Schizophrenia affects about 1% of the population worldwide , and induces neuropsychological impairment , as well as structural brain changes . Among the many comorbidities associated with schizophrenia, polydipsia is defined as either chronic or intermittent ingestion of large volumes of water. Polydipsia occurs frequently among patients with schizophrenia and may be present in more than 20% of chronic psychiatric inpatients . Polydipsia is not explained by medically induced polyuria, but it may lead to hyponatremic symptoms and can cause neurological symptoms. These neurological symptoms include: nausea, vomiting, delirium, ataxia, seizures, and even death, and are often referred to as “water intoxication” . Up to 5% of chronic inpatients develop water intoxication, although mild cases may go undetected .
Neuroendocrine studies revealed that schizophrenia patients with hyponatremia secreted excess antidiuretic hormone (ADH) in a hypo-osmolemic serum state [5, 6]. ADH controls the reabsorption of water molecules in the tubules of the kidneys and plays a key role in the regulation of water. Therefore, excessive ADH secretion may accelerate a hyponatremic state and produce water intoxication [6, 7]. The pathophysiology of polydipsia on the other hand remains to be elucidated.
Previous imaging studies indicate the brains of polydipsic hyponatremic schizophrenia patients present with volume reductions in the anterior medial temporal lobe [8, 9], especially in the anterior hippocampus relative to nonpolydipsic schizophrenia using region of interest (ROI) analysis . Indeed, one study reported that polydipsic, hyponatremic schizophrenia patients exhibited bilateral inward deformations in the anterior lateral hippocampal surface . However, structural differences in other brain regions of these polydipsic hyponatremic schizophrenia patients were not assessed. Interestingly, hyponatremic patients presented with poorer neuropsychological functioning compared to patients without a water imbalance [12–15]. Polydipsic hyponatremic schizophrenia patients scored lower on the Mini-Mental State Examination (MMSE)  with significant impairments in visual memory and information processing , intelligence, learning/memory, and facial discrimination  compared to control patients. Thus, it is considered that the structural changes in the anterior hippocampus, as well as in the associated prefrontal/limbic brain regions contribute to the underlying pathophysiology in polydipsic hyponatremic schizophrenia [11, 15]. To our knowledge, these brain regions have not been examined using voxel-based morphometry (VBM)  in polydipsic schizophrenia patients. VBM is an efficient whole brain unbiased technique capable of analyzing structural magnetic resonance images (MRI), such as the differences between brains of schizophrenia patients with or without water imbalances. Lastly, previous studies  have not evaluated executive functions, which are impaired in schizophrenia [17–20], nor have they included healthy control subjects.
To assess the pathophysiology of polydipsic schizophrenia (PS), we used the VBM approach and evaluated neuropsychological function, including executive functions, to compare the difference between PS, nonpolydipsic schizophrenia (NS) and healthy controls (HC). In the VBM analysis, the main aim of this study was to compare brain structural volumes between PS and NS. As a preliminary exploration, we also compared PS with HC.