The relationship between event-related potential components and suicide risk in major depressive disorder.

BACKGROUND: Suicide is a serious global issue, with major depressive disorder (MDD) being a significant risk factor for suicidal thoughts and behaviors. There is an urgent need to determine whether event-related potential components (ERPs) could be used as an indicator to assess suicidal risk. METHODS: From 2020 to 2023, 258 participants in total were recruited into the study. All participants were divided into four groups: MDD patients at high (n = 66), moderate (n = 66), and low risk (n = 56) of suicide, and healthy controls (HCs)(n = 70). Each participant provided socio-demographic information and underwent evaluations using clinical psychological scales such as 7-item Generalized Anxiety Disorder (GAD-7), Health Questionnaire-9 items (PHQ-9), and Nurses' Global Assessment of Suicide Risk (NGASR). The auditory brainstem response test and ERP examination were performed for all subjects. RESULTS: Our study found that the amplitude of P2-P3 and N2-P3 was significantly reduced in MDD patients at moderate and high risk of suicide, and these were negatively correlated with NGASR total score (all P < 0.05). Point B latency was positively correlated with NGASR total score (P < 0.05). Patients with MDD patients at low risk for suicide had a lower A-B amplitude compared to HCs (P < 0.05). No differences were found in MMN or P50 components between the four groups (all P > 0.05). CONCLUSIONS: MDD patients at higher risk of suicide exhibited severe impairment of cognitive function. ERP indices, such as the amplitude of P2-P3 and N2-P3, could be associated with the risk of suicide in MDD patients.

Effects of antidepressant on FKBP51 mRNA expression and neuroendocrine hormones in patients with panic disorder.

OBJECTIVE: The purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD). METHODS: Seventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment. RESULTS: At baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01). CONCLUSIONS: The results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.

Brain-derived neurotrophic factor levels across psychiatric disorders: A systemic review and network meta-analysis.

As an important neurotrophic factor in the central nervous system, Brain-derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of psychiatric disorders in many studies. However, its value as a biomarker for the diagnosis and differential diagnosis of mental disorders is still controversial, and its change patterns among different mental disorders have not been compared. We conducted a network meta-analysis of BDNF levels in different psychiatric disorders including schizophrenia(SCZ), major depressive disorder(MDD), bipolar disorder(BD), panic disorder(PD), post-traumatic stress disorder(PTSD), obsessive-compulsive disorder(OCD), generalized anxiety disorder(GAD) and insomnia. Studies were identified by searching electronic databases through 31/05/2023. BDNF levels decreased in patients with BD, MDD, OCD, PD, SCZ compared with controls, while significantly increased in patients with PTSD. According to the network meta-analysis, BDNF levels were significantly decreased in MDD and SCZ compared with BD (-2.6, 95% CIs [-5.32 to -0.15] and - 2.68 95% CIs [-5.18 to -0.23] respectively). However, in the traditional meta-analysis, there was a trend towards lower BDNF levels in SCZ compared to BD, with no significant difference (SMD = -0.20, 95% CIs [-0.49 to 0.08]). In conclusion, abnormal BDNF levels have been found in psychiatric disorders, and the changes in peripheral BDNF levels in patients with psychiatric disorders were reconfirmed in this study, which suggests BDNF exhibits promising clinical utility and may hold diagnostic value in distinguishing between MDD and BD.

Abnormal multi-layered dynamic cortico-subcortical functional connectivity in major depressive disorder and generalized anxiety disorder.

