Depressive Phenotype Research Articles

Assessing the effect of interaction between gut microbiome and inflammatory bowel disease on the risks of depression

BackgroundGut microbiome and inflammatory bowel disease (IBD) are implicated in the development of depression, but the effect of their interactions on the risk of depression remains unclear. We aim to analyze the effect of interactions between gut microbiome and IBD on the risk of depression, and explore candidate genes involving the interactions. MethodsUsing the individual genotype and depression traits data from the UK Biobank, we calculated the polygenetic risk scores (PRS) of 114 gut microbiome, ulcerative colitis (UC), Crohn's disease (CD), and total IBD (CD + UC) respectively. The effects of interactions between gut microbiome and IBD on depression were assessed through a linear regression model. Moreover, for observed significant interactions between gut microbiome PRS and IBD PRS, PLINK software was used to test pair-wise single nucleotide polymorphisms (SNPs) interaction of corresponding gut microbiome PRS and IBD PRS on depression. ResultsWe found 64 candidate interactions between gut microbiome and IBD on four phenotypes of depression, such as F_Lachnospiraceae (RNT) × (CD + UC) for patient health questionnaire-9 (PHQ-9) score (P = 1.48 × 10−3), F_Veillonellaceae (HB) × UC for self-reported depression (P = 2.83 × 10−3) and P_Firmicutes (RNT) × CD for age at first episode of depression (P = 8.50 × 10−3). We observed interactions of gut-microbiome-associated SNPs × IBD-associated SNPs, such as G_Alloprevotella (HB)-associated rs147650986 (GPM6A) × IBD-associated rs114471990 (QRICH1) (P = 2.26 × 10−4). ConclusionOur results support the effects of interactions between gut microbiome and IBD on depression risk, and reported several novel candidate genes for depression.

Apathy in depression: An arterial spin labeling perfusion MRI study

IntroductionApathy, as defined as a deficit in goal-directed behaviors, is a critical clinical dimension in depression associated with chronic impairment. Little is known about its cerebral perfusion specificities in depression. To explore neurovascular mechanisms underpinning apathy in depression by pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI). MethodsPerfusion imaging analysis was performed on 90 depressed patients included in a prospective study between November 2014 and February 2017. Imaging data included anatomical 3D T1-weighted and perfusion pCASL sequences. A multiple regression analysis relating the quantified cerebral blood flow (CBF) in different regions of interest defined from the FreeSurfer atlas, to the Apathy Evaluation Scale (AES) total score was conducted. ResultsAfter confound adjustment (demographics, disease and clinical characteristics) and correction for multiple comparisons, we observed a strong negative relationship between the CBF in the left anterior cingulate cortex (ACC) and the AES score (standardized beta = −0.74, corrected p value = 0.0008). ConclusionOur results emphasized the left ACC as a key region involved in apathy severity in a population of depressed participants. Perfusion correlates of apathy in depression evidenced in this study may contribute to characterize different phenotypes of depression.

Effects of early life stress and subsequent re-exposure to stress on neuronal activity in the lateral habenula

Early life stress can result in depression in humans and depressive-like behaviour in rodents. In various animal models of depression, the lateral habenula (LHb) has been shown to become hyperactive immediately after early life stress. However, whether these pathological changes persist into adulthood is less well understood. Hence, we utilised the maternal separation (MS) model of depression to study how early life stress alters LHb physiology and depressive behaviour in adult mice. We find that only a weak depressive phenotype persists into adulthood which surprisingly is underpinned by LHb hypoactivity in acute slices, accompanied by alterations in both excitatory and inhibitory signalling. However, while we find the LHb to be less active at rest, we report that the neurons reside in a sensitised state where they are more responsive to re-exposure to stress in adulthood in the form of acute restraint, thus priming them to respond to aversive events with an increase in neuronal activity mediated by changes in glutamatergic transmission. These findings thus suggest that in addition to LHb hyperactivity, hypoactivity likely also promotes an adverse phenotype. Re-exposure to stress results in the reappearance of LHb hyperactivity offering a possible mechanism to explain how depression relapses occur following previous depressive episodes.

