We examined alexithymia in asymptomatic individuals with HIV and its relation to cognition, mood, and quality of life. First, we found HIV-related changes in multiple cognitive domains in the early, asymptomatic stage of the disease. The affected domains included attention, executive function and visuospatial function, which is reflective of frontostriatal and parietal dysfunction associated with HIV. Second, HIV+ participants were significantly more alexithymic than the HIV− group, implicating disruption of specific fronto-striatal neural pathways. The extent of alexithymia and two of its processing components (Factor 2, DDF, and Factor 3, EOT), but not depression, significantly correlated with performance on neuropsychological measures of attention, executive and visuospatial function, which are the cognitive domains associated with fronto-striatal pathology. Third, the HIV+ group showed higher apathy ratings than HIV− participants. While there was a significant association between apathy and alexithymia ratings, apathy level correlated with only a single aspect of cognition (spatial working memory). Further analyses revealed correlations between two alexithymia factors (DIF and DDF) and apathy. Finally, we found that alexithymia ratings in HIV were associated with multiple aspects of quality of life, particularly for the categories of cognitive functioning, general health, and health distress.
Recent HIV and alexithymia research has implicated common affected brain areas, such as prefrontal cortex and ACC. We hypothesized that alexithymia may be secondary to (or concurrent with) HIV because of the disruption of frontostriatal circuitry in HIV. The prediction was that there should be a correlation between extent of alexithymia and cognitive dysfunction associated with these brain areas, including attention, executive function, and visuospatial processing. Our results supported this hypothesis by demonstrating a significant association between severity of alexithymia (TAS-20) and performance on the predicted subset of neuropsychological measures. To our knowledge, this is the first study that has related alexithymia to cognitive performance in HIV.
Our finding of executive dysfunction in HIV is in accord with the “frontal” alexithymia model that postulates that alexithymia is the result of dysfunctional mechanisms in the frontal cortex (Davidson et al., 1990
; Gainotti, 1989
; Lane et al., 1997
). A second cognitive domain affected is visuospatial, reflecting parietal dysfunction. The ACC, which has been implicated in alexithymia, has multiple connections with the prefrontal and parietal cortices, which may explain the significant relation between visuospatial dysfunction and the extent of alexithymia in the HIV+ group. These findings support the idea that HIV-related cognitive deficits and alexithymia may involve overlapping neural systems that include ACC and prefrontal cortex. Our findings accord with neuroimaging research (Gundel, Lopez-Sala, Ceballos-Baumann, Deus, Cardoner, Marten-Mittag et al., 2004
; Huber et al., 2002
; Kano, Fukudo, Hongo, Itoh, & Yanai, 2003
) demonstrating the roles of the prefrontal cortex and ACC in executive and regulatory aspects of emotional processing and self-awareness in alexithymia.
In the healthy HIV− control group, there were no correlations between alexithymia ratings and any neuropsychological measures. It appears that the interaction between the processing components of alexithymia and cognitive dysfunction occurs only in the presence of cognitive deficits, or our measures of alexithymia are sensitive to this interaction only in such afflicted individuals.
Dissociations between affective and cognitive aspects of alexithymia reflected by individual alexithymia factors have been reported in several clinical and non-clinical populations (Larsen, Brand, Bermond, & Hijman, 2003
). Our results revealed dissociations between the three TAS-20 factors and cognitive performance in asymptomatic HIV+ individuals, reflecting the underlying dimensions of alexithymia affected in this population. There were specific associations between the two processing components of alexithymia (Factors 2 [DDF] and 3 [EOT]) and cognitive performance in HIV, whereas there was no association between Factor 1 (DIF) and cognitive performance. DIF reflects the affective dimension of alexithymia, and was found to be strongly associated with depression ratings in a clinically depressed group (Bankier et al., 2001
). Our results are consistent with this finding, as neither depression ratings nor DIF correlated with cognitive performance in either group. By contrast, the other two factors, DDF and EOT (a cognitive style that is concrete and reality based) significantly correlated with the cognitive performance of the HIV+ group. Notably, EOT showed significant association with most of the executive and visuospatial cognitive tests, suggesting the possibility of overlap in neural systems subserving these cognitive functions and the processing component of alexithymia measured by EOT. As noted earlier, EOT was found to be significantly associated with smaller rostral ACC volume in healthy adults (Paradiso et al., 2008
). Similarly, Bankier and colleagues (2001)
reported a significant association of EOT with diagnosis of obsessive-compulsive disorder, a fronto-striato-thalamocortical disorder associated with dysfunction of the orbitofrontal cortex, ACC, thalamus and caudate nucleus (Adler et al., 2000
; Kwon, Jang, Choi, & Kang, 2009
; Saxena, Brody, Schwartz, & Baxter, 1998
Taken together, these findings by other investigators provide indirect evidence for the possibility of anatomically and functionally distinct neural substrates for the processing components of alexithymia. Our findings provide additional support for this idea. Specifically, EOT was related to cognitive performance on verbally and non-verbally mediated tasks of executive and visuospatial function, while DDF was associated only with a specific (non-verbally mediated) subset of executive and visuospatial measures. Another notable dissociation between the two factors was on the fluency tasks: DDF was only associated with category fluency, while EOT was associated only with verbal (letter) fluency. As noted earlier, another study related EOT to smaller rostral ACC, and associated alexithymia with performance on verbal fluency (Paradiso et al., 2008
). It is possible that EOT is more dependent on the neural areas serving verbally mediated executive functioning tasks (including rostral ACC), while DDF is more dependent on the areas involved in non-verbally mediated executive tasks. This idea is consistent with earlier reports of DDF but not EOT being related to right-hemisphere lesions (Spalletta et al., 2001
In our study, DIF was not associated with any of the cognitive measures, suggesting potentially distinct neural regions associated with this factor, which appears to be affected differently from the other factors by HIV-related neural injury. There are at least three potential reasons: (1) DIF is not associated with executive or visuospatial function; (2) the underlying neural substrate for this factor is not affected by HIV neurodegenerative processes, or (3) it was too early in the course of the disease to detect the change in our sample. Future studies are needed to better determine the relation between DIF and cognition in HIV.
