Individuals infected with HIV had elevated levels of anxiety, depression, apathy, and irritability and experienced decrements in dual-task performance. The effect size for the presence of the psychiatric symptomatology was consistently in the moderate range, and the effect size for dual-task decrements was more subtle, although significant. Apathy and irritability, but not depression and anxiety, were associated with declines in dual-task performance and, thus, may be associated with the frontal–subcortical systems dysregulation observed in HIV.
Although the dual-task paradigm has been consistently found to be sensitive to frontal–subcortical systems, it was the only probe of frontal–subcortical systems used in the current study. However, these findings are consistent with other studies that used frontal–subcortical systems-dependent tests investigating cognitive flexibility, Stroop interference, working memory, and a different form of dual-task performance, each finding a similar relationship between performance on these tasks and the presence of apathy and/or irritability symptomatology (Castellon et al., 1998
; Paul et al., 2005a
). The current study furthered this work by providing a direct comparison of apathy and irritability with anxiety and depression and by quantifying the extent to which apathy and irritability share predictive variance with dual-task performance. Depression and anxiety uniquely accounted for 0.9% of variance in dual-task performance, while apathy and irritability uniquely accounted for 3.4% variance (which was more than the combined demographic variables of age, sex, ethnicity, and years of education).
Given the nominal relationship of depression and anxiety with dual-task performance, it is unlikely that these psychiatric features are associated with frontal–subcortical dysfunction in HIV-infected individuals. It is possible that depression and anxiety symptomatology may relate to other neural systems affected by HIV that were not measured in the current study, although other work evaluating primary neuropsychological domains have thus far not found that to be the case (Castellon et al., 1998
; Grant et al., 1993
; Hinkin et al., 1992
; Mapou et al., 1993
; Perdices et al., 1992
; Rabkin et al., 2000
). Alternatively, these psychiatric features may be more related to psychological and psychosocial factors (Perdices et al., 1992
Potential limitations of this study include the cross-sectional design. It cannot be ruled out that some of the psychiatric symptoms and/or frontal–subcortical system dysregulation could have predated HIV infection as these symptoms could lead to an increased risk of contracting HIV. Also, while it is possible that poor performance on neuropsychological testing could have unduly influenced the self-report psychiatric measures that followed, it is not anticipated that adverse reaction to neuropsychological performance would differentially influence apathy and irritability versus anxiety and depression. Another potential limitation is that the psychiatric symptoms predicted to be associated with frontal–subcortical systems were measured with same instrument (i.e., NPI) and that the psychiatric symptoms predicted to not be associated with frontal–subcortical systems were also measured with the same instrument (i.e., Beck), which could introduce measurement error into the tested hypothesis.
The coexistence of the psychiatric symptoms of apathy and irritability is not a symptomatology profile unique to HIV infection, as it has been observed in other patient populations in which frontal and/or subcortical systems are disrupted (i.e., AD, Huntington’s disease, and Parkinson’s disease). For instance, the psychiatric symptoms of apathy and irritability in AD are thought to be generated by frontal lobe dysfunction (Cummings, 1997
), and decrements in dual-task performance are also present (Della Sala et al., 1995
). Even though AD pathology is primarily cortical while HIV is more subcortical, the symptomatology overlap between AD and HIV infection lends further support to frontal systems involvement in prominent apathy and irritability in HIV-infected individuals. Along these lines, it is of interest that cholinomimetic therapy in AD patients has been found to ameliorate symptoms of apathy and irritability (Cummings, 1997
) as this treatment might prove efficacious for treatment of these psychiatric symptoms in HIV-infected individuals.
The introduction of HAART has substantially improved the survival of individuals infected with HIV and reduced the severity of both cognitive and psychiatric symptoms experienced. However, individuals continue to experience significant CNS disturbances. Recent evidence provided by Thompson et al. (2005)
demonstrated the impressive extent to which HIV exerts deleterious effects on the CNS, even during successful HAART treatment. The authors reported several brain regions to be reduced as much as 15% in volume. Findings from the current study and others (Castellon et al., 1998
; Paul et al., 2005a
) converge on not only neuropsychological functioning as a representative biomarker of HIV effects on the CNS, but also the possibility of using psychiatric features such as apathy and irritability. These neuropsychological and psychiatric biomarkers will be necessary gauges for the success of experimental neuroprotective therapies (e.g., memantine, N
-methyl-D-aspartate receptor antagonists, and CPI-1189) for individuals infected with HIV.