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Frontiers in Pharmacology 2024Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic...
Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD. High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1β in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot. The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors. Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.
PubMed: 38948463
DOI: 10.3389/fphar.2024.1294122 -
Neurobiology of Stress Jul 2024Chronic pain can induce mood disorders and cognitive dysfunctions, such as anxiety, depression, and learning and memory impairment in humans. However, the specific...
Hyperexcitation of the glutamatergic neurons in lateral hypothalamus induced by chronic pain contributes to depression-like behavior and learning and memory impairment in male mice.
Chronic pain can induce mood disorders and cognitive dysfunctions, such as anxiety, depression, and learning and memory impairment in humans. However, the specific neural network involved in anxiety- and depression-like behaviors and learning and memory impairment caused by chronic pain remains poorly understood. In this study, behavioral test results showed that chronic pain induced anxiety- and depression-like behaviors, and learning and memory impairment in male mice. c-Fos immunofluorescence and fiber photometry recording showed that glutamatergic neurons in the LH of mice with chronic pain were selectively activated. Next, the glutamatergic neurons of LH in normal mice were activated using optogenetic and chemogenetic methods, which recapitulates some of the depressive-like behaviors, as well as memory impairment, but not anxiety-like behavior. Finally, inhibition of glutamatergic neurons in the LH of mice with chronic pain, effectively relieved anxiety- and depression-like behaviors and learning and memory impairment. Taken together, our findings suggest that hyperexcitation of glutamatergic neurons in the LH is involved in depression-like behavior and learning and memory impairment induced by chronic pain.
PubMed: 38948390
DOI: 10.1016/j.ynstr.2024.100654 -
Computational Psychiatry (Cambridge,... 2024Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their...
Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their ability to know and regulate their body and particularly their interoceptive states. While clinical questionnaire studies have provided ample evidence on the role of such beliefs in the onset, maintenance, and treatment of AN, psychophysical studies have typically focused on perceptual and 'local' beliefs. Across two experiments, we examined how women at the acute AN (N = 86) and post-acute AN state (N = 87), compared to matched healthy controls (N = 180) formed and updated their self-efficacy beliefs retrospectively (Experiment 1) and prospectively (Experiment 2) about their heartbeat counting abilities in an adapted heartbeat counting task. As preregistered, while AN patients did not differ from controls in interoceptive accuracy , they hold and maintain 'pessimistic' interoceptive, metacognitive self-efficacy beliefs after performance. Modelling using a simplified computational Bayesian learning framework showed that neither local evidence from performance, nor retrospective beliefs following that performance (that themselves were suboptimally updated) seem to be sufficient to counter and update pessimistic, self-efficacy beliefs in AN. AN patients showed lower learning rates than controls, revealing a tendency to base their posterior beliefs more on prior beliefs rather than prediction errors in both retrospective and prospective belief updating. Further explorations showed that while these differences in both explicit beliefs, and the latent mechanisms of belief updating, were not explained by general cognitive flexibility differences, they were explained by negative mood comorbidity, even after the acute stage of illness.
PubMed: 38948255
DOI: 10.5334/cpsy.109 -
Nature. Mental Health 2024Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical...
Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( = 1,384) of medication-free individuals with first-episode and recurrent MDD ( = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals ( = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter ( = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter ( = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) ( = -18.3, 95% CI (-34.3 to -2.3), = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.
PubMed: 38948238
DOI: 10.1038/s44220-023-00187-w -
Theranostics 2024: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the...
: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the Hippo/YAP/14-3-3η signaling pathway mediates mitochondrial abnormalities that result in the onset of major depressive disorder (MDD) in a mouse model. : The ROC algorithm was used to identify a subpopulation of mice that were exposed to chronic unpredictable mild stress (CUMS) and exhibited the most prominent depressive phenotype (Dep). Electron microscopy, biochemical assays, quantitative PCR, and immunoblotting were used to evaluate synaptic and mitochondrial changes in the basolateral amygdala (BLA). RNA sequencing was used to explore changes in the Hippo pathway and downstream target genes. pharmacological inhibition and immunoprecipitation was used to confirm YAP/14-3-3η interaction and its role in neuronal mitochondrial dysfunction. We used virus-mediated gene overexpression and knockout in YAP transgenic mice to verify the regulatory effect of the Hippo/YAP/14-3-3η pathway on depressive-like behavior. : Transcriptomic data identified a large number of genes and signaling pathways that were specifically altered from the BLA of Dep mice. Dep mice showed notable synaptic impairment in BLA neurons, as well as mitochondrial damage characterized by abnormal mitochondrial morphology, compromised function, impaired biogenesis, and alterations in mitochondrial marker proteins. The Hippo signaling pathway was activated in Dep mice during CUMS, and the transcriptional regulatory activity of YAP was suppressed by phosphorylation of its Ser127 site. 14-3-3η was identified as an important co-regulatory factor of the Hippo/YAP pathway, as it can respond to chronic stress and regulate cytoplasmic retention of YAP. Importantly, the integrated Hippo/YAP/14-3-3η pathway mediated neuronal mitochondrial dysfunction and depressive behavior in Dep mice. : The integrated Hippo/YAP/14-3-3η pathway in the BLA neuron is critical in mediating depressive-like behaviors in mice, suggesting a causal role for this pathway in susceptibility to chronic stress-induced depression. This pathway therefore may present a therapeutic target against mitochondrial dysfunction and synaptic impairment in MDD.
