title: Dissecting negative symptoms in schizophrenia: opportunities for translation into new treatments.
abstract: Among the constellation of symptoms that characterize schizophrenia, negative symptoms have emerged as a critical feature linked to the functional impairment experienced by affected individuals. Despite advances in our understanding of the role of negative symptoms in the illness, effective treatments for these debilitating symptoms have remained elusive. In this review we explore the contemporary conceptualization of negative symptoms in schizophrenia, including the identification of two key subdomains of diminished expression and amotivation, and clarifications around hedonic capacity. We then explore strategies for clinical assessments of negative symptoms, followed by findings using objective paradigms for evaluating discrete aspects of these negative symptoms in clinical populations and animal models, both for symptoms of diminished expression and within the multifaceted motivation system. We conclude with a consideration of current strategies for drug development for these negative symptoms, the role of heterogeneity in the clinical presentation of symptoms in schizophrenia and opportunities for personalized assessment and treatment approaches, as well as a commentary on current clinical drug trial design and the role of environmental opportunities for novel treatments to effect change and improve outcomes for affected individuals.
authors.affiliation: Campbell Family Mental Health Research Institute, and Schizophrenia Division - Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada Institute of Medical Science, University of Toronto, Toronto, ON, Canada george.foussias@camh.ca.
authors.forename: George
authors.initials: G
authors.lastname: Foussias
authors.affiliation: Campbell Family Mental Health Research Institute, and Schizophrenia Division - Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Ishraq
authors.initials: I
authors.lastname: Siddiqui
authors.affiliation: Campbell Family Mental Health Research Institute, and Schizophrenia Division - Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Gagan
authors.initials: G
authors.lastname: Fervaha
authors.affiliation: Campbell Family Mental Health Research Institute, and Schizophrenia Division - Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Ofer
authors.initials: O
authors.lastname: Agid
authors.affiliation: Campbell Family Mental Health Research Institute, and Schizophrenia Division - Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology*; D012565:Schizophrenic Psychology
chemical_list: D014150:Antipsychotic Agents
keywords: Motivational deficits; affective flattening; alogia; expressive deficits; hedonic capacity; objective paradigms