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Tijdschrift voor Psychiatrie 49 (2007) 3, 169 - 178

Review article

Adolescence, schizophrenia and drug abuse: interactive vulnerability. A hypothesis

L. van Nimwegen, L. de Haan, N. van Beveren, W. van den Brink, D. Linszen

Many studies have reported an interactive vulnerability between adolescence, schizophrenia and drug abuse.
aim To discuss neurobiological and psychosocial developmental factors in adolescence and early adulthood which may contribute to this co-occurrence.
method We studied the literature by means of PubMed, manuals and bibliographic references and used the search terms: 'adolescence', 'neurodevelopment', 'psychosis', 'schizophrenia', 'dopamine', 'substance (ab)use'.
results Adolescence is a period of psychosocial challenges and changes in the brain which, in the case of predisposed persons, can increase the probability of the onset of both schizophrenia and substance abuse. The loss of exceptionally large numbers of dopaminergic neurons can lead to mesocortical hypofrontality combined with anhedonia and dysphoria, both of which are important risk factors for substance abuse. In turn, mesocortical hypofrontality can contribute to hyperactivity of the mesolimbic system, a condition associated with psychoses. We failed to find any other neurobiological explanations for the simultaneous occurrence of schizophrenia and substance abuse and for the fact that they both begin in adolescence and early adulthood. It should be noted, however, that there is a possible interaction between the gaba-glutamate and the dopaminergic neurotransmission.
conclusion The partly overlapping pathogenesis and the simultaneous occurrence of drug abuse and schizophrenia call for integrated treatment. In treatment involving antipsychotics it is important to prevent the development of dysphoria and anhedonia which can adversely affect the patient's well-being and treatment compliance and even increase drug abuse.

keywords adolescent, dopamine, drug usage, neuronal development, schizophrenia