Sex differences in serum trace elements and minerals levels in unmedicated patients with major depressive episode: The role of suicidal ideation.

BACKGROUND: We aimed to examine the influence of gender on serum trace elements and minerals levels in depression, as well as the impact of suicidal ideation (SI) on these gender dimorphisms. METHODS: A total of 260 unmedicated patients with a current major depressive episode were enrolled. The Beck Scale for Suicide Ideation was utilized to evaluate SI. The serum levels of copper, zinc, iron, calcium, phosphorus, and magnesium were quantified. RESULTS: Within the non-SI (NSI) group, females exhibited higher levels of copper (p = 0.001) and phosphorus (p = 0.008), and lower levels of zinc (p = 0.022) and calcium (p = 0.008) compared to males. Conversely, no discernible gender disparities were observed in the SI group (all p > 0.05). Also, no group differences in these trace elements/minerals were observed between the SI and NSI groups (all p > 0.05). Notably, serum iron levels exhibited a significant group-by-sex interaction effect (p = 0.024). Further analysis revealed that iron levels were higher in the SI group than in the NSI group among females (p = 0.048), but lower in females than in males within the NSI group (p < 0.001). Moreover, a positive association between the fourth quantile of serum iron and SI was detected in females (odds ratio [OR] = 2.88, 95 % confidence interval [CI]: 1.08-8.11). CONCLUSIONS: Gender effects on serum trace element/mineral levels were different in depressed patients with and without SI. Female patients were susceptible to SI when serum iron was at the upper end of normal.

Association between serum copper, zinc, and selenium concentrations and depressive symptoms in the US adult population, NHANES (2011-2016).

BACKGROUND: Evidence suggests that alterations in serum trace element concentrations are closely associated with mental illness. However, ​studies on the relationship between serum copper, zinc, and selenium concentrations and depressive symptoms are limited and with controversial results. We aimed to investigate the association between serum concentrations of these trace elements and depressive symptoms in US adults. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) (2011-2016) were used in this cross-sectional study. The Patient Health Questionnaire-9 Items (PHQ-9) was employed to assess depressive symptoms. Multiple logistic regression was performed to determine the relationship between the serum concentrations of copper, zinc, and selenium and depressive symptoms. RESULTS: A total of 4552 adults were included. Subjects with depressive symptoms had higher serum copper concentrations (123.88 ± 1.87) than those without depressive symptoms (116.99 ± 0.86) (p < 0.001). In Model 2, weighted logistic regression analysis showed that the second (Q2) quartile of zinc concentrations (odds ratio [OR] = 1.534, 95% confident interval [CI]: 1.018 to 2.313) were significantly associated with an increased risk of depressive symptoms. Subgroup analysis revealed that the third (Q3) and fourth (Q4) quartiles of copper concentrations (Q3: OR = 2.699, 95% CI: 1.285 to 5.667; Q4: OR = 2.490, 95% CI: 1.026 to 6.046) were also positively associated with depressive symptoms in obese individuals after controlling for all confounders. However, no significant relationship between serum selenium concentrations and depressive symptoms was observed. CONCLUSIONS: Obese US adults with high serum copper concentrations, as well as US adults in general with low serum zinc concentrations, were susceptible to depressive symptoms. Nevertheless, the causal mechanisms underlying these relationships need to be further explored.

Association between serum zinc levels and suicidal ideation in US adults: A population-based cross-sectional study.

BACKGROUND: Evidence suggests that the homeostatic disruption of zinc, copper, and selenium might contribute to the pathophysiology of mental disorders. However, the specific relationship between the serum levels of these trace elements with suicidal ideation remains poorly understood. This study aimed to investigated the association among suicidal ideation on serum levels of zinc, copper, and selenium. METHODS: The cross-sectional study was conducted using data from a nationally representative sample of the National Health and Nutrition Examination Survey (NHANES) 2011-2016. Suicidal ideation was assessed using Item #9 of the Patient Health Questionnaire-9 Items. Multivariate regression models and restricted cubic splines were performed and E-value was calculated. RESULTS: A total of 4561 participants aged 20 years and older were analyzed, of whom 4.08 % had suicidal ideation. The serum zinc levels were lower in the suicidal ideation group than in the non-suicidal ideation group (P = 0.021). In Crude Model, the serum zinc levels were associated with a higher suicidal ideation risk in the second quartile compared with the highest quartile [odds ratio (OR) = 2.63; 95 % confidence interval (CI): 1.53-4.53]. The association persisted (OR = 2.35; 95 % CI: 1.20-4.58) after full adjustment, with E-value 2.44. A nonlinear relationship was observed between serum zinc levels and suicidal ideation (P = 0.028). No relationship was observed between suicidal ideation and serum copper or selenium levels (all P > 0.05). CONCLUSIONS: Decreased serum zinc levels may increase susceptibility to suicidal ideation. Future studies are needed to validate the findings of this study.

