Distinct proteomic profiles in prefrontal subareas of elderly major depressive disorder and bipolar disorder patients.

We investigated for the first time the proteomic profiles both in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) of major depressive disorder (MDD) and bipolar disorder (BD) patients. Cryostat sections of DLPFC and ACC of MDD and BD patients with their respective well-matched controls were used for study. Proteins were quantified by tandem mass tag and high-performance liquid chromatography-mass spectrometry system. Gene Ontology terms and functional cluster alteration were analyzed through bioinformatic analysis. Over 3000 proteins were accurately quantified, with more than 100 protein expressions identified as significantly changed in these two brain areas of MDD and BD patients as compared to their respective controls. These include OGDH, SDHA and COX5B in the DLPFC in MDD patients; PFN1, HSP90AA1 and PDCD6IP in the ACC of MDD patients; DBN1, DBNL and MYH9 in the DLPFC in BD patients. Impressively, depending on brain area and distinct diseases, the most notable change we found in the DLPFC of MDD was 'suppressed energy metabolism'; in the ACC of MDD it was 'suppressed tissue remodeling and suppressed immune response'; and in the DLPFC of BD it was differentiated 'suppressed tissue remodeling and suppressed neuronal projection'. In summary, there are distinct proteomic changes in different brain areas of the same mood disorder, and in the same brain area between MDD and BD patients, which strengthens the distinct pathogeneses and thus treatment targets.

Antinuclear Antibodies and Thyroid Autoantibodies in the Serum of Chinese Patients with Acute Psychiatric Disorders: A Retrospective Study.

Background: It has been shown that autoimmune diseases are associated with psychiatric disorders in epidemiological studies. The acute psychiatric disorder patients have higher frequency of autoantibodies in the blood, including antinuclear antibodies, anti-thyroid peroxidase, and thyroglobulin [thyroid antibody carriers]. However, large clinical studies with more relevant control groups in China are few. Methods: This was a retrospective study. A total of 1669 sera were tested for autoantibodies in the clinical laboratory of the Fourth Affiliated Hospital, Zhejiang University School of Medicine from October 2016 to March 2021. All data available during this time period were analyzed. Only the first entry for each patient from inpatient care units was used for analysis. The clinical information and laboratory data of patients were retrospectively collected and analyzed. Results: A significantly lower prevalence of antinuclear antibodies was observed in the healthy control group than in the patient group (21.7% vs 28.8%, P < .05). There was a significant difference in the prevalence of antinuclear antibodies between thyroglobulin-antibody carriers and thyroid peroxidase-antibody- and thyroglobulin-antibody-seronegative individuals in the unipolar depressive disorder group (P < .05). A positive anti-thyroid peroxidase test was significantly associated with patients having nonaffective psychoses (P < .05). Conclusion: The results showed that psychiatric disorders were associated with antinuclear antibodies and thyroid autoantibodies in our large sample of patients admitted to acute psychiatric hospitalization, and autoimmune autoantibodies were potential biomarkers of psychotic disorders. The results might lead to new research directions for the study of psychiatric disorders in the future.

Psychological Status of Clinical Laboratory Staff During the COVID-19 Outbreak.

Background: In early December 2019, during the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first detected in Wuhan, COVID-19 was suspected, detected, and confirmed in an increasing number of patients every day. The clinical laboratory staff have always played an important role in the laboratory diagnosis of patients. Currently, there are many research studies on the mental health of the first-line doctors or nurses managing the COVID-19 outbreak, both domestically and overseas, but data of the mental health and associated factors among the clinical laboratory staff who handle the blood or biological samples of confirmed cases and are consequently exposed to COVID-19 are limited. Methods: This cross-sectional survey-based study was performed via an online survey in a single designated hospital from April 20 to April 23, 2020 in Yiwu,China. The online survey included questions on sociodemographic and clinical variables. Totally, 45 clinical laboratory staff and 20 nonmedical health workers participated. Mental health variables were assessed via 4 Chinese versions of validated measurement tools : Zung's Self-rating Depression Scale (SDS), Zung's Self-rating Anxiety Scale (SAS), the Pittsburgh Sleep Quality Index (PSQI), and the Eysenck Personality Questionnaire (EPQ). Results: Significant differences were observed in the SDS and SAS scores, between the clinical laboratory staff and the nonmedical health workers (P < .001, P < .003, respectively). The scores for exposure risk and neuroticism of participants were the main factors influencing both the SDS scores of the clinical laboratory staff (P = .002, P = .005, respectively), and also their SAS scores (P = .003 P = .006, respectively). Conclusions: The results showed that a significant proportion of clinical laboratory staff experienced anxiety and depression symptoms. Their scores for mental health problems, exposure risk, and neuroticism were associated with severe symptoms of depression and anxiety. Therefore, the high-risk group of the clinical laboratory staff and those individuals with higher neuroticism scores may need special attention.

High concentrations of serum interleukin-6 and interleukin-8 in patients with bipolar disorder.

