Association; 2013.
    [CROSSREF]
  7. Siegert RJ. Culture, cognition and schizophrenia. In: Schumaker JF, Ward T (Eds.) Cultural cognition and psychopathology. Westport, CT: Praeger; 2000, p. 171-190.
  8. Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry 2007;64(10):1123-1131.
    [PUBMED] [CROSSREF]
  9. Kirkbride JB, Fearon P, Morgan C, et al. Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center aesop study. Arch Gen Psychiatry 2006;63(3):250-8.
    [PUBMED] [CROSSREF]
  10. Madaan V, Dvir Y, Wilson DR. Child and adolescent schizophrenia: Pharmacological approaches. Expert Opin Pharmacother 2008;9(12):2053–68.
    [PUBMED] [CROSSREF]
  11. Armando M, Pontillo M, Vicari S. Psychosocial interventions for very early and early-onset schizophrenia: a review of treatment efficacy. Curr Opin Psychiatry 2015;28(4):312-323.
    [PUBMED] [CROSSREF]
  12. Remschmidt H. Schizophrenia in children and adolescents. Cambridge, U.K.; New York: Cambridge University Press; 2001.
    [CROSSREF]
  13. Hollis C. (2000). Adult outcomes of child- and adolescent-onset schizophrenia: Diagnostic stability and predictive validity. Am J Psychiatry 2000;157(10):1652-9.
    [PUBMED] [CROSSREF]
  14. Weinberger D, Harrison PJ (Eds.) Schizophrenia. 3rd ed. Hoboken, NJ: Wiley-Blackwell; 2011.
  15. Berlim MT, Mattevi BS, Belmonte-de-Abreu P, Crow TJ. (2003). The etiology of schizophrenia and the origin of language: overview of a theory. Compr Psychiatry 2003;44(1):7-14.
    [PUBMED] [CROSSREF]
  16. van Os J, Kapur S. Schizophrenia. Lancet 2009;374(9690):635-645.
    [PUBMED] [CROSSREF]
  17. Aukes MF, Alizadeh BZ, Sitskoorn MM, et al. (2008). Finding suitable phenotypes for genetic studies of schizophrenia: heritability and segregation analysis. Biol Psychiatry 2008;64(2):128-136.
    [PUBMED] [CROSSREF]
  18. Tuulio-Henriksson A, Haukka J, Partonen T, et al. Heritability and number of quantitative trait loci of neurocognitive functions in families with schizophrenia. Am J Med Genet 2002;114(5):483-490.
    [PUBMED] [CROSSREF]
  19. Sherman SL, DeFries JC, Gottesman II, et al. Recent developments in human behavioral genetics: past accomplishments and future directions. Am J Hum Genet 1997;60(6):1265-1275.
    [PUBMED] [CROSSREF]
  20. Andreasen NC. Linking mind and brain in the study of mental illnesses: a project for a scientific psychopathology. Science 1997;275(5306):1586-1593.
    [PUBMED] [CROSSREF]
  21. Maas JW, Bowden CL, Miller AL, et al. Schizophrenia, psychosis, and cerebral spinal fluid homovanillic acid concentrations. Schizophr Bull 1997;23(1):147-154.
    [PUBMED] [CROSSREF]
  22. Howes OD, McDonald C, Cannon M, Arseneault L, Boydell J, Murray RM. (2004). Pathways to schizophrenia: the impact of environmental factors. Int J Neuropsychopharmacol 2004;7 Suppl 1:S7-S13.
    [PUBMED] [CROSSREF]
  23. McGrath J, Saha S, Chant D, Welham J. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev 2008;30: 67-76.
    [PUBMED] [CROSSREF]
  24. Morgan C, Fisher H. (2007). Environment and schizophrenia: environmental factors in schizophrenia: childhood trauma--a critical review. Schizophre Bull 2007;33(1):3-10.
    [CROSSREF]
  25. Varese F, Smeets F, Drukker M, et al. Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective-and cross-sectional cohort studies. Schizophr Bull 2012;38(4):661-671.
    [PUBMED] [CROSSREF]
  26. Krabbendam L, van Os J. (2005). Schizophrenia and urbanicity: a major environmental influence-conditional on genetic risk. Schizophr Bull 2005;31(4):795-9.
    [PUBMED] [CROSSREF]
  27. Cantor-Graae E, Selten JP. (2005). Schizophrenia and migration: a meta-analysis and review. Am J Psychiatry 2005;162(1):12-24.
    [PUBMED] [CROSSREF]
  28. Karon BP, Widener AJ. (1999). The tragedy of schizophrenia: its myth of incurability. Ethical Hum Sci Serv 1999;1(3):195-211.
