**1. Introduction**

82 Neuroendocrinology and Behavior

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Derangement of hormonal milieu has been associated with the pathophysiology of psychiatric illnesses, such as schizophrenia, mood disorders, and developmental disorders [1; 2; 3]. Among them, schizophrenia is a relatively common neuropsychiatric disorder, and has been associated with debilitating consequences if not treated properly [4; 5]. The illness is characterized by positive (e.g., delusions, hallucinations, bizarre thoughts) and negative (blunt affect, avolition, anhedonia, social withdrawal) symptoms, as well as deficits in various cognitive abilities, e.g. verbal memory, working memory, attention/vigilance, and information processing [4; 6; 7]. Minor impairments of social cognition are often observed during the premorbid stage of the disease [8].

The role for endocrinological dysregulation in the development of psychotic symptoms has been suggested by brain imaging studies. For example, a larger than normal volume of the pituitary gland has been reported in patients with first-episode schizophrenia [9] (Fig. 1). Further, these patients exhibit an increase in the pituitary volume overtime, unlike the case with normal volunteers, the degree of which is correlated with the change in positive symptoms [9]. These findings, representing mainly a morphological change of the anterior pituitary [9], are consistent with the concept of HPA axis hyperactivity in response to stress during psychotic experience [10].

Hormones secreted from the posterior portion of the pituitary gland, i.e. vasopressin and oxytocin, have also been a focus in schizophrenia research from the perspective of social behavior disturbances [2; 11; 12]. In this chapter, we provide an overview of preclinical and clinical evidence for contribution of the vasopressin and oxytocin systems in social behavior deficits of schizophrenia and related disorders, as well as their treatment. Related discussions on the role of these neuropeptides in the coping of stressors and psychiatric conditions are provided in other Chapters [3; 13].

© 2012 Sumiyoshi et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Sumiyoshi et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Role for Pituitary Neuropeptides in Social Behavior Disturbances of Schizophrenia 85

**Figure 2.** Arginine-vasopressin in the brain and periphery. Extracted from Frank E and Landgraf R. *Eur* 

Social behaviors comprise various domains, such as social (learning) memory and social bonding [20; 21]. The intracerebroventricular administration of AVP has been shown to facilitate social memory, as measured by the social discrimination test (SDT), in rats [22; 23]. The neural substrates governing the ability of AVP to enhance sociality include the lateral septum (LS), bed nucleus of the stria terminalis, and medial amygdala [24]. Specifically, overexpression of the V1A receptors in the LS enhanced SDT performance, an effect blocked

**3. Sociality deficits in animal models of schizophrenia; Effect of** 

*J Psychopharmacol* 583;226-42, 2008 (Permission obtained from Elsevier)

**neuropeptides** 

**Figure 1.** Sagittal (A) and coronal (B) views of the pituitary gland manually traced (in blue). The pituitary stalk was excluded from the tracings. (Takahashi T et al. *Prog Neuropsychopharmacol Biol Psychiatry* 35;177-83, 2011 (Permission obtained from Elsevier)