PubMed: 38948066
DOI: 10.7150/thno.92676 -
MedRxiv : the Preprint Server For... Jun 2024Cannabis is one of the most widely used drugs globally. Decriminalization of cannabis is further increasing cannabis consumption. We performed genome-wide association...
Cannabis is one of the most widely used drugs globally. Decriminalization of cannabis is further increasing cannabis consumption. We performed genome-wide association studies ( ) of lifetime ( 131,895) and frequency ( 73,374) of cannabis use. Lifetime cannabis use GWAS identified two loci, one near (rs11922956, =2.40E-11) and another near (rs12673181, =6.90E-09). Frequency of use GWAS identified one locus near (rs4856591, =8.10E-09; =0.76 with rs11922956). Both traits were heritable and genetically correlated with previous GWASs of lifetime use and cannabis use disorder ( ), as well as other substance use and cognitive traits. Polygenic scores ( ) for lifetime and frequency of cannabis use associated cannabis use phenotypes in participants. Phenome-wide association study of lifetime cannabis use PGS in a hospital cohort replicated associations with substance use and mood disorders, and uncovered associations with celiac and infectious diseases. This work demonstrates the value of GWASs of CUD transition risk factors.
PubMed: 38947071
DOI: 10.1101/2024.06.14.24308946 -
MedRxiv : the Preprint Server For... Jun 2024Impulsivity can be a risk factor for serious complications for those with mood disorders. To understand intra-individual impulsivity variability, we analyzed...
Impulsivity can be a risk factor for serious complications for those with mood disorders. To understand intra-individual impulsivity variability, we analyzed longitudinal data of a novel gamified digital Go/No-Go (GNG) task in a clinical sample (n=43 mood disorder participants, n=17 healthy controls) and an open-science sample (n=121, self-reported diagnoses). With repeated measurements within-subject, we disentangled two aspects of GNG: reaction time and accuracy in response inhibition (i.e., incorrect No-Go trials) with respect to diurnal and potential learning effects. Mixed-effects models showed diurnal effects in reaction time but not accuracy, with a significant effect of hour on reaction time in the clinical sample and the open-science sample. Moreover, subjects improved on their response inhibition but not reaction time. Additionally, significant interactions emerged between depression symptom severity and time-of-day in both samples, supporting that repeated administration of our GNG task can yield mood-dependent circadian rhythm-aware biomarkers of neurocognitive function.
PubMed: 38947017
DOI: 10.1101/2024.06.12.24308834 -
MedRxiv : the Preprint Server For... Jun 2024Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative....
IMPORTANCE
Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment outcomes. However, little is known about the extent of whole-brain structural connectivity changes with inpatient treatment and abstinence in iHUD.
OBJECTIVE
To assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL).
DESIGN
Longitudinal cohort study (12/2020-09/2022) where iHUD and CTL underwent baseline magnetic resonance imaging (MRI#1) and follow-up (MRI#2) scans, (mean interval of 13.9 weeks in all participants combined).
SETTING
The iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively.
PARTICIPANTS
Thirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women).
INTERVENTION
Between scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals.
MAIN OUTCOMES AND MEASURES
Changes in white matter diffusion metrics [fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivities (RD)] in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance).
RESULTS
Main findings showed HUD-specific WM microstructure changes encompassing mostly frontal major callosal, projection, and association tracts, characterized by increased FA (.949<1- p<.986) and decreased MD (.949<1-p<.997) and RD (.949<1-p<.999). The increased FA (r=- 0.72, p<.00001) and decreased MD (r=0.69, p<.00001) and RD (r=0.67, p<.0001) in the genu and body of the corpus callosum and the left anterior corona radiata in iHUD were correlated with a reduction in baseline craving (.949<1-p<.999). No other WM correlations with outcome variables reached significance.