Comorbidity has been frequently observed between generalized anxiety disorder (GAD) and major depressive disorder (MDD), however, common and distinguishable alterations in the topological organization of functional brain networks remain poorly understood. We sought to determine a robust and sensitive functional connectivity marker for diagnostic classification and symptom severity prediction. Multi-layered dynamic functional connectivity including whole brain, network-node and node-node layers via graph theory and gradient analyses were applied to functional MRI resting-state data obtained from 31 unmedicated GAD and 34 unmedicated MDD patients as well as 33 age and education matched healthy controls (HC). GAD and MDD symptoms were assessed using Penn State Worry Questionnaire and Beck Depression Inventory II, respectively. Three network measures including global properties (i.e., global efficiency, characteristic path length), regional nodal property (i.e., degree) and connectivity gradients were computed. Results showed that both patient groups exhibited abnormal dynamic cortico-subcortical topological organization compared to healthy controls, with MDD > GAD > HC in degree of randomization. Furthermore, our multi-layered dynamic functional connectivity network model reached 77% diagnostic accuracy between GAD and MDD and was highly predictive of symptom severity, respectively. Gradients of functional connectivity for superior frontal cortex-subcortical regions, middle temporal gyrus-subcortical regions and amygdala-cortical regions contributed more in this model compared to other gradients. We found shared and distinct cortico-subcortical connectivity features in dynamic functional brain networks between GAD and MDD, which together can promote the understanding of common and disorder-specific topological organization dysregulations and facilitate early neuroimaging-based diagnosis.

Pilot study of genome-wide DNA methylation and gene expression for treatment response to escitalopram in panic disorder.

BACKGROUND: Antidepressants, particularly selective serotonin reuptake inhibitors, are currently considered the first-line treatment for panic disorder (PD). However, little is known about the relationship between the biomarkers that may predict better treatment. AIM: To compare genome-wide methylation and gene expression patterns between responsive and non-responsive patients with PD after 4 wk of escitalopram treatment. METHODS: Thirty patients with PD were enrolled in this study (responders = 13; non-responders = 17). All patients were assessed using the PD Severity Scale-Chinese version before and after treatment. The Illumina Infinium MethylationEPIC (850k) BeadChip for genome-wide methylation screening and mRNA sequencing was used in all patients with PD. RESULTS: A total of 701 differentially methylated positions (DMPs) were found between responders and non-responders (|Δß| ≥ 0.06, q < 0.05), and the hyper- and hypomethylated CpG sites were 511 (72.9%) and 190 (27.1%), respectively. Relative to non-responders, there were 59 differential transcripts, of which 20 were downregulated and 39 were upregulated (q < 0.05). However, no differentially expressed genes were identified by mRNA sequencing after correcting for multiple testing (|log2(FC)| > 1, q > 0.05). CONCLUSION: This preliminary study showed that DMPs might be associated with the treatment response to escitalopram in PD; however, these DMPs need to be verified in large samples.

Glutamate decarboxylase 1 gene polymorphisms are associated with respiratory symptoms in panic disorder.

BACKGROUND: Genetic factors play an important role in the pathogenesis of panic disorder (PD). However, the effect of genetic variants on PD remains controversial. AIM: To evaluate the associations between glutamate decarboxylase 1 (GAD1) gene polymorphisms and PD risk and assess the effect of GAD1 gene polymorphisms on the severity of clinical symptoms in PD. METHODS: We recruited 230 PD patients and 224 healthy controls in this study. All participants were assessed for anxiety and panic symptom severity using the Hamilton Anxiety Rating Scale (HAM-A) and Panic Disorder Severity Scale (PDSS). GAD1 gene polymorphisms (rs1978340 and rs3749034) were genotyped and assessed for allele frequencies. RESULTS: There were no significant differences between cases and controls in the genotype distributions or allele frequencies of GAD1 (rs1978340 and rs3749034). In addition, the effect of GAD1 (rs1978340 and rs3749034) on PD severity was not significant. However, regarding respiratory symptoms, patients with the GAD1 rs1978340 A/A genotype had significantly higher scores than those with the A/G or G/G genotype. CONCLUSION: Here, we showed that the A/A genotype of GAD1 rs1978340 was associated with increased severity of respiratory symptoms in patients with PD.

The differences of event-related potential components in patients with comorbid depression and anxiety, depression, or anxiety alone.

