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CNS effects in the correct perspective

The brain's mechanisms may be conceived of as a series of increasingly complex levels, the ®rst or lowest of which are the basal functions. The most basic aspect of brain function that can be measured is simple reaction time (SRT). This takes place at the cortical level ± thus, it is not a re ̄ex ± and has a latency of around 200 ms. It may be fractionated into motor and processing tasks, the latter accounting for the greater part. At the intermediate level of function, a variety of tasks can be performed such as continuous performance tests (CPT) and the classical vigilance tasks, while above this level there is simultaneous capacity. A major theoretic question to be answered is whether these levels are separate elements or are integrated. However, when the individual mechanisms are measured, they form quite high correlations among themselves. For instance, SRT correlates with complex reaction time (CRT) at about 0.7, or approximately 50% shared variance. In addition, SRT correlates with various contingency performance tests, at around 0.5 or 25% shared variance, and also correlates with simultaneous capacity. The tasks at this level do not require intelligence for performance (1). Above these levels are aptitudes which deal with problem solving ± the traditional IQ variables. There are three main modules for problem-solving: the verbal or language-type module, the reasoning or logical module, and the visuospatial module. The ®rst two are located predominantly in the left hemisphere of the brain, while the visuospatial capacity is located mainly in the right hemisphere. In addition to these are the shortand long-term memory functions, which are further subdivided into visuospatial and languageprocessing modes. Short-term memory consists of the ``sketch-pad'' memory, in which an image can be kept for a few minutes if one concentrates, and the phonologic loop memory, in which sequences of verbal material are stored. The long-term memory has a similar organization: the episodic memory is the right hemisphere-type in which the entire setting is remembered, facilitating the retrieval of details at a later date; the semantic memory is that in which simple facts are stored. Finally, and most importantly, above these levels is an executive which is in overall control of the system and directs work to the appropriate effector sections within the brain. It is also the level concerned with self-monitoring, spontaneous fantasies, memories of the past, and awareness of one's future. To date, virtually no work has been undertaken to assess the effects of antihistamines in this area. Much work has been done in recent years on schizophrenia, as it is now recognized to be a dementia disease in which all the above functions deteriorate. Executive function, short-term working memory, continuous performance tasks, and simple reaction time are impaired to the greatest degree. There are a number of anomalies with regard to the use of these drugs in schizophrenia, as most of the drugs are strong antihistamines and are centrally active. It has been observed that neuroleptics can cause epileptic seizures; however, it is not known whether this is dopaminergic or H1-mediated. Sudden deaths are common among schizophrenics, around 1% dying of a suspected cardiac event. The most striking feature of schizophrenics is their enormous tolerance of the sedative effects of neuroleptics. This is in contrast to normal subjects, who become sedated when receiving neuroleptics; some rapidly become habituated to the sedative properties of the drug, whereas others continue to be heavily sedated even on very small doses (2). We are currently looking into the cognitive impairments of schizophrenia but, to date, have no information on antihistamines. The drugs currently classed as second-generation antihistamines are recognized as being highly effective treatments for allergic-based disease and are among the Allergy 2000: 55: 35±39 Printed in UK. All rights reserved Copyright # Munksgaard 2000