Comparison of brain serotonin transporter using [I-123]-ADAM between obese and non-obese young adults without an eating disorder

<div><p>Cerebral serotonin metabolism has an important but controversial role in obesity. However, it is not given enough attention in morbidly obese young adults. We used single photon emission computed tomography (SPECT) with [I-123]-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) to investigate changes in serotonin transporter (SERT) availability in 10 morbidly obese young adults without an eating disorder (M/F = 5/5, body mass index (BMI): 40.3 ± 4.1 kg/m², percentage of body fat (BF%): 46.0 ± 3.9%) and 10 age- and sex-matched non-obese controls (BMI: 20.3 ± 1.2 kg/m², BF%: 20.6 ± 8.9%). All participants underwent SPECT at 10 min and 6 h after an injection of 200 MBq of [I-123]-ADAM. The SERT binding site (midbrain) was drawn with cerebellum normalization. The BF% and fat distribution were measured using dual-energy X-ray absorptiometry. The midbrain/cerebellum SERT binding ratios (2.49 ± 0.46 vs. 2.47 ± 0.47; <i>p</i> = 0.912) at 6 h were not significantly different between groups, nor was the distribution of the summed images at 10 min (1.36 ± 0.14 vs. 1.35 ± 0.11; <i>p</i> = 0.853). There were no significant correlations between midbrain/cerebellum SERT binding ratio and age, BMI, BF%, or fat distribution. No significant difference in SERT availability in the midbrain between morbidly obese and non-obese young adults without an eating disorder indicates an unmet need for investigating the role of cerebral serotonin in obesity.</p></div

Clinical characteristics of the obese and non-obese groups.

<p>Clinical characteristics of the obese and non-obese groups.</p

Correlation coefficients^† between the distribution of midbrain/cerebellum ratios (MID/CE) in [I-123]-ADAM SPECT image and body composition in 20 morbidly obese and non-obese young adults.

<p>Correlation coefficients<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170886#t002fn002" target="_blank">^†</a> between the distribution of midbrain/cerebellum ratios (MID/CE) in [I-123]-ADAM SPECT image and body composition in 20 morbidly obese and non-obese young adults.</p

The aldehyde dehydrogenase 2 polymorphisms on neuropsychological performance in bipolar II disorder with or without comorbid anxiety disorder

<div><p>Anxiety disorders (ADs), the most common comorbid illnesses with bipolar disorder (BP) has been reported to associate with dopamine system. Dopamine, metabolized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenase 2 (ALDH2), and the distribution of the <i>ALDH2*1/*1</i>, and <i>ALDH2*1/*2+ALDH*2/*2</i> alleles in the Han Chinese general population is relatively equal. The association between dopamine metabolic enzymes and cognitive performance in patients with bipolar II disorder (BP-II) comorbid with AD is unclear. This study proposed to explore the role of <i>ALDH2</i> polymorphisms on neuropsychological performance between BP-II comorbid with or without AD. One hundred ninety-seven BP-II patients with and without a comorbid AD were recruited and compared with 130 healthy controls (HCs). A polymerase chain reaction and a restriction fragment length polymorphism analysis were used to determine genotypes for <i>ALDH2</i>, and study participants underwent neuropsychological tests. An interaction between AD comorbidity and the <i>ALDH2</i> polymorphisms was found in different domain of cognitive dysfunction in the BP-II patients. The <i>ALDH2</i> polymorphisms might have different effects on the neuropsychological performance of BP-II patients with and without comorbid AD.</p></div

Neuropsychological performance in memory between patient groups and healthy controls.

<p>Neuropsychological performance in memory between patient groups and healthy controls.</p

Demographic data comparisons between patient groups and healthy controls.

<p>Demographic data comparisons between patient groups and healthy controls.</p

Neuropsychological performance in attention and executive function between patient groups and healthy controls.

<p>Neuropsychological performance in attention and executive function between patient groups and healthy controls.</p

Inflammation’s Association with Metabolic Profiles before and after a Twelve-Week Clinical Trial in Drug-Naïve Patients with Bipolar II Disorder

<div><p></p><p>Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP) and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naïve patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naïve patients (n = 117) diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI) and plasma cytokines (TNF-α, CRP, IL-6, and TGF-β) were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0%) patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (<i>P</i> = 1.7E-7) and triglyceride (<i>P</i> = 0.005) levels. Changes in plasma TGF-β1 were significantly associated with changes in BMI (<i>P</i> = 8.2E-6), cholesterol (<i>P</i> = 0.004), and triglyceride (<i>P</i> = 0.006) levels. However, changes in plasma TNF-α and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (<i>P</i> = 0.003) levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (<i>P</i> = 0.006) and TNF-α (<i>P</i> = 0.039) levels. Plasma CRP and TGF-β1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology of clinical symptoms and metabolic disturbance in BP-II.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01188148" target="_blank">NCT01188148</a>.</p></div

Mean HDRS score, YMRS score, and cytokine and metabolic profiles before and after pharmacological treatment.

<p>VPA: valproate; HDRS: Hamilton Depression Rating Scale; YMRS: Young Mania Rating Scale; CRP: C-reactive protein; TGF-β1: transforming growth factor β1; TNF-α: tumor necrosis factor α; IL-6: interleukin 6.</p

Correlation of changes in metabolic profiles and cytokines before and after 12 weeks of pharmacological treatment.

<p>CRP: C-reactive protein; TGF-β1: transforming growth factor β1; TNF-α: tumor necrosis factor α; IL-6: interleukin 6.</p>**<p><b><i>P</i></b><0.001.</p