Immune system dysregulation plays a key role in the physiopathology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether interleukins might be biomarkers to distinguish these 2 affective disorders is unclear. Here, we assessed the differences in serum levels of interleukin 6 (IL-6) and interleukin 8 (IL-8) as well as C-reactive protein (CRP) in patients with MDD and BD. In total, we enrolled 21 MDD patients, 26 BD patients, and 20 healthy controls. We collected a total of 35 samples from BD patients in 3 different phases, depression phase, manic phase, and remission stage, and 27 samples from MDD patients in acute and remission phases. Serum IL-6 and IL-8 levels were assessed with solid phase sandwich ELISA-based quantitative arrays, and CRP levels were determined with an automatic analyzer. Both serum IL-6 and IL-8 levels were elevated in BD patients but not MDD patients. Subgroup analysis indicated elevated serum IL-6 in both the depression and manic phases in BD patients. The serum CRP levels did not change in either BD or MDD patients. However, sex differences in CRP concentrations were observed in healthy controls. Furthermore, there were linear correlations between the CRP levels and Bech-Rafaelsen Mania Rating Scale (BRMS) scores in BD patients. IL-6 and IL-8 levels may serve as biomarkers to differentiate between MDD and BD patients, even when the clinical manifestations are atypical. IL-6 may be used for the differential diagnosis of MDD and depressive episodes in BD.

The changes in, and relationship between, plasma nitric oxide and corticotropin-releasing hormone in patients with major depressive disorder.

There is strong evidence of roles of the hypothalamus-pituitary-adrenal axis and nitric oxide (NO) synthase-NO system in depression, but the relationship between them is unknown. The aim of this study, therefore, was to elucidate whether there is any correlation between NO and corticotropin-releasing hormone (CRH) in major depressive disorder (MDD) patients. In 16 outpatients with MDD and 18 healthy controls, the plasma amino acids citrulline (Cit) and arginine (Arg) were determined by high-performance liquid chromatography, and CRH levels was measured by radioimmunoassay. The Cit/Arg ratio was calculated as an index of NO synthesis. Correlations between NO and CRH were examined with the Spearman test. Before treatment, no significant correlation was observed between the plasma NO level and CRH levels in MDD patients. The plasma NO levels were significantly higher in MDD patients. A significant correlation was found between NO levels and Hamilton Depression Rating Scale (HAMD) scores in MDD patients. The plasma CRH levels were significantly higher in MDD patients than in controls. After monotherapy for 2 months, the NO levels had dramatically declined but were also higher than those in the controls. This study is the first report of the absence of a significant correlation between plasma NO and CRH levels, although both levels are elevated in MDD patients. Furthermore, the strong links between the plasma NO levels and the HAMD scores, as well as the increased NO reduction after remission, suggest that NO plays a key role in depression and may be an indicator of therapeutic success.

Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder.

Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (P<0.001). Plasma CORT levels were increased in male CUS rats (P=0.001), while male MDD patients did not show a significant change in cortisol levels. In conclusion, the changes in plasma and hypothalamic NOS-NO of CUS rats and MDD were similar. The male CUS rat model may thus help us with our investigation of the mechanism underlying NOS-NO alterations in depression.

Decreased plasma neuroactive amino acids and increased nitric oxide levels in melancholic major depressive disorder.

BACKGROUND: Amino acid neurotransmitters and nitric oxide (NO) are involved in the pathogenesis of major depressive disorder (MDD). Here we want to establish whether changes in their plasma levels may serve as biomarker for the melancholic subtype of this disorder. METHODS: Plasma levels of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), and NO were determined in 27 medicine-naïve melancholic MDD patients and 30 matched controls. Seven of the MDD patients participated also in a follow-up study after 2 months' antidepressant treatment. The relationship between plasma and cerebral-spinal fluid (CSF) levels of these compounds was analyzed in an additional group of 10 non-depressed subjects. RESULTS: The plasma levels of Asp, Gly and GABA were significantly lower whereas the NO levels were significantly higher in melancholic MDD patients, also after 2 months of fluoxetine treatment. In the additional 10 non-depressed subjects, no significant correlation was observed between plasma and CSF levels of these compounds. CONCLUSION: These data give the first indication that decreased plasma levels of Asp, Gly and GABA and increased NO levels may serve as a clinical trait-marker for melancholic MDD. The specificity and selectivity of this putative trait-marker has to be investigated in follow-up studies.

[Alterations of plasma aspartic acid, glycine and asparagine levels in patients with major depressive disorder].

OBJECTIVE: To evaluate the changes of plasma levels of the excitatory amino acid neurotransmitter aspartic acid (Asp), inhibitory neurotransmitter glycine (Gly) and asparagine (Asn) in patients with major depressive disorder (MDD). METHODS: Plasma samples were collected from 15 MDD patients (9 males and 6 females, aged 32-64 y) and 14 healthy subjects (7 males and 7 females, aged 30-65 y); and also collected from 7 MDD patients (5 males and 2 females) 2 months after antidepressant treatment. The plasma levels of amino acids were determined by high performance liquid chromatography with fluorescence detection method. RESULTS: Plasma Asp and Gly levels were significantly lower in MDD patients than those in controls (P<0.04). There were positive correlations between plasma levels of Gly and Asp, and between Gly and Asn (P<0.005) in the control group; while in MDD patients, a significant positive correlation was found only between plasma levels of Gly and of Asp (P<0.001). MDD patients did not show significant changes in plasma Asp, Asn and Gly levels after antidepressant treatment compared to those before treatment. CONCLUSION: The reduced plasma Asp and Gly levels may serve as a clinical biomarker for MDD.