Adipose tissue as a target for second-generation (atypical) antipsychotics: A molecular view

Ferreira, Vítor; Grajales, Diana; Valverde, Ángela M.

doi:10.1016/j.bbalip.2019.158534

Cited by 23 publications

(29 citation statements)

References 169 publications

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“…AP-, we did not find the levels to be significantly modified by AP use. While several studies report low levels of adiponectin with AP use, and in particular in patients receiving second generation AP treatment (30,32), few of these studies compare with HC which in our study showed similar levels as in SMI. The differences in L/A ratio between SMI and HC in our study largely reflect leptin levels, since no major dysregulation in adiponectin was detected.…”

Section: Discussioncontrasting

confidence: 66%

“…Increased fat mass is accompanied by infiltration of various myeloid immune cells (such as neutrophils, monocytes and macrophages) in adipose tissue, and altered secretion of adipokines including reduced expression of the insulin sensitizing adiponectin (25)(26)(27). Furthermore, AP treatment has been shown to promote monocyte infiltration, macrophage effector functions and inflammation in adipose tissue in experimental studies (28)(29)(30), as well as to regulate adiponectin expression and secretion (30). Thus, dysregulated adiponectin levels could be expected to be particularly low in AP treatment users.…”

Section: Discussionmentioning

confidence: 99%

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Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment

et al. 2021

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Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, and quetiapine have been associated with high leptin levels in SMI. However, the link between inflammatory dysregulation of leptin and adiponectin and CVD risk in SMI, and how this risk is influenced by body mass and AP medication, is still not completely understood. We investigated herein if leptin, adiponectin or their ratio (L/A ratio) could predict increased CVD risk in SCZ, BD, and in subgroups according to use of antipsychotic (AP) treatment, independent of other cardio-metabolic risk factors.Methods: We measured fasting plasma levels of leptin and adiponectin, and calculated the L/A ratio in n = 1,092 patients with SCZ and BD, in subgroups according to AP treatment, and in n = 176 healthy controls (HC). Differences in the levels of adipokines and L/A between groups were examined in multivariate analysis of covariance, and the correlations between adipokines and body mass index (BMI) with linear regression. CVD risk was defined by total cholesterol/high-density lipoprotein (TC/HDL) and triglyceride/HDL (TG/HDL) ratios. The adipokines and L/A ratios ability to discriminate individuals with TG/HDL and TC/HDL ratios above threshold levels was explored by ROC analysis, and we investigated the possible influence of other cardio-metabolic risk factors on the association in logistic regression analyses.Results: We observed higher leptin levels and L/A ratios in SMI compared with HC but found no differences in adiponectin. Both adipokines were highly correlated with BMI. The low adiponectin levels showed a fair discrimination in ROC analysis of individuals with CVD risk, with AUC between 0.7 and 0.8 for both TC/HDL and TG/HDL, in all groups examined regardless of diagnosis or AP treatment. Adiponectin remained significantly associated with an elevated TC/HDL and TG/HDL ratio in SMI, also after further adjustment with other cardio-metabolic risk factors.Conclusions: Adiponectin is not dysregulated in SMI but is associated with CVD risk regardless of AP treatment regime.

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Section: Discussioncontrasting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment

et al. 2021

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“…The storage of lipophilic drugs in fatty tissue also accounts for adverse effects such as weight gain, more prevalent in women than in men. For this reason, adipose tissue is now being targeted by developers of antipsychotic drugs [19].…”

Section: Gender Differences In Schizophreniamentioning

confidence: 99%

“…Hyperprolactinemia is more prevalent in women because baseline levels are already higher than they are in men [20,21]. High prolactin disrupts menstrual cycles, diminishes fertility and leads to galactorrhea, amenorrhea, hirsutism and acne [19]. It is an important cause of osteoporosis and has been suspected of contributing to breast cancer risk [23].…”

Section: Gender Differences In Schizophreniamentioning

confidence: 99%

Women with Schizophrenia over the Life Span: Health Promotion, Treatment and Outcomes