Involvement of kynurenine pathway between inflammation and glutamate in the underlying etiopathology of CUMS-induced depression mouse model

Inflammation and glutamate (GLU) are widely thought to participate in the pathogenesis of depression, and current evidence suggests that the development of depression is associated with the activation of the kynurenine pathway (KP). However, the exact mechanism of KP among the inflammation, GLU and depression remain poorly understood. In this study, we examined the involvement of KP, inflammation and GLU in depressive phenotype induced by chronic unpredictable mild stress (CUMS) in C57B/6 J mice. Our results showed that CUMS caused depressive like-behavior in the sucrose preference test, tail suspension test and forced swimming test. From a molecular perspective, CUMS upregulated the peripheral and central inflammatory response and activated indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of KP, which converts tryptophan (TRP) into kynurenine (KYN). KYN is a precursor for QA in microglia, which could activate the N-methyl-D-aspartate receptor (NMDAR), increasing the GLU release, mirrored by increased IDO activity, quinolinic acid and GLU levels in the hippocampus, prefrontal cortex and serum. However, intervention with IDO inhibitor 1-methyl-DL-tryptophan (50 mg/kg/s.c.) and 1-methyl-L-tryptophan (15 mg/kg/i.p.) reversed the depressive-like behaviors and adjusted central and peripheral KP’s metabolisms levels as well as GLU content, but the inflammation levels were not completely affected. These results provide certain evidence that KP may be a vital pathway mediated by IDO linking inflammation and glutamate, contributing to depression.

Habenula as a Possible Target for Treatment-Resistant Depression Phenotype in Wistar Kyoto Rats

The mechanisms of treatment-resistant depression (TRD) are not clear and are difficult to study. An animal model resembling human TRD is the Wistar Kyoto rat strain. In the present study, we focused on selecting miRNAs that differentiate rats of the WKY strain from Wistar Han (WIS) rats in two divisions of the habenula, the lateral and medial (LHb and MHb, respectively). Based on our preliminary study and literature survey, we identified 32 miRNAs that could be potentially regulated in the habenula. Six miRNAs significantly differentiated WKY rats from WIS rats within the MHb, and three significantly differentiated WKY from WIS rats within the LHb. Then, we selected relevant transcripts regulated by those miRNAs, and their expression in the habenular nuclei was investigated. For mRNAs that differentiated WKY rats from WIS rats in the MHb (Cdkn1c, Htr7, Kcnj9, and Slc12a5), their lower expression correlated with a higher level of relevant miRNAs. In the LHb, eight mRNAs significantly differentiated WKY from WIS rats (upregulated Htr4, Drd2, Kcnj5, and Sstr4 and downregulated Htr2a, Htr7, Elk4, and Slc12a5). These data indicate that several important miRNAs are expressed in the habenula, which differentiates WKY rats from WIS rats and in turn correlates with alterations in the expression of target transcripts. Of particular note are two genes whose expression is altered in WKY rats in both LHb and MHb: Slc12a5 and Htr7. Regulation of KCC2 via the 5-HT7 receptor may be a potential target for the treatment of TRD.

Resistance Training Modulates Hippocampal Neuroinflammation and Protects Anxiety-Depression-like Dyad Induced by an Emotional Single Prolonged Stress Model.

Stress is a triggering factor for anxious and depressive phenotypes. Exercise is known for its action on the central nervous system. This study aimed to evaluate the role of resistance exercise in an anxiety-depression-like dyad in a model of stress. Male Swiss mice (35-day-old) were exercised, three times a week for 4 weeks on nonconsecutive days. The resistance exercise consisted of climbing a 1-m-high ladder 15 times. After mice were subjected to an emotional single prolonged stress (Esps) protocol. Seven days later, they were subjected to anxiety and depression predictive behavioral tests. The results showed that exercised mice gain less weight than sedentary from weeks 3 to 5. Resistance exercise was effective against an increase in immobility time in the forced swim test and tail suspension test and a decrease in grooming time of mice subjected to Esps. Resistance exercise protected against the decrease in the percentage of open arms time and open arm entries, and the increase in the anxiety index in Esps mice. Four-week resistance exercise did not elicit an antidepressant/anxiolytic phenotype in non-stressed mice. Esps did not alter plasma corticosterone levels but increased the hippocampal glucocorticoid receptor content in mice. Resistance exercise protected against the decrease in hippocampal levels of tropomyosin kinase B (TRκB), the p-Akt/Akt, and the p-mTOR/mTOR ratios of Esps mice. Resistance exercise proved to be effective in decreasing hippocampal neuroinflammation in Esps mice. Resistance exercise protected against the increase in the hippocampal Akt/mTOR pathway and neuroinflammation, and anxiety/depression-like dyad in Esps exposed mice.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12035-022-03069-x.

