Pathophysiological mechanisms of increased cardiometabolic risk in people with schizophrenia and other severe mental illnesses

Henderson, David C.; Vincenzi, Brenda; Andrea, Nicolas V; Ulloa, Melissa; Copeland, Paul M.

doi:10.1016/s2215-0366(15)00115-7

Cited by 233 publications

(184 citation statements)

References 129 publications

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“…In schizophrenia, the reduced life expectancy carries higher cardio-metabolic risks compared to the general population [32]. Pharmacotherapy focusing on the cross-talks of metabolic pathways and neural plasticity has met with marginal progress in improving the general well-being of patients with schizophrenia.…”

Section: Nmda-glutamate Signaling and Curcuminmentioning

confidence: 99%

“…In the primary retinal and hippocampal neuronal culture using whole-call patch-clamp, curcumin treatment protected against NMDA cell death through reduction of NMDA-induced [Ca(2+)] (i) current rise: the kinetics was time-and dose-dependent. Furthermore, curcumin neuroprotection correlated significantly with increased activity of NMDA-NR2A level.In schizophrenia, the reduced life expectancy carries higher cardio-metabolic risks compared to the general population [32]. Pharmacotherapy focusing on the cross-talks of metabolic pathways and neural plasticity has met with marginal progress in improving the general well-being of patients with schizophrenia.…”

mentioning

confidence: 99%

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Targeting Epigenetics Signaling with Curcumin: A Transformative Drug Lead in Treatment of Schizophrenia?

Chiu¹,

Woodbury-Fariña²,

Terpstra³

et al. 2017

J Clin Epigenet

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While pharmacotherapy of second generation of atypical antipsychotics: clozapine, olanzapine, risperidol, quetiapine, ziprasidone, aripiprazole bring about significant improvement in the positive symptoms of schizophrenia [1], overall psychosocial outcomes in schizophrenia remain modest. Significant functional impairment related to negative symptoms (lack of volition, apathy, sociality, poverty of speech and affective flattening), active positive symptoms (delusions, hallucinations and bizarre behavioral disturbances) and neuro-cognition deficits, persists in 20-30% of patients with schizophrenia refractory to AbstractDespite advances in pharmacotherapy, schizophrenia continues to carry a high societal disease burden related to positive and negative symptoms, and neurocognitive deficits and severe functional impairment. Findings from epigenetics have yet to translate the epigenetics targets to efficacious drug therapy. We review the repertoire of CNS pharmacology of curcumin derived from Curcuma Longa, commonly known as "turmeric": the well-known curry extract. We highlight the body of evidence in support of the emerging role of curcumin as a panhistone deacetylase (HDAC) inhibitor regulating the expression of genes involved in inflammation and NMDA N-methyl-aspartic acid (NMDA)-glutamate systems, as related to schizophrenia. Based on the findings from translational studies of curcumin extracts, curcumin C-3 complex formulation (Supercurcumin TM ) and patented liposome-based curcumin (Lipocurc TM ), we propose that intravenous infusion of Lipocurc TM holds promise as the novel drug lead and preferred targeted brain delivery mode in reprogramming faculty epigenetics network and in remodeling restrictive chromatin configuration in schizophrenia. Phase II/Phase III epigenetics-biomarker-based randomized placebo-controlled trials in treatment resistant schizophrenia are warranted. Our approach of intravenous infusion of Lipocurc TM behaving as pan HDAC inhibitor represents a new paradigm of drug development in combining targeting epigenetics footprints with brain-specific drug delivery system in schizophrenia. Lipocurc TM can open the Pandora box in unexplored therapeutics vistas in modifying the phenotype of treatment resistant schizophrenia. [2]. Major breakthroughs in schizophrenia therapeutics are yet forthcoming. It becomes imperative to design molecular genetics and epigenetic tools to predict treatment responses, and to translate novel CNS drug targets for accelerating the development of new therapeutics for treatment refractory schizophrenia. Drug platforms require refinement of translational models of schizophrenia to catalyze clinical trials and to predict treatment responses. In the post-genomic era, deciphering the epigenetic code of the human genomes represents a major challenge in CNS disorders. A growing body of evidence supports dysregulation of epigenetics signaling: DNA methylation, histone modifications and microRNA, plays a significant role in schizophrenia [3][4][5]. Findings from studies of p...

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Section: Nmda-glutamate Signaling and Curcuminmentioning

confidence: 99%

mentioning

confidence: 99%

Targeting Epigenetics Signaling with Curcumin: A Transformative Drug Lead in Treatment of Schizophrenia?