The evidence from our results and others’ studies of emotional cognition, alexithymia and HIV points to the specific areas of potential overlap of neural substrates of the cognitive processing component (EOT) and HIV-associated cognitive deficits: ACC (rostral subdivision) and its projections. There is converging evidence that while rostral and dorsal ACC subdivisions are differentially involved in emotional and cognitive processing, they are anatomically and functionally connected as part of the overlapping networks subserving complex emotional and cognitive functions/ processes (Lane, 2000
; Mohanty et al., 2007
). Both ACC subdivisions may support cognitive processing component of alexithymia, and this topic warrants further research.
In our study, the severity of depression co-varied with alexithymia ratings but did not correlate with performance on any of the cognitive tests. To evaluate whether positively endorsed somatic items on the BDI–II might have influenced the outcome of the analyses in our study, we calculated cognitive-affective and somatic sub-scores. Neither was associated with cognitive performance in our asymptomatic HIV+ sample. These findings are consistent with those of a previous study (Bornstein et al., 1993
) that showed that neuropsychological abnormalities observed in asymptomatic HIV+ participants cannot be attributed to depression.
Previous studies have related apathy and alexithymia to cognitive dysfunction in HIV, specifically to poor performance on measures of executive and visuospatial function (in alexithymia), suggesting that apathy, alexithymia and HIV-related cognitive dysfunction may share common neurophysiological substrates within the fronto-striatal circuits and their cortical projections. To further examine this potential overlap, we investigated the relation of apathy to cognition and to alexithymia in asymptomatic HIV+ individuals. HIV+ participants showed greater apathy than the HIV− group. There was a significant association between apathy and alexithymia ratings in the asymptomatic HIV+ sample, in particular between apathy and DIF and DDF, but not EOT, suggesting distinct neural substrates for the individual processing components of emotional cognition. When we examined the interaction between apathy, alexithymia and cognition, the following pattern emerged: whereas apathy correlated significantly with only one cognitive measure (spatial working memory), alexithymia correlated with multiple measures of attention and working memory, category fluency, spatial reasoning, and visuospatial organization, indicating differential contributions of apathy and alexithymia to cognition in HIV. These findings suggest that while apathy and alexithymia may share common neurophysiological susbtrates, they can be dissociated in this population, implying partially overlapping but distinct neural substrates within frontostriatal circuits.
We found strong correlations between alexithymia ratings and several items on the QoL self-report measure (HIV MOS). Greater alexithymia was reported among HIV+ individuals with lower ratings of quality of life. Affected aspects of daily life included cognitive functioning, general health, and health distress. By contrast, there were no significant correlations between QoL ratings and current immune status (current CD4 cell count, which may fluctuate in the course of the disease), or disease duration. Past immune status (nadir CD4 cell count since diagnosis) was associated with the Pain subscale of the HIV MOS. Living with pain significantly affects QoL. Alexithymic patients, who have difficulty using adaptive processes to regulate affect, such as tolerating painful emotions and using social support, can be in double jeopardy dealing with the effects of HIV disease. Alexithymia may contribute to the exacerbation and course of disease by causing heightened physiological arousal and physical symptoms, and by affecting already compromised immune function of HIV+ individuals. Our findings emphasize the importance of assessment and treatment of the emotional processing deficits associated with HIV infection, given that the extent of alexithymia substantially correlated with both cognitive functioning and quality of life in our asymptomatic sample. The assessment of alexithymia in HIV should be recommended in medical and mental health settings to understand the clinical presentation, inform the treatment, and predict response to treatment.