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Psychiatry Research Sep 2023Consumption of a high-fat diet (HFD) has been associated with reduced wakefulness and various behavioral deficits, including anxiety, depression, and anhedonia. The...
Consumption of a high-fat diet (HFD) has been associated with reduced wakefulness and various behavioral deficits, including anxiety, depression, and anhedonia. The dopaminergic system, which plays a crucial role in sleep and ADHD, is known to be vulnerable to chronic HFD. However, the association between HFD-induced behavioral and molecular changes remains unclear. Therefore, we investigated the effects of a HFD on the dopaminergic system and its association with behavioral deficits in male mice. The mice were divided into normal diet and HFD groups and were analyzed for sleep patterns, behavior tests, and transcription levels of dopamine-related genes in the brain. The HFD group showed decreased wakefulness, increased REM sleep with fragmented patterns, decreased time spent in the center zone of the open field test, shorter immobile time in the tail suspension test, impaired visuospatial memory, and reduced sucrose preference. Additionally, the HFD group had decreased mRNA levels of D1R, COMT, and DAT in the nucleus accumbens, which negatively correlated with REM sleep proportion and REM sleep bout count. The results suggest that HFD-induced behavioral deficits were resemblance to ADHD-like behavioral phenotypes and disturbs REM sleep by dysregulating the dopaminergic system.
Topics: Male; Animals; Mice; Sleep Deprivation; Sleep, REM; Diet, High-Fat; Attention Deficit Disorder with Hyperactivity; Dopamine
PubMed: 37607442
DOI: 10.1016/j.psychres.2023.115412 -
Research Square Jun 2023Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent...
Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.
PubMed: 37461693
DOI: 10.21203/rs.3.rs-3093428/v1 -
Journal of Affective Disorders Nov 2023The external behavioural manifestations and internal neural mechanisms of anhedonia are sexually dimorphic. This study aimed to explore the sex differences in the...
OBJECTIVE
The external behavioural manifestations and internal neural mechanisms of anhedonia are sexually dimorphic. This study aimed to explore the sex differences in the regional brain neuroimaging features of anhedonia in the context of major depressive disorder (MDD).
METHOD
The resting-fMRI by applying amplitude of low-frequency fluctuation (ALFF) method was estimated in 414 patients with MDD (281 high anhedonia [HA], 133 low anhedonia [LA]) and 213 healthy controls (HC). The effects of two factors in patients with MDD were analysed using a 2 (sex: male, female) × 2 (group: HA, LA) ANOVA concerning the brain regions in which statistical differences were identified between patients with MDD and HC. We followed up with patients with HA at baseline, and 43 patients completed a second fMRI scan in remission. Paired t-test was performed to compare the ALFF values of anhedonia-related brain regions between the baseline and remission periods.
RESULTS
For the sex-by-group interaction, the bilateral insula, right hippocampus, right post cingulum cortex, and left putamen showed significant differences. Furthermore, the abnormally elevated ALFF values in anhedonia-related brain regions at baseline decreased in remission.
CONCLUSION
Our findings point to the fact that the females showed unique patterns of anhedonia-related brain activity compared to males, which may have clinical implications for interfering with the anhedonia symptoms in MDD. Using task fMRI, we can further examine the distinct characteristics between consumption anhedonia and anticipation anhedonia in MDD.
