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Premenstrual dysphoric disorder (PMDD) affects nearly 5% of women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, has greatly hindered its effective treatment. In the present study, analysis of genomic sequencing-based copy number variations (CNVs) called from 100 kb white blood cell DNA sequence windows by means of semisupervized clustering led to the segregation of patient genomes into the D and V groups, which correlated with the depression and invasion clinical types, respectively, with 89.0% consistency. Application of diagnostic CNV features selected using the correlation-based machine learning method enabled the classification of the CNVs obtained into the D group, V group, total patient group, and control group with an average accuracy of 83.0%. The power of the diagnostic CNV features was 0.98 on average, suggesting that these CNV features could be used for the molecular diagnosis of the major clinical types of PMDD. This demonstrated concordance between the CNV profiles and clinical types of PMDD supported the validity of symptom-based diagnosis of PMDD for differentiating between its two major clinical types, as well as the predominantly genetic nature of PMDD with a host of overlaps between multiple susceptibility genes/pathways and the diagnostic CNV features as indicators of involvement in PMDD etiology.

Premenstrual dysphoric disorder (PMDD) affects nearly 5% women of reproductive age. The symptomatic heterogeneity, along with largely unknown genetics, of PMDD have greatly hindered its effective treatment. In the present study, 127 Chinese PMDD patients of the ‘invasion’ and ‘depression’ subtypes clinically differentiated by us earlier were analyzed together with 108 non-PMDD controls for genome-wide copy number variations (CNVs). Germline genomic DNA samples from white blood cells were subjected to AluScan sequencing-based CNV profiling, which enabled clustering of patient samples readily into the V and D groups, dominated by the “invasion” and “depression” clinical subtypes, respectively; the CNVs obtained with 100-kb windows yielded two clusters that were correlated with these subtypes with a consistency of up to 89.8%. Diagnostic correlation- and frequency-based CNV features of either CNV-gain (CNVG) or CNV-loss (CNVL) that could differentiate between V and D subtypes were selected and analyzed. CNVG features located preferentially in S2-phase replicating regions and enriched with steroid hormone biosynthesis pathway of genes were found protective against PMDD. Moreover, machine learning employing the correlation-based CNV features could predict with >80% accuracy whether a genomic sample was D-type, V-type or control. In terms of their CNV profiles, the D- and V-types differed more from one another than from the controls, thereby providing a genomic basis for the clinical D-V subtyping of PMDD. Genome-wide profiling of CNVs, as a new approach to complex disease genetics, has revealed recurrent CNVs and genomic features beyond individual genes and mutations underlying PMDD clinical diversity.

Objective Although single-nucleotide polymorphisms in GABRB2, the gene encoding for GABAA receptors β2 subunit, have been associated with schizophrenia (SCZ), it is unknown whether there is any association of copy number variations (CNVs) in this gene with either SCZ or premenstrual dysphoric disorder (PMDD). Methods In this study, the occurrences of the recurrent CNVs esv2730987 in Intron 6 and nsv1177513 in Exon 11 of GABRB2 in Chinese and German SCZ, and Chinese PMDD patients were compared to controls of same ethnicity and gender by quantitative PCR (qPCR). Results The results demonstrated that copy-number-gains were enriched in both SCZ and PMDD patients with significant odds ratios (OR). For combined-gender SCZ patients versus controls, about two-fold increases were observed in both ethnic groups at both esv2730987 (OR = 2.15, p = 5.32E-4 in Chinese group; OR = 2.79, p = 8.84E-3 in German group) and nsv1177513 (OR = 3.29, p = 1.28E-11 in Chinese group; OR = 2.44, p = 6.17E-5 in German group). The most significant copy-number-gains were observed in Chinese females at nsv1177513 (OR = 3.41), and German females at esv2730987 (OR=3.96). Copy-number-gains were also enriched in Chinese PMDD patients versus controls at esv2730987 (OR = 10.53, p = 4.34E-26) and nsv1177513 (OR = 2.39, p = 3.19E-5). Conclusion These findings established for the first time the association of highly recurrent CNVs with SCZ and PMDD, suggesting the presence of an overlapping genetic basis with shared biomarkers for these two common psychiatric disorders.

