Faculty Mentor(s)

Dr. Leah Chase, Neuroscience; Dr. Andrew Gall, Psychology

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Event Date



Bipolar disorder is a neuropsychiatric disease characterized by cyclical fluctuations of mood states between mania and depression. Circadian rhythm abnormalities and inconsistent sleep patterns are two common symptoms of bipolar disorder (Millar, Epsie, & Scott, 2004). Elevated levels of homocysteine, in the blood or cerebrospinal fluid, commonly occurs in patients with neuropsychiatric illnesses, including bipolar disorder (Bell et al., 1992; Boushey, Beresford, Omenn, & Motulsky, 1995). Homocysteic acid (HCA), an endogenous metabolite of homocysteine, has been implicated as a harmful neurotoxin and agonist of NMDA receptors. We have previously shown that postnatal administration of HCA (from postnatal day 3-21) in Sprague Dawley rats results in both mania-like and depressive-like behaviors, suggesting that this may serve as a novel animal model for bipolar disorder. The purpose of the present study was to characterize any circadian abnormalities that may be present in HCA-treated rats, as sleep and circadian dysfunction are common symptoms of bipolar disorder. In addition, we also characterized the developmental onset of the mania-like and depressive-like behaviors in this model. Prior to puberty, we found that HCA-treated rats exhibited no manic-like behaviors and only a trend toward depressive-like behaviors. After puberty, however, HCA-treated rats presented a mixed mood-state of both manic-like and depressive-like behaviors, along with significant dysfunction in the circadian clock. Specifically, both the free-running period and the amplitude of the rhythm were significantly reduced following HCA treatment. We are currently using microarray analyses to determine differences in circadian gene expression levels between HCA treated animals and controls. Additionally, we are examining the therapeutic role of lithium for reversing the circadian disruptions exhibited by the HCA-treated animals. Altogether, the findings of the present study provide strong evidence in support of the HCA model’s face validity for bipolar disorder, allowing us to better understand the mechanisms underlying the development of this disease.


This research was generously supported by the Jacob E. Nyenhuis Grant for Faculty-Student Collaboration and by the Towsley Scholars Research Award at Hope College.