Agoraphobia and panic attacks complicated by primary aldosteronism improved by treatment with eplerenone: a case report.

BACKGROUND: Primary aldosteronism (PA) is an adrenal gland disease, that induces increased secretion of the mineralocorticoid, aldosterone, resulting in symptoms such as hypertension. This study reports a patient with agoraphobia and panic attacks, associated with PA. This patient's psychiatric symptoms improved after treatment with eplerenone, a mineralocorticoid receptor antagonist. CASE PRESENTATION: The patient was a 40-year-old female with agoraphobia, which refers to the irrational fear of situations that may cause anxiety, and panic attacks characterized by profuse sweating, palpitations, and generalized weakness. She was diagnosed with hypertension from PA. Subsequently, she received treatment with eplerenone, which improved her agoraphobia and panic attacks. CONCLUSIONS: There have been no previous reports on PA associated with agoraphobia and panic attacks that improved with pharmacotherapy. Patients with agoraphobia and panic attacks should be evaluated for PA. In patients with PA, pharmacotherapy with eplerenone should be considered.

Association between salivary mature brain-derived neurotrophic factor and psychological distress in healthcare workers.

INTRODUCTION: Previous studies have suggested association between brain-derived neurotrophic factor (BDNF) and the stress level of workers. However, no studies have investigated the potential of salivary mature BDNF (mBDNF) level as a noninvasive biomarker for psychological distress. This study aimed to explore the reliability of salivary mBDNF as a biomarker for psychological distress in healthcare workers. Furthermore, we examined the relationship between salivary and plasma mBDNF levels and their correlation with age, sex, body mass index (BMI), and exercise habits. METHODS: Fifty-one healthy healthcare workers (26 men) from the University of Occupational and Environmental Health, Japan, participated in this study. In this cross-sectional study, participants provided demographic information. Psychological distress was assessed using the Kessler 6 (K6). Saliva and blood samples were collected, and mBDNF was measured by ELISA. Spearman's rank correlation coefficient was performed to analyze the relationship between mBDNF (saliva and plasma) and K6. Statistical analyses were conducted using Stata 17.0, and a significance level of p < .05 was applied. RESULTS: The median K6 score was 1 (interquartile range [IQR]: 0-3). The median (IQR) salivary mBDNF was 1.36 (1.12-1.96) pg/mL, whereas the mean (standard deviation) plasma mBDNF was 1261.11 (242.98) pg/mL. No correlation was observed between salivary and plasma mBDNF concentrations or with the K6 score. Additionally, there were no associations between salivary or plasma mBDNF concentrations and age, sex, or exercise habits. Finally, an association between plasma mBDNF concentration and BMI was found only in univariate analysis. CONCLUSION: Our findings indicate that salivary mBDNF can be accurately measured noninvasively in healthcare workers. Within our study sample, salivary mBDNF did not demonstrate any correlation with K6 and plasma mBDNF. Future studies with a larger study sample and a diverse study population consisting of healthy participants and patients with psychiatric disorders are warranted.

Acute pancreatitis during valproic acid administration in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms: a case report.

BACKGROUND: Valproic acid (VPA) is a relatively safe drug widely used for the treatment of epileptic seizures and mania in bipolar disorder, as well as the prevention of migraine headaches. Here, we present a case of VPA-induced pancreatitis in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms. He had no distinctive abdominal symptoms. CASE PRESENTATION: A 66-year-old Japanese man was treated with VPA for agitation and violent behavior due to vascular dementia, epileptic seizures, and psychiatric symptoms. During admission, he experienced a sudden decrease in consciousness and blood pressure. Abdominal findings were unremarkable; however, blood tests showed an inflammatory response and elevated amylase levels. Contrast-enhanced abdominal computed tomography showed diffuse pancreatic enlargement and inflammation extending to the subrenal pole. VPA-induced acute pancreatitis was diagnosed, VPA was discontinued, and high-dose infusions were administered. Acute pancreatitis resolved after treatment initiation. CONCLUSIONS: Clinicians should be aware of this relatively rare side effect of VPA. Diagnosis may be challenging in elderly people and patients with dementia as they may present with non-specific symptoms. Clinicians should consider the risk of acute pancreatitis when using VPA in patients who cannot report spontaneous symptoms. Blood amylase and other parameters should be measured accordingly.

Risk Factors in Japanese Drug Overdose Patients: Identifying Their Associations With Suicide Risk.

