Neuropsychological Dysfunction among HIV Infected Drug Abusers

Abstract

Human immunodeficiency virus (HIV) has been documented to cause direct and indirect central nervous system dysfunction that can be observed as a progressive decline in neuropsychological functioning in a large proportion of persons with HIV and AIDS. Neuropsychological decline in individuals with HIV is characterized by cognitive and motor slowing, attentional deficits, executive dysfunction and memory impairment (characterized by intact recognition and deficits in learning and delayed recall). Dementia occurs in a relatively small proportion of HIV infected individuals, though milder NP deficits are observed in 30-50% of persons with advanced disease. Recent evidence suggests that drug users, especially stimulant users, are at risk for accelerated progression of their HIV disease, including a greater risk of neuropsychological dysfunction. Methamphetamine may potentiate HIV Tat protein mediated neurotoxicity giving rise to striatal proinflammatory cytokine stimulation and activation of redox-regulated transcription factors. Oxidative stress due to mitochondrial dysfunction is another candidate process underlying the synergistic effects of stimulant use and HIV. Damage to neurotransmitter systems including the dopaminergic, serotonergic and glutamatergic systems which are affected by both stimulant use and HIV is an alternate explanation. Methamphetamine has also been shown to impede the effectiveness of HAART, which could then in turn allow for more rapid HIV disease progression. A greater prevalence of psychiatric disorders, particularly mood, anxiety and substance use disorders are also observed in HIV positive samples relative to the general population. The changing nature of the HIV pandemic is an ongoing challenge to investigators and clinicians working in this field. Emerging issues requiring additional attention are study of the interactive effects of normal aging and HIV on neurocognition as well as study of the effects of co-infection with Hepatitis C.

Expression of HIV-Tat protein is associated with learning and memory deficits in the mouse

“…It is conceivable that the deficits in novel object recognition may be due to Tat-mediated deficits in attention. Although attentional deficits are associated with the cognitive decline of HIV patients [53], the effect of Tat protein on attention has not been studied in animal models. The novel object recognition test may be configured differently to examine attention [54], but the present study did not examine this effect.…”

HIV-Associated Neurocognitive Disorders: The Relationship of HIV Infection with Physical and Social Comorbidities

“…Other psychiatric disorders such as schizophrenia or bipolar disease are often seen in a subset of HIV-infected persons who have substance abuse and tenuous social and economic support. They are at extremely high risk for medication nonadherence and may have the “perfect storm” of cofactors that result in neurocognitive impairment [ 61 , 66 ].…”

The impact of cognitive training in substance use disorder: the effect of working memory training on impulse control in methamphetamine users

“…Substance use disorder (SUD) is one example of a psychiatric condition that is characterised by deficits in impulse control, as well as alterations in dopaminergic reward pathways in the brain, which has been substantiated by a large meta-analysis of 97 studies (Smith et al 2014). More specifically, methamphetamine use disorder (MUD) is the most prevalent SUD in South African (Plüddemann and Parry 2012) and is associated with impulsive behaviours and deficits in executive functioning that may underlie the South African pandemic of HIV and risky sexual behaviour and other neuropsychological deficits associated with social problems (Weber et al 2012; Marquine et al 2014; Durvasula and Hinkin 2006). Impulsive behaviour, while perhaps exacerbated by MUD for example, is also suggested to be an endophenotypic trait—behaviour derived from genetic susceptibility that predicts vulnerability for compulsive drug taking (Belin et al 2015), as well as altered brain processes that underscore a higher likelihood of relapse after a course of treatment (Everitt 2014).…”