Although the amygdalae play a central role in threat perception and reactions, the direct contributions of the amygdalae to specific aspects of threat perception, from ambiguity resolution to reflexive or deliberate action, remain ill understood in humans. Animal studies show that a detailed understanding requires a focus on the different subnuclei, which is not yet achieved in human research. Given the limits of human imaging methods, the crucial contribution needs to come from individuals with exclusive and selective amygdalae lesions. The current study investigated the role of the basolateral amygdalae and their connection with associated frontal and temporal networks in the automatic perception of threat. Functional activation and connectivity of five individuals with Urbach-Wiethe disease with focal basolateral amygdalae damage and 12 matched controls were measured with functional MRI while they attended to the facial expression of a threatening face-body compound stimuli. Basolateral amygdalae damage was associated with decreased activation in the temporal pole but increased activity in the ventral and dorsal medial prefrontal and medial orbitofrontal cortex. This dissociation between the prefrontal and temporal networks was also present in the connectivity maps. Our results contribute to a dynamic, multirole, subnuclei-based perspective on the involvement of the amygdalae in fear perception. Damage to the basolateral amygdalae decreases activity in the temporal network while increasing activity in the frontal network, thereby potentially triggering a switch from resolving ambiguity to dysfunctional threat signaling and regulation, resulting in hypersensitivity to threat.

Infection with human immunodeficiency virus (HIV) is associated with neuroimaging alterations. However, little is known about the topological organization of whole-brain networks and the corresponding association with cognition. As such, we examined structural whole-brain white matter connectivity patterns and cognitive performance in 29 HIV+ young adults (mean age = 25.9) with limited or no HIV treatment history. HIV+ participants and demographically similar HIV- controls (n = 16) residing in South Africa underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural network models were constructed using diffusion MRI-based multifiber tractography and T₁-weighted MRI-based regional gray matter segmentation. Global network measures included whole-brain structural integration, connection strength, and structural segregation. Cognition was measured using a neuropsychological global deficit score (GDS) as well as individual cognitive domains. Results revealed that HIV+ participants exhibited significant disruptions to whole-brain networks, characterized by weaker structural integration (characteristic path length and efficiency), connection strength, and structural segregation (clustering coefficient) than HIV- controls (p < 0.05). GDSs and performance on learning/recall tasks were negatively correlated with the clustering coefficient (p < 0.05) in HIV+ participants. Results from this study indicate disruption to brain network integrity in treatment-limited HIV+ young adults with corresponding abnormalities in cognitive performance.

Epigenetic age (EA) acceleration is associated with higher risk of chronic disease and mortality in adults. However, little is known about whether and how in utero exposures might shape gestational EA acceleration at birth. We aimed to explore associations between maternal psychosocial risk factors and offspring gestational EA acceleration at birth in a South African birth cohort study - the Drakenstein Child Health Study. Maternal psychosocial risk factors included trauma/stressor exposure; posttraumatic stress disorder (PTSD); depression, psychological distress; and alcohol/tobacco use. Offspring gestational EA acceleration at birth was calculated using an epigenetic clock previously devised for neonates. Bivariate linear regression was used to explore unadjusted associations between maternal risk factors and offspring gestational EA acceleration at birth. A stepwise regression method was then used to determine the best multivariable model for adjusted associations. Data from 272 maternal-offspring dyads were included in the current analysis. In the stepwise regression model, maternal trauma exposure (β = 7.92; p&lt;0.01) or PTSD (β = 7.46; p&lt;0.01) were significantly associated with offspring gestational EA acceleration at birth, controlling for ethnicity, offspring sex, head circumference at birth, maternal HIV status, and prenatal tobacco or alcohol use. In site-stratified models, these associations retained statistical significance and direction of effect. Maternal trauma exposure or PTSD may thus be associated with offspring gestational EA acceleration at birth. Given the novelty of this preliminary finding, and its potential translational relevance, further studies to delineate underlying biological pathways and to explore clinical implications of EA acceleration are warranted.

High mentalization may serve as a coping mechanism to attenuate ED symptoms.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h²_SNP) for European-American females of 29% that is similar to h²_SNP for schizophrenia and is substantially higher than h²_SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Although pathological skin-picking has been documented in the medical literature since the 19th century, it has only recently been included as a distinct entity in psychiatric classification systems. In the <i>Diagnostic and Statistical Manual of Mental Disorders</i>, 5th Edition and the proposed International Classification of Diseases, Eleventh Revision, excoriation (skin-picking) disorder (ED), also known as neurotic excoriation, psychogenic excoriation, or dermatillomania), is described as recurrent picking of skin, leading to skin lesions and significant distress or functional impairment. ED is listed as one of the obsessive-compulsive and related disorders, given its overlap with conditions such as trichotillomania (hair-pulling disorder). Arguably, its inclusion and delineation in the diagnostic nomenclature will lead to increased awareness of the condition, more research, and ultimately in treatment advances. This systematic review aims to provide readers with an up-to-date view of current treatment options for ED. A MEDLINE search of the ED treatment literature was conducted to collate relevant articles published between 1996 and 2017. The findings indicate that a number of randomized controlled trails on ED have now been published, and that current management options include behavioral therapy (habit reversal or acceptance-enhanced behavior therapy), and medication (selective serotonin reuptake inhibitors or <i>N</i>-acetyl cysteine).

These results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.Declaration of interestThe authors have declared that no competing interests exist.

The lack of significant association between schizophrenia PRS and brain structural changes may indicate that intermediate phenotypes other than brain structure should be the focus of future work. Alternatively, however, the lack of association found here may point to limitations of the current evidence-base, and so point to the need for future better powered studies.

<h3>Importance</h3> Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. <h3>Objective</h3> To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes. <h3>Design, Settings, and Participants</h3> Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. <h3>Main Outcomes and Measures</h3> Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. <h3>Results</h3> There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. <h3>Conclusions and Relevance</h3> Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts.