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Psychological Medicine Jul 2023Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a...
BACKGROUND
Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders.
METHODS
We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients ( = 557).
RESULTS
Both these networks revealed anhedonia severity and depression symptom severity as central to the network. Results suggest that anhedonia severity may be predictive of the severity of symptom clusters of MDD, AS, ADHD, and ASD. MDD symptom severity may be predictive of AS and ADHD symptom severity.
CONCLUSIONS
The results suggest that anhedonia may serve as a common underlying transdiagnostic psychopathology feature, predictive of the severity of symptom clusters of depression, AS, ADHD, and ASD. Thus, anhedonia may be associated with the high comorbidity between these symptom clusters and disorders. If our results will be replicated in future studies, it is recommended for clinicians to be more vigilant about screening for anhedonia and/or depression severity in individuals diagnosed with an anxiety disorder, ADHD and/or ASD.
Topics: Adult; Humans; Anhedonia; Depressive Disorder, Major; Autism Spectrum Disorder; Syndrome; Cross-Sectional Studies; Attention Deficit Disorder with Hyperactivity
PubMed: 35348051
DOI: 10.1017/S0033291722000575 -
Journal of Neural Transmission (Vienna,... Sep 2023The brain is built with hemispheric asymmetries in structure and function to enable fast neuronal processing. In neuroimaging studies, several mental disorders have been... (Review)
Review
The brain is built with hemispheric asymmetries in structure and function to enable fast neuronal processing. In neuroimaging studies, several mental disorders have been associated with altered or attenuated hemispheric asymmetries. However, the exact mechanism linking asymmetries and disorders is not known. Here, studies in animal models of mental disorders render important insights into the etiology and neuronal alterations associated with both disorders and atypical asymmetry. In this review, the current literature of animal studies in rats and mice focusing on anxiety and fear, anhedonia and despair, addiction or substance misuse, neurodegenerative disorders as well as stress exposure, and atypical hemispheric asymmetries is summarized. Results indicate overall increased right-hemispheric neuronal activity and a left-sided behavioral bias associated with symptoms of anxiety, fear, anhedonia, behavioral despair as well as stress exposure. Addiction behavior is associated with right-sided bias and transgenic models of Alzheimer's disease indicate an asymmetrical accumulation of fibrillar plaques. Most studies focused on changes in the bilateral amygdala and frontal cortex. Across studies, two crucial factors influencing atypical asymmetries arose independently of the disorder modeled: sex and developmental age. In conclusion, animal models of mental disorders demonstrate atypical hemispheric asymmetries similar to findings in patients. Particularly, increased left-sided behavior and greater right-hemispheric activity were found across models applying stress-based paradigms. However, sex- and age-dependent effects on atypical hemispheric asymmetries are present that require further investigation. Animal models enable the analysis of hemispheric changes on the molecular level which may be most effective to detect early alterations.
Topics: Rats; Animals; Mice; Rodentia; Anhedonia; Brain; Neuroimaging; Mental Disorders; Functional Laterality; Magnetic Resonance Imaging
PubMed: 36842091
DOI: 10.1007/s00702-023-02610-z -
Frontiers in Pharmacology 2023The core symptoms of depression are anhedonia and persistent hopelessness. Selective serotonin reuptake inhibitors (SSRIs) and their related medications are commonly... (Review)
Review
The core symptoms of depression are anhedonia and persistent hopelessness. Selective serotonin reuptake inhibitors (SSRIs) and their related medications are commonly used for clinical treatment, despite their significant adverse effects. Traditional Chinese medicine with its multiple targets, channels, and compounds, exhibit immense potential in treating depression. Autophagy, a vital process in depression pathology, has emerged as a promising target for intervention. This review summarized the pharmacological mechanisms of antidepressants by regulating autophagy. We presented insights from recent studies, discussed current research limitations, and proposed new strategies for basic research and their clinical application in depression.
PubMed: 38026940
DOI: 10.3389/fphar.2023.1287234 -
MedRxiv : the Preprint Server For... Jul 2023Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to...
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and aetiological subtypes. There are several challenges to integrating symptom data from genetically-informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data. We conducted genome-wide association studies of major depressive symptoms in three clinical cohorts that were enriched for affected participants (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors. The best fitting model had a distinct factor for symptoms and an additional measurement factor that accounted for missing data patterns in the community cohorts (use of Depression and Anhedonia as gating symptoms). The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analysing genetic association data.