Several suicide attempts presented at the emergency department are due to drug overdose associated with psychiatric disorders. We examined and identified the major risk factors among Japanese drug overdose patients and several close associations of suicide risk. We enrolled 101 patients who attempted suicide by drug overdose between January 2015 and April 2018, assessed their background using the SAD PERSONS scale, and performed association rule analysis to characterize the major risk factors and their associations. We identified three main nodes-depressive state, social support lacking, and no spouse-as considerable risk factors. Furthermore, we identified several close associations of suicide risk and their intensity; in cases with previous suicide attempts and ethanol abuse or substance use, a simultaneous social support lacking is likely. These findings align with previous studies that used conventional statistical analysis on suicide and suicide attempt risk and highlight its importance.

Comparison of Serum Metabolomics Pathways and Patterns between Patients with Major Depressive Disorder with and without Type 2 Diabetes Mellitus: An Exploratory Study.

BACKGROUND: A close relationship exists between major depressive disorder (MDD) and diabetes mellitus. The metabolomic difference and similarity between patients with and without diabetes mellitus have not been well studied in the context of MDD. We aimed to examine these differences and common serum metabolomics patterns, pathways and biomarkers that can comprehensively reflect the pathogenetic difference and similarity between these MDD groups. METHODS: We performed a metabolomics analysis of serum samples of healthy controls (n = 6), patients with MDD and type 2 diabetes mellitus (n = 13), and patients with MDD without type 2 diabetes mellitus (n = 27). Metabolomics analysis was conducted using capillary electrophoresis Fourier transform mass spectrometry and a candidate compound was assigned to the 496 (290 cation, 206 anion) peaks. Moreover, we evaluated the sensitivity and specificity of the candidate biomarkers for distinguishing between MDD patients with or without type 2 diabetes mellitus. RESULTS: Principal component analysis revealed no clear distinction among the three groups, while naive partial least squares discriminant analysis yielded three relatively good and distinct populations based on the first principal component. Energy conversion by the tricarboxylic acid cycle represented the highest percentage among the top 30 positive factors of the first principal component, and glutamate metabolism and urea cycle represented the highest percentage among the top 30 negative factors of the first principal component. Synthesis and degradation of ketone bodies had high impact in MDD with type 2 diabetes mellitus group and taurine and hypotaurine metabolism had high impact in MDD without type 2 diabetes mellitus group for the pathway. CONCLUSIONS: Patterns of serum metabolites may be different among MDD with type 2 diabetes mellitus, MDD without type 2 diabetes mellitus, and healthy controls groups. Specifically, comorbid type 2 diabetes mellitus could affect metabolomics pathway and alter the distribution of serum metabolites in patients with MDD. These findings may shed light on the influence of the type 2 diabetes on the pathophysiology of MDD.

Increased Stimulation Intensity Helped to Cope with Prolonged Seizures During the Next Round of Modified Electroconvulsive Therapy: A Case Report.

Background: Numerous protocols exist to counteract prolonged seizures during modified electroconvulsive therapy (mECT), such as anaesthetic adjustments and ventilation. Evidence on methods for deciding whether to continue with the next round of mECT after a prolonged seizure and to prevent recurrent seizures is currently not well established. Case Presentation: The patient was a 76-year-old woman with major depressive disorder. She suffered from depressive symptoms such as decreased appetite, anxiety, and agitation. She was admitted to our hospital for mECT for the fifth time. The mECT was bilateral and started at 35% stimulus intensity, and effective convulsions were obtained for the first time. During the 8th mECT at the same intensity (35% stimulus intensity), an unexpected prolonged seizure of 966 s (over 16 minutes) occurred. The seizure was abruptly stopped with diazepam 10 mg and midazolam 2 mg. During the ninth mECT session, the stimulation intensity was increased to 50%, which resulted in effective seizures and no prolonged seizures. Subsequently, appropriate convulsions were obtained with the same stimulation intensity, and she completed 12 sessions. Her depressive symptoms improved, and she was discharged on the 45th day of hospitalization. Conclusion: Prolonged seizures in mECT can be prevented by raising the stimulation intensity during the following cycle.

The Molecular Mechanism of Exercise for Treatment of Patients with Major Depression: A Preliminary Report on the Dynamics of Metabolites of Nitric Oxide and Catecholamines.

