Stress in Musicians with and Without Focal Dystonia Is Not Reflected in Limbic Circuit Activation.

BACKGROUND: Musicians' dystonia (MD) is a movement disorder with several established risk factors, but the exact pathophysiology remains unknown. Recent research suggests dysfunction in sensory-motor, basal ganglia, cerebellar, and limbic loops as potential causes. Adverse childhood experiences are also considered risk factors. OBJECTIVE: This study aimed to investigate whether MD patients have experienced more childhood trauma, leading to increased stress reactivity and neural vulnerability to movement disorders. METHODS: Using functional magnetic resonance imaging and the Montreal Imaging Stress Task, 40 MD patients were compared with 39 healthy musicians (HMs). Whole-brain analysis and regions of interest analysis were performed. Parameter estimates and subjective stress levels were compared between groups and correlated with the Childhood Trauma Questionnaire. RESULTS: MD patients reported significantly higher childhood trauma scores than healthy control subjects, but they did not differ in their subjective stress experiences. Stress-related activity of limbic areas was neither found in the whole sample nor between the two groups. Instead, increased activity of visual association and temporal areas was observed, but this activation did not differ between patients and HMs. However, patients showed a tendency toward reduced precuneus activity under stress. Adverse childhood experiences were negatively correlated with precuneus, thalamus, and substantia nigra activity across all participants. CONCLUSIONS: Overall, MD patients and HMs had similar subjective and neurological reactions to stress but differed in childhood trauma experiences and precuneus activity under stress. Further research about the functional connectivity between precuneus, cerebellum, thalamus, and basal ganglia in musicians is needed. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effects of glabellar botulinum toxin injections on resting-state functional connectivity in borderline personality disorder.

Meta-analyses suggest a sustained alleviation of depressive symptoms through glabellar botulinum toxin (BTX) injections. This can be explained by the disruption of facial feedback loops, which may moderate and reinforce the experience of negative emotions. Borderline personality disorder (BPD) is characterized by excessive negative emotions. Here, a seed-based resting-state functional connectivity (rsFC) analysis following BTX (N = 24) or acupuncture (ACU, N = 21) treatment in BPD is presented on areas related to the motor system and emotion processing. RsFC in BPD using a seed-based approach was analyzed. MRI data were measured before and 4 weeks after treatment. Based on previous research, the rsFC focus was on limbic and motor areas as well as the salience and default mode network. Clinically, after 4 weeks both groups showed a reduction of borderline symptoms. However, the anterior cingulate cortex (ACC) and the face area in the primary motor cortex (M1) displayed aberrant rsFC after BTX compared to ACU treatment. The M1 showed higher rsFC to the ACC after BTX treatment compared to ACU treatment. In addition, the ACC displayed an increased connectivity to the M1 as well as a decrease to the right cerebellum. This study shows first evidence for BTX-specific effects in the motor face region and the ACC. The observed effects of BTX on rsFC to areas are related to motor behavior. Since symptom improvement did not differ between the two groups, a BTX-specific effect seems plausible rather than a general therapeutic effect.

Fine motor control improves in older adults after 1 year of piano lessons: Analysis of individual development and its coupling with cognition and brain structure.

Musical training can improve fine motor skills and cognitive abilities and induce macrostructural brain changes. However, it is not clear whether the changes in motor skills occur simultaneously with changes in cognitive and neurophysiological parameters. In this study, 156 healthy, musically naïve and right-handed older adults were recruited and randomly assigned to a piano training or a music listening group. Before, after 6 and 12 months, participants were scanned using MRI and assessed for fine motor skills, auditory working memory and processing speed. A Bayesian multilevel modelling approach was used to examine behavioural and neurophysiological group differences. The relationships between motor and cognitive and between motor and neurophysiological parameters were determined using latent change score models. Compared with music listening, practicing piano resulted in greater improvement in fine motor skills and probably working memory. Only in the piano group, unimanual fine motor skills and grey matter volume of the contralateral M1 changed together during the 6-12-month period. Additionally, M1 co-developed with ipsilateral putamen and thalamus. Playing piano induced more prevalent coupling between the motor and cognitive domains. However, there is little evidence that fine motor control develops concurrently with cognitive functions. Playing an instrument promotes motor, cognitive and neural development into older age. During the learning process, the consolidation of piano skills appears to take place in sensorimotor networks, enabling musicians to perform untrained motor tasks with higher acuity. Relationships between the development of motor acuity and cognition were bidirectional and can be explained by a common cause as well as by shared resources with compensatory mechanisms.

