Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection

Abstract

Apathy is a relatively common psychiatric syndrome in HIV infection, but little is known about its neural correlates. In the present study, we examined the associations between apathy and diffusion tensor imaging (DTI) indices in key frontal white matter regions in the thalamocorticostriatal circuit that has been implicated in the expression of apathy. Nineteen participants with HIV infection and 19 demographically comparable seronegative comparison subjects completed the Apathy subscale of the Frontal Systems Behavioral Scale as a part of a comprehensive neuropsychiatric research evaluation. When compared to the seronegative participants, the HIV+ group had significantly more frontal white matter abnormalities. Within HIV+ persons, and as predicted, higher ratings of apathy were associated with greater white matter alterations in the anterior corona radiata, genu, and orbital medial prefrontal cortex. The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current CD4 counts. All told, these findings indicate that apathy is independently associated with white matter abnormalities in anterior, medial brain regions in persons infected with HIV, particularly in the setting of lower current immune functioning, which may have implications for antiretroviral therapy.

Neurobehavioral Disturbances During Acute and Early HIV Infection

“…In chronically HIV-infected groups, neural abnormalities in the nucleus accumbens and frontal cortex are associated with aspects of neurobehavioral disturbances (Kamat et al, 2014; Paul et al, 2005; Hoare et al, 2010). For example, our research group recently reported that higher apathy ratings in a group of chronically HIV-infected persons were associated with greater white matter abnormalities in the anterior corona radiata, genu, and orbital medial prefrontal cortex (Kamat et al, 2014).…”

“…For example, our research group recently reported that higher apathy ratings in a group of chronically HIV-infected persons were associated with greater white matter abnormalities in the anterior corona radiata, genu, and orbital medial prefrontal cortex (Kamat et al, 2014). The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current CD4 cell counts.…”

“…There were no associations with disinhibition. Thus, since frontostriatal regions appear to be particularly vulnerable to neural damage in persons with early AEH (Ances et al, 2009; Lentz et al, 2009, 2011; Young et al, 2014), early HIV-associated neural abnormalities might underlie these individuals’ neurobehavioral disturbances (eg, Bonelli and Cummings, 2007; Kamat et al, 2014). …”

“…Because our participants were relatively young, few had caregivers who could have provided collateral information for informant reports. Still, the construct validity of the FrSBe in HIV-infected cohorts is supported by its relationships with other measures of neurobehavioral disturbance (Marquine et al, 2014) and neuroimaging (Kamat et al, 2014). Moreover, FrSBe data from other groups with frontostriatal system injury show agreement between self- and informant-reported neurobehavioral disturbances (Barrett et al, 2013; Chiaravalloti and DeLuca, 2003; Grace et al, 1997).…”

Neuroimaging as a biomarker in symptom validity and performance validity testing

“…Considerable attention has been directed to how white matter integrity and connectivity are factors in affective disorder (Bracht et al 2014;Nave and Ehrenreich 2014;Ota et al 2014) as well as in disorders where apathy may occur (Kamat et al 2014). Imposing injury either as an emotional trauma that occurs in PTSD or physical trauma related to acceleration/deceleration, blunt force or blast, white matter is vulnerable to injury, ranging from not apparent or minimal (Ilvesmaki et al 2014) to distinctly demonstrable microstructural abnormalities Waljas et al 2014).…”