The Effectiveness of Eye Movement Desensitization and Reprocessing Toward Adults With Major Depressive Disorder: A Meta-Analysis of Randomized Controlled Trials.

The practice-based evidence suggests that it is possible to use eye movement desensitization and reprocessing (EMDR) to treat major depressive disorder (MDD), but its specific efficacy is unknown. A systematic search was carried out for randomized controlled trials comparing EMDR with a control condition group in MDD patients. Two meta-analyses were conducted, with symptom reduction as primary outcome and remission as exploratory outcome. Eight studies with 320 participants were included in this meta-analysis. The first meta-analysis showed that EMDR outperformed "No Intervention" in decreasing depressive symptoms (standardized mean difference [SMD] = -0.81, 95% CI = -1.22 to -0.39, p < 0.001, low certainty), but statistically significant differences were not observed in improving remission (risk ratio = 1.20, 95% CI = 0.87-1.66, p = 0.25, very low certainty). The second showed the superiority of EMDR over CBT in reducing depressive symptoms (mean difference [MD] = -7.33, 95% CI = -8.26 to -6.39, p < 0.001, low certainty), and improving remission (risk ratio = 1.95, 95% CI = 1.24-3.06, p = 0.004, very low certainty). Besides, anxiety symptoms and level of functioning could not be included as secondary outcome due to the lack of data. The present meta-analysis suggests that EMDR is more effective in treating MDD than "No Intervention" and CBT, particularly in individuals who have traumatic experience. However, this result should be considered with caution due to small sample size and low quality of trails.

Correlations Among mRNA Expression Levels of ATP7A, Serum Ceruloplasmin Levels, and Neuronal Metabolism in Unmedicated Major Depressive Disorder.

BACKGROUND: Previous studies have found that elevated copper levels induce oxidation, which correlates with the occurrence of major depressive disorder (MDD). However, the mechanism of abnormal cerebral metabolism of MDD patients remains ambiguous. The main function of the enzyme ATPase copper-transporting alpha (ATP7A) is to transport copper across the membrane to retain copper homeostasis, which is closely associated with the onset of mental disorders and cognitive impairment. However, less is known regarding the association of ATP7A expression in MDD patients. METHODS: A total of 31 MDD patients and 21 healthy controls were recruited in the present study. Proton magnetic resonance spectroscopy was used to assess the concentration levels of N-acetylaspartate, choline (Cho), and creatine (Cr) in brain regions of interest, including prefrontal white matter (PWM), anterior cingulate cortex (ACC), thalamus, lentiform nucleus, and cerebellum. The mRNA expression levels of ATP7A were measured using polymerase chain reaction (SYBR Green method). The correlations between mRNA expression levels of ATP7A and/or ceruloplasmin levels and neuronal biochemical metabolite ratio in the brain regions of interest were evaluated. RESULTS: The decline in the mRNA expression levels of ATP7A and the increase in ceruloplasmin levels exhibited a significant correlation in MDD patients. In addition, negative correlations were noted between the decline in mRNA expression levels of ATP7A and the increased Cho/Cr ratios of the left PWM, right PWM, and right ACC in MDD patients. A positive correlation between elevated ceruloplasmin levels and increased Cho/Cr ratio of the left PWM was noted in MDD patients. CONCLUSIONS: The findings suggested that the decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels induced oxidation that led to the disturbance of neuronal metabolism in the brain, which played important roles in the pathophysiology of MDD. The decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels affected neuronal membrane metabolic impairment in the left PWM, right PWM, and right ACC of MDD patients.

Associations between executive function impairment and biochemical abnormalities in bipolar disorder with suicidal ideation.

