A neurobiological basis for substance abuse comorbidity in schizophrenia

R. Chambers, John H. Krystal, David W. Self

Research output: Contribution to journalArticle

370 Citations (Scopus)

Abstract

It is commonly held that substance use comorbidity in schizophrenia represents self-medication, an attempt by patients to alleviate adverse positive and negative symptoms, cognitive impairment, or medication side effects. However, recent advances suggest that increased vulnerability to addictive behavior may reflect the impact of the neuropathology of schizophrenia on the neural circuitry mediating drug reward and reinforcement. We hypothesize that abnormalities in the hippocampal formation and frontal cortex facilitate the positive reinforcing effects of drug reward and reduce inhibitory control over drug-seeking behavior. In this model, disturbances in drug reward are mediated, in part, by dysregulated neural integration of dopamine and glutamate signaling in the nucleus accumbens resulting form frontal cortical and hippocampal dysfunction. Altered integration of these signals would produce neural and motivational changes similar to long-term substance abuse but without the necessity of prior drug exposure. Thus, schizophrenic patients may have a predilection for addictive behavior as a primary disease symptom in parallel to, and in many cases independent from, their other symptoms.

Original languageEnglish (US)
Pages (from-to)71-83
Number of pages13
JournalBiological Psychiatry
Volume50
Issue number2
DOIs
StatePublished - Jul 15 2001
Externally publishedYes

Fingerprint

Substance-Related Disorders
Comorbidity
Schizophrenia
Reward
Addictive Behavior
Pharmaceutical Preparations
Drug-Seeking Behavior
Self Medication
Nucleus Accumbens
Frontal Lobe
Glutamic Acid
Hippocampus
Dopamine

Keywords

  • Dependence
  • Dopamine
  • Dual diagnosis
  • Hippocampus
  • Nucleus accumbens
  • Schizophrenia
  • Substance abuse

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

A neurobiological basis for substance abuse comorbidity in schizophrenia. / Chambers, R.; Krystal, John H.; Self, David W.

In: Biological Psychiatry, Vol. 50, No. 2, 15.07.2001, p. 71-83.

Research output: Contribution to journalArticle

Chambers, R. ; Krystal, John H. ; Self, David W. / A neurobiological basis for substance abuse comorbidity in schizophrenia. In: Biological Psychiatry. 2001 ; Vol. 50, No. 2. pp. 71-83.
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