Evidence for an intrinsic relationship between sleep, cognition and the symptomatic manifestations of
schizophrenia is accumulating. This review presents evidence for the possible utility of
GABA(B) receptor agonists for the treatment of subjective and objective sleep abnormalities related to
schizophrenia. At the phenotypic level, sleep disturbance occurs in 16-30% of patients with
schizophrenia and is related to reduced quality of life and poor coping skills. On the neurophysiological level, studies suggest that sleep deficits reflect a core component of
schizophrenia. Specifically, slow-wave sleep deficits, which are inversely correlated with cognition scores, are seen. Moreover, sleep plays an increasingly well documented role in memory consolidation in
schizophrenia. Correlations of slow-wave sleep deficits with impaired reaction time and declarative memory have also been reported. Thus, both behavioural
insomnia and sleep architecture are critical therapeutic targets in patients with
schizophrenia. However, long-term treatment with
antipsychotics often results in residual sleep dysfunction and does not improve slow-wave sleep, and adjunctive
GABA(A) receptor modulators, such as
benzodiazepines and
zolpidem, can impair sleep architecture and cognition in
schizophrenia.
GABA(B) receptor agonists have therapeutic potential in
schizophrenia. These agents have minimal effect on rapid eye movement sleep while increasing slow-wave sleep. Preclinical associations with increased expression of genes related to slow-wave sleep production and circadian rhythm function have also been reported.
GABA(B) receptor deficits result in a sustained hyperdopaminergic state and can be reversed by a
GABA(B) receptor agonist. Genetic, postmortem and electrophysiological studies also associate
GABA(B) receptors with
schizophrenia. While studies thus far have not shown significant effects, prior focus on the use of
GABA(B) receptor agonists has been on the positive symptoms of
schizophrenia, with minimal investigation of
GABA(B) receptor agonists such as
baclofen or
gamma-hydroxybutyric acid and their effects on sleep architecture, cognition and negative symptoms in patients with
schizophrenia. Further study is needed.