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Background: Upregulation of the endocannabinoid enzyme fatty acid amide hydrolase (FAAH) has been linked to abnormal activity in frontoamygdalar circuits, a hallmark of posttraumatic stress disorder. We tested the hypothesis that FAAH levels in the amygdala were negatively correlated with functional connectivity between the amygdala and prefrontal cortex, subserving stress and affect control. Methods: Thirty-one healthy participants completed positron emission tomography (PET) imaging with the FAAH probe [C-11]CURB, and resting-state functional MRI scans. Participants were genotyped for the FAAH polymorphism rs324420, and trait neuroticism was assessed. We calculated amygdala functional connectivity using predetermined regions of interest (including the subgenual ventromedial prefrontal cortex [sgvmPFC] and the dorsal anterior cingulate cortex [dACC]) and a seed-to-voxel approach. We conducted correlation analyses on functional connectivity, with amygdala [C-11]CURB binding as a variable of interest. Results: The strength of amygdala functional connectivity with the sgvmPFC and dACC was negatively correlated with [C-11]CURB binding in the amygdala (sgvmPFC: r = -0.38, q = 0.04; dACC: r = -0.44; q = 0.03). Findings were partly replicated using the seed-to-voxel approach, which showed a cluster in the ventromedial prefrontal cortex, including voxels in the dACC but not the sgvmPFC (cluster-level, family-wise error rate corrected p < 0.05). Limitations: We did not replicate earlier findings of a relationship between an FAAH polymorphism (rs324420) and amygdala functional connectivity. Conclusion: Our data provide preliminary evidence that lower levels of FAAH in the amygdala relate to increased frontoamygdalar functional coupling. Our findings were consistent with the role of FAAH in regulating brain circuits that underlie fear and emotion processing in humans., Introduction Emotion dysregulation--characterized by the inability to manage negative emotions such as fear, anger or sadness--is a common symptom of many mental health disorders. Elevated amygdala hyperactivity has been linked [...]

Olivopontocerebellar atrophies are a group of disorders in which there is degeneration of the cerebellum, the underlying pons, and the olivary nuclei deep within the cerebellum. In about one third of cases, there is evidence of a genetic basis; most such cases are inherited as a dominant genetic trait. Families have been identified in which the gene responsible for this degeneration lies on the short arm of chromosome 6 (chromosome 6p). However, the exact cause of the degeneration remains unclear. One possibility is that abnormalities in neurotransmitter substances might contribute to the degeneration of brain cells within the affected regions. To examine this possibility, brains obtained at autopsy from six patients afflicted with chromosome 6p-linked dominantly inherited olivopontocerebellar atrophy were chemically analyzed. The amino acids aspartate and glutamate, both of which serve as neurotransmitter substances for some neurons, were reduced by 70 and 40 percent, respectively, in the cortex of the cerebellum in the affected brains. While some reductions would be expected in virtually any substance measured because of the reduction in the number of cells in the atrophied tissues, these reductions are larger than can be accounted for in this way. Aspartate and glutamate, as well as the related substance gamma aminobutyric acid, were also reduced in many other brain regions outside of the obviously affected areas. These reductions, which ranged from 10 to 30 percent, suggest that the metabolic abnormality responsible for the degeneration is not necessarily limited to the most obviously affected areas. In contrast, other important neurochemical substances, including taurine, glutamine, and ortho-phosphoethanolamine, appear not to be directly involved in the disease process and were found to be normal in all brain regions examined. The data from these six patients, all of whom were from the same affected family, indicate that a reduction in amino acid metabolism may be responsible for at least some cases of dominantly inherited olivopontocerebellar atrophy. Furthermore, the observed atrophy may be merely the most prominent symptom of a general defect affecting the rest of the brain as well. (Consumer Summary produced by Reliance Medical Information, Inc.)