Recent studies have shown that a proportion of HCV+ individuals have mild cognitive impairment, including impairment on tests designed to assess frontal systems (Cordoba et al., 2003
). Despite these findings, no study has examined self-reported behavioral symptoms, as measured by the FrSBe among individuals with HCV. Results from the present study show that HCV+ individuals endorse greater levels of overall behavioral symptom disruptions, as well as impairments in the domains of apathy, disinhibition and executive dysfunction as compared to individuals without HCV. These medium effects were found in the absence of traditionally confounding variables such as HIV infection, current substance abuse or dependence, and current major depressive disorder.
Across all subscales, a significantly higher proportion of HCV+ individuals had clinically elevated T-scores, however, apathy was the only FrSBe subscale to be clinically elevated at a group level among HCV+ participants. Indeed, only 38.4% of HCV+ individuals reported clinically elevated behavioral symptoms on the FrSBe total, while 44.1% reported elevated apathy symptoms, 32.4% reported elevated disinhibition symptoms, and 38.2% reported elevated executive dysfunction symptoms. Although only a subset of HCV infected individuals reported clinically elevated behavioral symptoms, the proportion of HCV+ individuals classified as having elevated FrSBe T-scores on apathy was three times that of HCV− individuals and over twice as many HCV+ individuals were classified as having clinically elevated FrSBe T-scores on disinhibition and executive dysfunction as HCV− individuals. These results suggest that a subset of HCV-infected individuals may experience more difficulties initiating spontaneous behaviors, may have more irritability and emotional lability, and may have problems with the planning and execution of self-generated activities. The current study design does not allow us to determine whether the observed behavioral disruptions are HCV-induced or whether they were pre-existing among persons who became HCV-infected. For example, it has been shown that a high proportion of HCV+ individuals met criteria for substance abuse and dependence (Abou-Saleh & Foley, 2008
), which in turn has been shown to affect frontal systems (Garavan & Stout, 2005
). Moreover, individuals with substance abuse disorders have been shown to report clinically elevated behavioral symptoms (Verdejo-Garcia, Rivas-Perez, Lopez-Torrecillas, & Perez-Garcia, 2006
). Nonetheless, clinicians should be aware that behavioral disruptions occur more frequently among HCV+ persons as compared to those without HCV infection.
In terms of neuropsychological functioning, a significantly greater proportion of HCV+ individuals were considered neuropsychologically impaired than HCV− individuals. These findings are consistent with the literature on neuropsychological functioning in HCV, which shows that neuropsychological deficits are present in about a third of the HCV+ individuals even in the absence of greater liver disease (e.g., Cherner et al., 2005
; Ryan et al., 2004
). Our findings are consistent with those of the McAndrews et al. (2005)
, who found the severity of overall NP impairment among HCV+ individuals to be generally mild.
These data also revealed that neuropsychological impairment was associated with elevated FrSBe T-scores. Within the HCV+ group, a cognitive summary score was related to self-reported difficulties with FrSBe executive dysfunction T-scores and overall FrSBe T-scores. Although correlation coefficients were relatively small (possibly due to differences in mode of ascertainment and measure content), these correlations were nonetheless significant. When accounting for all factors, however, neuropsychological impairment was not a significant predictor of FrSBe scores above and beyond other factors (e.g., HCV status, age). One possible explanation for our study findings is that HCV disrupts prefrontal systems, and leads to the self-reported behavioral problems reported herein. Alternatively, it could be that persons with HCV infection have pre-existing behavioral symptoms such as differences in personality, temperament, sensation seeking, and anxiety as compared to HCV negative individuals. For example, individuals that are highly disinhibited tend to engage in risky behaviors (e.g., sharing needles to inject drugs, having sex without protection), which could have led them to contract HCV infection. Due to the cross-sectional nature of the present study, we are unable to determine whether HCV drives behavioral disturbance or whether these factors are pre-existing among individuals who contract HCV.
Findings from this study also suggest that age is associated with elevated FrSBe T-scores, especially with apathy. This finding is consistent with the literature on apathy, which has reported that apathy is a common disorder among older individuals (Marin, 1990
). However, the aforementioned findings have been reported mostly among people 50 and older. Since our cohort is relatively young (age mean: 44.1, SD: 11.6) with only 31.8% over the age of 50, we believe it is unlikely that the self-reported FrSBe apathy T-scores are due to the aging process alone. Supporting this argument is the fact that HCV remained a significant independent predictor of apathy after controlling for age.