PubMed: 37461564
DOI: 10.1101/2023.07.05.23292214 -
BioRxiv : the Preprint Server For... Aug 2023Hundreds of neuroimaging studies spanning two decades have revealed differences in brain structure and functional connectivity in depression, but with modest effect...
Hundreds of neuroimaging studies spanning two decades have revealed differences in brain structure and functional connectivity in depression, but with modest effect sizes, complicating efforts to derive mechanistic pathophysiologic insights or develop biomarkers. Furthermore, although depression is a fundamentally episodic condition, few neuroimaging studies have taken a longitudinal approach, which is critical for understanding cause and effect and delineating mechanisms that drive mood state transitions over time. The emerging field of precision functional mapping using densely-sampled longitudinal neuroimaging data has revealed unexpected, functionally meaningful individual differences in brain network topology in healthy individuals, but these approaches have never been applied to individuals with depression. Here, using precision functional mapping techniques and 11 datasets comprising n=187 repeatedly sampled individuals and >21,000 minutes of fMRI data, we show that the frontostriatal salience network is expanded two-fold in most individuals with depression. This effect was replicable in multiple samples, including large-scale, group-average data (N=1,231 subjects), and caused primarily by network border shifts affecting specific functional systems, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was unexpectedly stable over time, unaffected by changes in mood state, and detectable in children before the subsequent onset of depressive symptoms in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in specific frontostriatal circuits that tracked fluctuations in specific symptom domains and predicted future anhedonia symptoms before they emerged. Together, these findings identify a stable trait-like brain network topology that may confer risk for depression and mood-state dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.
PubMed: 37645792
DOI: 10.1101/2023.08.09.551651 -
Journal of Neurology, Neurosurgery, and... Oct 2023Motivational symptoms such as apathy and anhedonia are common in Parkinson's disease (PD), respond poorly to treatment, and are hypothesised to share underlying neural...
BACKGROUND
Motivational symptoms such as apathy and anhedonia are common in Parkinson's disease (PD), respond poorly to treatment, and are hypothesised to share underlying neural mechanisms. Striatal dopaminergic dysfunction is considered central to motivational symptoms in PD but the association has never been examined longitudinally. We investigated whether progression of dopaminergic dysfunction was associated with emergent apathy and anhedonia symptoms in PD.
METHODS
Longitudinal cohort study of 412 newly diagnosed patients with PD followed over 5 years as part of the Parkinson's Progression Markers Initiative cohort.Apathy and anhedonia were measured using a composite score derived from relevant items of the 15-item Geriatric Depression Scale (GDS-15) and part I of the MDS-Unified Parkinson's Disease Rating Scale. Dopaminergic neurodegeneration was measured using repeated striatal dopamine transporter (DAT) imaging.
RESULTS
Linear mixed-effects modelling across all contemporaneous data points identified a significant negative relationship between striatal DAT specific binding ratio (SBR) and apathy/anhedonia symptoms, which emerged as PD progressed (interaction:β=-0.09, 95% CI (-0.15 to -0.03), p=0.002). Appearance and subsequent worsening of apathy/anhedonia symptoms began on average 2 years after diagnosis and below a threshold striatal DAT SBR level. The interaction between striatal DAT SBR and time was specific to apathy/anhedonia symptoms, with no evidence of a similar interaction for general depressive symptoms from the GDS-15 (excluding apathy/anhedonia items) (β=-0.06, 95% CI (-0.13 to 0.01)) or motor symptoms (β=0.20, 95% CI (-0.25 to 0.65)).
CONCLUSIONS
Our findings support a central role for dopaminergic dysfunction in motivational symptoms in PD. Striatal DAT imaging may be a useful indicator of apathy/anhedonia risk that could inform intervention strategies.
Topics: Humans; Aged; Apathy; Parkinson Disease; Anhedonia; Dopamine Plasma Membrane Transport Proteins; Longitudinal Studies; Dopamine
PubMed: 37221053
DOI: 10.1136/jnnp-2022-330790 -
Neurobiology of Stress Sep 2023Major depressive disorder (MDD), a common psychiatric condition, adversely affects patients' moods and quality of life. Despite the development of various treatments,...
