World Journal of Biological Psychiatry最新文献

Objectives: Schizophrenia (SZ) and intellectual disability (ID) are both included in the continuum of neurodevelopmental disorders (NDDs). DNA methylation is known to be important in the occurrence of NDDs. The family study is conducive to eliminate the effects of relative epigenetic backgrounds, and to screen for differentially methylated positions (DMPs) and regions (DMRs) that are truly associated with NDDs.

Methods: Four monozygotic twin families were recruited, and both twin individuals suffered from NDDs (either SZ, ID, or SZ plus ID). Genome-wide methylation analysis was performed in all samples and each family. DMPs and DMRs between NDD patients and unaffected individuals were identified. Functional and pathway enrichment analyses were performed on the annotated genes.

Results: Two significant DMPs annotated to CYP2E1 were found in all samples. In Family One, 1476 DMPs mapped to 880 genes, and 162 DMRs overlapping with 153 unique genes were recognised. Our results suggested that the altered methylation levels of FYN, STAT3, RAC1, and NR4A2 were associated with the development of SZ and ID. Neurodevelopment and the immune system may participate in the occurrence of SZ and ID.

Conclusions: Our findings suggested that DNA methylation participated in the development of NDDs by affecting neurodevelopment and the immune system.

Objectives: Despite the increasingly high prevalence and serious consequences of depression in adolescents, there is a lack of economical and reliable biomarkers to aid the diagnostic process. Recent findings suggest that red blood cell distribution width (RDW) is an easily obtainable biomarker of depression in adults. Here, we aimed to replicate the finding of increased RDW in clinically depressed adolescents.

Methods: Data from depressed adolescent female patients (n = 93) and healthy controls (HC) (n = 43) aged 12-17 years from the AtR!Sk-bio cohort study were retrospectively analysed. We compared RDW between groups and tested whether there was an association between RDW and depression severity and global (psychiatric) symptom severity. We also examined the influence of age on RDW.

Results: There was no significant difference between depressed patients and healthy controls and no association between RDW and depression severity. However, higher RDW values were associated with greater global symptom severity. Regardless of group, there was a positive association between RDW and age.

Conclusions: RDW appears to be unfit as an aid for clinical diagnosis of depression in adolescents, but may be useful in assessing global psychiatric symptom burden.

Objectives: Thus far, the diagnosis of insomnia is based on purely clinical criteria. Although a broad range of altered physiological parameters has been identified in insomniacs, the evidence to establish their diagnostic usefulness is very limited. Purpose of this WFSBP Task Force consensus paper is to systematically evaluate a series of biomarkers as potential diagnostic tools for insomnia.

Methods: A newly created grading system was used for assessing the validity of various measurements in establishing the diagnosis of insomnia; these measurements originated from relevant studies selected and reviewed by experts.

Results: The measurements with the highest diagnostic performance were those derived from psychometric instruments. Biological measurements which emerged as potentially useful diagnostic instruments were polysomnography-derived cyclic alternating pattern, actigraphy, and BDNF levels, followed by heart rate around sleep onset, deficient melatonin rhythm, and certain neuroimaging patterns (mainly for the activity of frontal and pre-frontal cortex, hippocampus and basal ganglia); yet, these findings need replication, as well as establishment of commonly accepted methodology and diagnostic cut-off points. Routine polysomnography, EEG spectral analysis, heart rate variability, skin conductance, thermoregulation, oxygen consumption, HPA axis, and inflammation indices were not shown to be of satisfactory diagnostic value.

Conclusions: Apart from psychometric instruments which are confirmed to be the gold standard in diagnosing insomnia, six biomarkers emerge as being potentially useful for this purpose.

Objectives: This study investigated the effects of electroacupuncture (EA) on the depression-like behaviours in a mouse model of chronic restraint stress (CRS) and explored the underlying neural mechanisms.