Hypothalamic volume in pedophilia with or without child sexual offense.

The hypothalamus regulates sexual behavior and is simultaneously associated with aggression and violence. Consequently, this brain region is relevant in research of pedophilia and child sexual offenses (CSO). The distinction between these two phenomena is of great importance and was the object of consideration of this study. We analyzed exclusively men, including 73 pedophilic offenders who committed CSO, an equal number of people with pedophilia but without such offenses, and 133 non-pedophilic, non-offending subjects who formed the control group. All data were collected in a multicenter in vivo study and analyzed using a semi-automated segmentation algorithm for 3-Tesla magnetic resonance images. Men with pedophilia who committed CSO on average had a 47 mm3 smaller hypothalamus per side than people without committed CSO. This effect was driven by both the group of non-offending people with pedophilia and the control group. By contrast, the exploratory comparison of pedophilic persons without CSO with the control group showed no significant difference. The present study demonstrates a deviant hypothalamic structure as a neurobiological correlate of CSO in pedophiles, but not in people with pedophilia who have not committed CSO. Thus, it strengthens the argument to distinguish between sexual offending and paraphilic sexual preferences.

The Use of Botulinum Toxin for Treatment of Depression.

A series of clinical studies have shown that botulinum toxin can treat major depression. Subjects suffering from unipolar depression may experience a quick, strong, and sustained improvement in the symptoms of depression after a single glabellar treatment with botulinum toxin.Preliminary data suggest that botulinum toxin therapy may also be effective in the treatment of other mental disorders characterized by an excess of negative emotions, such as borderline personality disorder.The mood-lifting effect of botulinum toxin therapy is probably mediated by the interruption of a proprioceptive feedback loop from the facial musculature to the emotional brain.

Train the brain with music (TBM): brain plasticity and cognitive benefits induced by musical training in elderly people in Germany and Switzerland, a study protocol for an RCT comparing musical instrumental practice to sensitization to music.

BACKGROUND: Recent data suggest that musical practice prevents age-related cognitive decline. But experimental evidence remains sparse and no concise information on the neurophysiological bases exists, although cognitive decline represents a major impediment to healthy aging. A challenge in the field of aging is developing training regimens that stimulate neuroplasticity and delay or reverse symptoms of cognitive and cerebral decline. To be successful, these regimens should be easily integrated in daily life and intrinsically motivating. This study combines for the first-time protocolled music practice in elderly with cutting-edge neuroimaging and behavioral approaches, comparing two types of musical education. METHODS: We conduct a two-site Hannover-Geneva randomized intervention study in altogether 155 retired healthy elderly (64-78) years, (63 in Geneva, 92 in Hannover), offering either piano instruction (experimental group) or musical listening awareness (control group). Over 12 months all participants receive weekly training for 1 hour, and exercise at home for ~ 30 min daily. Both groups study different music styles. Participants are tested at 4 time points (0, 6, and 12 months & post-training (18 months)) on cognitive and perceptual-motor aptitudes as well as via wide-ranging functional and structural neuroimaging and blood sampling. DISCUSSION: We aim to demonstrate positive transfer effects for faculties traditionally described to decline with age, particularly in the piano group: executive functions, working memory, processing speed, abstract thinking and fine motor skills. Benefits in both groups may show for verbal memory, hearing in noise and subjective well-being. In association with these behavioral benefits we anticipate functional and structural brain plasticity in temporal (medial and lateral), prefrontal and parietal areas and the basal ganglia. We intend exhibiting for the first time that musical activities can provoke important societal impacts by diminishing cognitive and perceptual-motor decline supported by functional and structural brain plasticity. TRIAL REGISTRATION: The Ethikkomission of the Leibniz Universität Hannover approved the protocol on 14.08.17 (no. 3604-2017), the neuroimaging part and blood sampling was approved by the Hannover Medical School on 07.03.18. The full protocol was approved by the Commission cantonale d'éthique de la recherche de Genève (no. 2016-02224) on 27.02.18 and registered at clinicaltrials.gov on 17.09.18 ( NCT03674931 , no. 81185).

Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy Women: A Laboratory Paradigm.

