Circulating T-cell subsets discrepancy between bipolar disorder and major depressive disorder during mood episodes: A naturalistic, retrospective study of 1015 cases.

AIMS: We aimed to investigate whether peripheral T-cell subsets could be a biomarker to distinguish major depressive disorder (MDD) and bipolar disorder (BD). METHODS: Medical records of hospitalized patients in the Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2015 to September 2020 with a discharge diagnosis of MDD or BD were reviewed. Patients who underwent peripheral blood examination of T-cell subtype proportions, including CD3+, CD4+, CD8+ T-cell, and natural killer (NK) cells, were enrolled. The Chi-square test, t-test, or one-way analysis of variance were used to analyze group differences. Demographic profiles and T-cell data were used to construct a random forest classifier-based diagnostic model. RESULTS: Totally, 98 cases of BD mania, 459 cases of BD depression (BD-D), and 458 cases of MDD were included. There were significant differences in the proportions of CD3+, CD4+, CD8+ T-cell, and NK cells among the three groups. Compared with MDD, the BD-D group showed higher CD8+ but lower CD4+ T-cell and a significantly lower ratio of CD4+ and CD8+ proportions. The random forest model achieved an area under the curve of 0.77 (95% confidence interval: 0.71-0.83) to distinguish BD-D from MDD patients. CONCLUSION: These findings imply that BD and MDD patients may harbor different T-cell inflammatory patterns, which could be a potential diagnostic biomarker for mood disorders.

Targeted visual cortex stimulation (TVCS): a novel neuro-navigated repetitive transcranial magnetic stimulation mode for improving cognitive function in bipolar disorder.

A more effective and better-tolerated site for repetitive transcranial magnetic stimulation (rTMS) for treating cognitive dysfunction in patients with bipolar disorder (BD) is needed. The primary visual cortex (V1) may represent a suitable site. To investigate the use of the V1, which is functionally linked to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), as a potential site for improving cognitive function in BD. Seed-based functional connectivity (FC) analysis was used to locate targets in the V1 that had significant FC with the DLPFC and ACC. Subjects were randomly assigned to 4 groups, namely, the DLPFC active-sham rTMS (A1), DLPFC sham-active rTMS (A2), ACC active-sham rTMS (B1), and ACC sham-active rTMS groups (B2). The intervention included the rTMS treatment once daily, with five treatments a week for four weeks. The A1 and B1 groups received 10 days of active rTMS treatment followed by 10 days of sham rTMS treatment. The A2 and B2 groups received the opposite. The primary outcomes were changes in the scores of five tests in the THINC-integrated tool (THINC-it) at week 2 (W2) and week 4 (W4). The secondary outcomes were changes in the FC between the DLPFC/ACC and the whole brain at W2 and W4. Of the original 93 patients with BD recruited, 86 were finally included, and 73 finished the trial. Significant interactions between time and intervention type (Active/Sham) were observed in the scores of the accuracy of the Symbol Check in the THINC-it tests at baseline (W0) and W2 in groups B1 and B2 (F = 4.736, p = 0.037) using a repeated-measures analysis of covariance approach. Group B1 scored higher in the accuracy of Symbol Check at W2 compared with W0 (p < 0.001), while the scores of group B2 did not differ significantly between W0 and W2. No significant interactions between time and intervention mode were seen between groups A1 and A2, nor was any within-group significance of FC between DLPFC/ACC and the whole brain observed between baseline (W0) and W2/W4 in any group. One participant in group B1 experienced disease progression after 10 active and 2 sham rTMS sessions. The present study demonstrated that V1, functionally correlated with ACC, is a potentially effective rTMS stimulation target for improving neurocognitive function in BD patients. Further investigation using larger samples is required to confirm the clinical efficacy of TVCS.

Characteristics of the gut microbiota in bipolar depressive disorder patients with distinct weight.

