Hormonal Correlates of Clozapine-Induced Weight Gain in Psychotic Children: An Exploratory Study

Sporn, Alexandra; Bobb, Anne; Gogtay, Nitin; Stevens, Hanna E.; Greenstein, Deanna; Clasen, Liv S.; Tossell, Julia W.; Nugent, Thomas F.; Gochman, Peter; Sharp, Wendy; Mattai, Anand; Lenane, Marge; Yanovski, Jack A.; Rapoport, Judith L.

doi:10.1097/01.chi.0000170552.15798.dd

Cited by 45 publications

(28 citation statements)

References 45 publications

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“…These studies indicate conclusively that, when matched appropriately with nonpsychiatric subjects, patients with schizophrenia do not exhibit greater than expected serum leptin levels regardless of antipsychotic drug exposure (Baptista et al, 2001;Eder et al, 2001;Herran et al, 2001;Hagg et al, 2001;Zhang et al, 2003;Arranz et al, 2004;Sporn et al, 2005;Haupt et al, 2005;Gergerlioglu et al, 2006;Atmaca et al, 2007). The one controlled comparative study of medication-treated bipolar patients vs. matched controls also reported no significant difference in leptin levels between the psychiatric patients and their peers (Gergerlioglu et al, 2006).…”

Section: Diagnosis Effectsmentioning

confidence: 76%

“…As patients gained substantial amounts of weight on clozapine and olanzapine, serum leptin also rose, but neither weight nor leptin changes were seen in patients exposed to haloperidol or in those who did not receive antipsychotic medication (Kraus et al, 1999). Numerous subsequent prospective trials of olanzapine-treated patients (Eder et al, 2001;Graham et al, 2005b;Ebenbichler et al, 2005;Murashita et al, 2005;Hosojima et al, 2006) and clozapine-treated patients (Monteleone et al, 2002;Kivircik et al, 2003;Sporn et al, 2005;Theisen et al, 2005) confirmed the association between use of these medications, weight gain, and increased serum leptin levels. For agents with less weight gain liability, such as high potency typicals (Hagg et al, 2001;Atmaca et al, 2003a;Atmaca et al, 2003c), sulpiride (Baptista et al, 2000), quetiapine (Atmaca et al, 2003c), or risperidone (Fitzgerald et al, 2003;McIntyre et al, 2003;Martin et al, 2004;Chiu et al, 2006), comparative trials noted modest weight gain and leptin changes, while olanzapine and clozapine exposed subjects experienced marked increases in adiposity, weight and serum leptin.…”

Section: Leptin Drug Effectsmentioning

confidence: 81%

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Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin

Jin

Meyer

Mudaliar

et al. 2008

Schizophrenia Research

128

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Background-Many adverse effects of atypical antipsychotic treatment are associated with antagonism of monoamine receptors; however, data indicate that important metabolic effects, such as hypertriglyceridemia and impairment in glucose/insulin homeostasis, may not be related to these mechanisms, leading investigators to explore alternative hypotheses. Promising candidates include a possible impact of antipsychotics on peptide hormonal regulators of metabolic control such as leptin, ghrelin, and adiponectin. The purpose of this review is to summarize recent data on changes in these hormones during atypical antipsychotic treatment.

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Section: Diagnosis Effectsmentioning

confidence: 76%

Section: Leptin Drug Effectsmentioning

confidence: 81%

Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin

Jin

Meyer

Mudaliar

et al. 2008

Schizophrenia Research

128

View full text Add to dashboard Cite

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“…In contrast, SGAs' leptin effects (Monteleone et al, 2002;Melkersson and Dahl, 2003;Ebenbichler et al, 2005;Murashita et al, 2005;Sporn et al, 2005;Theisen et al, 2005) seem to be entirely attributable to increased adiposity (Haupt et al, 2005;Sporn et al, 2005). In a cross-sectional study of plasma leptin and adiposity in schizophrenic patients treated with olanzapine (N ¼ 27), risperidone (N ¼ 24), or a typical antipsychotic (N ¼ 21), and in 124 healthy controls, BMI correlated with leptin levels in the entire sample.…”

Section: Putative Mechanisms Of Sgas-induced Weight Gainmentioning

confidence: 99%

“…Increases (Murashita et al, 2005;Palik et al, 2005), decreases (Togo et al, 2004), and no change (Sporn et al, 2005;Theisen et al, 2005;Himmerich et al, 2005) in plasma ghrelin levels were reported in patients treated with SGAs; a consensus regarding clinical significance of these changes has not yet transpired. Likewise, potential contributions to weight gain of norepinephrine (Elman et al, 2002(Elman et al, , 2004 and prolactin (Melkersson, 2005;Mann et al, 2006) increases associated with SGA treatment are still unclear.…”

Section: Putative Mechanisms Of Sgas-induced Weight Gainmentioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

133

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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“…The assertion that these problems may arise due to increases in ghrelin secretion from the stomach produced by the secondgeneration antipsychotic agents (SGAs) is however undermined by the following considerations: (a) preponderance of the studies reporting no or inverse relationship between plasma ghrelin levels and SGAs-induced weight gain (Togo et al, 2004;Palik et al, 2005;Theisen et al, 2005;Sporn et al, 2005;Hosojima et al, 2006); (b) the lack of reported evidence on ghrelin alterations in drug-free patients who are also prone for glucoregulatory abnormalities and for obesity; and (c) undetermined (primary vs secondary) mechanisms of the SGAs ghrelin effects. We have discussed the inconclusive ghrelin findings in the text (page 15) and in the tabulated format (Elman et al, 2006).…”

Section: Sirmentioning

confidence: 99%