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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Hepatitis C virus (HCV) infection is a major public-health-care problem, with over 170 million infected worldwide. Patients with chronic HCV infection often complain of various cognitive problems as well as symptoms of depression, anxiety, and fatigue. Relatively little is known, however, about the specific cognitive deficits that are common among HCV patients, and the influence of psychiatric symptomatology on cognitive functioning. In the current study of 21 chronically infected HCV patients, we assessed subjective cognitive dysfunction, depression, anxiety, and fatigue and compared these symptom areas to cognitive tests assessing visuoconstruction, learning, memory, visual attention, psychomotor speed, and mental flexibility. Results revealed that cognitive impairment ranged from 9% of patients on a visuoconstruction task to 38% of patients on a measure of complex attention, visual scanning and tracking, and psychomotor speed, and greater HCV disease severity as indicated by liver fibrosis was associated with greater cognitive dysfunction. Objective cognitive impairment was not related to subjective cognitive complaints or psychiatric symptomatology. These findings suggest that a significant portion of patients with chronic HCV experience cognitive difficulties that may interfere with activities of daily living and quality of life. Future research using cognitive measures with HCV-infected patients may assist researchers in identifying if there is a direct effect of HCV infection on the brain and which patients may be more likely to progress to cirrhosis and hepatic encephalopathy.

The California Verbal Learning Test was used to characterize the learning and memory impairment in schizophrenia (SC) and to evaluate potential clinical and demographic factors associated with this impairment. SC patients (n= 175) performed worse than normal comparison (NC) subjects (n= 229) on all learning, recall, and recognition memory measures. The most important clinical correlates of these impairments were earlier age of onset, more negative symptoms, and greater anticholinergic medication dosage. SC patients showed a prominent retrieval deficit as indicated by disproportionate improvement when tested in a recognition, rather than a free recall, format. A residual impairment seen with recognition testing suggests a mild encoding deficit as well. In contrast, the relative absence of a storage deficit is suggested by the lack of rapid forgetting. Using a discriminant function analysis that differentiates cortical dementia [i.e., Alzheimer's disease (AD)], subcortical dementia [i.e., Huntington's disease (HD)], and normals, it was found that 5070 of the SC patients were classified as having a subcortical memory profile and 35% were classified as having a normal profile, whereas only 15% were classified as having a cortical memory profile. Although these findings reflect the clinical heterogeneity often found in SC, results suggest that most SC patients demonstrate a pattern of learning and memory impairments that resembles the pattern seen in patients with primary subcortical (specifically striatal) pathology. (JINS, 1995,I, 88–99.)

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