Similar to the findings in Vigil et al. (2008)
, HCV+ individuals were significantly more likely to be dependent on instrumental activities of daily living than HCV− individuals. FrSBe T-scores of apathy, executive dysfunction and total subscales were significantly higher among those individuals that were dependent on IADLs, regardless of HCV status (as a clarification note, this study’s cohort is different from Vigil’s 2008
cohort). Our finding is consistent with previous studies on HCV+ individuals, which reported significant declines in health related quality of life in HCV (Cordoba et al, 2003
; Hussain et al., 2001
). Our findings indicate that individuals with elevated FrSBe T-scores are at a higher risk for everyday functioning difficulties and points to the need to identify this possibility in clinical evaluations.
Several limitations of the present study must be acknowledged. The sample size of the present study is relatively small; however, our sample size is comparable to previously published studies examining cognitive and daily functioning deficits in HCV. Furthermore, our sample represents a carefully screened cohort of HCV infected individuals that excluded persons with several other comorbidities known to affect the frontal cortex (e.g., HIV, current and past methamphetamine dependence, current major depressive disorder). More importantly, this is the first study that examines the association between HCV and behavioral symptoms as measured by the FrSBe.
Another potential limitation of the present study is that the FrSBe was initially designed for neuropsychological conditions with distinct neurological onsets (e.g., Traumatic Brain Injury) and the lack of an acute onset in HCV may limit the usefulness of the FrSBe in this population. Despite this weakness, we still observed significant group effects by HCV status. We also recognize that the FrSBe, as well as the ADL scale, are self-report measures, and that spurious correlations are possible due to inaccurate or inflated self report. Given the relatively mild neurocognitive impairment in this group and the fact that we excluded individuals with major depressive disorder makes this possibility less likely. Also, no other collateral measure, such as the FrSBe caregiver report, was administered. This limitation could have affected our results in the sense that HCV+ individuals could have either maximized or minimized their current behavioral symptoms. Findings from Batistuzzo and colleagues (2009)
, suggest that symptom minimization is more likely since they reported significant differences between the FrSBe self-report form and the Family form, where individuals with a diagnosis of refractory obsessive compulsive disorder scored significantly lower on each of the self-report form subscales as compared to the Family report subscales. However, future studies using the FrSBe should strongly consider administering a collateral form, such as the caregiver form, since self-report could be affected by the very own disruption of frontal systems resulting in an individual’s poor insight into his/her condition. Also, other measures of frontal dysfunction such as the Neurospychiatric Inventory (Cummings, et al, 1994
) and/or the Frontal Behavioural Inventory (Kertesz, Davidson & Fox,1997
) may prove useful in HCV+ cohorts.
Additionally, we only report “current” FrSBe ratings and not “before the illness” ratings because it can be very difficult for HCV+ individuals to clearly identify the symptoms as being present “before” or “after” the insidious onset of HCV symptoms. We acknowledge that the use of “current” FrSBe ratings does not allow us to directly attribute these behavioral problems to HCV infection. As such, FrSBe elevations may reflect a variety of different pre-existing influences, including sensation seeking, anxiety, and mild mood disturbances. Finally, it is important to acknowledge that the FrSBe has been normed on a Caucasian population. Since our population is not exclusively Caucasian, the results of this study need to be interpreted with caution.
Overall, these findings highlight the presence of higher levels of self-reported behavioral symptoms among HCV+ persons as compared to HCV− persons as well as clinically significant elevations in apathy. Elevations in self-reported FrSBe T-scores could compromise an individual’s ability to function and live independently, and our results suggest that HCV+ individuals with elevated FrSBe T-scores appear to have increased difficulties in activities of daily living as compared to comparable HCV− individuals. This is important for both clinicians and family members because behavioral problems can be more distressing to caregivers than cognitive deficits (Allegri, et al, 2006
). The exact etiology of behavioral symptoms among HCV+ persons is unclear. Regardless of whether these symptoms are preexisting among HCV+ persons or whether they develop as a result of the neurovirulence of HCV, behavioral symptoms appear to impact everyday functioning. The possibility that a significant proportion of HCV+ persons may have elevated behavioral symptoms regardless of the ultimate etiology seems useful for clinicians working with this population. Future studies examining behavioral symptoms in HCV would benefit from a prospective design, collateral reports of behavioral symptoms, and multimodal assessments to help tease apart the role of pre-existing conditions as compared to processes attributable to HCV.