  29. Harding CM, Brooks GW, Ashikaga T, Strauss JS, Breier A. The Vermont longitudinal study of persons with severe mental illness, II: Long-term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia. Am J Psychiatry 1987;144(6):727-735.
    [PUBMED] [CROSSREF]
  30. Alaghband-Rad J, McKenna K, Gordon CT, et al. (1995). Childhood-onset schizophrenia: the severity of premorbid course. J Am Acad Child Adolesc Psychiatry 1995;34(10):1273-1283.
    [PUBMED] [CROSSREF]
  31. Jones P, Rodgers B, Murray R, Marmot M. Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 1994;344(8934):1398-402.
    [PUBMED] [CROSSREF]
  32. Häfner H, Nowotny B. Epidemiology of early-onset schizophrenia. Eur Arch Psychiatry Clin Neurosci 1995;245(2):80-92.
    [PUBMED] [CROSSREF]
  33. Fleischhaker C, Schulz E, Tepper K, Martin M, Hennighausen K, Remschmidt H. Long-term course of adolescent schizophrenia. Schizophr Bull 2005;31(3):769-780.
    [PUBMED] [CROSSREF]
  34. Schmidt M, Blanz B, Dippe A, Koppe T, Lay B. (1995). Course of patients diagnosed as having schizophrenia during first episode occurring under age 18 years. Eur Arch Psychiatry Clin Neurosci 1995;245(2):93-100.
    [PUBMED] [CROSSREF]
  35. Lachman, A. (2014). New developments in diagnosis and treatment update: Schizophrenia/first episode psychosis in children and adolescents. J Child Adolesc Ment Health 2014;26(2),109-124.
    [PUBMED] [CROSSREF]
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FIGURES & TABLES

REFERENCES

  1. Where next with psychiatric illness? (Editorial) Nature 1988; 336(6195):95-96.
    [PUBMED] [CROSSREF]
  2. Remschmidt H. Schizophrenia in children and adolescents. Biol Child Psychiatry 2008;24(8):118-137.
    [CROSSREF]
  3. Tandon R, Keshavan MS Nasrallah HA. (2008). Schizophrenia, “just the facts”: what we know in 2008 part 1: overview. Schizophr Res 2008;100(1-3):4-19.
    [PUBMED] [CROSSREF]
  4. Mueser KT, McGurk SR. Schizophrenia. Lancet 2004;363(9426):2063-2072.
    [PUBMED] [CROSSREF]
  5. Rice DP, Kelman S, Miller LS. The economic burden of mental illness. Hosp Community Psychiatry 1992;43(12):1227-1232.
    [PUBMED] [CROSSREF]
  6. APA. Diagnostic and statistical manual of mental disorders: DSM-5. Arlington, VA: American Psychiatric Association; 2013.
    [CROSSREF]
  7. Siegert RJ. Culture, cognition and schizophrenia. In: Schumaker JF, Ward T (Eds.) Cultural cognition and psychopathology. Westport, CT: Praeger; 2000, p. 171-190.
  8. Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry 2007;64(10):1123-1131.
    [PUBMED] [CROSSREF]
  9. Kirkbride JB, Fearon P, Morgan C, et al. Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center aesop study. Arch Gen Psychiatry 2006;63(3):250-8.
    [PUBMED] [CROSSREF]
  10. Madaan V, Dvir Y, Wilson DR. Child and adolescent schizophrenia: Pharmacological approaches. Expert Opin Pharmacother 2008;9(12):2053–68.
    [PUBMED] [CROSSREF]
  11. Armando M, Pontillo M, Vicari S. Psychosocial interventions for very early and early-onset schizophrenia: a review of treatment efficacy. Curr Opin Psychiatry 2015;28(4):312-323.
    [PUBMED] [CROSSREF]
  12. Remschmidt H. Schizophrenia in children and adolescents. Cambridge, U.K.; New York: Cambridge University Press; 2001.
    [CROSSREF]
  13. Hollis C. (2000). Adult outcomes of child- and adolescent-onset schizophrenia: Diagnostic stability and predictive validity. Am J Psychiatry 2000;157(10):1652-9.
    [PUBMED] [CROSSREF]
  14. Weinberger D, Harrison PJ (Eds.) Schizophrenia. 3rd ed. Hoboken, NJ: Wiley-Blackwell; 2011.
  15. Berlim MT, Mattevi BS, Belmonte-de-Abreu P, Crow TJ. (2003). The etiology of schizophrenia and the origin of language: overview of a theory. Compr Psychiatry 2003;44(1):7-14.
