Schizophrenia subtypes

Histamine produces its pharmacological actions by three subtypes of receptors the postsynaptic Hi and H2 receptors and the presynaptic H3 receptor. The H3 receptor is mainly located in the central nervous system (CNS), where it acts as an inhibitory autoreceptor in the central histaminergic neuronal pathways [176]. A number of therapeutic applications have been proposed for selective H3 receptor antagonists, including several CNS disorders such as Alzheimer s disease. Attention Deficit Hyperactivity Disorder, Schizophrenia, or for enhancing memory or obesity control. 

Another crucial problem for any neurochemical model is cause and effect. Neuroleptics have a high affinity for dopamine receptors, particularly the D2-subtype. There is also a highly significant positive correlation (r > +0.9) between this receptor binding and their clinical potency (Seeman, 1980). But, this does not necessarily implicate elevated dopamine levels as the cause of schizophrenia. Moreover, blockade of dopamine receptors happens very rapidly, whereas clinical benefits are only seen after chronic treatment. Rose (1973) has criticised the reductionist statement that an abnormal biochemistry causes schizophrenia because it relates cause and effect at different organisational levels (namely, the molecular and behavioural). But, while it can be legitimate to discuss cause and effect at the same level that chlorpromazine blocks dopamine receptors (one molecule altering the response of another), it is not valid to infer that increased dopamine activity causes schizophrenia. Put another way ... 

Masellis M, Basile V, Meltzer HY, Lieberman JA, Sevy S, Macciardi FM et al. Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacology 1998 19(2) 123—132. 

Dopamine receptor blocking agents. Many of the neuroleptics used in the treatment of schizophrenia frequently produce parkinsonian symptoms as unwanted effects. Neuroleptics block dopamine receptors and their therapeutic effect seems to be related to this action. Although these drugs act on DA systems without distinction, some are more selective. Thioridazine, clozapine and molindone, for example, have electrophysiological effects in the limbic region of the brain but little action in the nigro-striatal area. This selectivity may be related to receptor subtype specificity (see Chs 12 and 54). 

Mental disorders, for example, multiple subtypes of anxiety, chronic fatigue syndrome, depression, sometimes together with chronic pain, posttraumatic stress disorders (PTSD), and schizophrenia... 

Amphetamine and cocaine psychoses mimic subtypes of schizophrenia, but there is no classic thought disorder and there are no negative symptoms. 

Phencyclidine (PCP) psychosis faithfully masquerades as schizophrenia, though some say it resembles mania. PCP is discovered to block NMDA subtypes of glutamate receptors. Glycine and cycloserine, which stimulate NMDA receptors, are antipsychotic. 

Mattson DT, Berk M, Lucas MD. (1997). A neuropsychological study of prefrontal lobe function in the positive and negative subtypes of schizophrenia. J Genet Psychol. 158(4) 487-94. 

Some first-generation agents, such as haloperidol, are rather specific for one subtype of dopamine receptor, D2. This suggests that some degree of both efficacy and side effects are associated with dopamine antagonism at this receptor. However, the situation is complex, as usual. There are five classes of dopamine receptors known Di through D5. To complicate matters further, several of these classes have subclasses. In total, there are at least 15 dopamine receptors. Which of these is important for relief of the symptoms of schizophrenia Which is responsible for movement disorders The answers to these questions are incomplete. We do have a few hints. 

Mood Disorder with Psychotic Features. One subtype of major depression and many episodes of mania are associated with psychotic symptoms. Like schizophrenia, the most prominent psychotic symptoms of psychotic depression or mania are delusions and auditory hallucinations. Unless a longitudinal history is available, it is often difficult to distinguish schizophrenia from a psychotic mood disorder. 

Dopamine has been implicated in a number of psychiatric conditions of which schizophrenia and the affective disorders are the most widely established. Five major subtypes of dopamine receptors have now been cloned. These are divided into two main groups, and D2 respectively. The receptors consist of Di and D5 types and are positively linked to the adenylate cyclase second messenger system, while the D2 group consists of the D2, D3 and D4 receptors which are negatively linked to the adenylate cyclase system. 

Masellis, M., Basile, V., Meltzer, H.Y., Lieberman, J.A., Sevy, S., Macciardi, EM., Cola, P., Howard, A., Badri, E, Nothen, M.M., Kalow, W., and Kennedy, J.L. (1998) Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacology 19 123-132. 

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