BACKGROUND: There was a high comorbidity rate of major depressive disorder (MDD) and generalized anxiety disorder (GAD), showing a poor prognosis and significant detrimental impact on functioning. The study aimed to find whether patients with comorbid GAD and MDD had some differences in cognitive functions from patients with MDD or GAD alone. METHODS: 360 adult patients were enrolled from inpatient department of psychiatry from 2020 to 2022. They were divided into three groups with 120 patients for each group: MDD, GAD, and MDD + GAD. All the patients completed psychological evaluation scales including patient health questionnaire-9 (PHQ-9) and 7-item generalized anxiety disorder (GAD-7). All the patients underwent examinations of auditory brainstem response and event-related potentials (ERPs). RESULTS: In MDD + GAD group, P3b latency was significantly longer than patients with MDD alone, and P300 reaction time was positively correlated with total score of GAD-7 and PHQ-9, and PHQ-9 total score was also significantly positively correlated with P2-P3b amplitude (all p < 0.05). In addition, MDD patients had significantly longer P300 reaction time and lower P2-P3b amplitude than the GAD group (p < 0.05). LIMITATIONS: It was a single-center and cross-sectional study, and we used self-report scales as assessment tools. CONCLUSIONS: Patients with MDD and GAD comorbidity might have a worse cognitive function than MDD patients, and the severity of cognitive impairments was positively correlated with the severity of anxiety and depression symptoms.

Common and distinct patterns of task-related neural activation abnormalities in patients with remitted and current major depressive disorder: A systematic review and coordinate-based meta-analysis.

Whether remitted major depressive disorder (rMDD) and MDD present common or distinct neuropathological mechanisms remains unclear. We performed a meta-analysis of task-related whole-brain functional magnetic resonance imaging (fMRI) using anisotropic effect-size signed differential mapping software to compare brain activation between rMDD/MDD patients and healthy controls (HCs). We included 18 rMDD studies (458 patients and 476 HCs) and 120 MDD studies (3746 patients and 3863 HCs). The results showed that MDD and rMDD patients shared increased neural activation in the right temporal pole and right superior temporal gyrus. Several brain regions, including the right middle temporal gyrus, left inferior parietal, prefrontal cortex, left superior frontal gyrus and striatum, differed significantly between MDD and rMDD. Meta-regression analyses revealed that the percentage of females with MDD was positively associated with brain activity in the right lenticular nucleus/putamen. Our results provide valuable insights into the underlying neuropathology of brain dysfunction in MDD, developing more targeted and efficacious treatment and intervention strategies, and more importantly, providing potential neuroimaging targets for the early screening of MDD.

Brain-derived neurotrophic factor blood levels after electroconvulsive therapy in patients with mental disorders: A systematic review and meta-analysis.

OBJECTIVE: Multiple studies have indicated that electroconvulsive therapy (ECT) could increase brain-derived neurotrophic factor (BDNF) concentrations in patients with different mental disorders. The aim of this synthesis was to evaluate post-ECT BDNF concentrations in patients with various mental disorders. METHODS: The Embase, PubMed and Web of Science databases were systematically searched for studies in English comparing BDNF concentrations before and after ECT through 11/2022. We extracted the pertinent information from the included studies and evaluated their quality. The standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated to quantify BDNF concentration differences. RESULTS: In total, 35 studies assessed BDNF concentrations in 868 and 859 patients pre and post-ECT treatment, respectively. Post-ECT-treatment BDNF concentrations were significantly higher than the pretreatment concentrations (Hedges'g = -0.50, 95% CI (-0.70, -0.30), heterogeneity I2 = 74%, p < 0.001). The analysis that combined both ECT responders and non-responders demonstrated a marked increase in total BDNF levels subsequent to ECT treatment (Hedges'g = -0.27, 95% CI (-0.42, -0.11), heterogeneity I2 = 40%, p = 0.0007). CONCLUSION: Irrespective of the effectiveness of ECT, Our study shows that peripheral BDNF concentrations increase significantly after the entire course of ECT, which may enhance our comprehension of the interplay between ECT treatment and BDNF levels. However, BDNF concentrations were not associated with the effectiveness of ECT, and abnormal concentrations of BDNF may be linked to the pathophysiological process of mental illness, necessitating more future research.

Peripheral cytokine levels across psychiatric disorders: A systematic review and network meta-analysis.