Topics: Female; Humans; Male; Depressive Disorder, Major; Anhedonia; Sex Characteristics; Magnetic Resonance Imaging; Brain
PubMed: 37591350
DOI: 10.1016/j.jad.2023.08.083 -
Frontiers in Neuroscience 2023Bipolar disorder (BD) is characterized by extreme mood swings ranging from manic/hypomanic to depressive episodes. The severity, duration, and frequency of these... (Review)
Review
Bipolar disorder (BD) is characterized by extreme mood swings ranging from manic/hypomanic to depressive episodes. The severity, duration, and frequency of these episodes can vary widely between individuals, significantly impacting quality of life. Individuals with BD spend almost half their lives experiencing mood symptoms, especially depression, as well as associated clinical dimensions such as anhedonia, fatigue, suicidality, anxiety, and neurovegetative symptoms. Persistent mood symptoms have been associated with premature mortality, accelerated aging, and elevated prevalence of treatment-resistant depression. Recent efforts have expanded our understanding of the neurobiology of BD and the downstream targets that may help track clinical outcomes and drug development. However, as a polygenic disorder, the neurobiology of BD is complex and involves biological changes in several organelles and downstream targets (pre-, post-, and extra-synaptic), including mitochondrial dysfunction, oxidative stress, altered monoaminergic and glutamatergic systems, lower neurotrophic factor levels, and changes in immune-inflammatory systems. The field has thus moved toward identifying more precise neurobiological targets that, in turn, may help develop personalized approaches and more reliable biomarkers for treatment prediction. Diverse pharmacological and non-pharmacological approaches targeting neurobiological pathways other than neurotransmission have also been tested in mood disorders. This article reviews different neurobiological targets and pathophysiological findings in non-canonical pathways in BD that may offer opportunities to support drug development and identify new, clinically relevant biological mechanisms. These include: neuroinflammation; mitochondrial function; calcium channels; oxidative stress; the glycogen synthase kinase-3 (GSK3) pathway; protein kinase C (PKC); brain-derived neurotrophic factor (BDNF); histone deacetylase (HDAC); and the purinergic signaling pathway.
PubMed: 37592949
DOI: 10.3389/fnins.2023.1228455 -
Trends in Cognitive Sciences Jun 2024Anhedonia is a reduction in enjoyment, motivation, or interest. It is common across mental health disorders and a harbinger of poor treatment outcomes. The enjoyment... (Review)
Review
Anhedonia is a reduction in enjoyment, motivation, or interest. It is common across mental health disorders and a harbinger of poor treatment outcomes. The enjoyment aspect, termed 'consummatory anhedonia', in particular poses fundamental questions about how the brain constructs rewards: what processes determine how intensely a reward is experienced? Here, we outline limitations of existing computational conceptualisations of consummatory anhedonia. We then suggest a richer reinforcement learning (RL) account of consummatory anhedonia with a reconceptualisation of subjective hedonic experience in terms of goal progress. This accounts qualitatively for the impact of stress, dysfunctional cognitions, and maladaptive beliefs on hedonic experience. The model also offers new views on the treatments for anhedonia.
Topics: Humans; Anhedonia; Reward; Reinforcement, Psychology; Models, Psychological; Brain; Motivation
PubMed: 38423829
DOI: 10.1016/j.tics.2024.01.006 -
Nutrients Jun 2024: Emerging evidence suggests that essential trace elements, including iodine, play a vital role in depressive disorders. This study investigated whether prenatal dietary...
: Emerging evidence suggests that essential trace elements, including iodine, play a vital role in depressive disorders. This study investigated whether prenatal dietary iodine intake alone and in combination with supplemental iodine intake during pregnancy were associated with antepartum and postpartum depressive and anhedonia symptoms. : The study population included 837 mothers in the PRogramming of Intergenerational Stress Mechanisms (PRISM) study. The modified BLOCK food frequency questionnaire was used to estimate prenatal dietary and supplemental iodine intake, while the 10-item Edinburg Postpartum Depression Scale (EPDS) ascertained depressive symptoms. Analyses considered the global EPDS score and the anhedonia and depressive symptom subscale scores using dichotomized cutoffs. Logistic regression estimating odds ratios and 95% confidence intervals (CIs) assessed associations of iodine intake in the second trimester of pregnancy and 6-month postpartum depressive and anhedonia symptoms considering dietary intake alone and combined dietary and supplementary intake in separate models. : Most women were Black/Hispanic Black (43%) and non-Black Hispanics (35%), with 39% reporting a high school education or less. The median (interquartile range, IQR) dietary and supplemental iodine intake among Black/Hispanic Black (198 (115, 337) µg/day) and non-Black Hispanic women (195 (126, 323) µg/day) was higher than the overall median intake level of 187 (116, 315) µg/day. Relative to the Institute of Medicine recommended iodine intake level of 160-220 µg/day, women with intake levels < 100 µg/day, 100-<160 µg/day, >220-<400 µg/day and ≥400 µg/day had increased adjusted odds of 6-month postpartum anhedonia symptoms (aOR = 1.74 (95% CI: 1.08, 2.79), 1.25 (95% CI: 0.80, 1.99), 1.31 (95% CI: 0.82, 2.10), and 1.47 (95% CI: 0.86, 2.51), respectively). The corresponding estimates for postpartum global depressive symptoms were similar but of smaller magnitude. Prenatal iodine intake, whether below or above the recommended levels for pregnant women, was most strongly associated with greater anhedonia symptoms, particularly in the 6-month postpartum period. Further studies are warranted to corroborate these findings, as dietary and supplemental iodine intake are amenable to intervention.