PURPOSE: The neuropeptide oxytocin (OXT) has a variety of physiological functions in maternal behavior and attachment including sexual behavior. Based on animal research and our previous human studies, we set out to investigate intranasal administration of OXT and hypothesized that OXT should be able to modulate sexual function in women. METHODS: In a double-blind, placebo-controlled, crossover laboratory setting, the acute effects of intranasal administered OXT (24 international units) on sexual drive, arousal, orgasm, and refractory aspects of sexual behavior were analyzed in 27 healthy females (mean age ± SD, 27.52 ± 8.04) together with physiological parameters using vaginal photoplethysmography. FINDINGS: Oxytocin administration showed no effect on subjective sexual parameters (eg, postorgasmic tension; P = 0.051). Physiological parameters (vaginal photoplethysmography amplitude and vaginal blood volume) showed a response pattern towards sexual arousal but were not affected by OXT. IMPLICATIONS: Using a well-established laboratory paradigm, we did not find that intranasal OXT influences female sexual parameters. Also, sexual drive and other functions were not affected by OXT. These findings indicate that OXT is not able to significantly increase subjective and objective parameters of sexual function in a setting with high internal validity; however, this might be different in a more naturalistic setting.

Reduction of Risk Factors for Pedophilic Sexual Offending.

INTRODUCTION: Exploratory analysis of characteristics and reduction of risk factors for child sexual abuse (CSA) in a sample treated in the Prevention Projects Dunkelfeld Hannover and Regensburg. AIM: To evaluate a treatment program aimed at reducing dynamic risk factors (DRF) for CSA. METHODS: Using a psychometric test battery based on self-report questionnaires, intergroup analysis between treatment group (TG, n = 35), treatment refusers (TR, n = 51), and drop-out group (DO, n = 14) was conducted with pretreatment data. Intragroup analysis compared data of TG from pre- and posttreatment. The test battery included sociodemographic and sociosexual data, as well as questionnaires measuring DRF. MAIN OUTCOME MEASURE: This study investigated effects of treatment on pedophilic men who are at risk for offending and observed reductions in important risk factors for CSA. RESULTS: TG, TR (consisting of persons who were offered but refused therapy), and DO did not differ regarding sociodemographic and sociosexual variables before therapy. There were no significant differences in education, relationship status, living solitarily, and being a father/stepfather. TR and DO lived farther away from treatment site than TG. In the TG, a reduction in offense-supportive attitudes, coping self-efficacy deficits, and child identification were revealed at second assessment. In TG no participants started the consumption of child abuse content during the course of the study. CLINICAL IMPLICATIONS: Future treatment concepts should focus on the reduction of empirically relevant risk factors for child sexual offending. STRENGTH & LIMITATIONS: The present article is the first that compares TG to TR and DO before assessment regarding DRF and sociosexual variables. Moreover, it is only the second study that investigated treatment effects on a population of pedophilic men who are at risk for offending. These preliminary findings are limited by moderate group size and a missing control group. CONCLUSION: A reduction in some but not all assessed risk factors for sexual offending against minors could be seen within the time frame of therapy. Findings are in line with results from a previous evaluation study. Engel J, Körner M, Schuhman P. Reduction of risk factors for pedophilic sexual offending. J Sex Med 2018;15:1629-1637.

Lack of Increase in Sexual Drive and Function After Dopaminergic Stimulation in Women.

Human and animal data indicate that the dopaminergic system plays a crucial role in sexual drive and function. Using a double-blind, placebo-controlled crossover design, this prototype study investigated the effect of the D2 dopamine agonist cabergoline on sexual parameters in 13 healthy women. Cardiovascular and genital parameters were monitored continuously. Sexual drive and function were measured using self-report sexual experience scales. In contrast to previous theories and assumptions, we found that cabergoline did not alter objective and subjective sexual parameters in healthy women. This finding suggests that there may be sex differences in the influence of the dopaminergic system on human sexual functioning.

Evidence for superior neurobiological and behavioral inhibitory control abilities in non-offending as compared to offending pedophiles.

Neurobehavioral models of pedophilia and child sexual offending suggest a pattern of temporal and in particular prefrontal disturbances leading to inappropriate behavioral control and subsequently an increased propensity to sexually offend against children. However, clear empirical evidence for such mechanisms is still missing. Using a go/nogo paradigm in combination with functional magnetic resonance imaging (fMRI) we compared behavioral performance and neural response patterns among three groups of men matched for age and IQ: pedophiles with (N = 40) and without (N = 37) a history of hands-on sexual offences against children as well as healthy non-offending controls (N = 40). As compared to offending pedophiles, non-offending pedophiles exhibited superior inhibitory control as reflected by significantly lower rate of commission errors. Group-by-condition interaction analysis also revealed inhibition-related activation in the left posterior cingulate and the left superior frontal cortex that distinguished between offending and non-offending pedophiles, while no significant differences were found between pedophiles and healthy controls. Both areas showing distinct activation pattern among pedophiles play a critical role in linking neural networks that relate to effective cognitive functioning. Data therefore suggest that heightened inhibition-related recruitment of these areas as well as decreased amount of commission errors is related to better inhibitory control in pedophiles who successfully avoid committing hands-on sexual offences against children. Hum Brain Mapp 38:1092-1104, 2017. © 2016 Wiley Periodicals, Inc.

Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?!

One of the most disabling symptoms of hepatitis C virus (HCV) infection is chronic fatigue. While this is accepted for HCV polymerase chain reaction (PCR)-positive patients, a relationship between HCV infection and chronic fatigue is questioned after successful virus eradication. As fatigue is a subjective criterion, we aimed to evaluate in addition mood alterations and cognitive function in HCV-exposed patients with only mild liver disease and to assess a) possible interrelationships between these factors and health-related quality of life and b) the impact of viremia and former interferon treatment. One hundred and fifty-nine anti-HCV-positive individuals without advanced liver disease answered health-related quality of life (HRQoL), fatigue and depression questionnaires and underwent a battery of attention and memory tests. Accompanying diseases which could distort the results of the study such as HIV co-infection or drug addiction were exclusion criteria. The patients were subdivided into four groups according to their viremia status and interferon treatment history. Patients' data were evaluated with respect to norms given in the respective test manuals and in addition compared to those of 33 age-matched healthy controls. Eighty-five per cent of the patients had chronic fatigue, 50-60% mild depression or anxiety, 45% memory deficits and 30% attention deficits, irrespective of their HCV viremia status or treatment history. HRQoL correlated negatively with chronic fatigue (P<.001), while cognitive deficits-especially memory function-were independent from fatigue and depression. HCV infection may cause long-standing cerebral dysfunction that significantly impairs HRQoL and may even persist after clearance of the virus.

Executive Functioning in Pedophilia and Child Sexual Offending.

OBJECTIVES: Pedophilia (P) is a psychiatric disease associated with sexual attraction toward children and often accompanied by child sexual offending (CSO). Consequently, it is important to address the understanding of executive dysfunctions that may increase the probability of CSO. Moreover, this research field has been lacking to disentangle executive deficits associated with pedophilia (as a deviant sexual preference) from those associated with CSO (as a deviant sexual behavior). METHODS: The German multi-sided research network NeMUP offers the opportunity to overcome these limitations. By applying the Cambridge Automated Neuropsychological Test Battery in four carefully matched groups of men: (1) pedophiles with (N=45) and (2) without (N=45) a history of sexual offending against children; (3) child molesters without pedophilia (N=19), and (4) non-offending controls (N=49), we were able to analyze executive functioning in pedophilia and CSO independently. RESULTS: Both CSO groups as compared to both non-CSO groups exhibited worsened response inhibition ability. However, only non-pedophilic offenders showed additionally disabled strategy use ability. Regarding set-shifting abilities, the P+CSO group showed the best performance. We also found that performances were affected by age: only in pedophiles, response inhibition worsened with age, while age-related deficits in set-shifting abilities were restricted to non-pedophilic participants. The latter also differentiated between both sexual preference groups. CONCLUSIONS: Our results are the first to demonstrate that executive dysfunctions are related to offense status rather than pedophilic preference. Furthermore, there was evidence for differentiating age and performance correlations between pedophiles and non-pedophiles, which warrants further investigation. (JINS, 2017, 23, 460-470).

HCV encephalopathy - an artefact due to medical care?

Anti-HCV positive individuals frequently complain about chronic disabling fatigue, mood alterations and deficits in concentration and memory. Several data provide evidence that such alterations are unrelated to hepatitis C virus (HCV) viremia. Thus, merely being exposed to HCV in the past may be sufficient to trigger, but the HCV exposure itself. This commentary reviews the available data upon this topic with special reference to the paper by Lowry and colleagues published in this issue of the Journal of Viral hepatitis. We will carefully discuss scientific reasons, why HCV may be directly involved in the development of neuropsychiatric symptoms independent from ongoing detectable viremia, as suggested by epidemiological data.

Cortico-pallidal oscillatory connectivity in patients with dystonia.