BACKGROUND: There has been increasing evidence that exercise therapy is effective in the treatment and prevention of major depression (MD). However, the basic molecular mechanisms underlying the effects of exercise on MD remain unclear. We conducted a preliminary study to clarify the effect of exercise therapy on MD, focusing on the dynamics of nitric oxide (NO) and catecholamine metabolites, which have been found to be associated with MD. METHODS: Eleven outpatients with mild to moderate MD and 37 healthy controls (HC) were included in the study. The participants' clinical records and questionnaires were screened for their past medical history. For their exercise therapy, the participants were instructed to walk the equivalent of 17.5 kcal/kg/week for 8 weeks. Blood samples were collected from all participants at baseline, 4 weeks, and 8 weeks after the start of exercise therapy, and plasma metabolites of NO (NOx), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were analyzed. We also assessed the 17-item Hamilton Rating Scale for Depression (HRSD-17) in patients with MD. A mixed-effects regression model was used to compare the mean values by time (baseline, 4, and 8 weeks) for the three corresponding groups (NOx, MHPG, and HVA). RESULTS: HRSD-17 scores decreased significantly in the MD group after 8 weeks of exercise therapy. NOx and MHPG increased, but there was no significant change in HVA in the MD group after the exercise therapy. NOx decreased after exercise, and HVA increased significantly from baseline after 4 weeks of exercise but decreased after 8 weeks of exercise in the HC group. CONCLUSIONS: The effects of exercise on NOx, MHPG, and HVA may differ between MD and HC. The potential mechanisms for the benefits of walking exercise in MD patients will be the subject for future research.

Hippocampal Volume and Plasma Brain-Derived Neurotrophic Factor Levels in Patients With Depression and Healthy Controls.

The aim of the present study was to investigate associations between hippocampal subfield volumes and plasma levels of brain-derived neurotrophic factor (BDNF) in patients experiencing a first episode of major depression (MD) (n = 30) as compared to healthy controls (HC) (n = 49). Covariate-adjusted linear regression was performed to compare the MD and healthy groups, adjusting for age, sex, and total estimated intracranial volume. We demonstrated that there were no differences in total hippocampal volume between the MD and HC groups. However, the volumes of the hippocampus-amygdala-transition-area (HATA) on the left side of the brain as well as the parasubiculum, presubiculum, and fimbria on the right side were statistically significantly smaller in the MD group than in the HC group. Furthermore, the volume of the hippocampal fissure on the right side was statistically significantly smaller in the HC group than in the MD group. In the MD group, we found a positive linear correlation between hippocampal volume and plasma BDNF concentrations in the CA4 area on the left side (p = 0.043). In contrast, in the HC group, we found a negative linear correlation between parasubiculum volume on the right side and plasma BDNF concentrations (p = 0.04). These results suggest that some hippocampal subfields may already be atrophic at the start of MD. In addition, our findings suggest that the sensitivity of the right parasubiculum region to BDNF may differ between MD and HC groups. These findings guide future research directions and, if confirmed, may ultimately inform medical guidelines.

Volume of Amygdala Subregions and Plasma Levels of Brain-Derived Neurotrophic Factor and Cortisol in Patients with s/s Genotype of Serotonin Transporter Gene Polymorphism of First-Episode and Drug-Naive Major Depressive Disorder: An Exploratory Study.

The amygdala is a prominent region of the brain that plays a critical role in the pathophysiology of major depressive disorder (MDD). The amygdala is formed from a collection of interconnected substructures (nuclei) that relay signals from multiple brain areas, which suggests that the amygdala has different functions depending on its subregion. There are two main alleles of serotonin transporter gene polymorphism (5-HTTLPR): a 44-bp insertion (l-allele) or deletion (s-allele). The transcriptional activity of the l-allele of the gene is twice that of the s-allele. The present study aimed to investigate the association between the volume of the whole amygdala and subregions of the amygdala in 25 first-episode and drug-naive patients with MDD and 46 healthy controls (HCs) with the s/s genotype of 5-HTTLPR and plasma levels of brain-derived neurotrophic factor (BDNF) or cortisol. No significant difference was observed in the amygdala total and subregion volumes between the HC and MDD groups. No significant difference was found in the plasma levels of BDNF and cortisol between the two groups. In addition, no correlations were found between the total and subregion amygdala volume and plasma levels of cortisol or BDNF.

Pre-treatment plasma cytokine levels as potential predictors of short-term remission of depression.