Risk factor profiles for depression following childbirth or a chronic disease diagnosis: case-control study.

Progress towards understanding the aetiology of major depression is compromised by its clinical heterogeneity. The variety of contexts underlying the development of a major depressive episode may contribute to such heterogeneity. To compare risk factor profiles for three subgroups of major depression according to episode context. Using self-report questionnaires and administrative records from the UK Biobank, we characterised three contextual subgroups of major depression: postpartum depression (3581 cases), depression following diagnosis of a chronic disease (409 cases) and a more typical (named heterogeneous) major depression phenotype excluding the two other contexts (34 699 cases). Controls with the same exposure were also defined. We tested each subgroup for association with the polygenic risk scores (PRS) for major depression and with other risk factors previously associated with major depression (bipolar disorder PRS, neuroticism, reported trauma in childhood and adulthood, socioeconomic status, family history of depression, education). Major depression PRS was associated with all subgroups, but postpartum depression cases had higher PRS than heterogeneous major depression cases (OR = 1.06, 95% CI 1.02-1.10). Relative to heterogeneous depression, postpartum depression was more weakly associated with adulthood trauma and neuroticism. Depression following diagnosis of a chronic disease had weaker association with neuroticism and reported trauma in adulthood and childhood relative to heterogeneous depression. The observed differences in risk factor profiles according to the context of a major depressive episode help provide insight into the heterogeneity of depression. Future studies dissecting such heterogeneity could help reveal more refined aetiological insights.

Mechanism of lily bulb and Rehmannia decoction in the treatment of lipopolysaccharide-induced depression-like rats based on metabolomics study and network pharmacology

Context Lily bulb and Rehmannia decoction (LBRD), consisting of Lilium henryi Baker (Liliaceae) and Rehmannia glutinosa (Gaertn) DC (Plantaginaceae), is a specialized traditional Chinese medicine formula for treating depression. However, the underlying mechanisms, especially the relationship between LBRD efficacy and metabolomics, remains unclear. Objective This study was aimed to investigate the metabolic mechanism of LBRD in treating depression. Materials and methods Network pharmacology was conducted using SwissTargetPrediction, DisGeNET, DrugBank, Metascape, etc., to construct component-target-pathway networks. The depression-like model was induced by intraperitoneal injection with lipopolysaccharide (LPS) (0.3 mg/kg) for 14 consecutive days. After the administration of LBRD (90 g/kg) and fluoxetine (2 mg/kg) for 14 days, we assessed behaviour and the levels of neurotransmitter, inflammatory cytokine and circulating stress hormone. Prefrontal metabolites of rats were detected by using liquid chromatography–mass spectrometry metabolomics method. Results The results of network pharmacology showed that LBRD mainly acted on neurotransmitter and second messenger pathways. Compared to the model group, LBRD significantly ameliorated depressive phenotypes and increased the level of 5-HT (13.4%) and GABA (24.8%), as well as decreased IL-1β (30.7%), IL-6 (32.8%) and TNF-α (26.6%). Followed by LBRD treatment, the main metabolites in prefrontal tissue were contributed to retrograde endocannabinoid signalling, glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, autophagy signal pathway, etc. Discussion and conclusions LBRD were effective at increasing neurotransmitter, attenuating proinflammatory cytokine and regulating glycerophospholipid metabolism and glutamatergic synapse, thereby ameliorating depressive phenotypes. This research will offer reference for elucidating the metabolomic mechanism underlying novel antidepressant agents contained LBRD formula.

High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens

Comorbidity exists between metabolic disorders and depressive syndrome with unclear mechanisms. To characterize the causal relationship, we adopted a 12-week high-fat diet (HFD) to induce metabolic disorder and depressive phenotypes in mice. Initially, we identified an enhanced glutamatergic input in the nucleus accumbens of HFD mice. Retrograde tracing and chemogenetic inhibition showed that the hyperactive ventral hippocampal glutamatergic afferents to the nucleus accumbens determined the exhibition of depression-like behavior in HFD mice. Using lentiviral knockdown and overexpression approaches, we proved that HFD-induced downregulation of glial glutamate transporters, GLAST and GLT-1, contributed to the observed circuit maladaptations and subsequent depression-like behaviors. Finally, we identified a potential therapeutic agent, riluzole, which could mitigate the HFD-induced behavioral deficits by normalizing the expressions of GLAST and GLT-1 and ventral hippocampal glutamatergic afferents to the nucleus accumbens. Overall, astrocyte-mediated disturbance in glutamatergic transmission underlies the metabolic disorder-related depressive syndrome and represents a therapeutic target for this subtype of depressive mood disorders.

