Context Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, raising the question of whether they are in fact the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these two disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. Objective We used a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM), to quantify exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Design Static group comparison. Setting Psychiatric hospital. Participants 15 bipolar mania and 16 schizophrenia subjects were compared to 26 healthy volunteers in the human BPM. The effects of amphetamine, the selective dopamine transporter (DAT) inhibitor GBR12909, and genetic knockdown of the DAT were compared to controls in the mouse BPM. Measures The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Results Bipolar manic subjects demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Schizophrenia subjects did not show the expected habituation of motor activity. Selective genetic or pharmacological inhibition of the DAT matched the mania phenotype better than the “gold standard” model of mania (amphetamine). Conclusion These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to identify neurobiological underpinnings of neuropsychiatric disorders.

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Hepatitis C is the most common cause of chronic liver disease in the United States and it significantly reduces quality of life. The role of cognitive deficits contributing to the morbidity of this disease has not been well characterized. The purpose of this study was to examine cognitive functioning in patients with chronic hepatitis C and to investigate relationships among parameters of disease severity and performance on neuropsychological tests. Sixty-six patients with chronic hepatitis C and 14 patients with other chronic liver diseases were administered a brief battery of neuropsychological tests assessing attention, visuoconstructional ability, learning, memory, and psychomotor speed. Cognitive impairment in patients with chronic hepatitis C ranged from 0% on a visuoconstructional task to 82% on a measure of sustained attention and concentration. Test scores of patients with chronic hepatitis C did not differ from those of patients with other chronic liver diseases. Hence, patients with and without chronic hepatitis C experience cognitive deficits, especially in tasks requiring attention and psychomotor speed. In addition, there was a significant relationship between fibrosis stage and test performance, with greater fibrosis associated with poorer performance. However, both patients with and without cirrhosis exhibited cognitive dysfunction. In conclusion, these findings suggest that progressive hepatic injury may result in cognitive problems even before the development of cirrhosis. Future studies need to determine the effect of this decrease in cognitive function on quality of life. T he hepatitis C virus (HCV) is the most common cause of chronic liver disease in the United States and the leading indication for liver transplantation. 1 According to a population-based study conducted from 1988 to 1994, an estimated 2.7 million individuals are currently infected with HCV. 2 The proportion of HCV-infected patients with cirrhosis is expected to increase from the 15.6% noted in 1988 to an estimated 28.9% by 2018. 3 Increases of 84% and 63% are expected in the rates of hepatic decompensation and hepatocellular carcinoma, respectively, and deaths related to HCV are expected to triple over the next 2 decades. 3 Multiple studies have revealed that infection with HCV significantly reduces quality of life (QOL), even in the absence of cirrhosis. 4,5 Currently, there is no clear explanation for this reduction. Koff 6 suggested that pathophysiological events resulting from infection may be contributing to decreased QOL in HCV-infected patients. This decrease may be related to the impact of HCV infection on cognitive abilities, such as attention and memory functioning. In patients with cirrhosis and end-stage liver disease, neuropsychological impairment has been well documented. 7,8 These deficits have been attributed to molecules and toxins accumulating in the blood that are not effectively cleared by the cirrhotic liver. In patients with HCV infection, it often takes more than 20 years of chronic hepatic injury bef...

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