OBJECTIVES: The response to antidepressants varies significantly among individuals and is difficult to predict before treatment. In this randomised control trial, we explored cytokines that correlate with the therapeutic effect of mirtazapine (MIR) and selective serotonin reuptake inhibitors (SSRIs) and whether they could be predictors of remission for each antidepressant. METHODS: Plasma cytokines, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were assayed in 95 participants before medication and assayed by the enzyme-linked immunosorbent assay. The Hamilton Rating Scale for Depression assessed depressive symptoms over 4 weeks. RESULTS: In the SSRI group, the baseline GM-CSF level was significantly higher in the remission group than in the non-remission group (p = .022). In the MIR group, the baseline level of TNF-α was significantly higher (p = .039) and IL-2 was lower (p = .032) in the remission group than in the non-remission group. In patients prescribed with MIR, the cut-off values of TNF-α (10.035 pg/mL) and IL-2 (1.170 pg/mL) calculated from the receiver operating characteristic curve suggested that the remission rate, which corresponds to a positive predictive value, could be increased from 31.3% to 60.0% and 50.0%, respectively. For those prescribed with SSRIs, the remission rate was 37.0% and using the cut-off value of GM-CSF (0.205 pg/mL), the remission rate could be almost doubled to 70%. CONCLUSIONS: Our study shows that pre-treatment plasma concentrations of TNF-α, IL-2, and GM-CSF may suggest the predictability of remission by SSRIs or MIR.

Associations Between the Kynurenine Pathway, Proinflammatory Cytokines, and Brain-Derived Neurotrophic Factor in Hospitalized Patients With Chronic Schizophrenia: A Preliminary Study.

Purpose: The kynurenine (Kyn) pathway may play a role in the pathophysiology of schizophrenia. This pathway shows crosstalk with proinflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α), and/or brain-derived neurotrophic factor (BDNF). Moreover, Kyn metabolites affect neurotransmission and cause neurotoxicity. To date, the influence of the Kyn pathway on proinflammatory cytokines and BDNF remains to be fully elucidated. The aim of this study was to investigate the relationships of the Kyn pathway with proinflammatory cytokines, BDNF, and psychiatric symptoms in patients with schizophrenia. Methods: Thirty patients with schizophrenia and ten healthy control participants were recruited for this study. All patients were diagnosed with schizophrenia using the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5). The healthy controls were those who did not fulfill any of the diagnostic criteria in the DSM-5. The serum levels of Kyn and its metabolites, proinflammatory cytokines, and BDNF were measured in patients with schizophrenia and healthy controls. Patients with schizophrenia were also assessed for psychiatric symptoms using the Positive and Negative Syndrome Scale (PANSS). Results: Patients with schizophrenia and healthy controls showed no significant differences in the levels of Kyn and its metabolites, proinflammatory cytokines, and BDNF. A significant positive correlation was found between the serum levels of TNF-α and Kyn (r = 0.53, p = 0.0026) and the Kyn/tryptophan (Trp) value (r = 0.67, p = 0.000046) in the schizophrenia group, but not in the healthy control group. Conclusion: TNF-α affects the Kyn pathway in patients with chronic schizophrenia, but not in the healthy individuals, although serum TNF-α levels showed no difference between the two groups. Associations between the Kyn pathway and the levels of proinflammatory cytokines and BDNF or psychotic symptoms might be complicated in hospitalized patients with chronic schizophrenia.

A Metabolomics Study of Serum in Hospitalized Patients With Chronic Schizophrenia.