Men's Depression, Externalizing, and DSM-5-TR: Primary Signs and Symptoms or Co-occurring Symptoms?

Men's Depression, Externalizing, and DSM-5-TR: Primary Signs and Symptoms or Co-occurring Symptoms?

Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice

BackgroundAsthma is a major public health problem worldwide. Emerging data from epidemiological studies show that allergies and allergic diseases may be linked to anxiety, depression and cognitive decline. However, little is known about the effect of asthma, an allergic lung inflammation, on cognitive decline/behavioral changes. Therefore, we investigated the hypothesis that allergic lung inflammation causes inflammation in the brain and leads to neurobehavioral changes in mice.MethodsWild-type C57BL/6J female mice were sensitized with nasal house dust mite (HDM) antigen or control PBS for 6 weeks to induce chronic allergic lung inflammation. A series of neurocognitive tests for anxiety and/or depression were performed before and after the intranasal HDM administration. After the behavior tests, tissues were harvested to measure inflammation in the lungs and the brains.ResultsHDM-treated mice exhibited significantly increased immobility times during tail suspension tests and significantly decreased sucrose preference compared with PBS controls, suggesting a more depressed and anhedonia phenotype. Spatial memory impairment was also observed in HDM-treated mice when assessed by the Y-maze novel arm tests. Development of lung inflammation after 6 weeks of HDM administration was confirmed by histology, bronchoalveolar lavage (BAL) cell count and lung cytokine measurements. Serum pro-inflammatory cytokines and Th2-related cytokines levels were elevated in HDM-sensitized mice. In the brain, the chemokine fractalkine was increased in the HDM group. The c-Fos protein, a marker for neuronal activity, Glial Fibrillary Acidic Protein (GFAP) and chymase, a serine protease from mast cells, were increased in the brains from mice in HDM group. Chymase expression in the brain was negatively correlated with the results of sucrose preference rate in individual mice.Conclusions6 weeks of intranasal HDM administration in mice to mimic the chronic status of lung inflammation in asthma, caused significant inflammatory histological changes in the lungs, and several behavioral changes consistent with depression and altered spatial memory. Chymase and c-Fos proteins were increased in the brain from HDM-treated mice, suggesting links between lung inflammation and brain mast cell activation, which could be responsible for depression-like behavior.

Postpartum depression in rats causes poor maternal care and neurochemical alterations on dams and long-lasting impairment in sociability on the offspring

Postpartum depression is a mentally disabling disease with multifactorial etiology that affects women worldwide. It can also influence child development and lead to behavioral and cognitive alterations. Despite the high prevalence, the disease is underdiagnosed and poorly studied. To study the postpartum depression caused by maternal separation model in rats, dams were separated from their litter for 3 h daily starting from lactating day (LD) 2 through LD12. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day (PND) 2 through PND90. The stress caused by the dam-offspring separation led to poor maternal care and a transient increase in anxiety in the offspring detected during infancy. The female offspring also exhibited a permanent impairment in sociability during adult life. These changes were associated with neurochemical alterations in the prefrontal cortex and hippocampus, and low TSH concentrations in the dams, and in the hypothalamus, hippocampus and striatum of the offspring. These results indicate that the postpartum depression resulted in a depressive phenotype, changes in the brain neurochemistry and in thyroid economy that remained until the end of lactation. Changes observed in the offspring were long-lasting and resemble what is observed in children of depressant mothers.

Hierarchical Inflammatory Phenotypes of Depression: A Novel Approach Across Five Independent Samples and 27,730 Adults