González-Rodríguez

Guàrdia²,

Pedrero

et al. 2020

IJERPH

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Women with schizophrenia show sex-specific health needs that differ according to stage of life. The aim of this narrative review is to resolve important questions concerning the treatment of women with schizophrenia at different periods of their life—paying special attention to reproductive and post-reproductive stages. Review results suggest that menstrual cycle-dependent treatments may be a useful option for many women and that recommendations re contraceptive options need always to be part of care provision. The pregnancy and the postpartum periods—while constituting vulnerable time periods for the mother—require special attention to antipsychotic effects on the fetus and neonate. Menopause and aging are further vulnerable times, with extra challenges posed by associated health risks. Pregnancy complications, neurodevelopmental difficulties of offspring, cancer risk and cognitive defects are indirect results of the interplay of hormones and antipsychotic treatment of women over the course of the lifespan. The literature recommends that health promotion strategies need to be directed at lifestyle modifications, prevention of medical comorbidities and increased psychosocial support. Careful monitoring of pharmacological treatment has been shown to be critical during periods of hormonal transition. Not only does treatment of women with schizophrenia often need to be different than that of their male peers, but it also needs to vary over the course of life.

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“…In particular, AP‐treated patients have been found to display both reduced adiponectin and elevated leptin compared to controls, 81–83 a pattern which is associated with poor metabolic health including increased adiposity and insulin resistance 8,84,85 . Beyond affecting adipokine release, APs may also directly disrupt lipid metabolism in adipose tissue by increasing the expression of lipogenic genes involved in fatty acid synthesis 86–90 . Furthermore, both pre‐clinical and clinical findings suggest that APs may increase expression of pro‐inflammatory cytokines such as interleukins, tumor necrosis factor‐α, and monocyte chemoattractant protein‐1 in adipose tissue, although whether this is a cause or consequence of AP‐associated adiposity is unclear 67,91–93 .…”

Section: Discussionmentioning

confidence: 99%

Adiposity in schizophrenia: A systematic review and meta‐analysis

Smith

Singh

Lee

et al. 2021

Acta Psychiatr Scand

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Objective Although a relationship between schizophrenia (SCZ), antipsychotic (AP) medication, and metabolic dysregulation is now well established, the effect of adiposity is less well understood. By synthesizing findings from imaging techniques that measure adiposity, our systematic review and meta‐analysis (PROSPERO CRD42020192977) aims to determine the adiposity‐related effects of illness and treatment in this patient population. Methods We searched MEDLINE, EMBASE, PsychINFO and Scopus for all relevant case‐control and prospective longitudinal studies from inception until February 2021. Measures of adiposity including percent body fat (%BF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were analyzed as primary outcomes. Results Our search identified 29 articles that used imaging methods to quantify adiposity among patients with SCZ spectrum disorders. Analyses revealed that patients have greater %BF (mean difference (MD) = 3.09%; 95% CI: 0.75–5.44), SAT (MD = 24.29 cm2; 95% CI: 2.97–45.61) and VAT (MD = 33.73 cm2, 95% CI: 4.19–63.27) compared to healthy controls. AP treatment was found to increase SAT (MD = 31.98 cm2; 95% CI: 11.33–52.64) and VAT (MD = 16.30 cm2; 95% CI: 8.17–24.44) with no effect on %BF. However, change in %BF was higher for AP‐free/AP‐naïve patients compared to treated patients. Conclusion Our findings indicate that patients with SCZ spectrum disorders have greater adiposity than healthy controls, which is increased by AP treatment. Young, AP‐naïve patients may be particularly susceptible to this effect. Future studies should explore the effect of specific APs on adiposity and its relation to overall metabolic health.

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Adipose tissue as a target for second-generation (atypical) antipsychotics: A molecular view

Cited by 23 publications

References 169 publications

Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment

Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment

Women with Schizophrenia over the Life Span: Health Promotion, Treatment and Outcomes

Adiposity in schizophrenia: A systematic review and meta‐analysis

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