Major depressive disorder (MDD), a common psychiatric condition, adversely affects patients' moods and quality of life. Despite the development of various treatments, many patients with MDD remain vulnerable and inadequately controlled. Since anhedonia is a feature of depression and there is evidence of leading to metabolic disorder, deep brain stimulation (DBS) to the nucleus accumbens (NAc) might be promising in modulating the dopaminergic pathway. To determine whether NAc-DBS alters glucose metabolism via mitochondrial alteration and neurogenesis and whether these changes increase neural plasticity that improves behavioral functions in a chronic social defeat stress (CSDS) mouse model. The Lab-designed MR-compatible neural probes were implanted in the bilateral NAc of C57BL/6 mice with and without CSDS, followed by DBS or sham stimulation. All animals underwent open-field and sucrose preference testing, and brain resting-state functional MRI analysis. Meanwhile, we checked the placement of neural probes in each mouse by T2 images. By confirming the placement location, mice with incorrect probe placement (the negative control group) showed no significant therapeutic effects in behavioral performance and functional connectivity (FC) after receiving electrical stimulation and were excluded from further analysis. Western blotting, seahorse metabolic analysis, and electron microscopy were further applied for the investigation of NAc-DBS. We found NAc-DBS restored emotional deficits in CSDS-subjected mice. Concurrent with behavioral amelioration, the CSDS DBS-on group exhibited enhanced FC in the dopaminergic pathway with increased expression of BDNF- and NeuN-positive cells increased dopamine D1 receptor, dopamine D2 receptors, and TH in the medial prefrontal cortex, NAc, ventral hippocampus, ventral tegmental area, and amygdala. Increased AMPK/total AMPK and PGC-1α levels, functions of oxidative phosphorylation, and mitochondrial biogenesis were also observed after NAc-DBS treatment. Our findings demonstrate that NAc-DBS can promote BDNF expression, which alters FC and metabolic profile in the dopaminergic pathway, suggesting a potential strategy for ameliorating emotional processes in individuals with MDD.
PubMed: 37664874
DOI: 10.1016/j.ynstr.2023.100566 -
Translational Psychiatry Dec 2023Activity changes within the anterior cingulate cortex (ACC) are implicated in the antidepressant effects of ketamine, but the ACC is cytoarchitectonically and... (Randomized Controlled Trial)
Randomized Controlled Trial
Activity changes within the anterior cingulate cortex (ACC) are implicated in the antidepressant effects of ketamine, but the ACC is cytoarchitectonically and functionally heterogeneous and ketamine's effects may be subregion specific. In the context of a double-blind randomized placebo-controlled crossover trial investigating the clinical and resting-state fMRI effects of intravenous ketamine vs. placebo in patients with treatment resistant depression (TRD) vs. healthy volunteers (HV), we used seed-based resting-state functional connectivity (rsFC) analyses to determine differential changes in subgenual ACC (sgACC), perigenual ACC (pgACC) and dorsal ACC (dACC) rsFC two days post-infusion. Across cingulate subregions, ketamine differentially modulated rsFC to the right insula and anterior ventromedial prefrontal cortex, compared to placebo, in TRD vs. HV; changes to pgACC-insula connectivity correlated with improvements in depression scores. Post-hoc analysis of each cingulate subregion separately revealed differential modulation of sgACC-hippocampal, sgACC-vmPFC, pgACC-posterior cingulate, and dACC-supramarginal gyrus connectivity. By comparing rsFC changes following ketamine vs. placebo in the TRD group alone, we found that sgACC rsFC was most substantially modulated by ketamine vs. placebo. Changes to sgACC-pgACC, sgACC-ventral striatal, and sgACC-dACC connectivity correlated with improvements in anhedonia symptoms. This preliminary evidence suggests that accurate segmentation of the ACC is needed to understand the precise effects of ketamine's antidepressant and anti-anhedonic action.
Topics: Humans; Ketamine; Gyrus Cinguli; Prefrontal Cortex; Antidepressive Agents; Magnetic Resonance Imaging
PubMed: 38040678
DOI: 10.1038/s41398-023-02674-1 -
Psychiatry Research May 2024Research on burnout has garnered considerable attention since its inception. However, the ongoing debate persists regarding the conceptual model of burnout and its...