Immune dysregulated cytokine production is involved in mental diseases. However, the results are inconsistent and the pattern of cytokine alterations has not been compared across disorders. We performed a network impact analysis of cytokine levels for different psychiatric disorders including schizophrenia, major depressive disorder, bipolar disorder, panic disorder, post-traumatic stress disorder and obsessive compressive disorder to evaluate their clinical impact across conditions. Studies were identified by searching the electronic databases up to 31/05/2022. A total of eight cytokines, together with (high-sensitivity) C-reactive proteins (hsCRP/CRP) were included in the network meta-analysis. The levels of proinflammatory cytokines, hsCRP/CRP and interleukin 6 (IL-6) were significantly increased in patients with psychiatric disorders when compared to controls. IL-6 showed no significant difference among comparisons between disorders according to the network meta-analysis. Interleukin 10 (IL-10) is significantly increased in patients with bipolar disorder compared to major depressive disorder. Further, the level of interleukin-1 beta (IL-1ß) was significantly increased in major depressive disorder as compared to bipolar disorder. The level of interleukin 8 (IL-8) varied among these psychiatric disorders based on the network meta-analysis result. Overall, abnormal cytokine levels were found in psychiatric disorders, and some of the cytokines displayed differential characteristics in these disorders, especially IL-8, pointing to a role as potential biomarkers for general and differential diagnosis.

Identification and characterization of noncoding RNAs-associated competing endogenous RNA networks in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a common and serious mental illness. Many novel genes in MDD have been characterized by high-throughput methods such as microarrays or sequencing. Recently, noncoding RNAs (ncRNAs) were suggested to be involved in the complicated environmental-genetic regulatory network of MDD occurrence; however, the interplay among RNA species, including protein-coding RNAs and ncRNAs, in MDD remains unclear. AIM: To investigate the RNA expression datasets downloaded from a public database and construct a network based on differentially expressed long noncoding RNA (lncRNAs), microRNAs (miRNAs), and mRNAs between MDD and controls. METHODS: Gene expression data were searched in NCBI Gene Expression Omnibus using the search term "major depressive disorder." Six array datasets from humans were related to the search term: GSE19738, GSE32280, GSE38206, GSE52790, GSE76826, and GSE81152. These datasets were processed for initial assessment and subjected to quality control and differential expression analysis. Differentially expressed lncRNAs, miRNAs, and mRNAs were determined, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed, and protein-protein interaction network was generated. The results were analyzed for their association with MDD. RESULTS: After analysis, 3 miRNAs, 12 lncRNAs, and 33 mRNAs were identified in the competing endogenous RNA network. Two of these miRNAs were earlier shown to be involved in psychiatric disorders, and differentially expressed mRNAs were found to be highly enriched in pathways related to neurogenesis and neuroplasticity as per Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The expression of hub gene fatty acid 2-hydroxylase was enriched, and the encoded protein was found to be involved in myelin formation, indicating that neurological development and signal transduction are involved in MDD pathogenesis. CONCLUSION: The present study presents candidate ncRNAs involved in the neurogenesis and neuroplasticity pathways related to MDD.

Heart rate variability in generalized anxiety disorder, major depressive disorder and panic disorder: A network meta-analysis and systematic review.

BACKGROUND: Heart rate variability (HRV) in patients with emotional disorders and healthy controls (HCs) has been investigated in many studies but the difference between these emotional disorders was unclear. METHODS: The PubMed, Embase, Medline and Web of Science databases were systematically searched for studies published in English that compared HCs with generalized anxiety disorder (GAD), major depressive disorder (MDD), panic disorder (PD) patients in HRV. We conducted a network meta-analysis to compare HRV in patients with GAD, MDD, PD and HCs. HRV outcomes, including time domain indices (the standard deviation of NN intervals (SDNN) and the root mean square of the successive differences between normal heartbeats (RMSSD)), and frequency domain indices (High-frequency (HF), Low-frequency (LF) and the ratio of LF to HF (LF/HF)) were obtained. A total of 4008 participants from 42 studies were included. RESULTS: The results of pairwise meta-analysis showed that compared with controls, GAD, PD and MDD patients exhibited significantly reduced HRV. Similar findings were also confirmed in network meta-analysis. The most important finding from network meta-analysis was that GAD patients had significantly lower SDNN than PD patients (SMD = -0.60, 95 % CI [-1.09, -0.11]). CONCLUSION: Our findings provided a potential objective biological marker to distinguish between GAD and PD. In the future, a large sample of research is needed to directly compare HRV of various mental disorders, which is crucial for finding biomarkers to distinguish them.