BACKGROUND: Preliminary studies have indicated metabolic dysfunction and gut dysbiosis in patients with bipolar disorder (BD). In this study, we aimed to clarify the impact of the gut microbial composition and function on metabolic dysfunction in BD patients with an acute depressive episode. METHODS: Fresh fecal samples were provided from 58 patients with BD depression, including 29 with normal weight (NW) and 29 with overweight/obesity (OW), and 31 healthy controls (HCs). The hypervariable region of 16 S rRNA gene (V3-V4) sequencing was performed using IonS5TMXL platform to evaluate the bacterial communities. Differences of microbial community and correlation to clinical parameters across different groups were analyzed. RESULTS: Compared to NW and HCs, the OW group showed a decreased tendency in alpha diversity index. Beta diversity was markedly different among these groups (PERMANOVA: R2  = 0.034, p = 0.01) and was higher in patients versus HCs. A total number of 24 taxa displayed significantly different abundance among OW, NW, and HCs. At the family level, the abundance of three taxa was remarkably increased in NW, one in OW, and one in HCs. At the genus level, five taxa were enriched in OW, eight in NW, and two in HCs. The relative abundance of the genera Megamonas was positively associated with BMI, while Eggerthella was negatively correlated with BMI. Functional prediction analysis revealed the metabolism of cofactors and vitamins and amino acid were highly enriched in OW compared to HCs. In addition, microbial functions involved in "lipid metabolism" were depleted while the "fructose and mannose metabolism" was enriched in OW compared to NW group. CONCLUSIONS: Specific bacterial taxa involved in pathways regulating the lipid, energy, and amino acid metabolisms may underlie the weight concerns in depressed BD patients. Potential targeting gut microbial therapy is provided for overweight/obesity patients with BD, which still need further studies in the future.

Brain-gut microbiota multimodal predictive model in patients with bipolar depression.

BACKGROUND: The "microbiota-gut-brain axis" which bridges the brain and gut microbiota is involved in the pathological mechanisms of bipolar disorder (BD), but rare is known about the exact association patterns and the potential for clinical diagnosis and treatment outcome prediction. METHODS: At baseline, fecal samples and resting-state MRI data were collected from 103 BD depression patients and 39 healthy controls (HCs) for metagenomic sequencing and network-based functional connectivity (FC), grey matter volume (GMV) analyses. All patients then received 4-weeks quetiapine treatment and were further classified as responders and non-responders. Based on pre-treatment datasets, the correlation networks were established between gut microbiota and neuroimaging measures and the multimodal kernal combination support vector machine (SVM) classifiers were constructed to distinguish BD patients from HCs, and quetiapine responders from non-responders. RESULTS: The multi-modal pre-treatment characteristics of quetiapine responders, were closer to the HCs compared to non-responders. And the correlation network analyses found the substantial correlations existed in HC between the Anaerotruncus_ unclassified，Porphyromonas_asaccharolytica，Actinomyces_graevenitzii et al. and the functional connectomes involved default mode network (DMN),somatomotor (SM), visual, limbic and basal ganglia networks were disrupted in BD. Moreover, in terms of the multimodal classifier, it reached optimized area under curve (AUC-ROC) at 0.9517 when classified BD from HC, and also acquired 0.8292 discriminating quetiapine responders from non-responders, which consistently better than even using the best unique modality. LIMITATIONS: Lack post-treatment and external validation datasets; size of HCs is modest. CONCLUSIONS: Multi-modalities of combining pre-treatment gut microbiota with neuroimaging endophenotypes might be a superior approach for accurate diagnosis and quetiapine efficacy prediction in BD.

Multi-omics analyses of serum metabolome, gut microbiome and brain function reveal dysregulated microbiota-gut-brain axis in bipolar depression.

The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.

Gut Microbiota - A Potential Contributor in the Pathogenesis of Bipolar Disorder.

Bipolar disorder (BD) is one of the major psychiatric disorders that is characterized by recurrent episodes of depression and mania (or hypomania), leading to seriously adverse outcomes with unclear pathogenesis. There is an underlying relationship between bacterial communities residing in the gut and brain function, which together form the gut-brain axis (GBA). Recent studies have shown that changes in the gut microbiota have been observed in a large number of BD patients, so the axis may play a role in the pathogenesis of BD. This review summarizes briefly the relationship between the GBA and brain function, the composition and changes of gut microbiota in patients with BD, and further explores the potential role of GBA-related pathway in the pathogenesis of BD as well as the limitations in this field at present in order to provide new ideas for the future etiology research and drug development.

Metagenomic analysis reveals gut bacterial signatures for diagnosis and treatment outcome prediction in bipolar depression.