BackgroundAlthough characterizing associations between inflammation and depression may prove critical for informing theory, research, and treatment decisions, extant research has been limited by ignoring the possibility that inflammation may be simultaneously associated with depression broadly and with a subset of symptoms. This lack of direct comparison has hampered attempts to understand inflammatory phenotypes of depression and critically fails to consider that inflammation might be uniquely associated with both depression broadly and individual symptoms. MethodsWe used moderated nonlinear factor analysis in 5 NHANES (National Health and Nutrition Examination Survey) cohorts (N = 27,730, 51% female, mean age = 46 years). ResultsC-reactive protein (CRP) is simultaneously associated with latent depression, appetite, and fatigue. Specifically, CRP was associated with latent depression in all 5 samples (rs: 0.044–0.089; ps: < .001–.002) and was associated with both appetite (significant rs: 0.031–0.049, significant ps: .001–.007) and fatigue (significant rs: 0.030–0.054, significant ps: < .001–.029) in 4 samples. These results were largely robust to covariates. ConclusionsMethodologically, these models indicate that the Patient Health Questionnaire-9 is scalar noninvariant as a function of CRP (i.e., identical Patient Health Questionnaire-9 scores may represent different constructs in those with high vs. low CRP levels). Therefore, mean comparisons of depression total scores and CRP might be misleading without accounting for symptom-specific associations. Conceptually, these findings indicate that studies investigating inflammatory phenotypes of depression should examine how inflammation is simultaneously related both to depression broadly and to specific symptoms, and whether these relations function via different mechanisms. This has the potential to yield new theoretical insights and may lead to the development of novel therapies for reducing inflammation-related symptoms of depression.

In Situ Observation of Lysosomal Hypobromous Acid Fluctuations in the Brain of Mice with Depression Phenotypes by Two-Photon Fluorescence Imaging.

Excessive oxidative stress is the main cause of neurotransmitter metabolism disorder in the brain with depression. Lysosomal hypobromic acid (HOBr) is an important reactive oxygen species produced in oxidative stress. Its abnormal content can lead to macromolecular damage and neurodegenerative diseases. However, due to the high reactivity and low concentration of HOBr and the lack of in situ imaging methods, the role of HOBr in depression is not clear. Herein, based on the HOBr-initiated aromatic substitution of a tertiary amine, we developed a novel two-photon (TP) fluorescence probe (NH-HOBr) for real-time visual monitoring of trace HOBr in living systems. NH-HOBr introduces N-(2-aminoethyl)-morpholine as a new recognition receptor for HOBr and a targeting group for lysosomes. It not only has excellent selectivity compared with other biomolecules (including hypochlorous acid), fast response (≤5 s) and high sensitivity (LOD = 15 nM) but also realizes sensitive detection of HOBr in cells, zebrafish, and mice tissues. It is worth noting that the in situ TP fluorescence imaging of mouse brain reveals the positive correlation between HOBr content and depression phenotype for the first time, providing strong direct evidence for the relationship between oxidative stress and depression. This work can provide reference to further study depression and the pathological mechanism of HOBr. In addition, HOBr-initiated aromatic substitution of a tertiary amine provides a new idea for the construction of specific and sensitive HOBr probes.

Multivariate genome-wide association study of depression, cognition, and memory phenotypes and validation analysis identify 12 cross-ethnic variants

To date, little is known about the pleiotropic genetic variants among depression, cognition, and memory. The current research aimed to identify the potential pleiotropic single nucleotide polymorphisms (SNPs), genes, and pathways of the three phenotypes by conducting a multivariate genome-wide association study and an additional pleiotropy analysis among Chinese individuals and further validate the top variants in the UK Biobank (UKB). In the discovery phase, the participants were 139 pairs of dizygotic twins from the Qingdao Twins Registry. The genome-wide efficient mixed-model analysis identified 164 SNPs reaching suggestive significance (P < 1 × 10−5). Among them, rs3967317 (P = 1.21 × 10−8) exceeded the genome-wide significance level (P < 5 × 10−8) and was also demonstrated to be associated with depression and memory in pleiotropy analysis, followed by rs9863698, rs3967316, and rs9261381 (P = 7.80 × 10−8−5.68 × 10−7), which were associated with all three phenotypes. After imputation, a total of 457 SNPs reached suggestive significance. The top SNP chr6:24597173 was located in the KIAA0319 gene, which had biased expression in brain tissues. Genes and pathways related to metabolism, immunity, and neuronal systems demonstrated nominal significance (P < 0.05) in gene-based and pathway enrichment analyses. In the validation phase, 12 of the abovementioned SNPs reached the nominal significance level (P < 0.05) in the UKB. Among them, three SNPs were located in the KIAA0319 gene, and four SNPs were identified as significant expression quantitative trait loci in brain tissues. These findings may provide evidence for pleiotropic variants among depression, cognition, and memory and clues for further exploring the shared genetic pathogenesis of depression with Alzheimer’s disease.