Opposing and emotion-specific associations between frontal activation with depression and anxiety symptoms during facial emotion processing in generalized anxiety and depression.

Major depression (MDD) and generalized anxiety disorder (GAD) have become one of the leading global causes of disability and both are characterized by marked interpersonal and social impairments. However, despite high comorbidity and overlapping social-emotional deficits, it remains unclear whether MDD and GAD share a common neural basis during interpersonal processing. In the present study, we combined an emotional face processing paradigm with fMRI and dimensional and categorical analyses in a sample of unmedicated MDD and GAD patients (N = 72) as well as healthy controls (N = 35). No group differences were found in categorical analyses. However, the dimensional analyses revealed that dorsolateral prefrontal cortex (dlPFC) reactivity to sad facial expressions was positively associated with depression symptom load, yet negatively associated with anxiety symptom load in the entire sample. On the network level depression symptom load was positively associated with functional connectivity between the bilateral amygdala and a widespread network including the anterior cingulate and insular cortex. Together, these findings suggest that the dlPFC - engaged in cognitive and emotional processing - exhibits symptom- and emotion-specific alteration during interpersonal processing. Dysregulated communication between the amygdala and core regions of the salience network may represent depression-specific neural dysregulations.

Integrated genome-wide methylation and expression analyses provide predictors of diagnosis and early response to antidepressant in panic disorder.

BACKGROUND: We investigated differentially methylated and expressed genes between panic disorder (PD) and healthy controls (HCs) to determine whether DNA methylation and expression level of candidate genes can be used as biomarkers for diagnosis and early response. METHODS: Illumina infiniun Methylation EPIC (850 k) Beadchip for genome-wide methylation screening and mRNA sequencing was conducted in a discovery set (30 patients with PD and 30 matched HCs). The candidate gene loci methylation and expression were verified in an independent validation sample (101 PD patients and 107 HCs). RESULTS: In the discovery set, there were 3613 differentially methylated cytosine phosphate guanosine sites and these differential methylation positions were located within 1938 unique genes, including 1758 hypermethylated genes, 150 hypomethylated genes, and the coexistence of hypermethylation and hypomethylation sites were found in 30 genes. There were 1111 differential transcripts in PD compared to normal controls (850 down-regulated and 261 up-regulated). Further, 212 differentially expressed genes were screened (40 up-regulated and 172 down-regulated). In the validation set, compared with HCs, there was no significant difference in DNA methylation level of Casitas B-lineage lymphoma (CBL) gene loci (cg07123846). The expression level of CBL gene in PD patients was lower (vs. HCs). After four weeks' treatment, the baseline expression level of CBL gene in the responders was higher than nonresponders. LIMITATIONS: The sample size was limited. We only chose CBL as a candidate gene. Follow-up periods were short. CONCLUSIONS: There are differences in genome-wide DNA methylation and mRNA expression between PD patients and HCs. The changes in expression level of CBL gene may be an important molecular marker for PD diagnosis and early response.

Heart rate variability changes in patients with obstructive sleep apnea: A systematic review and meta-analysis.

Obstructive sleep apnea is a common sleep breathing disorder related to autonomic nervous function disturbances. Heart rate variability is an important non-invasive indicator of autonomic nervous system function. The PubMed, Embase, Medline and Web of Science databases were systematically searched for English literature comparing patients with obstructive sleep apnea with controls up to May 2021. Heart rate variability outcomes, including integrated indices (parasympathetic function and total variability), time domain indices (the standard deviation of NN intervals and the root mean square of the successive differences between normal heartbeats) and frequency domain indices (high-frequency, low-frequency, very-low-frequency and the ratio of low-frequency to high-frequency) were derived from the studies. Twenty-two studies that included 2565 patients with obstructive sleep apnea and 1089 healthy controls were included. Compared with controls, patients with obstructive sleep apnea exhibited significantly reduced parasympathetic function. For the obstructive sleep apnea severity subgroup meta-analysis, patients with severe obstructive sleep apnea had significantly lower parasympathetic function, high-frequency, root mean square of the successive differences between normal heartbeats and standard deviation of NN intervals, and higher low-frequency and ratios of low-frequency to high-frequency. However, only the ratio of low-frequency to high-frequency was significantly higher in patients with moderate obstructive sleep apnea than in controls. Finally, for the collection time analysis, patients with obstructive sleep apnea had significantly higher low-frequency and ratio of low-frequency to high-frequency at night, significantly lower parasympathetic function, high-frequency, root mean square of the successive differences between normal heartbeats and standard deviation of NN intervals, and a higher ratio of low-frequency to high-frequency during the day than controls. Autonomic function impairment was more serious in patients with severe obstructive sleep apnea. During sleep, low-frequency can well reflect the impairment of autonomic function in obstructive sleep apnea, and the ratio of low-frequency to high-frequency may play an important role in obstructive sleep apnea diagnosis.

