ObjectivePanic disorder (PD) is a common and often chronic psychiatric illness, and serotonin-specific reuptake inhibitors (SSRIs) are the drugs of choice for the treatment of PD. Previous studies suggested the cerebral cortex and limbic brain structures played a major role in the development of PD, but the therapeutic effect of SSRIs on specific brain structures remains unclear in PD. We examined the changes in PD patients' glucose metabolism using the [18F] Fluorodeoxy-glucose-positron emission tomography (FDG-PET) before and after 12 weeks of paroxetine treatment.MethodsWe assessed the brain glucose metabolism of 5 PD patients, using the [18F]FDG-PET, and treated them with paroxetine (12.5-37.5 mg/day) for 12 weeks. Then, we compared before and after treatment PET images of the patients, using voxel-based statistical analysis and a post hoc regions of interest analysis. Furthermore, we measured the patients' clinical variables, including information from the Panic Disorder Severity Scale (PDSS), Clinical Global Impression for Severity (CGI-S), and Hamilton Anxiety Rating Scale (HAMA).ResultsAfter 12 weeks of paroxetine treatment, the patients showed significant clinical improvement in terms of PDSS, CGI-S and HAMA scores (12.8±1.8 vs. 3.8±2.3, 4.6±0.5 vs. 2.0±1.4, and 15.2±4.0 vs. 5.0±1.2, respectively; all p values<0.05). After treatment, patients' glucose metabolism increased significantly in global brain areas: the right precentral gyrus, right middle frontal gyrus, right amygdala, right caudate body, right putamen, left middle frontal gyrus, left precentral gyrus, left insula, left parahippocampal gyrus, and left inferior frontal gyrus (All areas were significant at uncorrected p<0.001 and cluster level corrected p<0.05).ConclusionIn these PD patients, cerebral cortex and limbic brain functions changed after short-term treatment with paroxetine. The therapeutic action of paroxetine may be related to altered glucose metabolism at both the cerebral cortex and limbic brain areas.

This contribution aims to integrate findings of our recently reported three brain imaging studies on young narcolepsy-cataplexy patients [1][2][3]. All brain images were acquired using 3.0 Tesla MRI. In our prior study of a voxel-based morphometry [1], narcoleptic patients showed gray matter (GM) deficits in the hypothalamus and fronto-limbic areas. Hypothalamic GM deficits correlated with severity of narcolepsy. In our diffusion tensor imaging study that assessed global white matter (WM) integrity [2], narcoleptic patients had decreased WM integrity especially in fronto-limbic areas, which were associated with sleepiness and attention deficit. Prefrontal metabolite concentration was measured in a proton magnetic resonance spectroscopy [3]. Narcoleptic patients had higher GABA levels in the medial prefrontal areas. This is potentially related to the compensation of nocturnal sleep disturbance. Hypothalamus seems to be a key structure in narcoleptic symptoms. However, both GM and WM abnormalities of fronto-limbic areas were also related to narcolepsy and its symptoms. Compensatory alteration of GABA was also found in the areas. Taken together, our reports suggest that fronto-limbic area, as well as hypothalamus, may be implicated in narcolepsy. References[1] Gray matter deficits in young adults with narcolepsy. Acta Neurol Scand 2009;119:61-7. [2] Decreased fractional anisotropy values in brains of young narcoleptic patients. 2009; presented in APSS. [3] Increased GABA levels in medial prefrontal cortex of young adults with narcolepsy.Two types of monoamine oxidase (MAO), type A (MAO-A) and type B (MAO-B), have been identified. Generally, MAO-A is highly expressed in noradrenergic/adrenergic neurons such as the locus coeruleus, whereas MAO-B is highly expressed in serotonergic and histaminergic neurons and distinct populations of glia such as tanicytes. On the other hand, it has been reported that non-catecholaminergic neurons also express MAOs in an adult rat brain. Extracellular serotonin (5-HT), norepinephrine / epinephrine (NE/E), and dopamine (DA) appear to be removed by a reuptake mechanism; subsequently, they are metabolized by intracellular MAO activity. In the hypothalamus, 5-HT and DBHpositive varicosities densely distribute around hypothalamic nucleus, likely MAO activity affecting the neuronal functions. In the present study, we investigated the distribution of MAOs and the anatomical relation to the neuropeptide-expressing neurons in the rat hypothalamus. We performed enzyme histochemistry for MAO-A or MAO-B, and use specific antibodies for MAO-A and MAO-B. In the result, we found moderate MAO-A enzyme activities in the distinct neuronal populations, and strong MAO-B activity in some glial cells including tanicytes. MAO-A-immunoreactivities (IR) were found in the varicosities of noradrenergic/adrenergic neurons and in the cell bodies of some neuropeptides-expressing neurons in the lateral hypothalamus. Especially, orexin neurons robustly express MAO-A, but not MAO-B. Objective:We have elucidated the p...