Adolescence As a Period of Vulnerability and Intervention in Schizophrenia: Insights from the MAM Model

Overview

Journal Neurosci Biobehav Rev

Specialties Neurology
Psychology
Social Sciences

Date 2016 May 29

PMID 27235082

Citations 59

Authors

Felipe V Gomes

Millie Rincon-Cortes

Anthony A Grace

Affiliations

Soon will be listed here.

Abstract

Adolescence is a time of extensive neuroanatomical, functional and chemical reorganization of the brain, which parallels substantial maturational changes in behavior and cognition. Environmental factors that impinge on the timing of these developmental factors, including stress and drug exposure, increase the risk for psychiatric disorders. Indeed, antecedents to affective and psychotic disorders, which have clinical and pathophysiological overlap, are commonly associated with risk factors during adolescence that predispose to these disorders. In the context of schizophrenia, psychosis typically begins in late adolescence/early adulthood, which has been replicated by animal models. Rats exposed during gestational day (GD) 17 to the mitotoxin methylazoxymethanol acetate (MAM) exhibit behavioral, pharmacological, and anatomical characteristics consistent with an animal model of schizophrenia. Here we provide an overview of adolescent changes within the dopamine system and the PFC and review recent findings regarding the effects of stress and cannabis exposure during the peripubertal period as risk factors for the emergence of schizophrenia-like deficits. Finally, we discuss peripubertal interventions appearing to circumvent the emergence of adult schizophrenia-like deficits.

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References

Spear L . The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev. 2000; 24(4):417-63. DOI: 10.1016/s0149-7634(00)00014-2. View

Sinclair D, Purves-Tyson T, Allen K, Weickert C . Impacts of stress and sex hormones on dopamine neurotransmission in the adolescent brain. Psychopharmacology (Berl). 2014; 231(8):1581-99. PMC: 3967083. DOI: 10.1007/s00213-013-3415-z. View

Tseng K, ODonnell P . Dopamine modulation of prefrontal cortical interneurons changes during adolescence. Cereb Cortex. 2006; 17(5):1235-40. PMC: 2204087. DOI: 10.1093/cercor/bhl034. View

Lodge D, Behrens M, Grace A . A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J Neurosci. 2009; 29(8):2344-54. PMC: 2754752. DOI: 10.1523/JNEUROSCI.5419-08.2009. View

Uhlhaas P, Roux F, Singer W, Haenschel C, Sireteanu R, Rodriguez E . The development of neural synchrony reflects late maturation and restructuring of functional networks in humans. Proc Natl Acad Sci U S A. 2009; 106(24):9866-71. PMC: 2687997. DOI: 10.1073/pnas.0900390106. View

Schiavone S, Sorce S, Dubois-Dauphin M, Jaquet V, Colaianna M, Zotti M . Involvement of NOX2 in the development of behavioral and pathologic alterations in isolated rats. Biol Psychiatry. 2009; 66(4):384-92. DOI: 10.1016/j.biopsych.2009.04.033. View

Lesh T, Niendam T, Minzenberg M, Carter C . Cognitive control deficits in schizophrenia: mechanisms and meaning. Neuropsychopharmacology. 2010; 36(1):316-38. PMC: 3052853. DOI: 10.1038/npp.2010.156. View

Giovanoli S, Engler H, Engler A, Richetto J, Voget M, Willi R . Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice. Science. 2013; 339(6123):1095-9. DOI: 10.1126/science.1228261. View

Freeman A, Bunney B . Activity of A9 and A10 dopaminergic neurons in unrestrained rats: further characterization and effects of apomorphine and cholecystokinin. Brain Res. 1987; 405(1):46-55. DOI: 10.1016/0006-8993(87)90988-7. View

10.

Thompson J, Pogue-Geile M, Grace A . Developmental pathology, dopamine, and stress: a model for the age of onset of schizophrenia symptoms. Schizophr Bull. 2005; 30(4):875-900. DOI: 10.1093/oxfordjournals.schbul.a007139. View

11.

Lieberman J, Stroup T, McEvoy J, Swartz M, Rosenheck R, Perkins D . Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005; 353(12):1209-23. DOI: 10.1056/NEJMoa051688. View

12.

Irwin I, DELANNEY L, McNeill T, Chan P, FORNO L, Murphy Jr G . Aging and the nigrostriatal dopamine system: a non-human primate study. Neurodegeneration. 1994; 3(4):251-65. View

13.

Heckers S, Konradi C . GABAergic mechanisms of hippocampal hyperactivity in schizophrenia. Schizophr Res. 2014; 167(1-3):4-11. PMC: 4402105. DOI: 10.1016/j.schres.2014.09.041. View

14.

Piontkewitz Y, Assaf Y, Weiner I . Clozapine administration in adolescence prevents postpubertal emergence of brain structural pathology in an animal model of schizophrenia. Biol Psychiatry. 2009; 66(11):1038-46. DOI: 10.1016/j.biopsych.2009.07.005. View

15.

Chergui K, Charlety P, Akaoka H, Saunier C, Brunet J, Buda M . Tonic activation of NMDA receptors causes spontaneous burst discharge of rat midbrain dopamine neurons in vivo. Eur J Neurosci. 1993; 5(2):137-44. DOI: 10.1111/j.1460-9568.1993.tb00479.x. View

16.

van Os J, Bak M, Hanssen M, Bijl R, de Graaf R, Verdoux H . Cannabis use and psychosis: a longitudinal population-based study. Am J Epidemiol. 2002; 156(4):319-27. DOI: 10.1093/aje/kwf043. View

17.

Guillin O, Abi-Dargham A, Laruelle M . Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol. 2007; 78:1-39. DOI: 10.1016/S0074-7742(06)78001-1. View

18.

Koenig T, van Swam C, Dierks T, Hubl D . Is gamma band EEG synchronization reduced during auditory driving in schizophrenia patients with auditory verbal hallucinations?. Schizophr Res. 2012; 141(2-3):266-70. DOI: 10.1016/j.schres.2012.07.016. View

19.

Cabungcal J, Steullet P, Morishita H, Kraftsik R, Cuenod M, Hensch T . Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proc Natl Acad Sci U S A. 2013; 110(22):9130-5. PMC: 3670388. DOI: 10.1073/pnas.1300454110. View

20.

Schobel S, Lewandowski N, Corcoran C, Moore H, Brown T, Malaspina D . Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Arch Gen Psychiatry. 2009; 66(9):938-46. PMC: 2797730. DOI: 10.1001/archgenpsychiatry.2009.115. View