A higher body mass index in Chinese inpatients with chronic schizophrenia is associated with elevated plasma orexin-A levels and fewer negative symptoms

Liu, Zhiwei; Zhang, Yulong; Zhao, Tuanjie; Wang, Juan; Xia, Lei; Zhong, Yi; Yang, Yating; Ning, Xiaoshuai; Zhang, Yelei; Ren, Zhenhua; Liu, Huanzhong

doi:10.1080/08039488.2020.1755995

Cited by 14 publications

(13 citation statements)

References 42 publications

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“…Similar to human studies, most animal studies support the idea that SPA and NEAT confer protection against obesity. Mechanisms controlling NEAT and exercise involve orexin neurons (Garland Jr. et al, 2011;Nixon et al, 2012;Teske et al, 2008), and our previous work shows that the orexin system is central for the regulation of vigilance states, SPA, NEAT, and energy balance (C. M. Kotz et al, 2017), and that LH orexin is protective against weight gain (Bunney et al, 2017;DePorter et al, 2017;Levin et al, 1997;Z. Liu et al, 2020;Teske et al, 2006).…”

Section: Orexin Spontaneous Physical Activity and Energy Expenditurementioning

confidence: 99%

Orexin, serotonin, and energy balance

Mavanji

Pomonis

Kotz

2021

WIREs Mechanisms of Disease

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The lateral hypothalamus is critical for the control of ingestive behavior and spontaneous physical activity (SPA), as lesion or stimulation of this region alters these behaviors. Evidence points to lateral hypothalamic orexin neurons as modulators of feeding and SPA. These neurons affect a broad range of systems, and project to multiple brain regions such as the dorsal raphe nucleus, which contains serotoninergic neurons (DRN) important to energy homeostasis. Physical activity is comprised of intentional exercise and SPA. These are opposite ends of a continuum of physical activity intensity and structure. Non-goal-oriented behaviors, such as fidgeting, standing, and ambulating, constitute SPA in humans, and reflect a propensity for activity separate from intentional activity, such as highintensity voluntary exercise. In animals, SPA is activity not influenced by rewards such as food or a running wheel. Spontaneous physical activity in humans and animals burns calories and could theoretically be manipulated pharmacologically to expend calories and protect against obesity. The DRN neurons receive orexin inputs, and project heavily onto cortical and subcortical areas involved in movement, feeding and energy expenditure (EE). This review discusses the function of hypothalamic orexin in energy-homeostasis, the interaction with DRN serotonin neurons, and the role of this orexin-serotonin axis in regulating food intake, SPA, and EE. In addition, we discuss possible brain areas involved in orexin-serotonin cross-talk; the role of serotonin receptors, transporters and uptake-inhibitors in the pathogenesis and treatment of obesity; animal models of obesity with impaired serotonin-function; single-nucleotide polymorphisms in the serotonin system and obesity; and future directions in the orexin-serotonin field.

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Section: Orexin Spontaneous Physical Activity and Energy Expenditurementioning

confidence: 99%

Orexin, serotonin, and energy balance

Mavanji

Pomonis

Kotz

2021

WIREs Mechanisms of Disease

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“…Down-regulation of ABCA13 expression affects lipid metabolism and leads to abnormal lipid metabolism in patients with schizophrenia. In fact, the malfunctions of lipid metabolism have been found in patients with schizophrenia in our previous studies 16 , 27 . In this study, we also found that ABCA13 mRNA levels were increased after 12 weeks antipsychotic therapy.…”

Section: Discussionmentioning

confidence: 74%

ATP-binding cassette transporter 13 mRNA expression level in schizophrenia patients

Chen

et al. 2020

Sci Rep

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The objective of this study was to investigate the expression and clinical role of ATP-binding cassette transporter 13 (ABCA13) gene previously shown to be associated with schizophrenia (SZ) through Genome-wide association studies studies. Thirty-two first-episode drug-naive SZ patients and forty-eight age and gender-matched healthy controls were enrolled in this study. We measured ABCA13 mRNA expression levels using quantitative real-time PCR at baseline and 12 weeks after antipsychotic therapy. Moreover, clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) at baseline and 12-week follow-up. We found that ABCA13 mRNA levels were significantly lower in SZ patients compared with healthy controls at baseline. SZ patients’ symptoms were decreased, but ABCA13 mRNA levels were increased after 12 weeks antipsychotic therapy. In addition, there was a significant difference in ABCA13 mRNA levels among SZ patients at baseline and 12-week follow-up. The ABCA13 mRNA levels were not associated with age, BMI, years of education. Of the clinical symptoms measured, the ABCA13 mRNA levels were negatively associated with the PANSS scores at baseline and 12-week follow-up. The results indicated that the ABCA13 mRNA expression level is of interest, and upon further studies, it could be used as a biomarker for SZ treatment outcome.

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“…Liu group found higher plasma hypocretin levels in obese SCZ patients and proposed that hypocretin might be a factor affecting the BMI of SCZ patients. 10 In addition, another study showed SCZ patients had significantly higher plasma hypocretin-1 levels than healthy controls. However, the finding that SCZ patients with high (>80 pg/ml) hypocretin levels had significantly fewer negative and disorganized symptoms than the patients with low (<80pg/mL) hypocretin levels was proposed to be related to the fact that all the SCZ patients in their study were taking antipsychotic treatments.…”

Section: Discussionmentioning

confidence: 99%

“…7 Although several clinical studies have reported changes in plasma hypocretin-1 levels in SCZ, their findings appear equivocal. Some studies showed that elevated plasma hypocretin-1 levels in SCZ patients were related to negative and disorganized symptoms, 5,8,9 or obesity, 10 whereas a meta-analysis showed no difference in plasma hypocretin-1 levels between SCZ and controls. 11 In addition, a disordered plasma hypocretin-1 circadian rhythm of was found in SCZ patients, with a peak phase delay of 4 hours.…”

Section: Introductionmentioning

confidence: 99%

Changes of Hypocretin (Orexin) System in Schizophrenia: From Plasma to Brain

Huang

et al. 2021

Schizophrenia Bulletin

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Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. In addition, we measured postmortem hypothalamic hypocretin-1-immunoreactivity (ir), ventricular cerebrospinal fluid (CSF) hypocretin-1 levels, and hypocretin receptor (Hcrt-R) mRNA expression in the superior frontal gyrus (SFG) in SCZ patients and controls We observed a significant decrease in the amount of hypothalamic hypocretin-1 ir in SCZ patients, which was due to decreased amounts in female but not male patients. Moreover, Hcrt-R2 mRNA in the SFG was decreased in female SCZ patients compared with female controls, while male SCZ patients showed a trend of increased Hcrt-R1 mRNA and Hcrt-R2 mRNA expression compared with male controls. We conclude that central hypocretin neurotransmission is decreased in SCZ patients, especially female patients, and this is reflected in the plasma.

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A higher body mass index in Chinese inpatients with chronic schizophrenia is associated with elevated plasma orexin-A levels and fewer negative symptoms

Cited by 14 publications

References 42 publications

Orexin, serotonin, and energy balance

Orexin, serotonin, and energy balance

ATP-binding cassette transporter 13 mRNA expression level in schizophrenia patients

Changes of Hypocretin (Orexin) System in Schizophrenia: From Plasma to Brain

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