Central nervous system disorders psychoses

The 5-HT3 receptors are found in both the peripheral nervous system and central nervous system (CNS), where they mediate last synaptic transmission at synapses (3). In the CNS, they are located predominantly at intemeurones, where they modulate the release of a range of neurotransmitters (4-9). There is some evidence that 5-HT3 receptors play roles in brain reward mechanisms and in neurological phenomena such as anxiety, psychosis, nociception, and cognitive function (10,11), and in the first few years following the discovery of these receptors, there was also much interest in the therapeutic potential of 5-HT3 receptor antagonists for antipsychotic, antinociceptive, and other psychiatric disorders (12-15). This potential has not yet been realized, but there is still active research in this area (16), and their current major therapeutic target is against emesis in cancer chemotherapy and irritable bowel syndrome (17,18). 

Central nervous system. Depression and psychosis can occur during the first few days of high dose administration, especially in those with a history of mental disorder. Other effects include euphoria, insomnia, and aggravation of schizophrenia and epilepsy. Long-term treatment may result in raised intracranial pressure with papilloedema, especially in children. 

Central nervous system adverse effects are common with felbamate, and consist mainly of insomnia, headache, impaired concentration, ataxia, dizziness, somnolence, behavioral disturbances, and mood changes. Movement disorders, psychosis, increased seizures, status epilepticus, and withdrawal seizures are less common (SEDA-19, 67) (SEDA-20, 61). The incidence of these effects is increased in the elderly, possibly owing to reduced drug clearance (4), whereas patients with mental retardation may be more prone to behavioral disorders (SEDA-19, 68). 

Irritability and aggressive behavior occur occasionally, and mentally retarded patients are possibly at greater risk (SEDA-22, 88). Rare central nervous system effects include insomnia, psychosis (SEDA-20, 63), downbeat nystagmus (SEDA-22, 89), movement disorders (SEDA-21, 72), and a Tourette-like syndrome. Lamotrigine can increase seizure frequency and severity in children with severe myoclonic epilepsy (SEDA-21, 72). 

Inborn errors of folate metabolism also shed light on the role of folates and products of folate metabolism in neurological function. Disorders that result in decreased levels of 5-CH3-THF in the central nervous system are frequently associated with development of seizures e.g. MTHFR deficiency, DHFR deficiency, MTHFDl deficiency, and autoimmune or genetic cases of cerebral folate deficiency due to malfunction of folate receptor alpha). Adult onset cases of MTHFR deficiency have in some cases been associated with psychosis. 

Psychiatric disorders must be considered to have a biochemical basis. Psychosis, neurosis, mental retardation, and behavior problems must, in the last analysis, be complex manifestations of some aberration of biochemical functioning of the central nervous system. Fig. 3 diagrams how one may conceptualize mental function in terms of intermediary metabolism. Mental function can be expressed in terms of an individual s intelligence, personality, and patterns of behavior. These outward manifestations of mental function can be considered to be complex expressions of consciousness (self-awareness), sensory perception (awareness of reality of the outside world), volition (decision making), memory, learning, creative ability (problem solving), and emotional reactivity (which is partially subconscious). All of these components are some function of the nerve network. How the nerve network gives rise to these components is unknown. It is apparent from... 

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