2. Academic Validation
  3. Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders

Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders

  • Trends Neurosci. 2023 Jan;46(1):60-74. doi: 10.1016/j.tins.2022.10.010.
Els F Halff 1,  Grazia Rutigliano 2,  Anna Garcia-Hidalgo 2,  Oliver D Howes 3
Affiliations

Affiliations

  • 1 Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; Psychiatric Imaging Group, Medical Research Council (MRC) London Institute of Medical Sciences, London, UK.
  • 2 Psychiatric Imaging Group, Medical Research Council (MRC) London Institute of Medical Sciences, London, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
  • 3 Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; Psychiatric Imaging Group, Medical Research Council (MRC) London Institute of Medical Sciences, London, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK; South London and Maudsley National Health Service (NHS) Foundation Trust, Camberwell, London, UK; H. Lundbeck A/S, St Albans, UK. Electronic address: [email protected].
PMID: 36369028 DOI: 10.1016/j.tins.2022.10.010
Abstract

Schizophrenia remains a major health burden, highlighting the need for new treatment approaches. We consider the potential for targeting the trace amine (TA) system. We first review genetic, preclinical, and clinical evidence for the role of TAs in the aetiopathology of schizophrenia. We then consider how the localisation and function of the trace amine-associated receptor 1 (TAAR1) position it to modulate key brain circuits for the disorder. Studies in rodents using Taar1 knockout (TAAR1-KO) and overexpression models show that TAAR1 agonism inhibits midbrain dopaminergic and serotonergic activity, and enhances prefrontal glutamatergic function. TAAR1 agonists also reduce hyperactivity, attenuate prepulse inhibition (PPI) deficits and social withdrawal, and improve cognitive measures in animal models. Finally, we consider findings from clinical trials of TAAR1 agonists and how this approach may address psychotic and negative symptoms, tolerability issues, and other unmet needs in the treatment of schizophrenia.

Keywords

antipsychotic; circuits; intracellular signalling; neurotransmitters; pathophysiology; psychosis.

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