BACKGROUND: We aimed to characterize gut microbial alterations in depressed patients with bipolar disorder (BD) following quetiapine monotherapy and explored its potential for disease diagnosis and outcome prediction. METHODS: Fecal samples were obtained from 60 healthy individuals and 62 patients in acute depressive episodes. All patients received one-month quetiapine treatment after enrollment. The structure of gut microbiota was measured with metagenomic sequencing, and its correlation with clinical profiles and brain function as indicated by resting-state functional magnetic resonance imaging was analyzed. Random forest models based on bacterial species were constructed to distinguish patients from controls, and responders from non-responders, respectively. RESULTS: BD patients displayed specific alterations in gut microbial diversity and composition. Quetiapine treatment increased the diversity of microbial communities and changed the composition. The abundance of Clostridium bartlettii was negatively associated with age, baseline depression severity, while positively associated with spontaneous neural oscillation in the hippocampus. Tree-based classification models for (1) patients and controls and (2) responders and non-responders showed an area under the curve of 0.733 and 0.800, respectively. CONCLUSION: Our findings add new evidence to the existing literature regarding gut dysbiosis in BD and reveal the potential of microbe-based biomarkers for disease diagnosis and treatment outcome prediction.

Discovery of new genetic loci for male sexual orientation in Han population.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Metformin acts on the gut-brain axis to ameliorate antipsychotic-induced metabolic dysfunction.

Antipsychotic-induced metabolic dysfunction (AIMD) is an intractable clinical challenge worldwide. The situation is becoming more critical as second-generation antipsychotics (SGAs), to a great extent, have replaced the role of first-generation antipsychotics in managing major psychiatric disorders. Although the exact mechanisms for developing AIMD is intricate, emerging evidence has indicated the involvement of the microbiota-gut-brain axis in AIMD. SGAs treatment may change the diversity and compositions of intestinal flora (e.g., decreased abundance of Bacteroidetes and Akkermansia muciniphila, and increased Firmicutes). Short-chain fatty acids and other metabolites derived from gut microbiota, on the one hand, can regulate the activity of intestinal endocrine cells and their secretion of satiety hormones (e.g., glucagon-like peptide 1, peptide YY, cholecystokinin and ghrelin); on the other hand, can activate the vagus nerve or transport into the brain to exert a central modulation of foraging behaviors via binding to neuropeptide receptors. Interestingly, metformin, a classical antidiabetic agent, is capable of alleviating AIMD possibly by regulating the microbiota-gut-brain axis. That is, metformin can not only partially reverse the alterations of gut microbial communities due to SGAs treatment, but also play a positive role in rectifying the disturbances of peripheral and central satiety-related neuropeptides. Current evidence has indicated a promising role for metformin on ameliorating AMID, but further verifications in well-designed clinical trials are still warranted.

Involvement of Kynurenine Metabolism in Bipolar Disorder: An Updated Review.

Bipolar disorder (BD) is a severe affective disorder, mainly characterized by alternative depressive and manic or hypomanic episodes, yet the pathogenesis of BD has not been fully elucidated. Recent researches have implicated the altered kynurenine (KYN) metabolism involved in the neurobiology of BD. Excessive activation of the immune system also occurs in patients with BD, which further accelerates the KYN pathway for tryptophan metabolism. Changes of the KYN metabolites have effects on neuronal receptors and are involved in neuroendocrine transmissions. Interactions between KYN metabolism and the immune system may contribute to the neuropathogenesis of BD. Various studies have shown that alterations of the KYN metabolites were associated with mood, psychotic symptoms, and cognitive functions in patients with BD. In this review, we briefly introduce the KYN pathway and describe the immune dysregulation in BD as well as their interactions. We then focus on the research advances on the KYN metabolism in BD, which hold promise for identifying novel treatment targets in patients stricken with this disorder.

Impaired blood-brain barrier in the microbiota-gut-brain axis: Potential role of bipolar susceptibility gene TRANK1.

Bipolar disorder (BD) is a common psychiatric illness with high prevalence and disease burden. Accumulating susceptibility genes for BD have been identified in recent years. However, the exact functions of these genes remain largely unknown. Despite its high heritability, gene and environment interaction is commonly accepted as the major contributing factor to BD pathogenesis. Intestine microbiota is increasingly recognized as a critical environmental factor for human health and diseases via the microbiota-gut-brain axis. BD individuals showed altered diversity and compositions in the commensal microbiota. In addition to pro-inflammatory factors, such as interleukin-6 and tumour necrosis factor-α, type 1 interferon signalling pathway is also modulated by specific intestinal bacterial strains. Disruption of the microbiota-gut-brain axis contributes to peripheral and central nervous system inflammation, which accounts for the BD aetiology. Administration of type 1 interferon can induce the expression of TRANK1, which is associated with elevated circulating biomarkers of the impaired blood-brain barrier in BD patients. In this review, we focus on the influence of intestine microbiota on the expression of bipolar gene TRANK1 and propose that intestine microbiota-dependent type 1 interferon signalling is sufficient to induce the over-expression of TRANK1, consequently causing the compromise of BBB integrity and facilitating the entrance of inflammatory mediators into the brain. Activated neuroinflammation eventually contributes to the occurrence and development of BD. This review provides a new perspective on how gut microbiota participate in the pathogenesis of BD. Future studies are needed to validate these assumptions and develop new treatment targets for BD.

