BackgroundOver the past decade, smartphone use has become widespread amongst today’s children and young people (CYP) which parallels increases in poor mental health in this group. Simultaneously, media concern abounds about the existence of ‘smartphone addiction’ or problematic smartphone use. There has been much recent research concerning the prevalence of problematic smartphone use is in children and young people who use smartphones, and how this syndrome relates to mental health outcomes, but this has not been synthesized and critically evaluated.AimsTo conduct a systematic review and meta-analysis to examine the prevalence of PSU and quantify the association with mental health harms.MethodsA search strategy using Medical Subject Headings was developed and adapted for eight databases between January 1, 1st 2011 to October 15th 2017. No language restriction was applied. Of 924 studies identified, 41 were included in this review, three of which were cohort studies and 38 were cross sectional studies. The mental health outcomes were self-reported: depression; anxiety; stress; poor sleep quality; and decreased educational attainment, which were synthesized according to an a priori protocol.ResultsThe studies included 41,871 CYP, and 55% were female. The median prevalence of PSU amongst CYP was 23.3% (14.0–31.2%). PSU was associated with an increased odds of depression (OR = 3.17;95%CI 2.30–4.37;I2 = 78%); increased anxiety (OR = 3.05 95%CI 2.64–3.53;I2 = 0%); higher perceived stress (OR = 1.86;95%CI 1.24–2.77;I2 = 65%); and poorer sleep quality (OR = 2.60; 95%CI; 1.39–4.85, I2 = 78%).ConclusionsPSU was reported in approximately one in every four CYP and accompanied by an increased odds of poorer mental health. PSU is an evolving public health concern that requires greater study to determine the boundary between helpful and harmful technology use. Policy guidance is needed to outline harm reduction strategies.

Objective-To determine whether microglial activity, measured using translocator-protein positron emission tomographic imaging (PET), is increased in unmedicated subjects presenting with sub-clinical symptoms indicating they are at ultra high risk of psychosis, and to determine if it is elevated in schizophrenia after controlling for a translocator specific genetic polymorphism.Method-Here we use the second generation radioligand [ 11 C]PBR28 and PET to image microglial activity in the brains of subjects at ultra high risk for psychosis. Subjects were recruited from early intervention centres. We also imaged a cohort of patients with schizophrenia and healthy controls for comparison, in total 56 subjects completed the study. At screening, subjects were genotyped to account for the rs6971 polymorphism in the gene encoding the 18Kd Translocator Protein. The main outcome measure was total grey matter [ 11 C]PBR28 binding ratio, representing microglial activity. Conclusion-Microglial activity is elevated in schizophrenia and in subjects with sub-clinical symptoms who are at ultra high risk of psychosis, and is related to at risk symptom severity. This indicates that neuroinflammation is linked to the risk of psychosis and related disorders, and the expression of sub-clinical symptoms. Follow up of ultra high risk subjects will determine whether this is specific to the later development of schizophrenia or risk factors in general. Results-[

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BP ND ). Here, we used blockade of the TSPO radioligand [ 11 C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (V ND ), and hence estimate the BP ND . A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [ 11 C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, V ND was estimated via the occupancy plot. Values of BP ND for all subjects were calculated using this V ND estimate. Total volume of distribution (V T ) of MABs (2.94±0.31) was lower than V T of HABs (4.33±0.29) (Po0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50 ¼ 0.34±0.13 mg/kg). The occupancy plot provided a V ND estimate of 1.98 (1.69, 2.26). Based on these V ND estimates, BP ND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [ 11 C]PBR28 V ND and hence BP ND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating V ND for TSPO targeting radioligands.

Objective: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [11 C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]).Methods: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [ 11 C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation.Results: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p , 0.01), with significant regional increases in the parietal (p 5 0.001) and occipital (p 5 0.046) lobes and in the globus pallidus (p 5 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p , 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p , 0.05).Conclusions: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment.

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Acamprosate is one of the few medications licensed for prevention of relapse in alcohol dependence, and over time it has proved to be significantly, if moderately, effective, safe and tolerable. Its use is now being extended into other addictions and neurodevelopmental disorders. The mechanism of action of acamprosate has been less clear, but in the decade or more that has elapsed since its licensing, a body of translational evidence has accumulated, in which preclinical findings are replicated in clinical populations. Acamprosate modulates N-methyl-D-aspartic acid receptor transmission and may have indirect effects on g-aminobutyric acid type A receptor transmission. It is known to decrease brain glutamate and increase b-endorphins in rodents and man. Acamprosate diminishes reinstatement in ethanolized rodents and promotes abstinence in humans. Although acamprosate has been called an anticraving drug, its subjective effects are subtle and relate to diminished arousal, anxiety and insomnia, which parallel preclinical findings of decreased withdrawal symptoms in animals treated with acamprosate. Further understanding of the pharmacology of acamprosate will allow appropriate targeting of therapy in individuals with alcohol dependence and extension of its use to other addictions.

Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [11C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [11C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [11C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [11C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [11C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.

The objective of this study was to assess microglial activation in lesions and in normal-appearing white matter (NAWM) of multiple sclerosis (MS) patients using PET. Thirty-four MS patients (7 with secondary progressive MS [SPMS], 27 with relapsing remitting MS [RRMS]) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO) binding status, underwent PET scanning with TSPO radioligands (C-PBR28 or F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudoreference region). White matter lesions (WMLs) were classified as "active" (DVR highest in the lesion), "peripherally active" (perilesional DVR highest), "inactive" (DVR highest in surrounding NAWM), or "undifferentiated" (similar DVR across lesion, perilesional and NAWM volumes). The mean DVR in NAWM of patients was greater than that of the healthy volunteer white matter for both radioligands. Uptake for individual WML in patients was heterogeneous, but the median WML DVR and NAWM DVR for individual patients were strongly correlated (ρ = 0.94, = 4 × 10). A higher proportion of lesions were inactive in patients with SPMS (35%) than RRMS (23%), but active lesions were found in all patients, including those on highly efficacious treatments. TSPO radioligand uptake was increased in the brains of MS patients relative to healthy controls with 2 TSPO radiotracers. WML showed heterogeneous patterns of uptake. Active lesions were found in patients with both RRMS and SPMS. Their independent prognostic significance needs further investigation.