Methods: Depression-like behaviours including sucrose preference test (SPT), open field test (OFT) and tail suspension test (TST) were carried out to evaluate the effects of CRS and EA treatment. Using immunohistochemistry to measure the expression of c-Fos. The Nucleus Accumbens Shell (NAc Shell) in C57BL/6J mice were activated or inhibited using Chemogenetics.

Results: All the CRS stimulated groups showed lower sucrose preference in the SPT and decreased centre times in the OFT, and increased immobility time in the TST when compared to the normal control. Interestingly, EA at LR3 or HT7 exerted anti-depressant effects, and LR3 EA exhibited a more significant restoration than HT7. Furthermore, EA at LR3 increased expression of c-Fos in the NAc Shell. Chemogenetic inhibition of NAc Shell blocked the effects of EA, whereas enhancement of NAc Shell activity profoundly reversed depressive phenotypes.

Conclusions: LR3 EA was effective in alleviating the depressive-like behaviours, and this therapeutic effect was associated with the activation of NAc Shell. Collectively, these findings revealed that EA may represent a promising therapeutic strategy for depression.

Background: Rates of Cannabis Use Disorder (CUD) are highest amongst young adults. Paucity of brain tissue samples limits the ability to examine the molecular basis of cannabis related neuropathology. Proteomic studies of neuron-derived extracellular vesicles (NDEs) isolated from the biofluids may reveal markers of neuropathology in CUD.

Methods: NDEs were extracted using ExoSORT, an immunoaffinity method to enrich NDEs from plasma samples from patients with young onset CUD and matched controls. Differential proteomic profiles were explored with Label Free Quantification (LFQ) mass spectrometry. Selected proteins were validated using orthogonal methods.

Results: A total of 231 (±10) proteins were identified in NDE preparations from CUD and controls of which 28 were differentially abundant between groups. The difference in abundance of properdin (CFP gene) was statistically significant. SHANK1 (SHANK1 gene), an adapter protein at the post-synaptic density, was nominally depleted in the CUD NDE preparations.

Conclusion: In this pilot study, we noted a decrease in SHANK1 protein, involved in the structural and functional integrity of glutamatergic post-synapse, a potential peripheral signature of CUD neuropathology. The study shows that LFQ mass spectrometry proteomic analysis of NDEs derived from plasma may yield important insights into the synaptic pathology associated with CUD.

Objectives: Kynurenine, kynurenic and quinolinic acid are important metabolites in tryptophan metabolism. Due to an involvement in glutamatergic neurotransmission and immune response, previous studies have investigated this pathway in mental disorders such as major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia (SCZ). Tryptophan and kynurenine have been shown to be decreased across disorders, hinting at the missing link how inflammation causes neurotoxicity and psychiatric symptoms. The main aim of our study was to investigate if individual catabolites could serve as diagnostic biomarkers for MDD, BD and SCZ.

Methods: We measured plasma levels of tryptophan, kynurenine, kynurenic acid, quinolinic acid and ratio of quinolinic acid/kynurenic acid using mass spectrometry in n = 175 participants with acute episodes and after remission, compared with controls.

Results: Decreased levels of all tryptophan catabolites were found in the whole patient group, driven by the difference between BD and HC. Manic and mixed phase BD individuals displayed significantly lower kynurenine and kynurenic acid levels. We could not find significant differences between disorders. Upon reaching remission, changes in catabolite levels partially normalised.

Conclusions: Our data suggests an involvement of the kynurenine pathway in mental disorders, especially BD but disqualifying those metabolites as biomarkers for differential diagnosis.

Objectives: The ability to identify persons at elevated risk for post-traumatic stress disorder (PTSD) soon after exposure to trauma, could aid clinical decision-making and treatment. In this study, we explored whether cytosine methylation of the 1 F promoter of the NR3C1 (glucocorticoid receptor [GR]) gene obtained immediately following a trauma could predict PTSD.