New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data.

Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring 'BD microbiota' following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.

Abnormal functional connectivity within the reward network: a potential neuroimaging endophenotype of bipolar disorder.

BACKGROUND: Reward circuit dysfunction underlies the pathogenesis of bipolar disorder (BD). This study aims to investigate whether nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC), two key reward regions for BD, have resting-state dysfunctional connectivity with other brain regions in depressed and euthymic BD. METHODS: 40 bipolar depressive (DE), 20 euthymic patients (EU) and 20 healthy controls (HC) were recruited to undergo resting-state functional MRI (rs-fMRI) scanning. Seed-based functional connectivity (FC) was calculated between NAcc/vmPFC and the whole brain. Group differences were calculated and their correlations with clinical characteristics were analyzed. Support vector machine was applied to classify BD patients and HC based on the FC between the cluster of group difference and NAcc/vmPFC. RESULTS: Whole brain networks of FC identified right anterior insular cortex (AIC) as a significant region with bilateral NAcc when compared among three groups. The right AIC-NAcc FC elevated in both patient groups and was highest in the EU group. Interestingly, vmPFC-based networks also identified the right AIC as a significant cluster. The right AIC-vmPFC FC elevated in both patient groups. However, FC between NAcc and vmPFC did not significantly differ BD patients from HC. Furthermore, the strength of FC between bilateral NAcc and the right AIC was positively associated with the illness course of BD. Notably, the NAcc/vmPFC-right AIC classifier acquired an accuracy of 68.75% and AUC-ROC of 78.17%. LIMITATIONS: Our sample size is modest. CONCLUSIONS: Our findings indicated that elevated NAcc/vmPFC-right AIC connectivity within the reward circuit could be a neuroimaging endophenotype of BD.

Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders.

Gut microbiome disturbances have been implicated in major depressive disorder (MDD). However, little is known about how the gut virome, microbiome, and fecal metabolome change, and how they interact in MDD. Here, using whole-genome shotgun metagenomic and untargeted metabolomic methods, we identified 3 bacteriophages, 47 bacterial species, and 50 fecal metabolites showing notable differences in abundance between MDD patients and healthy controls (HCs). Patients with MDD were mainly characterized by increased abundance of the genus Bacteroides and decreased abundance of the genera Blautia and Eubacterium These multilevel omics alterations generated a characteristic MDD coexpression network. Disturbed microbial genes and fecal metabolites were consistently mapped to amino acid (γ-aminobutyrate, phenylalanine, and tryptophan) metabolism. Furthermore, we identified a combinatorial marker panel that robustly discriminated MDD from HC individuals in both the discovery and validation sets. Our findings provide a deep insight into understanding of the roles of disturbed gut ecosystem in MDD.

Gut microbial clues to bipolar disorder: State-of-the-art review of current findings and future directions.

Trillions of microorganisms inhabiting in the human gut play an essential role in maintaining physical and mental health. The connections between gut microbiome and neuropsychiatric diseases have been recently identified. The pathogenesis of bipolar disorder, a spectrum of diseases manifesting with mood and energy fluctuations, also seems to be involved in the bidirectional modulation of the microbiome-gut-brain (MGB) axis. In this review, we briefly introduce the concept of MGB axis, and then focus on the previous findings in human studies associated with bipolar disorder. These studies provided preliminary evidences on the gut microbial alterations in bipolar disorder. Limitations in these studies and future directions in this research field, such as fecal microbiome transplantation and microbiome-targeted therapy, were discussed. A research framework linking gut microbiome to determinants and health-related outcomes in BD was also proposed. Better characterizing and understanding of gut microbial biosignatures in bipolar patients contribute to clarify the etiology of this intractable disease and pave the new way for treatment innovation.

Vortioxetine improves rapid eye movement sleep behavior disorder: A case report.