// Sheng Wei 1, 2, 3 , Xinyang Xiao 3 , Jieqiong Wang 2 , Shiguang Sun 4 , Zifa Li 3 , Kaiyong Xu 3 , Fang Li 5 , Jie Gao 2 , Dehao Zhu 3 and Mingqi Qiao 2 1 Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute, Shandong University, Jinan 250012, China 2 Lab of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan 250355, China 3 Lab of Behavioral Brain Analysis, Shandong University of Traditional Chinese Medicine, Jinan 250355, China 4 Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong Provincial Hospital of Integrated Medicine, Jinan 250001, China 5 Fengtai Maternal and Children’s Health Hospital of Beijing, Beijing 100069, China Correspondence to: Mingqi Qiao, email: qmingqi@163.com Sheng Wei, email: waysaint@163.com Keywords: stress before pregnancy, anger emotion, aggressive behavior test, resident intruder paradigm, monoamine neurotransmitters Received: June 21, 2017 Accepted: October 02, 2017 Published: October 24, 2017 ABSTRACT Previous studies have reported that maternal chronic stress or depression is linked to an increased risk of affective disorders in progeny. However, the impact of maternal chronic stress before pregnancy on the progeny of animal models is unknown. We investigated the behaviors and the neurobiology of 60-day-old male offspring of female rats subjected to 21 days of resident-intruder stress before pregnancy. An anger stressed parental rat model was established using the resident-intruder paradigm and it was evaluated using behavioral tests. Anger stressed maternal rats showed a significant increase in locomotion and aggression but a reduction in sucrose preference. Offspring subjected to pre-gestational anger stress displayed enhanced aggressive behaviors, reduced anxiety, and sucrose preference. Further, offspring subjected to pre-gestational stress showed significant impairments in the recognition index (RI) on the object recognition test and the number of platform crossings in the Morris water maze test. The monoaminergic system was significantly altered in pre-gestationally stressed offspring, and the expression of phosphorylated cyclic adenosine monophosphate response element binding protein (P-CREB), brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) levels in pre-gestational stressed offspring were altered in some brain regions. Fluoxetine was used to treat pre-gestational stressed maternal rats and it significantly reduced the changes caused by stress, as evidenced by both behaviors and neural biochemical indexes in the offspring in some but not all cases. These findings suggest that anger stress before pregnancy could induce aggressive behaviors, cognitive deficits, and neurobiological alterations in offspring.

Dendritic fibromyxolipoma, a rare subtype of lipoma, mainly occurs in the neck, back, and chest wall. Here, we describe the first reported case located in the parotid gland. It happened in a 24-year-old woman with a well-demarcated painless mass. Pathologically, the tumor was characterized by small spindle and stellate cells, an unequal number of mature fat cells, plentiful myxoid stroma, and collagenous fiber bundles. Immunochemistry demonstrated that the tumor cells were positive for vimentin, CD34, Bcl-2, and desmin, but not for keratin, EMA, SMA, or S-100. The tumor was successfully removed without complications. This report will bring to the attention of clinicians the clinical features and differential diagnosis of this unusual tumor.

A neutral pH fluorescent probe (Rh-Met) based on rhodamine spirolactam is firstly developed according to the modulation strategy of hydrogen bonds on pKa values. The pKa value of Rh-Met was 6.81 (±0.06) and higher than that of other rhodamine spirolactams known. Rh-Met showed a 240-fold enhancement of fluorescence intensity at 585 nm with attenuation of pH values from 9.7 to 3.5. In addition, Rh-Met displayed an excellent selectivity and reversible response to hydrogen ion. And it was successfully employed for imaging endocellular hydrogen ion in mitochondria and lipid droplets. These results suggested that Rh-Met could be a potential tool to assess pH fluctuation in mitochondria and lipid droplets, and would promote many new opportunities for studying the biological effect of pH in living cells.

The effects of the Shuyu capsule on5-HT3ARand5-HT3BRexpression in a rat model of premenstrual syndrome (PMS) depression and on5-HT3ARand5-HT3BRexpression and hippocampal neuron 5-HT3channel current were investigated, to elucidate its mechanism of action against PMS depression. PMS depression model rats were divided into depression and Shuyu- and fluoxetine-treated groups, which were compared to control rats for frontal lobe and hippocampal5-HT3ARand5-HT3BRexpression and behavior. The depressed model rats displayed symptoms of depression, which were reduced in treated and normal control rats. Frontal lobe and hippocampal5-HT3ARand5-HT3BRlevels were significantly higher in the model versus the control group and were significantly lower in the Shuyu group. As compared to control rats, the 5-HT3R channel current in the model group was significantly higher; the 5-HT3R channel current in hippocampal neurons treated with serum from Shuyu group rats was significantly lower than that in those treated with model group serum. Thus, PMS depression may be related to5-HT3ARand5-HT3BRexpression and increased 5-HT3channel current. Shuyu capsules rectified abnormal5-HT3ARand5-HT3BRexpression and 5-HT3channel current changes in a rat model; this finding may provide insight into treating PMS depression.

Objective.We discuss the influence of anger emotional stress upon VEGF/VEGFR2 and its induced PI3K/AKT/mTOR signal pathway.Methods.We created a rat model of induced anger (anger-out and anger-in) emotional response using social isolation and resident-intruder paradigms and assessed changes in hippocampus’ VEGF content, neuroplasticity, and the PI3K/AKT/mTOR signaling pathway.Results.The resident-intruder method successfully generated anger-out and anger-in models that differed significantly in composite aggression score, aggression incubation, open field behavior, sucrose preference, and weight gain. Anger emotional stress decreased synaptic connections and VEGFR2 expression. Anger emotional stress led to abnormal expression of VEGF/VEGFR2 mRNA and protein and disorderly expression of key factors in the PI3K/AKT/mTOR signal pathway. Fluoxetine administration ameliorated behavioral abnormalities and damage to hippocampal neurons caused by anger emotional stress, as well as abnormal expression of some proteins in VEGF/VEGFR2 and its induced PI3K/AKT/mTOR signal pathway.Conclusion.This research provides a detailed classification of anger emotion and verifies its influence upon VEGF and the VEGF-induced signaling pathway, thus providing circumstantial evidence of mechanisms by which anger emotion damages neurogenesis. As VEGFR2 can promote neurogenesis and vasculogenesis in the hippocampus and frontal lobe, these results suggest that anger emotional stress can result in decreased neurogenesis.