title: Evidence for disturbed cortical signal processing and altered serotonergic neurotransmission in generalized anxiety disorder.
abstract: BACKGROUND
  Current pathophysiological concepts of generalized anxiety disorder (GAD) assume a disturbed exteroceptive sensory system. Furthermore, central serotonergic neurotransmission has been shown to play an important role in anxiety disorder. Cortical signal processing as measured by auditory evoked potentials (AEPs) may reflect the integrity of the exteroceptive sensory system. Because a special aspect of AEP, the loudness dependence of the N1/P2-component (LD), has been related to central serotonergic activity, the LD may be useful for investigating serotonergic dysfunctions in GAD.
  
  
  METHODS
  The LD was recorded in 31 medication-free patients with GAD without any psychiatric co-morbidity and in 31 matched control subjects. Dipole source analysis was performed to separate the LD of regions including the primary (LD-tangential dipole) and regions including the secondary auditory cortex (LD-radial dipole).
  
  
  RESULTS
  A shallower LD-tangential was observed in patients with GAD as compared to healthy control subjects [F(1,60) = 6.727, p =.012; one-way analysis of variance]. The LD-radial showed no differences between groups. Severity of the anxiety symptoms was not related to the LDs.
  
  
  CONCLUSIONS
  The results indicate an altered exteroceptive sensory system in GAD occurring at the level of the primary but not secondary auditory cortex. Because a shallow LD of the primary auditory cortex was related to a high firing rate of neurons in the dorsal raphe nucleus, the results may support evidence for an enhanced serotonergic activity in GAD.
authors.affiliation: Max-Planck-Institute of Cognitive Neuroscience, Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Senkowski
authors.forename: Michael
authors.initials: M
authors.lastname: Linden
authors.forename: Doris
authors.initials: D
authors.lastname: Zubrägel
authors.forename: Thomas
authors.initials: T
authors.lastname: Bär
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000379:Agoraphobia / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D001007:Anxiety / Q000523:psychology; D001303:Auditory Cortex / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D003863:Depression / Q000523:psychology; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D012701:Serotonin