Primary dystonia has been associated with an underlying dysfunction of a wide network of brain regions including the motor cortex, basal ganglia, cerebellum, brainstem and spinal cord. Dystonia can be effectively treated by pallidal deep brain stimulation although the mechanism of this effect is not well understood. Here, we sought to characterize cortico-basal ganglia functional connectivity using a frequency-specific measure of connectivity-coherence. We recorded direct local field potentials from the human pallidum simultaneously with whole head magnetoencephalography to characterize functional connectivity in the cortico-pallidal oscillatory network in nine patients with idiopathic dystonia. Three-dimensional cortico-pallidal coherence images were compared to surrogate images of phase shuffled data across patients to reveal clusters of significant coherence (family-wise error P < 0.01, voxel extent 1000). Three frequency-specific, spatially-distinct cortico-pallidal networks have been identified: a pallido-temporal source of theta band (4-8 Hz) coherence, a pallido-cerebellar source of alpha band (7-13 Hz) coherence and a cortico-pallidal source of beta band (13-30 Hz) coherence over sensorimotor areas. Granger-based directionality analysis revealed directional coupling with the pallidal local field potentials leading in the theta and alpha band and the magnetoencephalographic cortical source leading in the beta band. The degree of pallido-cerebellar coupling showed an inverse correlation with dystonic symptom severity. Our data extend previous findings in patients with Parkinson's disease describing motor cortex-basal ganglia oscillatory connectivity in the beta band to patients with dystonia. Source coherence analysis revealed two additional frequency-specific networks involving the temporal cortex and the cerebellum. Pallido-cerebellar oscillatory connectivity and its association with dystonic symptoms provides further confirmation of cerebellar involvement in dystonia that has been recently reported using functional magnetic resonance imaging and fibre tracking.

Placebo and Nocebo Effects in Sexual Medicine: An Experimental Approach.

Few studies have investigated placebo and nocebo effects in a human sexuality context. Studying placebo and nocebo responses in this context may provide insight into their potential to modulate sexual drive and function. To examine such effects in sexual medicine, 48 healthy, male heterosexual participants were divided into four groups. Each group received instruction to expect stimulating effects, no effect, or an inhibitory effect on sexual functions. Only one group received the dopamine agonist cabergoline; all other groups received placebo or nocebo. Modulations in sexual experience were examined through an established experimental paradigm of sexual arousal and masturbation-induced orgasm during erotic film sequences with instruction to induce placebo or nocebo effects. Endocrine data, appetitive, consummatory, and refractory sexual behavior parameters were assessed using the Arizona Sexual Experience Scale (ASEX) and the Acute Sexual Experience Scale (ASES). Results showed increased levels of sexual function after administration of cabergoline with significant effects for several parameters. Placebo effects were induced only to a small degree. No negative effects on sexual parameters in the nocebo condition were noted. This paradigm could induce only small placebo and nocebo effects. This supports the view that healthy male sexual function seems relatively resistant to negative external influences.

The New Hamburg-Hannover Agitation Scale in Clinical Samples: Manifestation and Differences of Agitation in Depression, Anxiety, and Borderline Personality Disorder.

BACKGROUND/AIMS: Agitation is a burdening phenomenon that occurs in a variety of psychiatric disorders. The aim of this study was to give a first direction for agitation occurrence in depression, anxiety disorder, and borderline personality disorder (BPD) as well as in healthy controls with and without psychiatric record. METHODS: Using the Hamburg-Hannover Agitation Scale (H2A), an instrument that allows for the measurement of agitation independently of the presence of a specific disorder, a patient sample (n = 158) and a healthy control group (n = 685) with (n = 94) and without (n = 591) psychiatric record were examined. The data were mainly analysed using ANOVAs and post hoc tests. RESULTS: Patients showed significantly higher H2A agitation levels than healthy controls. Within the clinical sample, BPD patients exhibited the strongest manifestation of agitation, scoring significantly higher than the depression and the anxiety disorder sample, while these two subgroups did not significantly differ from each other. Moreover, healthy subjects with a psychiatric record experienced a significantly stronger agitation than subjects without a psychiatric record. CONCLUSION: Further studies are needed with larger, more balanced, and differentiated sample sizes including a wider range of clinical pictures. The results demonstrate that agitation occurs and differs in psychiatric patients as well as in healthy controls.

Functional characterization of bovine viral diarrhea virus nonstructural protein 5A by reverse genetic analysis and live cell imaging.