RATIONALE: Rapid eye movement sleep behavior disorder (RBD) is a kind of sleep disturbance characterized by a loss of normal paralysis of REM sleep with dream enactment behavior during REM sleep. The pharmacotherapy options for treating RBD are limited and the use of antidepressants remains controversial. Further, the role of vortioxetine in RBD has not been evaluated so far. PATIENT CONCERNS: A 72-year-old woman presented with recurrent peculiar behaviors such as shouting, punching, kicking or even walking around her bedroom during sleep for over 3 years. DIAGNOSIS: Clinical examinations and polysomnography indicated the diagnosis of RBD. INTERVENTIONS: The patient received treatment with paroxetine and melatonin for 1 year and then paroxetine was discontinued and vortioxetine was initiated in a daily dose of 10 mg. OUTCOMES: Treatment with paroxetine and melatonin for one year was ineffective. A trial of vortioxetine 10 mg per day over 3 months resulted in significant clinical improvement. LESSONS: To our knowledge, this is the first reported case of effective treatment of RBD with vortioxetine. Well-designed studies with large samples are needed to verify the clinical benefits.

Interactive effects of gender and sexual orientation on cortical thickness, surface area and gray matter volume: a structural brain MRI study.

BACKGROUND: Testosterone is thought to play a crucial role in sexual differentiation of the brain, and sexual orientation is programmed into our brain structures even when we are still fetuses. Although gender and sexual orientation differences have been shown respectively in many brain structures, the mechanism underlying the sexual differentiation of the brain is still unknown. The study is to investigate the interactive effects of gender and sexual orientation on cerebral structures in homosexual and heterosexual people. METHODS: Sexual orientation was evaluated by the Kinsey scale. We collected structural magnetic resonance image (MRI) data of local cortical thickness, surface area, and gray matter volume in all the subjects (29 homosexual and 29 heterosexual men, 17 homosexual and 17 heterosexual women). Statistical maps were generated using a general linear model (GLM) using FreeSurfer's Query, Design, Estimate, Contrast (QDEC) interface. We had sexual orientation and gender as 2 discrete factors with 2 levels, allowing for the generation of the interaction between sexual orientation and gender: homosexual women and heterosexual men versus heterosexual women and homosexual men. Coordinates were in Talairach space. All the cluster sizes were calculated with a P value of 0.01. RESULTS: Results revealed interactions concerning the area and gray matter volume between the factors of sexual orientation and gender. Regarding the thickness, an interaction was not found in any regions of the clusters. Regarding the area, an interaction was found in region of left middle temporal lobe, inferior temporal lobe, lateral occipital lobe, fusiform [(-58.1, -38.6, -14.7), maximum vertex-wise (MV) log10(P) =3.30, cluster size (CS) =1,286.90 mm2], and left rostral middle frontal lobe, pars opercularis, caudal middle frontal lobe [(-37.3, 23.6, 24.8), MV log10(P) =2.92, CS =1,194.40 mm2]. Regarding the gray matter volume, an interaction was found in the region of the left pars opercularis (inferior frontal gyrus) [(-42.9, 6.3, 18.5), MV log10(P) =1.31, CS =526.79 mm2]. CONCLUSIONS: The present study extends our understandings of how structural features differ in homosexual men, heterosexual men, homosexual women, and heterosexual women. Furthermore, it highlights the interactions between sexual orientation and gender in the left inferior frontal gyrus, bilateral temporal lobe, and the right rostral anterior cingulate cortex, which are suggested to play a critical role in the sexual differentiation of the human brain.

Fractional amplitude of low frequency fluctuation in drug-naïve first-episode patients with anorexia nervosa: A resting-state fMRI study.

To characterize the fractional amplitude of low-frequency fluctuation (fALFF) in drug-naïve first-episode female patients with anorexia nervosa (AN) using resting-state functional magnetic resonance imaging (rs-fMRI).Whole brain rs-fMRI data were collected from 7 drug-naïve first-episode female patients with DSM-5 AN and 14 age-matched healthy female controls. fALFF values were calculated and compared between the two groups using a two-sample t test. Correlation analysis between the fALFF values in the entire brain and body mass index (BMI) was performed.Compared with the healthy controls, increased fALFF values were observed in the AN patients in their right hippocampus and left superior frontal gyrus, while decreased fALFF values were observed in their left rectus and left middle occipital gyrus. Moreover, low BMI was significantly associated with decreased fALFF in the left inferior frontal gyrus but increased fALFF in the left calcarine. In particular, the z-standardized fALFF (zfALFF) value of the left rectus was positive associated with BMI.Our findings suggest that spontaneous brain activity in the frontal region, hippocampus and rectus, characterized by fALFF values, was altered in drug-naïve, first-episode female patients with AN.