healthcare Editorial Biological and Clinical Aspects on the Treatment of Schizophrenia and Related Disorders: New Challenges José Antonio Monreal 1,2, * and Alexandre González-Rodríguez 1 1 Department of Mental Health, Mutua Terrassa University Hospital, Fundació Docència I Recerca Mutua Terrassa, University of Barcelona (UB), CIBERSAM, 08221 Terrassa, Spain 2 Institut de Neurociències, Universitat Autònoma de Barcelona (UAB), 08221 Terrassa, Spain * Correspondence: jamonreal@mutuaterrassa.cat For several decades, it has been postulated that dopaminergic pathways explain the neurobiology of schizophrenia, the biological underpinnings of treatment responses and the main mechanisms of action of antipsychotics [1]. The dopamine hypothesis explains how the vast majority of antipsychotics exert their positive effects in schizophrenia; however, other neurotransmitter pathways seem to explain how these drugs work on the brain [2]. Glutamatergic and serotonergic neurotransmitter systems have also been implicated, as have other biological compounds (e.g., hormones, inflammatory markers, etc.). Patients with schizophrenia exhibit marked positive and negative symptoms, cognitive and affective symptoms and suicidal ideation and behavior [3]. In many cases, social and occupational deficits are present, and they remain therapeutic challenges. The associations between neurotransmitter systems and other biological pathways with symptom domains have been investigated in recent decades. Although antipsychotics are considered the gold standard in the treatment of schizophrenia and related disorders [4], preclinical and clinical studies report that almost one-third of patients with schizophrenia fail to respond to standard antipsychotic treatment. Patients are thus classified as responders, Citation: Monreal, J.A.; non-responders, or refractory. In treatment-resistant cases, clozapine can be indicated, as González-Rodríguez, A. Biological and Clinical Aspects on the well as its combination with other therapies, for instance, psychological interventions [5]. Treatment of Schizophrenia and Recent studies have indicated that adding cognitive remediation, especially coping and Related Disorders: New Challenges. compensatory skills, to employment support services may improve global functioning in Healthcare 2022, 10, 1806. https:// schizophrenia [5]. doi.org/10.3390/healthcare10091806 The present Special Issue aims to summarize new evidence on the roles of biolog- ical systems interacting with dopamine and other neurotransmitters implicated in the Received: 8 September 2022 occurrence of psychotic symptoms and treatment responses in schizophrenia and related Accepted: 15 September 2022 disorders. The roles of stress hormones and other hormonal compounds in clinical presen- Published: 19 September 2022 tation (phenotype), physical health and responses to treatment will be explored. Evidence Publisher’s Note: MDPI stays neutral for the effectiveness of pharmacological and non-pharmacological interventions to treat with regard to jurisdictional claims in schizophrenia and related disorders is also welcome, with a special emphasis on treatments published maps and institutional affil- targeting emotions, cognitive symptoms and suicidal behavior. The impact of physical iations. health on psychotic symptoms and vice versa, and the risk of suicide, are also topics of interest. Author Contributions: J.A.M. and A.G.-R. wrote the first draft of the manuscript, collaborated on Copyright: © 2022 by the authors. subsequent versions, revised the paper and critically reviewed the content. All authors have read Licensee MDPI, Basel, Switzerland. and agreed to the published version of the manuscript. This article is an open access article distributed under the terms and Funding: This research received no external funding. conditions of the Creative Commons Conflicts of Interest: J.A.M. has received consultancy and/or lecture honoraria from Sanofi, Pfizer, Attribution (CC BY) license (https:// Servier, Janssen and Lundbeck–Otsuka. A.G.-R. has received free registrations or travel funds for creativecommons.org/licenses/by/ congress from Janssen, Lundbeck–Otsuka and Angelini. 4.0/). Healthcare 2022, 10, 1806. https://doi.org/10.3390/healthcare10091806 https://www.mdpi.com/journal/healthcare Healthcare 2022, 10, 1806 2 of 2 References 1. Seeman, M.V. History of the dopamine hypothesis of antipsychotic action. World J. Psychiatry 2021, 11, 355–364. [CrossRef] [PubMed] 2. Stone, J.M.; Raffin, M.; Morrison, P.; McGuire, P.K. Review: The biological basis of antipsychotic response in schizophrenia. J. Psychopharmacol. 2010, 24, 953–964. [CrossRef] [PubMed] 3. Jauhar, S.; Johnstone, M.; McKenna, P.J. Schizophrenia. Lancet 2022, 399, 473–486. [CrossRef] 4. Guàrdia, A.; González-Rodríguez, A.; Seeman, M.V.; Álvarez, A.; Estrada, F.; Acebillo, S.; Labad, J.; Monreal, J.A. Dopamine, Serotonin, and Structure/Function Brain Defects as Biological Bases for Treatment Response in Delusional Disorder: A Systematic Review of Cases and Cohort Studies. Behav. Sci. 2021, 11, 141. [CrossRef] [PubMed] 5. Burns, A.M.N.; Erickson, D.H. Adding Cognitive Remediation to Employment Support Services: A Randomized Controlled Trial. Psychiatr. Serv. 2022; in press.