Methods: Our sample comprised 52 trauma survivors (28 women, 24 men), presenting to the Emergency Department (ED) within six hours of a traumatic event and followed for 13 months. Blood samples were taken at intake (n = 42) and again at the end of the study (13 months later, n = 27) to determine NR3C1-1F promoter methylation as well as plasma levels of cortisol, adrenocorticotropic-hormone (ACTH), and neuropeptide-Y (NPY).

Results: At the 13-month follow-up, participants who met the PTSD criteria (n = 4) showed significantly lower NR3C1-1F promoter sum percent methylation compared to the non-PTSD group (n = 38). Further, NR3C1-1F methylation at ED intake was inversely correlated with PTSD severity 13 months later, indicating that lower NR3C1-1F promoter methylation in the immediate aftermath of trauma was associated with the development of PTSD.

Conclusion: To the extent that reduced promoter methylation is associated with greater GR expression and responsivity, this finding is consistent with the hypothalamic-pituitary-adrenal dysregulation previously described for PTSD.

Borderline personality disorder (BPD) is characterised by impairments in emotional regulation, impulse control and interpersonal interaction. Comorbid depression is common. The orbitofrontal cortex (OFC) plays a crucial role in the biological substrate of BPD. We investigated the effects of 1 Hz repetitive transcranial magnetic stimulation (rTMS) targeting the OFC on depressive symptoms and symptoms of BPD in 15 patients suffering from both conditions to assess feasibility and effectiveness. Target treatment intensity was 120% of resting motor threshold (RMT) and intended duration four weeks. Treatment improved both symptoms of depression as measured by the Hamilton Depression Rating Scale and of BPD as measured by Borderline Symptom List-23 and Barratt Impulsivity Scale. Drop-out rates were high with 7/15 patients not completing the full course of rTMS, but only two drop-outs were related to treatment. Only a minority of patients tolerated target treatment intensity. Despite the limitations, the results suggest efficacy of treatment and welcome further research.

Purpose: Our article is dedicated to describing the state-of-the-art in imaging techniques for assessing prodromal dementia with Lewy bodies (pro-DLB) with a psychiatric-onset.

Materials and methods: Imaging biomarker techniques are discussed.

Results: (123)-I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography (123I-FP-CIT SPECT) seems to be a promising method as it reveals abnormalities in pro-DLB with a psychiatric-onset. New potential biomarkers can be revealed via novel techniques, such as manual segmentation in magnetic resonance imaging (MRI), which helps detect atrophy of the substantia innominata in pro-DLB with a psychiatric-onset as opposed to an onset with mild cognitive impairment (MCI). FDG-PET can also help us distinguish patients with mixed pro-DLB from those pro-DLB patients with a psychiatric-onset or MCI-onset. Changes in large-scale networks in the posterior standard mode and in attentional networks could be early signs in resting-state functional MRI to characterise pro-DLB.

Conclusions: In conclusion, there is a wide range of techniques that need to be explored in large-scale studies and are of promising value in understanding pro-DLB with a psychiatric-onset.

Objectives: Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that can be used to treat major depressive disorder by single or repeated infusions. However, the accessibility and scalability of oral ketamine make it preferred over intravenous ketamine. In this systematic review, we aim to evaluate the efficacy, tolerability, and safety of oral ketamine, esketamine and r-ketamine for unipolar and bipolar depression. Materials and methods: Electronic databases were searched from inception to September 2022 to identify relevant articles. Results: Twenty-two studies, including four randomized clinical trials (RCTs), one case series, six case reports, five open-label trials and six retrospective chart review studies involving 2336 patients with depression were included. All included studies reported significant improvement following ketamine administration. Ketamine was well tolerated without serious adverse events. However, RCTs had a high risk of bias due to analysis methods and adverse events monitoring. Ketamine dosage varied from 0.5 to 1.25 mg/kg. The frequency of administration was daily to monthly. Several important limitations were identified, most notably the small number of RCTs. Conclusions: Taken together, preliminary evidence suggests the potential for antidepressant effect of oral ketamine. However, further research with large sample size and long follow-up period is needed to better determine the antisuicidal effect and efficacy in treatment-resistant depression.