CONCLUSIONS AND RELEVANCE
Our findings suggest whole-brain normalization of structural connectivity with inpatient medically-assisted treatment in iHUD encompassing recovery in frontal WM pathways implicated in emotional regulation and top-down executive control. The association with decreases in baseline craving further supports the relevance of these WM markers to a major symptom in drug addiction, with implications for monitoring clinical outcomes.
KEY POINTS
Does white matter (WM) microstructure change with medication-assisted treatment in individuals with heroin use disorder (iHUD)? In this longitudinal cohort study, diffusion MRI was acquired in 34 inpatient iHUD and 25 healthy controls (CTL) twice, separated by a mean of 13.9 weeks. We found HUD- specific WM microstructure changes with time, characterized by increased anisotropy and decreased diffusivity in fronto-striatal WM pathways. These changes were correlated with decreased baseline drug craving with treatment. Frontal WM changes and associated drug craving decreases suggest brain-behavior recovery with inpatient treatment in iHUD, potentially contributing to reduced drug use and sustained abstinence.
PubMed: 38946983
DOI: 10.1101/2024.06.10.24308719 -
The Medical Journal of Australia Jul 2024To assess the effectiveness of the Cultural, Social and Emotional Wellbeing Program for reducing psychological distress and enhancing the social and emotional wellbeing...
OBJECTIVE
To assess the effectiveness of the Cultural, Social and Emotional Wellbeing Program for reducing psychological distress and enhancing the social and emotional wellbeing of Aboriginal women preparing for release from prison.
STUDY DESIGN
Mixed methods; qualitative study (adapted reflexive thematic analysis of stories of most significant change) and assessment of psychological distress.
SETTING, PARTICIPANTS
Aboriginal and Torres Strait Islander women at the Boronia Pre-release Centre for Women, Perth, Western Australia, May and July 2021.
INTERVENTION
Cultural, Social and Emotional Wellbeing Program (two days per week for six weeks). The Program involves presentations, workshops, activities, group discussions, and self-reflections designed to enhance social and emotional wellbeing.
MAIN OUTCOME MEASURES
Themes and subthemes identified from reflexive thematic analysis of participants' stories of most significant change; change in mean psychological distress, as assessed with the 5-item Kessler Scale (K-5) before and after the Program.
RESULTS
Fourteen of 16 invited women completed the Program; ten participated in its evaluation. They reported improved social and emotional wellbeing, reflected as enhanced connections to culture, family, and community. Mean psychological distress was lower after the Program (mean K-5 score, 11.3; 95% confidence interval [CI], 9.0-13.6) than before the Program (9.0; 95% CI, 6.5-11.5; P = 0.047).
CONCLUSION
The women who participated in the Program reported personal growth, including acceptance of self and acceptance and pride in culture, reflecting enhanced social and emotional wellbeing through connections to culture and kinship. Our preliminary findings suggest that the Program could improve the resilience of Aboriginal and Torres Strait Islander in contact with the justice system.
Topics: Humans; Female; Native Hawaiian or Other Pacific Islander; Adult; Mental Health; Western Australia; Program Evaluation; Psychological Distress; Qualitative Research; Middle Aged; Emotions; Prisoners; Stress, Psychological; Young Adult
PubMed: 38946642
DOI: 10.5694/mja2.52354 -
Predictors of Pain and Mood Disturbances Among Older People in Custody Using an interRAI Assessment.Journal of Correctional Health Care :... Jul 2024The population of people in federal custody in Canada is aging. Those in custody report experiencing poorer health and high rates of chronic health conditions. Two...
The population of people in federal custody in Canada is aging. Those in custody report experiencing poorer health and high rates of chronic health conditions. Two health concerns that are disproportionately higher among those in custody are mood disorders and pain. This cross-sectional study examined health indicators associated with pain and depressive symptoms among older people (50 years and above) from multiple facilities and security levels in federal custody in Canada. Participants were assessed using the interRAI Emergency Department Contact Assessment, which captures key health indicators. Chi square and logistic regression analyses were conducted to describe the population and identify health indicators associated with mood- and pain-related outcomes, respectively. Of the 1,422 participants in this study, the majority (55%) experienced pain and at least 1 out of 5 experienced depressive symptoms. Health indicators associated with depressive symptoms and/or pain were functional measures, including mobility, managing medication(s), and dyspnea. Depressive symptoms and pain are highly prevalent among older adults in federal custody. The relationship between functional health, depressive symptoms, and pain highlights the importance of interprofessional health care and biopsychosocial intervention(s).
PubMed: 38946596
DOI: 10.1089/jchc.23.06.0057