Nonstructural protein 5A (NS5A) of bovine viral diarrhea virus (BVDV) is a hydrophilic phosphoprotein with RNA binding activity and a critical component of the viral replicase. In silico analysis suggests that NS5A encompasses three domains interconnected by two low-complexity sequences (LCSs). While domain I harbors two functional determinants, an N-terminal amphipathic helix important for membrane association, and a Zn-binding site essential for RNA replication, the structure and function of the C-terminal half of NS5A are still ill defined. In this study, we introduced a panel of 10 amino acid deletions covering the C-terminal half of NS5A. In the context of a highly efficient monocistronic replicon, deletions in LCS I and the N-terminal part of domain II, as well as in domain III, were tolerated with regard to RNA replication. When introduced into a bicistronic replicon, only deletions in LCS I and the N-terminal part of domain II were tolerated. In the context of the viral full-length genome, these mutations allowed residual virion morphogenesis. Based on these data, a functional monocistronic BVDV replicon coding for an NS5A variant with an insertion of the fluorescent protein mCherry was constructed. Live cell imaging demonstrated that a fraction of NS5A-mCherry localizes to the surface of lipid droplets. Taken together, this study provides novel insights into the functions of BVDV NS5A. Moreover, we established the first pestiviral replicon expressing fluorescent NS5A-mCherry to directly visualize functional viral replication complexes by live cell imaging.

Diminished functional connectivity on the road to child sexual abuse in pedophilia.

BACKGROUND: Pedophilia is a disorder recognized for its impairment to the individual and for the harm it may cause to others. However, the neurobiology of pedophilia and a possible propensity to sexually abuse children are not well understood. In this study, we thus aimed at providing new insights in how functional integration of brain regions may relate to pedophilia or child sexual abuse (CSA). METHOD: By using functional magnetic resonance imaging (fMRI) technique, we compared functional connectivity at rest (RSFC) between pedophiles who engaged (P+CSA; N = 12) or did not engage (P-CSA; N = 14) in CSA and healthy controls (HCs; N = 14) within two networks: (i) the default mode network and (ii) the limbic network that has been linked to pedophilia before. RESULTS: Pedophiles who engaged in CSA show diminished RSFC in both networks compared with HC and P-CSA. Most importantly, they showed diminished RSFC between the left amygdala and orbitofrontal as well as anterior prefrontal regions. Though significant age differences between groups could not be avoided, correlation control analysis did not provide evidence for the assumption that the RSFC effects were related to age differences. CONCLUSION: We found significantly diminished RSFC in brain networks critically involved in widespread motivational and socio-emotional processes. These results extend existing models of the functional neuroanatomy of pedophilia and CSA as altered RSFC between these regions were related to CSA rather than pedophilia and thus may account for an increased propensity to engage in CSA in people suffering from pedophilia.

Impact of GB virus C viraemia on clinical outcome in HIV-1-infected patients: a 20-year follow-up study.

OBJECTIVES: The impact of coexisting GB virus C (GBV-C) infection on the clinical course of HIV infection remains controversial. Early data from HIV-1 infected patients attending the Hannover Medical School in 2001 suggested prognostic benefit in GBV-C viraemic patients. The aim of this study was to evaluate patterns in long-term mortality and morbidity outcomes in this cohort. The impact of the introduction of antiretroviral therapy (ART) on the perceived benefits of GBV-C viraemia was subsequently investigated. METHODS: A retrospective follow-up analysis of data in this cohort was performed. GBV-C status (GBV-C RNA positive, antibodies against GBV-C envelope protein E2 or no evidence of GBV-C exposure) had been determined at enrolment, with several markers of HIV disease progression (such as viral load and CD4 cell count) being collated from 1993/1994, 2000 and 2012. These eras were chosen to reflect variations in treatment strategies within the cohort. In addition, mortality and HIV-related morbidity data were collated for all patients. RESULTS: Complete data were available for 156 of 197 patients (79%). In highly active antiretroviral therapy (HAART)-naïve patients, GBV-C RNA positivity conferred significant improvements in the course of HIV infection and mortality as well as lower rates of HIV-related diseases. E2 positivity alone conferred no significant advantage. With the advent of HAART, however, the benefits GBV-C RNA positivity disappeared. CONCLUSIONS: Although GBV-C coinfection appears to inherently improve morbidity and mortality in HIV-infected patients, modern HAART has eradicated these advantages. Evidence of synergy between GBV-C status and HAART response exists, with further studies examining the role of GBV-C in existing treatment de-escalation strategies being required.