Activation of liver X receptors protects oligodendrocytes in CA3 of stress-induced mice

Depression is a complex disorder that is associated with various structural abnormalities. Oligodendrocyte (OL) dysfunction is associated with the pathogenesis of depression and the promotion of hippocampal oligodendrocyte maturation and myelination could be a novel therapeutic strategy for ameliorating depressive behaviors. Recent studies have shown that activation of liver X receptors (LXRs) by GW3965 improves depressive phenotypes, but the effects of GW3965 on OL function and myelination in the hippocampus of depression remain relatively unclear. To address this issue, we investigated the effects of GW3965 on mature OL in the hippocampus and on the myelin sheaths of mice subjected to chronic unpredictable stress (CUS). Behavioral tests were performed to assess depressive behaviors. Then, the number of mature OLs (CC1+) in each hippocampal subregion was precisely quantified with immunohistochemical and stereological methods, and the density of newborn mature OLs (BrdU+/Olig2+/CC1+ cells) in each hippocampal subregion was quantified with immunofluorescence. In addition, myelin basic protein (MBP) staining intensity in the cornu ammonis 3 (CA3) region was assessed by using immunofluorescence. We found that both the number of CC1+ OLs and the density of BrdU+/Olig2+/CC1+ cells were obviously decreased in each hippocampal subregion of mice subjected to CUS, and 4 weeks of GW3965 treatment reversed these effects only in the CA3 region. Furthermore, the decreased MBP expression in the CA3 region of mice subjected to CUS was ameliorated by GW3965 treatment. Collectively, these results suggested that improvement of OL maturation and enhancement of myelination may be structural mechanisms underlying the antidepressant effects of LXR agonists.

Depression and Suicidality in Patients With Psoriasis and the Role of Psoriatic Arthritis: ACross-sectional Study in a Tertiary Setting.

Depression is overrepresented in psoriasis. However, it is not clear whether the presence of psoriatic arthritis (PsA) independently increases patients' depressive burden. Furthermore, current evidence regarding suicidality risk of psoriasis populations is conflicting, and the role of PsA in suicidality outcomes of psoriasis is unknown. (i) To test whether PsA is associated with depression and lifetime suicidal ideation among patients with psoriasis; (ii) to capture different suicidal phenomena in these patients; and (iii) to investigate whether suicidality and depressive symptom severity are associated with clinical markers of psoriasis severity and chronicity. A cross-sectional survey of tertiary patients (n= 219, aged 18-65 years) with dermatologist-confirmed chronic plaque psoriasis, of whom 84 had rheumatologist-confirmed PsA, was undertaken. The Hospital Anxiety and Depression Scale and Sheehan-Suicidality Tracking Scale were used to assess depression and lifetime suicidality, respectively. PsA presence was associated with depression in patients with psoriasis, independent of other physical comorbidities (adjusted odds ratio 2.92, 95% confidence interval 1.53-5.68). Furthermore, patients with PsA experienced significantly higher levels of anhedonia and anxiety, after controlling for psychiatric history. Of all participants, 48.8% reported lifetime suicidal ideation with or without intent, 21.3% reported suicidal planning, and 9.4% reported suicide attempts. Lifetime suicidality prevalence did not differ between patients with and without PsA. Depressive symptom severity and lifetime suicidality scores were not associated with objective measures of psoriasis severity or treatment group. These data suggest that joint involvement in psoriasis is associated with higher depressive burden. There is a need for routine depression screening among patients with psoriasis, particularly when PsA is present. Anhedonia appears to be a particularly relevant symptom in the depression phenotype of this population. We did not find a statistically significant association between PsA and suicidality. Nevertheless, suicidality rates in tertiary patients with psoriasis appear to be higher than those in the general population. Suicidality monitoring is recommended to help in reducing future psychiatric morbidity and mortality in patients with psoriasis.

A tale of two transmitters: serotonin and histamine as in vivo biomarkers of chronic stress in mice