Task-related neural activation abnormalities in patients with remitted major depressive disorder: A coordinate-based meta-analysis.

Major depressive disorder (MDD) patients demonstrate abnormal neural activation even after complete remission. Many task-related functional magnetic resonance imaging (fMRI) studies have focused on changes in brain function in individuals with remitted MDD (rMDD). We conducted a meta-analysis of these studies to explore differences in brain activation between patients with rMDD and healthy controls (HCs). Our meta-analysis included 13 studies, encompassing 18 experiments, 304 rMDD patients and 321 HCs. Patients with rMDD showed increased neural activation in the left inferior parietal gyrus and right fusiform gyrus and decreased neural activation in the left superior frontal gyrus, right middle temporal gyrus and right Heschl gyrus. Meta-regression analysis revealed that patient age and the number of depressive episodes were negatively associated with brain activity in the left superior frontal gyrus. Our findings suggest abnormal brain function, especially in areas involved in cognitive function, emotion regulation and perception, in rMDD patients; alterations of these regions may be the primary or secondary neurophysiological mechanisms underlying MDD and provide potential neuroimaging targets for early screening.

Associations of DNA methylation of HPA axis-related genes and neuroendocrine abnormalities in panic disorder.

OBJECTIVE: The purpose of this study was to investigate the role of aberrant DNA methylation of hypothalamic-pituitary-adrenal (HPA) axis-related genes (CRHR1, CRHR2, CRH, FKBP5, HSP90AA1, NR3C1, and POMC) in panic disorder (PD) development. We investigated the correlation among gene methylation levels, adrenocorticotropic hormone (ACTH), cortisol, and PD severity in patients. METHODS: We compared the methylation levels of HPA axis-related genes between 178 patients with PD and 184 healthy controls using MethylTarget. We then measured ACTH and cortisol levels using chemiluminescence. Disease severity was assessed using the Panic Disorder Severity Scale. RESULTS: Compared with healthy controls, patients with PD displayed significantly higher levels of ACTH and cortisol, and significantly reduced methylation levels of CRHR1, FKBP5, HSP90AA1, and NR3C1 after correcting for multiple testing using the false discovery method. A significant positive correlation was observed between the methylation of CRHR1, CRHR2, and NR3C1 and ACTH levels in patients with PD, and methylation levels of CRHR1 and NR3C1 were significantly positively related to cortisol levels. In addition, a negative correlation was observed between PD severity and the methylation of CRH, CRHR1, CRHR2, and HSP90AA1. CONCLUSION: Aberrant methylation of HPA axis-related genes may predict PD development and impact ACTH and cortisol levels.

Disorder- and cognitive demand-specific neurofunctional alterations during social emotional working memory in generalized anxiety disorder and major depressive disorder.

BACKGROUND: Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) are both characterized by cognitive and social impairments. Determining disorder-specific neurobiological alterations in GAD and MDD by means of functional magnetic resonance imaging (fMRI) may promote determination of precise diagnostic markers. METHODS: This study aimed to examine disorder-specific behavioral and neural alterations at the intersection of social and cognitive processing in treatment-naïve first-episode GAD (n = 35) and MDD (n = 37) patients compared to healthy controls (n = 35) by employing a social-emotional n-back fMRI paradigm. RESULTS: No behavioral differences between patients and healthy controls were observed. However, GAD patients exhibited decreased bilateral dorsomedial prefrontal cortex (dmPFC) engagement during the 0-back condition yet increased dmPFC engagement during the 1-back condition compared to MDD and healthy participants. In contrast, MDD patients exhibited increased dmPFC-insula coupling during 0-back, yet decreased coupling during 1-back, compared to GAD and healthy participants. Dimensional symptom-load analysis confirmed that increased dmPFC-insula connectivity during 0-back was positively associated with depressive symptom load. LIMITATIONS: The moderate sample size in the present study did not allow us to further explore gender differences. In addition, some patients exhibited GAD and MDD comorbidity according to the M.I.N.I. interview. Finally, the paradigm we used did not allow to further disentangle emotion-specific effects on working memory. CONCLUSIONS: These findings suggest that the dmPFC engaged in integrating affective and cognitive components and self-other processing exhibits GAD-specific neurofunctional dysregulations whereas functional dmPFC communication with the insula, a region involved in salience processing, may represent an MDD-specific neurofunctional deficit.

Suicidality in patients with primary diagnosis of panic disorder: A single-rate meta-analysis and systematic review.

BACKGROUND: This study investigated the lifetime suicide attempt and ideation rates among patients with panic disorder (PD). METHODS: Online databases regarding lifetime suicide attempt and ideation rates in patients with PD were searched up to May 2021. RESULTS: The suicide attempt and ideation rates were 0.17 (95% CI: 0.16, 0.18) and 0.23 (95% CI: 0.22, 0.25). The suicide attempt rates among female and male patients were 0.17 (95% CI: 0.14, 0.20) and 0.15 (95% CI: 0.12, 0.19). When PD was comorbid with anxiety, depression, substance abuse, and personality disorders, the suicide attempt rates increased to 0.23 (95% CI: 0.20, 0.26), 0.23 (95% CI: 0.18, 0.27), 0.25 (95% CI: 0.20, 0.31), and 0.25 (95% CI: 0.23, 0.28), respectively. LIMITATIONS: The suicide attempt and ideation by age, suicide ideation by sex, and suicide ideation by comorbidity with other mental disorders were passed in our meta-analysis as sample size was small. Stratification analysis on ethnicity, marital status, education levels, resident location, and severity of PD should be considered in the future. CONCLUSION: The lifetime suicide ideation and attempt rates in patients with PD were higher than general populations but lower than patients with bipolar or depression. The lifetime suicide attempt rate in female patients was slightly higher than male patients. When PD was comorbid with one other mental illness, the lifetime suicide attempt rate increased by about 50%.

A panel of rhythm gene polymorphisms is involved in susceptibility to type 2 diabetes mellitus and bipolar disorder.

BACKGROUND: Biological rhythm is closely related to health. We aimed to identify the potential correlations of rhythm gene polymorphisms to type 2 diabetes mellitus (DM) or bipolar disorder (BD), which both have many abnormal rhythmic activities, in a sample of Chinese Han origin. METHODS: A total of 136 patients with BD, 166 patients with DM, and 130 healthy controls were collected. We screened 28 single nucleotide polymorphisms (SNPs) located in rhythm genes CLOCK, ARNTL, PER2, PER3, CRY1, and CRY2 respectively. Snapshot typing technology was used for genotyping. RESULTS: Both the rs10832022-G and rs11022765-A allele frequencies of the ARNTL gene were significantly higher in patients with DM than in those with BD (corrected P=0.03, 0.004, respectively). The frequency of rs10832022-G, rs1022765-A, and rs11022762-T haplotypes, which was significantly lower in patients with BD than in controls (P=0.003, OR =0.579), was significantly higher in patients with DM than in those with BD (P=0.0002, OR =1.878). The rs2292910-CC genotypic frequency of the CRY2 gene was significantly higher in patients with BD than in controls (OR of regression =2.203, P=0.01), while the frequency of the AA genotype was significantly lower than in patients with DM (P=0.01). The frequency of rs1972874-G and rs36124720-G haplotype of the PER2 gene was significantly higher in patients with DM than in controls (P=0.01, OR =1.577). CONCLUSIONS: Our study preliminarily suggested that both BD and type 2 DM could be considered as dysrhythmias with different rhythmic genetic backgrounds, which contribute to the early prediction of an individual's susceptibility to different rhythm disorders and early intervention.