Chronic phencyclidine administration remains the single best model for human psychosis. The crucial paper by Jentsch and colleagues (Jentsch et al., 1997), identifies every element needed for a satisfactory representation of the schizophrenia syndrome.

Though acute NMDA receptor antagonists induce hypermetabolism, prolonged phencyclidine induces a hypometabolic state (Wu et al., 1991; Tamminga et al., 1995) accompanied by severe dopaminergic disturbances (Aalto et al., 2005; Narendran et al., 2005).

Moghaddam's comments emphasize that there are multiple routes to psychosis, and these may converge on cortical glutamatergic/dopaminergic interactions (  Read more

View all comments by Henry Holcomb

Excellent overview. My daughter has been addicted to meth for over twenty years and I AM seeing her inability to make constructive, long-term decisions, even when "clean." Our oldest son has schizophrenia, and although he is highly functioning, shows some of the impairment(s) my daughter exhibits.

View all comments by Elizabeth Ryan

Moghaddam is correct in arguing that long-term intake of, or exposure to, amphetamine-like drugs produces a spectrum of changes in cortical and subcortical function that underlie cognitive and affective abnormalities that relate to the abuse potential of the drugs, as well as the associated drug-induced psychotic symptoms. This may be particularly true for methamphetamine (Yui et al., 1999). Indeed, Jane Taylor and I proposed 7 years ago now (Jentsch and Taylor, 1999) that dysregulation of frontal cortical function is a common feature of long-term exposure to drugs of abuse; today, this is a phenomenon that is generally accepted as contributing directly to the addictive process (London et al., 2000; Everitt et al., 2001;   Read more

View all comments by J David Jentsch

The acknowledgment that amphetamine psychosis (like schizophrenia) can have inverse effects (both hypo- and hyperfunction) on different regions of the prefrontal cortex (PFC) is an important one, and worth emphasizing. There is regional specificity of effects within the PFC, not just a global increase or decrease in function. In addition to the distinction between the orbital and medial PFC mentioned in the article, there is converging evidence from the working memory imaging literature that schizophrenia may have inverse effects on ventrolateral (VLPFC) and dorsolateral (DLPFC) prefrontal cortex, with increased VLPFC and decreased DLPFC activation in schizophrenia (Glahn et al., 2005). This has potentially important implications for understanding compensatory performance strategies, and for devising cognitive remediation interventions.

References:

Glahn, D.C., Ragland, J.D., Abramoff, A., Barrett, J., Laird, A.R., Bearden, C.E., Velligan, D.I.: Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia. Hum Brain Mapp. 2005 May;25(1):60-9. Abstract

View all comments by J. Daniel Ragland