Chiu¹,

Woodbury-Fariña²,

Terpstra³

et al. 2017

J Clin Epigenet

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“…Weight changes associated with use of antipsychotic drugs are related to their effect on different modulators of appetite and of energy balance [4]. Compared with conventional antipsychotics, olanzapine and clozapine rapidly increase leptin concentrations during the first 2 weeks after treatment and this increased level is maintained for several months [12].…”

Section: Antipsychotics-associated Weight Gainmentioning

confidence: 99%

“…It is thought that most of lipid abnormalities are related to weight gain in the course of antipsychotic treatments and to obesity-induced insulin resistance [4], but a direct effect of these drugs on lipid metabolism cannot be excluded.…”

Section: Antipsychotics-associated Dyslipidemiamentioning

confidence: 99%

“…The main causes of premature death are suicide, cancer, and cardiovascular disease [3]. Several categories of factors contribute to the reduced life expectancy in patients with schizophrenia and other SMI [3,4]: suboptimal lifestyle choices including unhealthy diet, low or no physical activity, excessive smoking and alcohol consumption; higher prevalence of comorbid conditions such as diabetes, cardiovascular disease and cancer; side effects of antipsychotic drugs (weight gain, glucose intolerance and new-onset diabetes, hyperlipidemia); late diagnosis and insufficient treatment of physical illnesses; risk of suicide and accidents.…”

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confidence: 99%

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Severe Mental Illnesses and Metabolic Syndrome: The Need for More Awareness and Better Care

Bala

Nita²,

Hâncu

2016

Romanian Journal of Diabetes Nutrition and Metabolic Diseases

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Developmental Trajectory of Body Weight in Youths at Risk for Major Mood Disorders

Adepalli,

Cumby,

Campbell

et al. 2023

JAMA Netw Open

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ImportanceMood disorders are associated with increased body weight, especially in females, but it remains unknown when the weight increase starts.ObjectivesTo examine sex-specific weight trajectories associated with familial mood disorder risk and determine the age at which youth at familial risk for mood disorders begin to diverge in weight from controls.Design, Setting, and ParticipantsThis community-based, single-center, acceleration cohort study of youth at familial risk for mood disorders and controls with yearly follow-ups (mean [SD], 5 [2.1] years) from January 1, 2014, to December 31, 2022, assessed 394 unaffected female and male offspring (aged 3 to 20 years) of parents with or without a mood disorder. Parents with mood (depressive or bipolar) disorders were recruited through adult mental health services. Parents of control participants were matched on age and socioeconomic factors and recruited through acquaintance referrals or schools.ExposuresThe youth in the familial mood risk group had at least 1 parent with a major mood disorder, whereas control youth did not have a parent with a mood disorder.Main Outcomes and MeasuresBody mass indexes (BMIs) were calculated as weight in kilograms divided by height in meters squared from measured weight and height at annual assessments and then converted to age- and sex-adjusted z scores (zBMIs). Repeated-measure regressions examined the association between zBMI and age in youth at familial risk of mood disorders and controls while accounting for sex. Sensitivity analyses accounted for socioeconomic status, prematurity, and birth weight.ResultsOf 394 participants (mean [SD] age, 11.5 [3.6] years; 203 [51.5%] female), youths at familial risk for mood disorders showed overall no difference in body weight (β = 0.12; 95% CI, 0.01-0.24) from controls. A sex-specific difference was detected, with females at familial risk showing a rapid peripubertal increase in body weight, leading to significantly increased zBMIs at 12 years and older compared with controls (β = 0.57; 95% CI, 0.31-0.82) independent of socioeconomic status, prematurity, or birth weight. Males did not differ from controls at any age.Conclusions and RelevanceIn this cohort study, females with a family history of mood disorders were prone to weight gain starting around puberty and predating mood disorder onset. Early interventions aiming to prevent adverse mental and physical outcomes in this vulnerable group need to start in childhood.

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Pathophysiological mechanisms of increased cardiometabolic risk in people with schizophrenia and other severe mental illnesses

Cited by 233 publications

References 129 publications

Targeting Epigenetics Signaling with Curcumin: A Transformative Drug Lead in Treatment of Schizophrenia?

Targeting Epigenetics Signaling with Curcumin: A Transformative Drug Lead in Treatment of Schizophrenia?

Severe Mental Illnesses and Metabolic Syndrome: The Need for More Awareness and Better Care

Developmental Trajectory of Body Weight in Youths at Risk for Major Mood Disorders

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