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HIV-associated neurocognitive disorders (HANDs) still persist despite improved life expectancy, reduced viral loads, and decreased infection severity. The number of patients affected by HANDs ranges from (30 to 50) % of HIV-infected individuals. The pathological mechanisms contributing to HANDs and the most serious manifestation of the disease, HIV-associated dementia (HAD), are not yet well understood. Evidence suggests that these mechanisms are likely multifactorial, producing neurocognitive complications involving disorders such as neurogenesis, autophagy, neuroinflammation, and mitochondrial dysfunction. Over the years, multiple pharmacological approaches with specific mechanisms of action acting upon distinct targets have been approved. Although these therapies are effective in reducing viral loading to undetectable levels, they also present some disadvantages such as common side effects, the need for administration with a very high frequency, and the possibility of drug resistance. Genetic studies on HANDs provide insights into the biological pathways and mechanisms that contribute to cognitive impairment in people living with HIV-1. Furthermore, they also help identify genetic variants that increase susceptibility to HANDs and can be used to tailor treatment approaches for HIV-1 patients. Identification of the genetic markers associated with disease progression can help clinicians predict which individuals require more aggressive management and by understanding the genetic basis of the disorder, it will be possible to develop targeted therapies to mitigate cognitive impairment. The main goal of this review is to provide details on the epidemiological data currently available and to summarise the genetic (specifically, the genetic makeup of the immune system), transcriptomic, and epigenetic studies available on HANDs to date. In addition, we address the potential pharmacological therapeutic strategies currently being investigated. This will provide valuable information that can guide clinical care, drug development, and our overall understanding of these diseases. [ABSTRACT FROM AUTHOR]

High-throughput sequencing of small RNA molecules such as microRNAs (miRNAs) has become a widely used approach for studying gene expression and regulation. However, analyzing miRNA-Seq data can be challenging because it requires multiple steps, from quality control and preprocessing to differential expression and pathway-enrichment analyses, with many tools and databases available for each step. Furthermore, reproducibility of the analysis pipeline is crucial to ensure that the results are accurate and reliable. Here, we present myBrain-Seq, a comprehensive and reproducible pipeline for analyzing miRNA-Seq data that incorporates miRNA-specific solutions at each step of the analysis. The pipeline was designed to be flexible and user-friendly, allowing researchers with different levels of expertise to perform the analysis in a standardized and reproducible manner, using the most common and widely used tools for each step. In this work, we describe the implementation of myBrain-Seq and demonstrate its capacity to consistently and reproducibly identify differentially expressed miRNAs and enriched pathways by applying it to a real case study in which we compared schizophrenia patients who responded to medication with treatment-resistant schizophrenia patients to obtain a 16-miRNA treatment-resistant schizophrenia profile. [ABSTRACT FROM AUTHOR]

Peer Victimization (PV) or being bullied in childhood/adolescence has been associated with several negative outcomes in mental health conditions beyond the time of its occurrence. However, its possible association with personality disorders has been slightly explored. In the present study we have compared the frequency of DSM IV personality disorders among adult patients with (N = 28) or without (N = 418) a reported history of PV. For this purpose, axis II was evaluated with the Self-Report Checklist for Preliminary Items for Major Categories, whereas self-esteem and self-assessment of functioning were evaluated with single questions. Patients with PV history have met the diagnostic criteria of the avoidant (60.7% vs. 12.2%), depressive (28.5% vs. 5.2%) and paranoid (17.9% vs. 5%) personality disorders more frequently than patients without history of PV. Moreover, these patients with antecedents of being bullied have also reported lower self-esteem (2 vs. 3) and in the assessment of social functioning (4 vs. 5). Our study indicated that there is a clear association between PV and avoidant, depressive and paranoid personality patterns. These results suggest that the stress related with the experience of PV threatens a basic psychobiological need such as social acceptance with implications for the beginning of long-term dysfunctional personality trajectories. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a serious mental disorder that is typically treated with antipsychotic medication. Treatment-resistant schizophrenia (TRS) is the condition where symptoms remain after pharmacological intervention, resulting in long-lasting functional and social impairments. As the identification and treatment of a TRS patient requires previous failed treatments, early mechanisms of detection are needed in order to quicken the access to effective therapy, as well as improve treatment adherence. In this study, we aim to find a microRNA (miRNA) signature for TRS, as well as to shed some light on the molecular pathways potentially involved in this severe condition. To do this, we compared the blood miRNAs of schizophrenia patients that respond to medication and TRS patients, thus obtaining a 16-miRNA TRS profile. Then, we assessed the ability of this signature to separate responders and TRS patients using hierarchical clustering, observing that most of them are grouped correctly (~70% accuracy). We also conducted a network, pathway analysis, and bibliography search to spot molecular pathways potentially altered in TRS. We found that the response to stress seems to be a key factor in TRS and that proteins p53, SIRT1, MDM2, and TRIM28 could be the potential mediators of such responses. Finally, we suggest a molecular pathway potentially regulated by the miRNAs of the TRS profile. [ABSTRACT FROM AUTHOR]

The current use of combined antiretroviral therapy (cART) is leading to a significant decrease in deaths and comorbidities associated with human immunodeficiency virus type 1 (HIV-1) infection. Nonetheless, none of these therapies can extinguish the virus from the long-lived cellular reservoir, including microglia, thereby representing an important obstacle to curing HIV. Microglia are the foremost cells infected by HIV-1 in the central nervous system (CNS) and are believed to be involved in the development of HIV-1-associated neurocognitive disorder (HAND). At present, the pathological mechanisms contributing to HAND remain unclear, but evidence suggests that removing these infected cells from the brain, as well as obtaining a better understanding of the specific molecular mechanisms of HIV-1 latency in these cells, should help in the design of new strategies to prevent HAND and achieve a cure for these diseases. The goal of this review was to study the current state of knowledge of the neuropathology and research models of HAND containing virus susceptible target cells (microglial cells) and potential pharmacological treatment approaches under investigation. [ABSTRACT FROM AUTHOR]