We're living much longer, but are we healthier?

This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc Advances in medicine mean that we are living longer and more economically productive lives. A triumph, no doubt, but one which needs to be tempered by the fact that the number of older people diagnosed with four or more diseases will double between 2015 and 2035 (Kingston et al., 2018). We are living longer, but for many, those extra years are blighted by ill health. Research in these past decades has highlighted the increase in the prevalence of neuropsychiatric disorders linked to changes in the physical and environmental stressors of our communities. These epidemiological studies have informed the development of novel neurodevelopmental models to study these psychiatric disorders. In fact, new and developing chronically stressful life situations, including recurrent infectious diseases such as viral epidemics, can increase the risk of developing psychosocial stress leading to depression, substance use disorders and pain disorders. Despite the epidemic scale of the problem and the unknown aetiology of these brain disorders as a consequence, the pharmacological or non-pharmacological treatments to stop or at least slow down their progression are not effective enough. In this Themed Issue, through a series of reviews and research articles focused on the aetiology of specific diseases, their symptomatology and new treatment strategies, how these disorders might be prevented is discussed. Cuadrado et al. (2022) address molecular fingerprints of resilient and susceptible phenotypes after a single traumatic exposure in mice. Deep analyses of microbiome, of circulating endocannabinoids, and long-term changes in brain phospholipid and transcript levels help to identify distinct sub-phenotypes within the trauma-exposed group. This approach may reveal future predictive biomarkers for the pharmacological treatment and prognosis of stress-related disorders. The current status of treatment-resistant depression in a wide spectrum of laboratory models and its pharmacological modalities is reviewed by Papp et al. (2022). The authors discuss both pharmacological (novel rapidly acting antidepressants targeting glutamate receptors or 5-HT1A receptors) and non-pharmacological (deep brain stimulation) strategies to treat people with major depressive disorders who do not respond adequately to a course of appropriate antidepressants. Bipolar disorder is discussed in detail in a paper authored by Wöhr (2022) where a valid measure for assessing mania-like elevated mood in rats with sufficient translational power is introduced. The author's perspective allows a better understanding of relevant pathophysiological mechanisms and the identification of new therapeutic targets. Personalized therapy treatment for major depressive disorder is emphasized by Borczyk et al. (2022) who address largely two pharmacogenes, CYP2D6 and CYP2C19, and variants related to drug metabolism, as guidelines for antidepressant prescriptions. Substance use disorder is a brain devastating disorder with a huge economic and social burden for modern society. Adolescence is an important ontogenetic period that can give rise to an increased risk of substance use. The article by Caffino et al. (2022) on “The Impact of Cocaine exposure in Adolescence” shows preclinical evidence on the interaction between psychostimulants and adolescence leading to dysfunctional brain neuroplasticity. The authors also indicate the translational interpretative framework for clinical studies involving addictive and affective or psychotic behaviours. Furthermore, in a research article, Fumagalli et al. (2022) bring evidence that rats with ablation of the serotonin transporter show increased cocaine intake after short or long duration access to cocaine self-administration, together with several disturbances in glutamate neural circuits. These data for the first time indicate that serotonin is pivotal for the maintenance of accumbal glutamate homeostasis and that its deletion sensitizes glutamatergic synapses after long access to cocaine. Apart from cocaine addiction, alcohol use disorder is still the most common and poorly treated psychiatric condition. This topic is discussed by Noworyta et al. (2022) in a review article on a novel concept of alcohol use disorder. The authors indicate that reinforcement-based cognitive biases (RBCBs) show neural, neurochemical, pharmacological correlates and trajectories of alcohol use disorder. Furthermore, reinforcement-based cognitive biases implicate various aspects of reinforcement sensitivity in the course of the disorder and their better understanding will certainly contribute to the development of new opportunities for both clinical and preclinical research in various aspects of alcohol use disorder. Several neurological disorders may also be associated with chronic pain, which can be challenging to manage. Indeed, clinical studies have revealed that chronic pain, as a stress state, often induces depression and that up to 85% of patients with chronic pain are affected by severe depression. Neuropathic pain, defined as a painful condition caused by neurological lesions or diseases, is difficult to treat. Bryk et al. (2022) address the functional properties and potential clinical applications of mesenchymal stem/stromal cells (MSCs) and their released extracellular vesicles (EVs), with a special focus on pain treatment. The analgesic, anti-inflammatory and regenerative properties of MSCs and EVs are discussed in detail for neuropathic pain, osteoarthritis and spinal cord injury. The pathophysiology of the diseases discussed above may overlap at multiple molecular levels and neurochemical pathways. It is well-known that many contributing factors, for example, signalling pathways, inflammatory processes, oxidative damage and mitochondrial impairment, are not exclusively related to a single pathology. The endocannabinoids (eCBs) 2-arachidonoylglycerol and anandamide are among the best-studied lipid messengers in the brain where they are implicated in molecular mechanisms and physiological functions. Elegantly, Kaczocha and Haj-Dahmane (2022) point out the new advances in the mechanisms of intracellular and synaptic eCB transport in the brain. On the other hand, the regulation of several neurotransmitters, oxidative homeostasis and inflammatory mediators by N-acetylcysteine (NAC), and its beneficial effects on different psychiatric disorders, including anxiety, bipolar disorder, depression and posttraumatic stress disorder, are reviewed by Smaga et al. (2021). Although NAC remains a strong candidate for adjunct treatment for many psychiatric disorders, more preclinical and clinical studies will help its future development. The important discoveries highlighted in the above articles were discussed during the Virtual 4th Central European Biomedical Congress (CEBC) titled The impact of bioinformatics and omics on biology and medicine. The Congress provided new information about the use of the latest technologies in biological and medical sciences, and new fields of science, such as proteomics, optogenomics, augmented reality and neural networks. We thank all authors, reviewers and editors for their contribution to this themed issue and the editors of the British Journal of Pharmacology for their continued support. The authors of this editorial wish to state that both have co-authored papers included in this themed issue (Smaga et al., 2021 and Bryk et al., 2022).