BACKGROUND: Executive dysfunction and biochemical abnormalities using proton magnetic resonance spectroscopy (1H-MRS) have been reported in bipolar disorder (BD). Much less is known about the information from BD with suicidal ideation (SI). This study aimed to assess alterations of execution function and biochemical metabolism in BD with SI, in BD without SI, and in healthy controls. The associations between execution function and biochemical metabolism in the two BD patient groups were also been studied. METHODS: 92 patients with bipolar disorder during a depressive episode (50 with current SI, and 42 without SI), as well as, 43 healthy controls were recruited in our study. Executive function was assessed by Wisconsin Card Sorting Test (WCST). Bilateral metabolite levels of prefrontal cortex (PFC), anterior cingulated cortex (ACC), lenticular nucleus (LN) of basal ganglia and thalamus were obtained by 1H-MRS at 3.0 T, then determined the ratios of N-acetyl aspartate (NAA), choline-containing compounds (Cho), myo-inositol (mI) to creatine (Cr). RESULTS: Number of categories completed (CC) in BD with SI was significantly less than healthy controls. NAA/Cr ratios of left PFC in the two BD patient groups (with or without SI) were significantly lower than healthy controls, and NAA/Cr ratios of left thalamus were significantly higher than healthy controls. Moreover, NAA/Cr ratio of right LN in BD without SI was higher than BD with SI and healthy controls. For BD with SI, NAA/Cr ratio of left thalamus was negatively correlated with number of CC. CONCLUSIONS: These results suggested that BD with or without SI may have abnormal NAA metabolism, and NAA/Cr ratio of right LN may distinguish SI from the BD patients. Further, BD with SI may have executive function impairment, which may be associated with the abnormal NAA metabolism in the left thalamus.

A Meta-Analysis of Oxidative Stress Markers in Depression.

OBJECT: Studies have suggested that depression was accompanied by oxidative stress dysregulation, including abnormal total antioxidant capacity (TAC), antioxidants, free radicals, oxidative damage and autoimmune response products. This meta-analysis aims to analyse the clinical data quantitatively by comparing the oxidative stress markers between depressed patients and healthy controls. METHODS: A search was conducted to collect the studies that measured the oxidative stress markers in depressed patients. Studies were searched in Embase, Medline, PsychINFO, Science direct, CBMDisc, CNKI and VIP from 1990 to May 2015. Data were subjected to meta-analysis by using a random effects model for examining the effect sizes of the results. Bias assessments, heterogeneity assessments and sensitivity analyses were also conducted. RESULTS: 115 articles met the inclusion criteria. Lower TAC was noted in acute episodes (AEs) of depressed patients (p<0.05). Antioxidants, including serum paraoxonase, uric acid, albumin, high-density lipoprotein cholesterol and zinc levels were lower than controls (p<0.05); the serum uric acid, albumin and vitamin C levels were increased after antidepressant therapy (p<0.05). Oxidative damage products, including red blood cell (RBC) malondialdehyde (MDA), serum MDA and 8-F2-isoprostanes levels were higher than controls (p<0.05). After antidepressant medication, RBC and serum MDA levels were decreased (p<0.05). Moreover, serum peroxide in free radicals levels were higher than controls (p<0.05). There were no differences between the depressed patients and controls for other oxidative stress markers. CONCLUSION: This meta-analysis supports the facts that the serum TAC, paraoxonase and antioxidant levels are lower, and the serum free radical and oxidative damage product levels are higher than controls in depressed patients. Meanwhile, the antioxidant levels are increased and the oxidative damage product levels are decreased after antidepressant medication. The pathophysiological relationships between oxidative stress and depression, and the potential benefits of antioxidant supplementation deserve further research.

Overlapping auditory M100 and M200 abnormalities in schizophrenia and bipolar disorder: a MEG study.

OBJECTIVES: Schizophrenia and bipolar disorder share common etiological factors and pathophysiological pathways and have overlapping clinical features. Only few studies have directly compared early auditory information processing in the two disorders. The objective of this study was to investigate the M100 and M200 auditory responses in patients with schizophrenia and bipolar disorder and compare them with healthy controls using magnetoencephalography (MEG). METHODS: Whole-head MEG data were acquired during an auditory oddball paradigm in 24 schizophrenia patients, 26 bipolar I disorder patients, and 31 healthy controls. The strengths and latencies of M100 and M200 in both hemispheres and the dipole source localizations were investigated from the standard stimuli. RESULTS: The M100 and M200 dipolar sources were localized to the left and right posterior portion of the superior temporal gyrus (STG) in all the subjects. An asymmetric pattern of M100 and M200 auditory response with more anterior sources in the right STG was observed in the healthy controls. However, both the schizophrenia and bipolar disorder patients showed a symmetric M100 and M200 source pattern. When compared with the healthy control group, both patient groups showed significantly reduced M100 and M200 source strength in both hemispheres. CONCLUSIONS: Our study suggests that early auditory information processing deficits may be similar in schizophrenia and bipolar disorder and may be related to abnormalities of the STG.

