Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association With Memory and Social Impairments and Abnormal Sensorimotor Gating

• Published in: The international journal of neuropsychopharmacology 2020-03, Vol.23 (1), p.53-65
• Main Authors: Vawter, Marquis P, Schulmann, Anton, Alhassen, Lamees, Alhassen, Wedad, Hamzeh, Abdul Rezzak, Sakr, Jasmine, Pauluk, Lucas, Yoshimura, Ryan, Wang, Xuejie, Dai, Qi, Sanathara, Nayna, Civelli, Olivier, Alachkar, Amal
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Behavior, Animal - physiology; Child; Child, Preschool; Development and progression; Diphtheria; Disabilities; Disease Models, Animal; Female; Fetus; Fishes; Free radicals; Genes; Genomes; Genomics; Health aspects; Hormone receptors; Hormones; Humans; Hyperactivity; Hypothalamic Hormones - metabolism; Infant; Male; Melanin; Melanins - metabolism; Memory disorders; Memory Disorders - etiology; Memory Disorders - physiopathology; Mice; Mice, Knockout; Middle Aged; Neurons; Phenotypes; Physiological aspects; Pituitary Hormones - metabolism; Prefrontal cortex; Prefrontal Cortex - metabolism; Receptors, Somatostatin - deficiency; Receptors, Somatostatin - metabolism; Regular s; RNA; RNA sequencing; Schizophrenia; Schizophrenia - complications; Schizophrenia - metabolism; Schizophrenia - physiopathology; Sensory gating; Sensory Gating - physiology; Young Adult
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1093/ijnp/pyz051

Abstract Background Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide melanin concentrating hormone system in modulating emotional and cognitive functions. Genome-wide association studies revealed a potential association between the melanin concentrating hormone receptor (MCHR1) gene locus and schizophrenia, and the largest genome-wide association study conducted to date shows a credible genome-wide association. Methods We analyzed MCHR1 and pro-melanin concentrating hormone RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the melanin concentrating hormone system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of melanin concentrating hormone expressing neurons using a Cre-inducible diphtheria toxin system. Results MCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (false discovery rate (FDR) P