Adult Attention Deficit Hyperactivity Disorder and Violence in the Population of England: Does Comorbidity Matter?

It is unclear whether the association between Attention Deficit/Hyperactivity Disorder (ADHD) and violence is explained by ADHD symptoms or co-existing psychopathology. We investigated associations of ADHD and its symptom domains of hyperactivity and inattention, among individuals reporting violence in the UK population. Methods We report data from the Adult Psychiatric Morbidity Survey (2007), a representative sample of the household population of England. A randomly selected sample of 7,369 completed the Adult Self-Report Scale for ADHD and the self-reported violence module, including repetition, injury, minor violence, victims and location of incidents. All models were weighted to account for non-response and carefully adjusted for demography and clinical predictors of violence: antisocial personality, substance misuse and anxiety disorders. Results ADHD was moderately associated with violence after adjustments (OR 1.75, p = .01). Hyperactivity, but not inattention was associated with several indicators of violence in the domestic context (OR 1.16, p = .03). Mild and moderate ADHD symptoms were significantly associated with violence repetition, but not severe ADHD where the association was explained by co-existing disorders. Stratified analyses further indicated that most violence reports are associated with co-occurring psychopathology. Conclusions The direct effect of ADHD on violence is only moderate at the population level, driven by hyperactivity, and involving intimate partners and close persons. Because violence associated with severe ADHD is explained by co-existing psychopathology, interventions should primarily target co-existing disorders

Recent Updates on the Melanin-Concentrating Hormone (MCH) and Its Receptor System: Lessons from MCH1R Antagonists

Melanin-concentrating hormone (MCH) is a 19-amino-acid cyclic peptide which was originally found to lighten skin color in fish that is highly conserved among many species. MCH interacts with two G-protein-coupled receptors, MCH1R and MCH2R, but only MCH1R is expressed in rodents. MCH is mainly synthesized in the lateral hypothalamus and zona incerta, while MCH1R is widely expressed throughout the brain. Thus, MCH signaling is implicated in the regulation of many physiological functions. The identification of MCH1R has led to the development of small-molecule MCH1R antagonists that can block MCH signaling. MCH1R antagonists are useful not only for their potential therapeutic value, but also for understanding the physiological functions of the endogenous MCH system. Here, we review the physiological functions of the MCH system which have been investigated using MCH1R antagonists such as food intake, anxiety, depression, reward, and sleep. This will help us understand the physiological functions of the MCH system and suggest some of the potential applications of MCH1R antagonists in human disorders

Synthesis and evaluation of an 18F-labeled derivative of F3 for targeting surface expressed nucleolin in cancer and tumor endothelial cells

Surface overexpression of nucleolin provides an anchor for specific attachment of biomolecules to cancer and angiogenic endothelial cells. The peptide F3 is a high affinity ligand of the nucleolin receptor (NR) thathas been investigated as a carrier to deliver biologically active molecules to tumors for both therapeutic and imaging applications. A site-specifically PEGylated F3 derivative was radiolabeled with [18F] AlF3. Binding affinity and cellular distribution ofthe compound was assessed in tumor (H2N) and tumor endothelial (2H-11) cells. Specific uptake via the NR was demonstrated by siRNA knockdown of nucleolin in both cell lines. Partition and plasma stability of the compound were assessed at 37°C. Enzyme-mediated site-specific modification of F3 to give NODA-PEG-F3 (NP-F3) was achieved. Radiolabeling with [18F] Al-F gave 18F-NP-F3. 18F-NP-F3 demonstrated high affinity for cancer and tumor endothelial cells. SiRNA knockdown of nucleolin resulted in a binding affinity reduction of 50-60 %, confirming cell surface binding via the NR. NP-F3 was stable in serum for 2 h. 18F-NP-F3 is reported as the first 18F-labeled F3 derivative. It was obtained in a site-specific, high-yield and efficient manner, and binds to surface NR in the low nanomolar range suggesting it has potentialas a tumor and angiogenesis tracer

Synthesis and evaluation of an 18F-labeled derivative of F3 for targeting surface expressed nucleolin in cancer and tumor endothelial cells

Surface overexpression of nucleolin provides an anchor for specific attachment of biomolecules to cancer and angiogenic endothelial cells. The peptide F3 is a high affinity ligand of the nucleolin receptor (NR) thathas been investigated as a carrier to deliver biologically active molecules to tumors for both therapeutic and imaging applications. A site-specifically PEGylated F3 derivative was radiolabeled with [18F] AlF3. Binding affinity and cellular distribution ofthe compound was assessed in tumor (H2N) and tumor endothelial (2H-11) cells. Specific uptake via the NR was demonstrated by siRNA knockdown of nucleolin in both cell lines. Partition and plasma stability of the compound were assessed at 37°C. Enzyme-mediated site-specific modification of F3 to give NODA-PEG-F3 (NP-F3) was achieved. Radiolabeling with [18F] Al-F gave 18F-NP-F3. 18F-NP-F3 demonstrated high affinity for cancer and tumor endothelial cells. SiRNA knockdown of nucleolin resulted in a binding affinity reduction of 50-60 %, confirming cell surface binding via the NR. NP-F3 was stable in serum for 2 h. 18F-NP-F3 is reported as the first 18F-labeled F3 derivative. It was obtained in a site-specific, high-yield and efficient manner, and binds to surface NR in the low nanomolar range suggesting it has potentialas a tumor and angiogenesis tracer