Purpose: Metabolomics has attracted attention as a new method for understanding the molecular mechanisms of psychiatric disorders. Current metabolomics technology allows us to measure over hundreds of metabolites at a time and is a useful indicator of the consequences of complex and continuous changes in metabolic profiles due to the execution of genomic information and external factors of biological activity. Therefore, metabolomics is imperative to the discovery of biomarkers and mechanisms associated with pathophysiological processes. In this study, we investigated metabolites changes in hospitalized patients with chronic schizophrenia compared to that in healthy controls, and examined the correlations between the metabolites and psychiatric symptoms. Patients and Methods: Thirty patients with schizophrenia and ten healthy controls participated in this study between September 2019 and June 2020. The mean duration of disease in patients with schizophrenia was 26 years. Clinical and neuropsychiatric symptoms of patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS). Metabolomics was conducted using Capillary Electrophoresis Fourier Transform Mass Spectrometry (CE-FTMS), using serum samples from patients with schizophrenia and healthy controls. Metabolomics assigned a candidate compound to the 446 (cation 279, anion 167) peaks. Hierarchical cluster analysis (HCA), principal component analysis (PCA), logistic regression analysis, receiver operating characteristic (ROC) analysis, and linear regression analysis were used to analyze the metabolites changes, identifying the disease and the relationship between metabolites and psychiatric symptoms. Results: HCA showed that approximately 60% of metabolites had lower peak values in patients with schizophrenia than in healthy controls. Glutamate metabolism and the urea cycle had the highest proportions in the metabolic pathway, which decreased in patients with schizophrenia. PCA showed a clear separation between patients with schizophrenia and healthy controls in the first principal component (the contribution ratio of the first principal component was 15.9%). Logistic regression analysis suggested that the first principal component was a predictor of disease (odds = 1.36, 95%CI = 1.11-1.67, p = 0.0032). ROC analysis showed a sensitivity of 93% and a specificity of 100% for the diagnosis of schizophrenia with a cut-off value of the first principal component; -3.33 (AUC = 0.95). We extracted the high factor loading for the first principal component. Gamma-glutamyl-valine (γ-Glu-Val) was significantly negatively correlated with PANSS total scores (r = -0.45, p = 0.012) and PANSS general scores (r = -0.49, p = 0.0055). Gamma-glutamyl-phenylalanine (γ-Glu-Phe) was significantly negatively correlated with PANSS total score (r = -0.40, p = 0.031) and PANSS general score (r = -0.41, p = 0.025). Tetrahydrouridine was significantly positively correlated with PANSS negative scores (r = 0.53, p = 0.0061). Conclusion: Metabolites changes in hospitalized patients with chronic schizophrenia showed extensive and generalized declines. Glutamate metabolism and the urea cycle had the highest proportions in the metabolic pathway, which decreased in the schizophrenia group. Metabolomic analysis was useful to identify chronic schizophrenia. Some glutamate compound metabolites had a relationship with psychiatric symptoms.

Volume of Amygdala Subregions and Clinical Manifestations in Patients With First-Episode, Drug-Naïve Major Depression.

We examined amygdala subregion volumes in patients with a first episode of major depression (MD) and in healthy subjects. Covariate-adjusted linear regression was performed to compare the MD and healthy groups, and adjustments for age, gender, and total estimated intracranial volume showed no differences in amygdala subregion volumes between the healthy and MD groups. Within the MD group, we examined the association between amygdala subregion volume and the 17-item Hamilton Rating Scale for Depression (HAMD) score and the HAMD subscale score, and found no association in the left amygdala. In the right amygdala, however, there was an inverse linear association between the HAMD total and the HAMD core and lateral nucleus and anterior-amygdaloid-regions. Furthermore, an inverse linear association was seen between the HAMD psychic and the lateral nucleus, anterior-amygdaloid-regions, transition, and whole amygdala. The findings of this study suggest that the severity of MD and some symptoms of MD are associated with right amygdala volume. There have been few reports on the relationship between MD and amygdala subregional volume, and further research is needed to accumulate more data for further validation.

Structural Changes in Hippocampal Subfields in Patients with Continuous Remission of Drug-Naive Major Depressive Disorder.

OBJECTIVE: Hippocampal volume is reduced in patients with major depressive disorder (MDD) compared with healthy controls. The hippocampus is a limbic structure that has a critical role in MDD. The aim of the present study was to investigate the changes in the volume of the hippocampus and its subfields in MDD patients who responded to antidepressants and subsequently were in continuous remission. SUBJECTS AND METHODS: Eighteen patients who met the following criteria were enrolled in the present study: the DSM-IV-TR criteria for MDD, drug-naïve at least 8 weeks or more, scores on the 17-items of Hamilton Rating Scale for Depression (HAMD) of 14 points or more, and antidepressant treatment response within 8 weeks and continuous remission for at least 6 months. All participants underwent T1-weighted structural MRI and were treated with antidepressants for more than 8 weeks. We compared the volumes of the hippocampus, including its subfields, in responders at baseline to the volumes at 6 months. The volumes of the whole hippocampus and the hippocampal subfields were measured using FreeSurfer v6.0. RESULTS: The volumes of the left cornu Ammonis (CA) 3 (p = 0.016) and the granule cell layer of the dentate gyrus (GC-DG) region (p = 0.021) were significantly increased after 6 months of treatment compared with those at baseline. CONCLUSIONS: Increases in volume was observed in MDD patients who were in remission for at least 6 months.

A single-nucleotide polymorphism influences brain morphology in drug-naïve patients with major depressive disorder.

