Neural Correlates of Weight Gain With Olanzapine Neural Correlates of Weight Gain With Olanzapine

Mathews J, Newcomer JW, Mathews JR, et al. — Sat, 01 Dec 2012 00:00:00 GMT

Context

Iatrogenic obesity caused by atypical antipsychotics increases the rate of death from all causes. Olanzapine is a commonly prescribed atypical antipsychotic medication that frequently causes weight gain. To our knowledge, the neural correlates of this weight gain have not been adequately studied in humans.

Objective

To test the hypothesis that olanzapine treatment disrupts the neural activity associated with the anticipation and receipt (consumption) of food rewards (chocolate milk and tomato juice).

Design

Event-related functional magnetic resonance imaging study, before and after a 1-week treatment with olanzapine.

Setting

A university neuroimaging center.

Participants

Twenty-five healthy individuals.

Main Outcome Measures

Changes in blood oxygen level–dependent activations to the anticipation and receipt of food rewards after olanzapine treatment.

Results

One week of olanzapine treatment caused significant increases in weight, food consumption, and disinhibited eating. Our imaging data showed enhanced activations in the inferior frontal cortex, striatum, and anterior cingulate cortex to the anticipation of a food reward. Activation in the caudate and putamen were enhanced to the receipt of the rewarding food. We also found a decrease in reward responsivity to receipt of the rewarding food in the lateral orbital frontal cortex, an area of the brain thought to exercise inhibitory control on feeding.

Conclusions

Olanzapine treatment enhanced both the anticipatory and consummatory reward responses to food rewards in the brain reward circuitry that is known to respond to food rewards in healthy individuals. We also noted a decrease in responsivity to food consumption in a brain area thought to inhibit feeding behavior.

Highly Penetrant Alterations of a Critical Region Including BDNF in Human Psychopathology and Obesity Involvement of BDNF in Human Psychopathology

Ernst C, Marshall CR, Shen Y, et al. — Sat, 01 Dec 2012 00:00:00 GMT

Context

Brain-derived neurotrophic factor (BDNF) is suspected of being a causative factor in psychiatric disorders based on case reports or studies involving large structural anomalies.

Objective

To determine the involvement of BDNF in human psychopathology.

Design

Case-control study.

Setting

Microarray-based comparative genomic hybridization data from 7 molecular diagnostic centers including 38 550 affected subjects and 28 705 unaffected subjects.

Patients

Subjects referred to diagnostic screening centers for microarray-based comparative genomic hybridization for physical or cognitive impairment.

Main Outcome Measures

Genomic copy number gains and losses.

Results

We report 5 individuals with psychopathology and genomic deletion of a critical region including BDNF. The defined critical region was never disrupted in control subjects or diagnostic cases without developmental abnormalities.

Conclusion

Hemizygosity of the BDNF region contributes to variable psychiatric phenotypes including anxiety, behavioral, and mood disorders.

JAMA Psychiatry: Obesity Topic Collection

Neural Correlates of Weight Gain With Olanzapine Neural Correlates of Weight Gain With Olanzapine

Highly Penetrant Alterations of a Critical Region Including BDNF in Human Psychopathology and Obesity Involvement of BDNF in Human Psychopathology