Serotonergic dysfunction in the prodromal, first-episode and chronic course of schizophrenia as assessed by the loudness dependence of auditory evoked activity

Schizophr Res. 2009 Apr;109(1-3):141-7. doi: 10.1016/j.schres.2009.02.008. Epub 2009 Mar 5.


Recent studies revealing evidence of increased serotonergic neurotransmission in schizophrenia has generated substantial interest in the role of serotonin in its pathophysiology. None of these studies, however, have queried whether dysfunctional serotonergic activity might already have been present in subjects of at-risk mental state for schizophrenia before the onset of psychotic symptoms, and whether serotonergic activity further increases during the development of schizophrenia and the chronic course. Although no valid indicator for measuring the activity level of serotonergic neurotransmission has yet been found, a series of evidence from human and animal studies suggests that a weak loudness dependence of auditory evoked potentials (LDAEP) indicates high serotonergic activity and vice versa. We examined the LDAEP (N1/P2 component) in 60 patients with at-risk mental state for schizophrenia who showed characteristic prodromal symptoms, 34 first-episode patients, 28 patients with a chronic course of schizophrenia and 57 healthy controls. Prodromal patients showed significantly weaker LDAEP in comparison to healthy volunteers, but similarly to that in first-episode and chronic patients. None of the covariates such as age, gender, medication, age of onset, or psychopathology had an influence on this finding. In a subsample of prodromal patients, LDAEP values remain the same after retesting 10 months later. These results indicate that serotonergic neurotransmission had already increased before the onset of the full-blown psychosis of schizophrenia and remains enhanced in the further course of the disease. A weak LDAEP may therefore represent a vulnerability marker rather than an expression of illness progression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / methods*
  • Adolescent
  • Adult
  • Age of Onset
  • Chronic Disease
  • Disease Progression
  • Evoked Potentials, Auditory / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Schizophrenia / diagnosis
  • Schizophrenia / physiopathology
  • Serotonin / physiology*
  • Synaptic Transmission / physiology


  • Serotonin