    [PUBMED] [CROSSREF]
  16. van Os J, Kapur S. Schizophrenia. Lancet 2009;374(9690):635-645.
    [PUBMED] [CROSSREF]
  17. Aukes MF, Alizadeh BZ, Sitskoorn MM, et al. (2008). Finding suitable phenotypes for genetic studies of schizophrenia: heritability and segregation analysis. Biol Psychiatry 2008;64(2):128-136.
    [PUBMED] [CROSSREF]
  18. Tuulio-Henriksson A, Haukka J, Partonen T, et al. Heritability and number of quantitative trait loci of neurocognitive functions in families with schizophrenia. Am J Med Genet 2002;114(5):483-490.
    [PUBMED] [CROSSREF]
  19. Sherman SL, DeFries JC, Gottesman II, et al. Recent developments in human behavioral genetics: past accomplishments and future directions. Am J Hum Genet 1997;60(6):1265-1275.
    [PUBMED] [CROSSREF]
  20. Andreasen NC. Linking mind and brain in the study of mental illnesses: a project for a scientific psychopathology. Science 1997;275(5306):1586-1593.
    [PUBMED] [CROSSREF]
  21. Maas JW, Bowden CL, Miller AL, et al. Schizophrenia, psychosis, and cerebral spinal fluid homovanillic acid concentrations. Schizophr Bull 1997;23(1):147-154.
    [PUBMED] [CROSSREF]
  22. Howes OD, McDonald C, Cannon M, Arseneault L, Boydell J, Murray RM. (2004). Pathways to schizophrenia: the impact of environmental factors. Int J Neuropsychopharmacol 2004;7 Suppl 1:S7-S13.
    [PUBMED] [CROSSREF]
  23. McGrath J, Saha S, Chant D, Welham J. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev 2008;30: 67-76.
    [PUBMED] [CROSSREF]
  24. Morgan C, Fisher H. (2007). Environment and schizophrenia: environmental factors in schizophrenia: childhood trauma--a critical review. Schizophre Bull 2007;33(1):3-10.
    [CROSSREF]
  25. Varese F, Smeets F, Drukker M, et al. Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective-and cross-sectional cohort studies. Schizophr Bull 2012;38(4):661-671.
    [PUBMED] [CROSSREF]
  26. Krabbendam L, van Os J. (2005). Schizophrenia and urbanicity: a major environmental influence-conditional on genetic risk. Schizophr Bull 2005;31(4):795-9.
    [PUBMED] [CROSSREF]
  27. Cantor-Graae E, Selten JP. (2005). Schizophrenia and migration: a meta-analysis and review. Am J Psychiatry 2005;162(1):12-24.
    [PUBMED] [CROSSREF]
  28. Karon BP, Widener AJ. (1999). The tragedy of schizophrenia: its myth of incurability. Ethical Hum Sci Serv 1999;1(3):195-211.
  29. Harding CM, Brooks GW, Ashikaga T, Strauss JS, Breier A. The Vermont longitudinal study of persons with severe mental illness, II: Long-term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia. Am J Psychiatry 1987;144(6):727-735.
    [PUBMED] [CROSSREF]
  30. Alaghband-Rad J, McKenna K, Gordon CT, et al. (1995). Childhood-onset schizophrenia: the severity of premorbid course. J Am Acad Child Adolesc Psychiatry 1995;34(10):1273-1283.
    [PUBMED] [CROSSREF]
  31. Jones P, Rodgers B, Murray R, Marmot M. Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 1994;344(8934):1398-402.
    [PUBMED] [CROSSREF]
  32. Häfner H, Nowotny B. Epidemiology of early-onset schizophrenia. Eur Arch Psychiatry Clin Neurosci 1995;245(2):80-92.
    [PUBMED] [CROSSREF]
  33. Fleischhaker C, Schulz E, Tepper K, Martin M, Hennighausen K, Remschmidt H. Long-term course of adolescent schizophrenia. Schizophr Bull 2005;31(3):769-780.
    [PUBMED] [CROSSREF]
  34. Schmidt M, Blanz B, Dippe A, Koppe T, Lay B. (1995). Course of patients diagnosed as having schizophrenia during first episode occurring under age 18 years. Eur Arch Psychiatry Clin Neurosci 1995;245(2):93-100.
    [PUBMED] [CROSSREF]
  35. Lachman, A. (2014). New developments in diagnosis and treatment update: Schizophrenia/first episode psychosis in children and adolescents. J Child Adolesc Ment Health 2014;26(2),109-124.
    [PUBMED] [CROSSREF]

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