OBJECTIVE: Recently, a genome-wide association study successfully identified genetic variants associated with major depressive disorder (MDD). The study identified 17 independent single-nucleotide polymorphisms (SNPs) significantly associated with diagnosis of MDD. These SNPs were predicted to be enriched in genes that are expressed in the central nervous system and function in transcriptional regulation associated with neurodevelopment. The study aimed to investigate associations between 17 SNPs and brain morphometry using magnetic resonance imaging (MRI) in drug-naïve patients with MDD and healthy controls (HCs). METHODS: Forty-seven patients with MDD and 42 HCs were included. All participants underwent T1-weighted structural MRI and genotyping. The genotype-diagnosis interactions associated with regional cortical thicknesses were evaluated using voxel-based morphometry for the 17 SNPs. RESULTS: Regarding rs301806, an SNP in the RERE genomic regions, we found a significant difference in a genotype effect in the right-lateral orbitofrontal and postcentral lobes between diagnosis groups. After testing every possible diagnostic comparison, the genotype-diagnosis interaction in these areas revealed that the cortical thickness reductions in the MDD group relative to those in the HC group were significantly larger in T/T individuals than in C-carrier ones. For the other SNPs, no brain area was noted where a genotype effect significantly differed between the two groups. CONCLUSIONS: We found that a RERE gene SNP was associated with cortical thickness reductions in the right-lateral orbitofrontal and postcentral lobes in drug-naïve patients with MDD. The effects of RERE gene polymorphism and gene-environment interactions may exist in brain structures of patients with MDD.

COMT polymorphism regulates the hippocampal subfield volumes in first-episode, drug-naive patients with major depressive disorder.

Purpose: Compared with healthy subjects (HS), patients with major depressive disorder (MDD) exhibit volume differences that affect the volume changes in several areas such as the limbic, cortical, subcortical, and white matter. Catechol-O-methyltransferase (COMT) is a methylation enzyme that catalyzes endogenous catecholamines. The Val158Met polymorphism of COMT has been reported to affect the dopamine (DA) levels, which plays an important role in psychiatric diseases. However, the relationships among both DA levels, COMT genotype, and brain morphology are complicated and controversial. In previous studies that investigated the hippocampal subfields, the greatest brain abnormalities in MDD patients were observed in Cornu Ammonis (CA)1 and the subiculum, followed by that in CA2-3. We have prospectively demonstrated the relationship between the single-nucleotide polymorphism of the Val158Met COMT gene (rs4680) and the hippocampal subfields in drug-naive MDD patients. Patients and methods: In this study, we compared 27 MDD patients and 42 HS who were divided into groups based on their COMT genotype. The effects of the diagnosis, genotype, and genotype-diagnosis interaction related to CA1 and the subiculum volumes, as well as the whole-brain cortical thickness, were evaluated by performing a FreeSurfer statistical analysis of high-resolution magnetic resonance imaging (MRI) findings. Results: The results revealed that there was a statistically significant interaction between the effects of diagnosis and genotype on the right subiculum (a component of the hippocampus). Conclusion: This Val158Met COMT polymorphism may influence the subiculum volume in drug-naive, first-episode MDD patients.

Relationship between VEGF-related gene polymorphisms and brain morphology in treatment-naïve patients with first-episode major depressive disorder.

Vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder (MDD). Recently, a genome-wide association study has revealed that four VEGF-related single nucleotide polymorphisms (SNPs) (i.e., rs4416670, rs6921438, rs6993770 and rs10738760) were independently associated with circulating VEGF levels. The current study investigated the relationship between brain volume and these four SNPs in first-episode drug-naïve MDD patients. A total of 38 first-episode drug-naïve MDD patients and 39 healthy subjects (HS) were recruited and underwent high-resolution T1-weighted imaging. Blood samples were collected from all the participants for serum VEGF assays and VEGF-related SNPs genotyping. Genotype-diagnosis interactions related to whole-brain cortical thickness and hippocampal subfield volumes were evaluated for the four SNPs. The results revealed a genotype-diagnosis interaction only for rs6921438 (i.e., the MDD patients and HS with the G/G genotype versus the MDD patients and HS with A-carrier genotype) in the subiculum of the left hippocampus (p < 0.05), and not the other SNPs. There was a volume reduction in the left subiculum of G/G genotype patients compared with the other groups. The "hypochondriasis" scores of the HAMD-17 scale were significantly higher in the G/G genotype patients than the A-carrier genotype patients. The association was observed between VEGF-related SNP rs6921438 and subiculum atrophy in first-episode drug-naïve MDD patients.