The glutamate hypothesis of schizophrenia based on the observations that administration of drugs that block N-methyl-D-aspartate (NMDA) glutamate receptors could induce schizophrenia-like symptoms. There are several evidences linking abnormal glutamatergic transmission to cognitive, negative, and positive symptoms of schizophrenia and the glutamatergic system is now a major focus for the development of new compounds in schizophrenia. The polyamines are omnipresent aliphatic molecules comprising putrescine, spermidine, spermine and agmatine. The polyamines and their biosynthetic enzymes are found throughout the body, including the central nervous system (CNS), where they display specific regional distributions in the CNS. The polyamines have an important role in the modulation of cell growth and on cell membrane functions. It was hypothesized that schizophrenia may be related to a general abnormality in neuronal membranes. Agmatine, a polyamine, selectively blocks the NMDA subclass of glutamate receptors in rat hippocampal neurons. There are also several evidences indicate that a relationship between polyamines and etiopathogenesis of schizophrenia. In this review, a new approach for understanding schizophrenia via NMDA receptors and their interaction with agmatine which is a biological active polyamine transmitter in brain is proposed.

Polyamines, including spermidine, spermine, and agmatine, serve several brain-specific functions. Polyamine transport mechanisms may account for the redistribution of these organic cations, which may also be synaptically released as neuromodulators or neurotransmitters, in the brain. Therefore, the localization of polyamine pathway enzymes, in addition to the localization and functional investigation of the polyamines itself, provides valuable insights regarding the identification of cell- and region-specific roles for polyamines, notably in the context of mental disorders and neurodegenerative diseases. Identified neuronal circuits are subject to physiological and pharmacological investigations. With this respect, we electrophysiologically studied the cerebellar cortex and the medial habenula, showing a prominent synaptic expression of spermidine synthase and agmatinase, respectively. In both areas, the relevant polyamines clearly influence the electrical activity. The medial habenula may be involved with the aetiology of major depressive disorder. In this context, the expression of agmatinase in other brain areas, e.g. the paraventricular thalamic nucleus, possibly also involved with depression, is discussed.

Blood injury injection phobia (BII) involves an intense fear of situations, in which an individual is directly or indirectly exposed to blood, injections or viewing injuries, along with a tendency to avoid these situations. BII phobia is highly prevalent in females as compared to males. It is virtually the only specific phobia and the only anxiety disorder, in which fainting occurs. Although fainting is much distressed to the BII phobic individuals, but it may have developed in the humans at the time when they needed it much as a survival mechanism. In this article we discuss how in the humans there may have developed the trait of BII phobia in the ancestors, including the variation in the symptoms among sexes. There are not studies which specifically examine the syncope related brain differences among genders. But there are other well defined studies which highlight marked differences among male and female brains. Considering this we also review some recent breakthrough discoveries showing differences in the brain of males and females at gene expression level which leads to the variation in brain and behaviour related problems among genders. There is an exigent need to understand the brain behavioral problems through multiple perspectives.