Individuals experience loneliness when they perceive a deficiency in the quality or quantity of their social relationships. In the present meta-analysis, we compiled data from 75 longitudinal studies conducted in Asia, Australia, Europe, and North America ( N = 83, 679) to examine the rank-order and mean-level development of loneliness across the life span. Data were analyzed using two- and three-level meta-analyses and generalized additive mixed models. The results indicate that the rank order of loneliness is as stable as the rank order of personality traits and follows an inverted U-shaped trajectory across the life span. Regarding mean-level development, loneliness was found to decrease throughout childhood and to remain essentially stable from adolescence to oldest old age. Thus, in contrast to other personality characteristics, changes in loneliness are not generally related to age. Implications for theory are discussed.

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Background: Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to manage chronic and acute surgical pain. The variability in response to methadone has been widely recognized. The purpose of this article is to review the literature on the pharmacogenetic factors underlying this variability. Materials & methods: This is a narrative overview of the literature on the genetic variants affecting pharmacodynamics and pharmacokinetics of methadone, retrieved from searches of databases such as PubMed and google scholar. Discussion: Clinical responses to methadone may be affected by genetic variants in the opioidergic, dopaminergic and neurotrophic pathways. Polymorphisms in genes related to disposition and elimination of methadone alter the pharmacokinetics, and possibly pharmacodynamics of methadone. Cytochrome P450 enzymes and P-glycoprotein variants contribute to the interindividual variability in methadone pharmacokinetics. Evidence for single gene variants affecting methadone response remains weak. Multiple genetic variants must be considered in conjunction to improve predictive ability. Conclusion: Evidence remains scarce at this time, to recommend pharmacogenetic testing before methadone administration. Well-powered clinical studies are needed with population pharmacokinetic-pharmacodynamic modeling and multigenetic signature-based predictions to enable tailored use of methadone in clinical practice.

Purpose of review The current review will discuss the current literature on genetics of pain and analgesia, with special emphasis on perioperative setting. We will also discuss pharmacogenetics-based management guidelines, current clinical status and future perspectives. Recent findings Recent literature suggests that the interindividual variability in pain and postoperative analgesic response is at least in part because of one’s genetic make-up. Some of the well characterized polymorphisms that are associated with surgical pain and opioid-related postoperative adverse outcomes are described in catechol-O-methyl transferase, CYP2D6 and μ-opioid receptor (OPRM1), ATP-binding cassette subfamily B member 1, ABCC3, organic cation transporter 1 genes. Clinical Pharmacogenetics Implementation Consortium has put forth recommendations on CYP2D6 genotype-based opioid selection and dosing. The list of drug–gene pairs studied continue to expand. Summary Pharmacogenetic approach marks the dawn of personalized pain medicine both in perioperative and chronic pain settings.