Transmitter dysfunction during the process of schizophrenia.
Transmitters that are primarily or secondarily involved in the pathogenesis of schizophrenia have been extensively studied for many years. This review will focus on the transmitter systems that are known to be directly or indirectly involved in the mode of action of the novel atypical antipsychotics and clozapine, i.e. the dopaminergic, serotonergic and glutamatergic systems. The consequences of transmitter dysfunction for perception and for the ability of the individual to adapt to a constantly changing environment are discussed, and a hypothesis that can explain how a primary cortical defect will progressively involve secondary transmitter dysfunction and spontaneous dopaminergic sensitization is proposed. According to the suggested hypothesis for the pathogenesis of development of schizophrenic symptoms, pharmacological treatment strategies should focus on flexible as opposed to rigid modulation of sensorimotor gating. The hypothetical effects of serotonergic and dopaminergic interactions on sensorimotor gating are illustrated, and the implications of the broader receptor profile of atypical antipsychotics for the reduced capacity to induce extrapyramidal side-effects and the supposedly superior effect on cognitive dysfunction and negative symptoms are discussed.
Glenthøj
B Y
BY
Department of Psychiatry, University Hospital Bispebjerg, Copenhagen, Denmark.
Hemmingsen
R
R
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D003342:Corpus Striatum / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D008032:Limbic System / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000502:physiology*; D017397:Prefrontal Cortex; D012095:Repression-Sensitization; D012559:Schizophrenia / Q000503:physiopathology*; D012684:Sensory Thresholds / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D013702:Temporal Lobe / Q000503:physiopathology; D013788:Thalamus / Q000503:physiopathology
D018377:Neurotransmitter Agents; D012701:Serotonin; D018698:Glutamic Acid; D004298:Dopamine