Auditory M50 and M100 sensory gating deficits in bipolar disorder: a MEG study.

OBJECTIVES: Auditory sensory gating deficits have been reported in subjects with bipolar disorder, but the hemispheric and neuronal origins of this deficit are not well understood. Moreover, gating of the auditory evoked components reflecting early attentive stage of information processing has not been investigated in bipolar disorder. The objectives of this study were to investigate the right and left hemispheric auditory sensory gating of the M50 (preattentive processing) and M100 (early attentive processing) in patients diagnosed with bipolar I disorder by utilizing magnetoencephalography (MEG). METHODS: Whole-head MEG data were acquired during the standard paired-click paradigm in 20 bipolar I disorder patients and 20 healthy controls. The M50 and the M100 responses were investigated, and dipole source localizations were also investigated. Sensory gating were determined by measuring the strength of the M50 and the M100 response to the second click divided by that of the first click (S2/S1). RESULTS: In every subject, M50 and M100 dipolar sources localized to the left and right posterior portion of superior temporal gyrus (STG). Bipolar I disorder patients showed bilateral gating deficits in M50 and M100. The bilateral M50 S2 source strengths were significantly higher in the bipolar I disorder group compared to the control group. LIMITATIONS: The sample size was relatively small. More studies with larger sample sizes are warranted. Bipolar subjects were taking a wide range of medications that could not be readily controlled for. CONCLUSIONS: These findings suggest that bipolar I disorder patients have auditory gating deficits at both pre-attentive and early attentive levels, which might be related to STG structural abnormality.

Absence of auditory M100 source asymmetry in schizophrenia and bipolar disorder: a MEG study.

BACKGROUND: Whether schizophrenia and bipolar disorder are the clinical outcomes of discrete or shared causative processes is much debated in psychiatry. Several studies have demonstrated anomalous structural and functional superior temporal gyrus (STG) symmetries in schizophrenia. We examined bipolar patients to determine if they also have altered STG asymmetry. METHODS: Whole-head magnetoencephalography (MEG) recordings of auditory evoked fields were obtained for 20 subjects with schizophrenia, 20 with bipolar disorder, and 20 control subjects. Neural generators of the M100 auditory response were modeled using a single equivalent current dipole for each hemisphere. The source location of the M100 response was used as a measure of functional STG asymmetry. RESULTS: Control subjects showed the typical M100 asymmetrical pattern with more anterior sources in the right STG. In contrast, both schizophrenia and bipolar disorder patients displayed a symmetrical M100 source pattern. There was no significant difference in the M100 latency and strength in bilateral hemispheres within three groups. CONCLUSIONS: Our results indicate that disturbed asymmetry of temporal lobe function may reflect a common deviance present in schizophrenia and bipolar disorder, suggesting the two disorders might share etiological and pathophysiological factors.

Frontal white matter biochemical abnormalities in first-episode, treatment-naive patients with major depressive disorder: a proton magnetic resonance spectroscopy study.

BACKGROUND: Previous neuroimaging studies found evidence of brain functional and structural abnormalities in patients with major depressive disorder (MDD), but they rarely excluded compounding effects of some important factors, such as medication and brain degeneration. This study sought to explore the brain biochemical changes of first-episode, treatment-naive, non-late-life adult patients with MDD in the frontal white matter and gray matter by using proton magnetic resonance spectroscopy (1H MRS). METHODS: Twenty-four first-episode, treatment-naive, non-late-life adult depressed patients and 13 healthy controls were enrolled in this study. Subjects underwent two-dimensional multivoxel 1H MRS at 1.5 T to obtain bilateral metabolite levels from the dorsolateral prefrontal white matter and anterior cingulate gray matter. RESULTS: Patients with MDD showed significantly lower N-acetylaspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr) ratios in the left dorsolateral prefrontal white matter, and lower NAA/Cr ratios in the right dorsolateral prefrontal white matter when compared with the control subjects. There were no significant differences in the metabolite ratios in the bilateral anterior cingulate gray matter. CONCLUSIONS: These findings suggest that biochemical abnormalities in prefrontal white matter may occur early in the course of MDD and may be related to the neuropathology of depression.