BackgroundStress-induced mental illnesses (mediated by neuroinflammation) pose one of the world’s most urgent public health challenges. A reliable in vivo chemical biomarker of stress would significantly improve the clinical communities’ diagnostic and therapeutic approaches to illnesses, such as depression.MethodsMale and female C57BL/6J mice underwent a chronic stress paradigm. We paired innovative in vivo serotonin and histamine voltammetric measurement technologies, behavioral testing, and cutting-edge mathematical methods to correlate chemistry to stress and behavior.ResultsInflammation-induced increases in hypothalamic histamine were co-measured with decreased in vivo extracellular hippocampal serotonin in mice that underwent a chronic stress paradigm, regardless of behavioral phenotype. In animals with depression phenotypes, correlations were found between serotonin and the extent of behavioral indices of depression. We created a high accuracy algorithm that could predict whether animals had been exposed to stress or not based solely on the serotonin measurement. We next developed a model of serotonin and histamine modulation, which predicted that stress-induced neuroinflammation increases histaminergic activity, serving to inhibit serotonin. Finally, we created a mathematical index of stress, Si and predicted that during chronic stress, where Si is high, simultaneously increasing serotonin and decreasing histamine is the most effective chemical strategy to restoring serotonin to pre-stress levels. When we pursued this idea pharmacologically, our experiments were nearly identical to the model’s predictions.ConclusionsThis work shines the light on two biomarkers of chronic stress, histamine and serotonin, and implies that both may be important in our future investigations of the pathology and treatment of inflammation-induced depression.

Different phenotypic assessment of depression prevalence in Russian population: DSM-criteria vs HADS

IntroductionBecause of different phenotypic approaches, data on depression prevalence is variable and controversial.ObjectivesThe aim was to evaluate the prevalence of different depressive phenotypes in the Russian population (DSM criteria based self-report vs HADS questionnaire).MethodsThe data was from the on-line survey of 5116 clients of Genotek Ltd. (males - 50,63%; age - Me=35 (Q1-30;Q3-42)). The survey included questions on sex, age; sel-report adapted major depression DSM-V criteria questionnaire and depression subscale of Hospital Anxiety and Depression Scale.ResultsDSM Major depression phenotype was detected with moderately-high prevalence - 17,67% (N=904). The DSM depression phenotype was more prevalent in women (22,72%) compared to men (12,74%, p&lt;0,001) and in younger individuals (10,18%, p&lt;0,001) compared to older ones (6,16%). HADS-D clinical depression phenotype (score&gt;11) was less prevalent (3,4%) with no significant differences for sex and age. However, the prevalence increased with HADS-D subclinical scores (&gt;8) - 14,97%. HADS-D scores were higher in DSM-depression phenotype individuals compared to ones without DSM phenotype (5,822(3,221) vs. 3,893(2,437), p&lt; 0,001).ConclusionsOur results showed variable prevalence of depression with different phenotypic approaches. The differences could be associated with the clinical severity of the symptoms and the life-time evaluation in DSM compared to only current symptoms for HADS. Further research is needed to understand the factors affecting the phenotyping approaches and providing the most effective and valid instrument for depression prevalence evaluation. Research is supported by an RSF grant №20-15-00132.DisclosureResearch is supported by an RSF grant №20-15-00132.

Mouse Model of Weak Depression Exhibiting Suppressed cAMP Signaling in the Amygdala, Lower Lipid Catabolism in Liver, and Correlated Gut Microbiota

To establish a mouse model of weak depression, we raised 6-week-old C57BL/6N mice in single (SH) or group housing (GH) conditions for 2 weeks. The SH group showed less social interaction with stranger mice, learning disability in behavioral tests, and lower plasma corticosterone levels. The cecal microbiota of the SH group showed significant segregation from the GH group in the principal coordinate analysis (PCoA). Transcriptome analysis of the amygdala and liver detected multiple differentially expressed genes (DEGs). In the amygdala of SH mice, suppression of the cyclic adenine monophosphate (cAMP) signal was predicted and confirmed by the reduced immunoreactivity of phosphorylated cAMP-responsive element-binding protein. In the liver of SH mice, downregulation of beta-oxidation was predicted. Interestingly, the expression levels of over 100 DEGs showed a significant correlation with the occupancy of two bacterial genera, Lactobacillus (Lactobacillaceae) and Anaerostipes (Lachnospiraceae). These bacteria-correlated DEGs included JunB, the downstream component of cAMP signaling in the amygdala, and carnitine palmitoyltransferase 1A (Cpt1a), a key enzyme of beta-oxidation in the liver. This trans-omical analysis also suggested that nicotinamide adenine dinucleotide (NAD) synthesis in the liver may be linked to the occupancy of Lactobacillus through the regulation of nicotinamide phosphoribosyltransferase (NAMPT) and kynureninase (KYNU) genes. Our results suggested that SH condition along with the presence of correlated bacteria species causes weak depression phenotype in young mice and provides a suitable model to study food ingredient that is able to cure weak depression.