Reduced anterior hippocampal formation volume in hyponatremic schizophrenic patients

Abstract

Diminished hippocampal volume occurs in the anterior segment of some schizophrenic patients, and in the posterior segment in others. The significance of hippocampal pathology in general and these segmental differences in specific is not known. Several lines of evidence suggest anterior hippocampal pathology underlies the life-threatening hyponatremia seen in a subgroup of patients with schizophrenia; therefore our goal was to determine if this region was preferentially diminished in hyponatremic patients. We studied seven polydipsic hyponatremic, ten polydipsic normonatremic, and nine nonpolydipsic normonatremic schizophrenic inpatients, as well as 12 healthy controls. All underwent structural scanning on a high resolution (3.0 T) magnetic resonance imaging (MRI) scanner. Hippocampal formation, amygdala, and third ventricle volumes were manually traced in each subject. The hippocampus was divided at the posterior extent of the uncus, and all structural volumes were corrected for whole brain volume and other significant recognized factors (i.e., age, gender, height, parental education). Despite being overhydrated, anterior hippocampal formation volume was diminished in those with polydipsia and hyponatremia relative to each of the other three groups. Third ventricle volume was larger in this group than in healthy controls but similar to the two patient groups. Posterior hippocampal and amygdala volumes did not differ between groups. Other potential confounds (e.g., water imbalance) either had no effect or accentuated these differences. We conclude the anterior hippocampal formation is smaller in hyponatremic schizophrenic patients, thereby linking an important and objective clinical feature of schizophrenia to a neural pathway that can be investigated in animal models. The findings strengthen the hypothesis that anterior hippocampal formation pathology disrupts functional connectivity with other limbic structures in schizophrenia.

Functional organization of the hippocampal longitudinal axis

“…In addition, the locus of pathology on the long axis is associated with specific cognitive impairments (for example, schizophrenia is associated with anterior hippocampal pathology and with impaired transitive inference [159][160] ) as well as with clinical manifestations of particular diseases. For example, in view of the greater connectivity between ventral (anterior) hippocampus and endocrine hypothalamic nuclei 26 , impaired hormonal regulation by the hypothalamus (such as hyponataraemic polydypsia reported in schizophrenia patients with decreased AH volume [161][162][163] ) may be a common finding in patients with AH damage -this is something that has been relatively under-investigated in medial temporal lobe epilepsy [164][165][166] . Furthermore, given the role of VH 111 -and ventral DG in particular 167 -in models of innate anxiety, this region could prove an important future target for a range of neurotic disorders.…”

Clinical Semiology and Neuroradiologic Correlates of Acute Hypernatremic Osmotic Challenge in Adults: A Literature Review

“…Hippocampal lesions were reported in more than one-third of patients and were associated with higher initial Na ϩ levels. The high hippocampal involvement may be related to its high vulnerability to the neurotoxic effects of osmotic derangements 49 and systemic stresses in general. 50,51 In reviewed cases, contrast enhancement associated with ODS lesions was reported in 1 patient, 23 which has also been reported in some cases of hyponatremia.…”

Neuroendocrine Responses to a Cold Pressor Stimulus in Polydipsic Hyponatremic and in Matched Schizophrenic Patients

“…Patients underwent an MRI scan during the fourth week as part of a related study (Goldman et al, 2005). Psychiatric diagnosis was confirmed at discharge in a multidisciplinary conference and relied largely on the Structured Clinical Interview for DSM-IV (Spitzer et al, 1992).…”

“…Thus this segment of the hippocampus normally constrains AVP and ACTH responses to psychological stress (Herman et al, 1995(Herman et al, , 2005Mueller et al, 2004;Nettles et al, 2000); the findings in patients are recreated in an animal model of schizophrenia, which disrupts the neurodevelopment of this brain region (Mitchell and Goldman, 2004); and this subset of patients exhibits diminished anterior hippocampal volume (Goldman et al, 2005) as well as other impairments indicative of hippocampal-mediated neuroendocrine dysfunction (Goldman et al, 2006). Finally, our unpublished data demonstrate a significant association between anterior hippocampal volume and the cold pressor AVP response in hyponatremic polydipsic patients (r ¼ À0.825, p ¼ 0.022).…”

“…Diminished volume of the anterior hippocampus is particularly prominent in schizophrenic patients with polydipsia and hyponatremia (Elkashef et al, 1996;Luchins et al, 1997;Goldman et al, 2005). About 20% of schizophrenic patients drink excessive amounts of water ('primary polydipsia') and about 20% of these retain enough of this excess water to produce a dilutional hyponatremia (de Leon et al, 1994).…”