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Biological markers for depression are of great interest to aid in elucidating the causes of major depression. We assess currently available biological markers to query their validity for aiding in the diagnosis of major depression. We specifically focus on neurotrophic factors, serotonergic markers, biochemical markers, immunological markers, neuroimaging, neurophysiological findings, and neuropsychological markers. We delineate the most robust biological markers of major depression. These include decreased platelet imipramine binding, decreased 5-HT1A receptor expression, increase of soluble interleukin-2 receptor and interleukin-6 in serum, decreased brain-derived neurotrophic factor in serum, hypocholesterolemia, low blood folate levels, and impaired suppression of the dexamethasone suppression test. To date, however, none of these markers are sufficiently specific to contribute to the diagnosis of major depression. Thus, with regard to new diagnostic manuals such as DSM-V and ICD-11 which are currently assessing whether biological markers may be included in diagnostic criteria, no biological markers for major depression are currently available for inclusion in the diagnostic criteria.

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A great number of human immunodeficiency virus (HIV)-infected patients develop a central nervous system disorder, commonly called HIV dementia or AIDS dementia complex (ADC). HIV dementia is independent of opportunistic infections and is due to the virus itself. Symptoms include psychomotor slowing, apathy and motor disorders similar to the bradykinesia and postural and gait abnormalities observed in late Parkinson's disease. Consequently, HIV has been discussed during the last few years as an additional cause for parkinsonism, and parkinsonian syndromes as manifestations of HIV dementia. Moreover, the early phase of HIV infection gains increasing interest because of studies which report subtle neurological symptoms at this stage. Accordingly, we found in SIV-infected monkeys that dopamine is reduced by 44% within as few as two months of infection, indicating that changes during early infection must be thoroughly evaluated. In this short review, we discuss alterations in the nigrostriatal dopaminergic system during early and late immunodeficiency virus infection and the common clinical and biochemical features shared by HIV dementia and Parkinson's disease.

Our results confirm the significant correlation between MRI changes and cognitive impairment in HIV infection. Furthermore, we could show that global brain atrophy and signal changes in basal ganglia are the typical MRI pattern in HAND. The correlation between cognitive impairment and total tau, but not phospho-tau, supports the hypothesis that HAND are not a subtype of Alzheimer's dementia.

Although there are a number of hypotheses to explain the pathobiochemistry of Parkinson's disease (PD), the one on oxidative stress (OS) has gained major interest. The evidence for OS participation as a cause of PD can be summarized as follows: 1) OS is involved in physiological aging, 2) there is ample evidence that OS is significantly enhanced in PD compared to age-matched healthy persons, 3) OS is an early feature of PD because OS-dependent aggregation of proteins in the form of advanced glycation end products can be imaged in Lewy bodies at a time in a person's life, when no phenotype of a neurodegenerative disorder is evident, 4) Experimental models of PD show OS and degeneration of dopaminergic neurons. The toxin-induced neurodegeneration can be blocked by antioxidants, and 5) Activated microglia, known to release free radicals and inflammatory cytokines, are present in brains of Parkinsonian patients. In conclusion, a great body of evidence points to the view that OS is a major component underlying the pathobiochemistry of PD. Together a genetic disposition and endogenous/exogenous toxic events of various origins result in a synergistic cascade of toxicity which leads to dysfunction and finally to cell death of dopaminergic neurons. Again, OS plays a significant role in generating cell death signals including apoptosis.

Functional MRI studies investigating the impact of HIV on the brain have implicated the involvement of fronto-striatal circuitry. However, to date there is no review and meta-analysis of this work. We systematically reviewed the literature and performed a meta-analysis of functional magnetic resonance imaging (fMRI) studies in HIV-infected individuals using a well validated tool recently developed for use in fMRI, 'GingerALE'. Twenty-one studies (468 HIV+, 270 HIV- controls) were qualitatively reviewed, of which six (105 HIV+, 102 controls) utilized fMRI paradigms engaging the fronto-striatal-parietal network, making a quantitative analysis possible. Our meta-analysis revealed consistent functional differences in the left inferior frontal gyrus and caudate nucleus between infected participants and controls across these studies. This fronto-striatal dysfunction was qualitatively related to cognitive impairment, disease progression and treatment effects. Although further work needs to be done to further delineate the potentially confounding influence of substance abuse and HIV-related comorbidities, as well as HIV's effect on functional haemodynamic vascular coupling, these findings indicate that further investigation of the fronto-striatal sub-networks in HIV-infected patients is warranted.

BackgroundThe World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients <25 years is representative for HIVDR in the rest of the therapy-naïve population.Methods and FindingsHIVDR was determined in 88 sequentially enrolled ART-naïve patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged <25 years and 68 patients were aged 25–63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072–0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients >25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095–0.28) versus 0%, P = 0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma.ConclusionsART-naïve patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naïve population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naïve HIV-infected population.