Pathways linking obesity to neuropsychiatric disorders.

Obesity has been associated with cognitive and behavioral syndromes. Individuals who are obese have higher risk for developing neuropsychiatric disorders such as depression and dementia than non-obese. Conversely, patients with neuropsychiatric conditions may exhibit some features that contribute to obesity development such as unhealthy behaviors and treatment with drugs that increase appetite. This review addresses the multiple pathways implicated in the relationship between obesity and neuropsychiatric disorders, mainly mood disorders, schizophrenia, and major neurocognitive disorder or dementia. Both obesity and neuropsychiatric disorders are characterized by a low-grade systemic inflammation and neuroinflammation. Obesity is frequently accompanied by neuroendocrine changes, particularly involving the hypothalamic-pituitary-adrenal (HPA) axis. Indeed, activation of the stress system is commonly seen as a trigger for mood episodes, psychosis exacerbation, and cognitive decline. Growing evidence suggests the role of gut microbiota in obesity and brain functioning through the modulation of the inflammatory response and HPA axis. Owing to the intricate relationship between obesity and neuropsychiatric disorders, tackling one of them may affect the other. Therefore, a better understanding of the pathways underlying the link between obesity and neuropsychiatric disorders can contribute to the development of therapeutic strategies for these conditions.

Selective Serotonin Reuptake Inhibitors Reduce Longitudinal Growth in Risperidone-Treated Boys.

OBJECTIVES: To examine whether selective serotonin reuptake inhibitors (SSRIs) inhibit longitudinal growth in children and adolescents, particularly in the early stages of puberty, using a sample of convenience comprising risperidone-treated boys. STUDY DESIGN: Data from four clinic-based studies in risperidone-treated 5- to 17-year-old boys with no general medical conditions were combined for this analysis. Anthropometric measurements and psychotropic treatment history were extracted from the medical and pharmacy records. Linear mixed effects regression analyses examined the association between SSRI use and change in age-sex-specific height and body mass index z scores, after adjusting for relevant confounders. RESULTS: Risperidone-treated boys (n = 267; age: 12.7 ± 2.7 years), 71% of whom had ever taken an SSRI, contributed to the analysis. After adjusting for age, psychostimulant and antipsychotic use, and time in the study, both the duration of SSRI use as well as the cumulative dose were inversely associated with height z score after age 11 years (P < .0001). After adjusting for baseline height, duration of SSRI use was most strongly inversely associated with height z score in Tanner stages 3 and 4 boys who took SSRIs continuously (r = -0.69, P < .009). No association was observed with body mass index z score. CONCLUSIONS: In risperidone-treated boys, SSRI use is associated with reduced longitudinal growth, particularly in those undergoing puberty. Whether adult height or other metabolic or psychological outcomes are affected remains to be determined.

The effect of psychostimulants on skeletal health in boys co-treated with risperidone.

OBJECTIVES: To examine the skeletal effects of chronic psychostimulant treatment in children and adolescents. STUDY DESIGN: Medically healthy 5- to 17-year-old males from 4 different clinic-based studies were combined for this analysis. They were divided by psychostimulant use into 3 groups: none to negligible, intermittent, and continuous use. Most (95%) had also received risperidone for 6 months or more. Treatment history was extracted from medical and pharmacy records. Anthropometric and bone measurements, using dual-energy x-ray absorptiometry and peripheral quantitative computed tomography, were obtained at each research visit. Multivariable linear regression analysis models examined whether age-sex-specific height Z-score and skeletal outcomes differed among the 3 psychostimulant-use groups. RESULTS: The sample consisted of 194 males with a mean age of 11.7 ± 2.8 years at study entry. The majority had an externalizing disorder. There was no significant difference across the 3 treatment groups in height Z-score or in skeletal outcomes at the radius, lumbar spine, or whole body. One hundred forty-four boys had valid follow-up skeletal data 1.4 ± 0.7 years after study entry. Again, neither height Z-score nor the skeletal outcomes were different among those who remained on psychostimulants between the 2 visits, started psychostimulants anew, or had not taken psychostimulants. CONCLUSIONS: Following chronic treatment, psychostimulants did not appear to significantly affect bone mass accrual in children and adolescents taking risperidone. There was a small, but statistically not significant, negative impact on longitudinal growth.

Rate of weight gain and cardiometabolic abnormalities in children and adolescents.

OBJECTIVE: To investigate whether the rate of weight gain is associated with cardiometabolic risk, independent of weight measured concurrently. STUDY DESIGN: Healthy 7- to 17-year-old risperidone-treated patients (N = 105, 88% were boys) had blood pressure, anthropometry, and laboratory tests performed. Growth history was extracted from medical records. The rate of change in age- and sex-adjusted weight and body mass index (BMI) z score after the initiation of risperidone was individually modeled. Multivariable linear regression analyses explored the association of the rate of weight or BMI z score change with cardiometabolic outcomes, independent of last measured weight or BMI z score, respectively. RESULTS: Following a mean of 1.9 years (SD = 1.0) of risperidone treatment, the absolute increase in weight and BMI z scores was 0.61 (SD = 0.61) and 0.62 (SD = 0.73), respectively. After controlling for the final weight z score, the rate of change in weight z score was significantly associated with final glucose (P < .04), C-peptide (P < .004), the homeostasis model assessment insulin resistance index (P < .02), high-density lipoprotein (HDL) cholesterol (P < .0001), a metabolic syndrome score (P < .005), adiponectin (P < .04), and high-sensitivity C-reactive protein (P < .04). After controlling for the final BMI z score, the rate of change in BMI z score was associated with final HDL cholesterol (P < .04), leptin (P < .03), and adiponectin (P < .04), with a suggestion of an association with the final homeostasis model assessment insulin resistance index (P < .08). CONCLUSIONS: Compared with weight measured concurrently, the rate of weight gain in risperidone-treated children accounts for an equal or larger share of the variance in certain cardiometabolic outcomes (eg, HDL cholesterol [ΔR(2) = 8% vs ΔR(2) = 11%] and high-sensitivity C-reactive protein [ΔR(2) = 5% vs ΔR(2) = 9%]) and may serve as a treatment target.