Research on burnout has garnered considerable attention since its inception. However, the ongoing debate persists regarding the conceptual model of burnout and its relationship with depression. Thus, we conducted a network analysis to determine the dimensional structure of burnout and the burnout-depression overlap. The Maslach Burnout Inventory-Student Survey and Patient Health Questionnaire-9 were used to measure burnout and depression among 1096 college students. We constructed networks for burnout, depression, and a burnout-depression co-occurrence network. The results showed that cynicism symptom was the most central to the burnout network. In the co-occurrence network, depressive symptoms ("anhedonia", "fatigue") and burnout symptom ("doubting the significance of studies") were the most significant in causing burnout-depression comorbidity. Community detection revealed three communities within burnout symptoms, aligning closely with their three dimensions identified through factor analysis. Additionally, there was no overlap between burnout and depression. In conclusion, our findings support a multidimensional structure of burnout, affirming it as a distinct concept separate from depression. Cynicism, rather than exhaustion, plays the most important role in burnout and the burnout-depression comorbidity.
Topics: Humans; Depression; Burnout, Professional; Burnout, Psychological; Students; Surveys and Questionnaires; Psychological Tests; Self Report
PubMed: 38518519
DOI: 10.1016/j.psychres.2024.115828 -
NeuroImage. Clinical 2024Social anhedonia is common within major depressive disorder (MDD) and associated with worse treatment outcomes. The orbitofrontal cortex (OFC) is implicated in both... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Social anhedonia is common within major depressive disorder (MDD) and associated with worse treatment outcomes. The orbitofrontal cortex (OFC) is implicated in both reward (medial OFC) and punishment (lateral OFC) in social decision making. Therefore, to understand the biology of social anhedonia in MDD, medial/lateral OFC metabolism, volume, and thickness, as well as structural connectivity to the striatum, amygdala, and ventral tegmental area/nucleus accumbens were examined. A positive relationship between social anhedonia and these neurobiological outcomes in the lateral OFC was hypothesized, whereas an inverse relationship was hypothesized for the medial OFC. The association between treatment-induced changes in OFC neurobiology and depression improvement were also examined.
METHODS
85 medication-free participants diagnosed with MDD were assessed with Wisconsin Schizotypy Scales to assess social anhedonia and received pretreatment simultaneous fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI), including structural and diffusion. Participants were then treated in an 8-week randomized placebo-controlled double-blind course of escitalopram. PET/MRI were repeated following treatment. Metabolic rate of glucose uptake was quantified from dynamic FDG-PET frames using Patlak graphical analysis. Structure (volume and cortical thickness) was quantified from structural MRI using Freesurfer. To assess structural connectivity, probabilistic tractography was performed on diffusion MRI and average FA was calculated within the derived tracts. Linear mixed models with Bonferroni correction were used to examine the relationships between variables.
RESULTS
A significantly negative linear relationship between pretreatment social anhedonia score and structural connectivity between the medial OFC and the amygdala (estimated coefficient: -0.006, 95 % CI: -0.0108 - -0.0012, p-value = 0.0154) was observed. However, this finding would not survive multiple comparisons correction. No strong evidence existed to show a significant linear relationship between pretreatment social anhedonia score and metabolism, volume, thickness, or structural connectivity to any of the regions examined. There was also no strong evidence to suggest significant linear relationships between improvement in depression and percent change in these variables.
CONCLUSIONS
Based on these multimodal findings, the OFC likely does not underlie social anhedonia in isolation and therefore should not be the sole target of treatment for social anhedonia. This is consistent with previous reports that other areas of the brain such as the amygdala and the striatum are highly involved in this behavior. Relatedly, amygdala-medial OFC structural connectivity could be a future target. The results of this study are crucial as, to our knowledge, they are the first to relate structure/function of the OFC with social anhedonia severity in MDD. Future work may need to involve a whole brain approach in order to develop therapeutics for social anhedonia.
Topics: Humans; Anhedonia; Depressive Disorder, Major; Depression; Fluorodeoxyglucose F18; Brain; Magnetic Resonance Imaging
PubMed: 38134743
DOI: 10.1016/j.nicl.2023.103553