Schizophrenia has a long history of misunderstanding that continues to challenge clinicians and researchers today. This devastating disease is surprisingly common, affecting approximately half to 1% of the world's population. Schizophrenia is a chronic psychiatric syndrome characterised by psychotic symptoms (e.g., delusions and hallucinations), emotional dysregulation, and deficits in attention and short‐term memory. This syndrome results from a complex interplay between environmental factors and genetic susceptibility, and is typically treated with antipsychotic medications and psychosocial therapies. Substantial evidence suggests that schizophrenia is a disorder of neurodevelopment and that psychotic symptoms may actually represent a late stage of the illness process, not the onset.

Key Concepts:

  • Schizophrenia is a chronic psychiatric syndrome characterised by delusions and hallucinations, emotional dysregulation and cognitive dysfunction.

  • Schizophrenia is caused by a complex interplay of environmental factors and inherited genetic susceptibility.

  • Schizophrenia is now considered to be a neurodevelopmental disorder in which psychosis represents a late, and potentially preventable, outcome of the illness.

  • The neurobiological basis of schizophrenia includes widespread impairments in cortical and subcortical neural circuits including the prefrontal cortex and alterations in a variety of neurotransmitter systems.

  • Schizophrenia is mainly treated with antipsychotic medications and psychosocial therapies.

Keywords: schizophrenia; psychosis; antipsychotic medications; neurobiology; neurotransmitter; development; prefrontal cortex; working memory; cognition

Figure 1.

Proposed developmental course of schizophrenia. This model illustrates that from gestation to late adolescence/young adulthood, a number of genetic liabilities and adverse environmental events (blue bars) increase the risk of developing schizophrenia. A number of neurodevelopmental processes appear to be disrupted in schizophrenia (green bars). Recent evidence shows that working memory performance improves at a slower rate during postnatal development in people who will eventually develop schizophrenia (dashed orange curve) relative to healthy comparison subjects (solid orange curve). In this neurodevelopmental model, psychosis onset (magenta bar) represents a late and potentially preventable outcome of earlier pathological processes.



Akbarian S, Kim JJ, Potkin SG et al. (1995) Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Archives of General Psychiatry 52(4): 258–266.

Andreasen NC and Flaum M (1991) Schizophrenia: the characteristic symptoms. Schizophrenia Bulletin 17(1): 27–49.

Baddeley A (1992) Working memory. Science 255(5044): 556–559.

Brown AS and Derkits EJ (2010) Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. American Journal of Psychiatry 167(3): 261–280.

Callicott JH, Mattay VS, Verchinski BA et al. (2003) Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. American Journal of Psychiatry 160(12): 2209–2215.

Eack SM, Hogarty GE, Cho RY et al. (2010) Neuroprotective effects of cognitive enhancement therapy against gray matter loss in early schizophrenia: results from a 2‐year randomized controlled trial. Archives of General Psychiatry 67: 674–682.

Goldman‐Rakic PS (1995) Cellular basis of working memory. Neuron 14(3): 477–485.

Gottesman I (ed.) (1991) Is schizophrenia inherited genetically? In: Schizophrenia Genesis: The Origins of Madness, 1st edn. New York, W.H. Freeman and Company. 84–103.

Guilmatre A, Dubourg C, Mosca AL et al. (2009) Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation. Archives of General Psychiatry 66(9): 947–956.

Insel TR (2010) Rethinking schizophrenia. Nature 468(7321): 187–193.

Insel TR and Scolnick EM (2006) Cure therapeutics and strategic prevention: raising the bar for mental health research. Molecular Psychiatry 11(1): 11–17.

Lesh TA, Niendam TA, Minzenberg MJ and Carter CS (2011) Cognitive control deficits in schizophrenia: mechanisms and meaning. Neuropsychopharmacology 36(1): 316–338.

Lewis DA (2012) Cortical circuit dysfunction and cognitive deficits in schizophrenia – implications for preemptive interventions. European Journal of Neuroscience 35(12): 1871–1878.

Lewis DA and Gonzalez‐Burgos G (2008) Neuroplasticity of neocortical circuits in schizophrenia. Neuropsychopharmacology 33(1): 141–165.

Lewis DA and Sweet RA (2009) Schizophrenia from a neural circuitry perspective: advancing toward rational pharmacological therapies. Journal of Clinical Investigation 119(4): 706–716.

Martin LF and Freedman R (2007) Schizophrenia and the alpha7 nicotinic acetylcholine receptor. International Review of Neurobiology 78: 225–246.

Miller EK and Cohen JD (2001) An integrative theory of prefrontal cortex function. Annual Review of Neuroscience 24: 167–202.

Miyamoto S, Miyake N, Jarskog LF, Fleischhacker WW and Lieberman JA (2012) Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents. Molecular Psychiatry 17(12): 1206–1227.

van Os J, Kenis G and Rutten BP (2010) The environment and schizophrenia. Nature 468(7321): 203–212.

Penn DL, Guynan K, Daily T et al. (1994) Dispelling the stigma of schizophrenia: what sort of information is best? Schizophrenia Bulletin 20(3): 567–578.

Reichenberg A, Caspi A, Harrington H et al. (2010) Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30‐year study. American Journal of Psychiatry 167(2): 160–169.

Stefansson H, Rujescu D, Cichon S et al. (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455(7210): 232–236.

Van Snellenberg JX, Torres IJ and Thornton AE (2006) Functional neuroimaging of working memory in schizophrenia: task performance as a moderating variable. Neuropsychology 20(5): 497–510.

Further Reading

Cooper JR, Bloom FE and Roth RH (2002) The Biochemical Basis of Neuropharmacology, 8th edn. New York: Oxford University Press.

Goff DC and Coyle JT (2001) The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. American Journal of Psychiatry 158: 1367–1377.

Lewis DA and Gonzalez‐Burgos G (2006) Pathophysiologically based treatment interventions in schizophrenia. Nature Medicine 12: 1016–1022.

Mueser KT and McGurk SR (2004) Schizophrenia. Lancet 363: 2063–2072.

Sadock BJ and Sadock VA (eds) (2000) Comprehensive Textbook of Psychiatry, 7th edn. Philadelphia, PA: Lippincott Williams and Wilkins.

Shatzberg AF and Nemeroff CB (eds) (2003) The American Psychiatric Publishing Textbook of Psychopharmacology, 3rd edn. Washington DC: American Psychiatric Publishing.

Spitzer M (1999) The Mind Within the Net: Models of Learning, Thinking, and Acting. Cambridge: Massachusetts Institute of Technology Press.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Hoftman, Gil D, and Lewis, David A(Oct 2013) Schizophrenia. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000062.pub3]