[Cholinergic hypothesis in psychosis following traumatic brain injury and cholinergic hypothesis in schizophrenia: a link?].

INTRODUCTION While traumatic brain injury is a major public health issue, schizophrenia-like psychosis following traumatic brain injury is relatively rare and poorly studied. Yet the risk of developing schizophrenia-like psychosis after traumatic brain injury is 3 times more important than in the general population. LITERATURE FINDINGS Risk factors associated with onset of psychosis after traumatic brain injury include: left hemispheric lesions, closed head injury and coma of duration superior to 24 hours. Most patients develop symptoms of psychosis after a moderate to severe traumatic brain injury and often have lesions of the frontal and temporal lobes. CHOLINERGIC HYPOTHESIS: ARGUMENTS Neuropathologic, electrophysiological and pharmacologic evidence show that cognitive impairment including attention, memory and executive functioning impairment may be related with cholinergic dysfunction in patients with traumatic brain injury. The cholinergic hypothesis is also incriminated in the genesis of schizophrenia. The same biochemical disorders found in schizophrenia which imply many neurotransmitters are often present immediately after traumatic brain injury. However in chronic cognitive disorders secondary to traumatic brain injury, the cholinergic system alone seems to be specifically implied. This is due to the fragility of the cholinergic fibres and a chronic yet reversible reduction of the cholinergic reserves after traumatic brain injury. Cholinergic function can be studied by the P50 evoked response to paired auditory stimuli.While this is disturbed in patients presenting with cognitive impairment after traumatic brain injury its normalisation can be obtained after administration of an acetylcholine esterase inhibitor. In schizophrenic patients there is also an abnormal P50 evoked response due in part to a low number of alpha 7 nicotinic receptors which are implicated in sensory filtering in the frontal lobe. Moreover in schizophrenia, post-mortem studies show a negative correlation between the activity of acetylcholine transferase in the parietal cortex and the severity of the cognitive deficits, as well as a lesser density of the muscarinic M1 and M4 receptors in the frontal lobe. The lower concentration of M1 receptors in the frontal cortex is correlated with the severity of the positive symptoms. THERAPEUTICAL PERSPECTIVES: Antipsychotics have emerged as the first line treatment of psychotic disorders. In research, their ability for enhancing cognitive function could result in the increase of acetylcholine in the medial prefrontal cortex. Acetylcholinesterase inhibitors have been widely used for treatment of cognitive impairment in Alzheimer's disease. Galantamine could be interesting in schizophrenia and psychosis following traumatic brain injury because it has a dual mechanism of action: selective competitive inhibition of acetylcholinesterase and allosteric potentialisation of nicotinic receptor response. Therefore Galantamine remains active in nicotine addicted schizophrenic patients who may smoke as an auto treatment. Galantamine has shown efficacy in adjunction to Risperidone in one patient presenting with psychosis following traumatic brain injury and in 3 case reports of schizophrenic patients. CONCLUSION Further systematic studies are needed to confirm this hypothesis.