Topics: Humans; Female; Pregnancy; Adult; Anhedonia; Depression, Postpartum; Iodine; United States; Cohort Studies; Dietary Supplements; Young Adult; Diet; Hispanic or Latino; Maternal Nutritional Physiological Phenomena; Black or African American; Prenatal Nutritional Physiological Phenomena
PubMed: 38892704
DOI: 10.3390/nu16111771 -
Biomolecules Dec 2023The role of altered brain mitochondrial regulation in psychiatric pathologies, including Major Depressive Disorder (MDD), has attracted increasing attention. Aberrant...
The role of altered brain mitochondrial regulation in psychiatric pathologies, including Major Depressive Disorder (MDD), has attracted increasing attention. Aberrant mitochondrial functions were suggested to underlie distinct inter-individual vulnerability to stress-related MDD syndrome. In this context, insulin receptor sensitizers (IRSs) that regulate brain metabolism have become a focus of recent research, as their use in pre-clinical studies can help to elucidate the role of mitochondrial dynamics in this disorder and contribute to the development of new antidepressant treatment. Here, following 2-week chronic mild stress (CMS) using predation, social defeat, and restraint, MDD-related behaviour and brain molecular markers have been investigated along with the hippocampus-dependent performance and emotionality in mice that received the IRS dicholine succinate (DS). In a sucrose test, mice were studied for the key feature of MDD, a decreased sensitivity to reward, called anhedonia. Based on this test, animals were assigned to anhedonic and resilient-to-stress-induced-anhedonia groups, using a previously established criterion of a decrease in sucrose preference below 65%. Such assignment was based on the fact that none of control, non-stressed animals displayed sucrose preference that would be smaller than this value. DS-treated stressed mice displayed ameliorated behaviours in a battery of assays: sucrose preference, coat state, the Y-maze, the marble test, tail suspension, and nest building. CMS-vulnerable mice exhibited overexpression of the inflammatory markers , , and , as well as and -R, in various brain regions. The alterations in hippocampal gene expression were the closest to clinical findings and were studied further. DS-treated, stressed mice showed normalised hippocampal expression of the plasticity markers , , , , , , and . DS-treated and non-treated stressed mice who were resilient or vulnerable to anhedonia were compared for hippocampal mitochondrial pathway regulation using Illumina profiling. Resilient mice revealed overexpression of the mitochondrial complexes NADH dehydrogenase, succinate dehydrogenase, cytochrome 1, cytochrome oxidase, F-type and V-type ATPases, and inorganic pyrophosphatase, which were decreased in anhedonic mice. DS partially normalised the expression of both ATPases. We conclude that hippocampal reduction in ATP synthesis is associated with anhedonia and pro-inflammatory brain changes that are ameliorated by DS.
Topics: Mice; Animals; Depression; Anhedonia; Depressive Disorder, Major; Resilience, Psychological; Mitochondrial Dynamics; N-Methylaspartate; Hippocampus; Mice, Inbred Strains; Sucrose; Adenosine Triphosphatases; Gene Expression
PubMed: 38136653
DOI: 10.3390/biom13121782 -
Cellular and Molecular Neurobiology Jul 2023Depression is the most common mental illness characterized by anhedonia, avolition and loss of appetite and motivation. The majority of conventional antidepressants are... (Review)
Review
Depression is the most common mental illness characterized by anhedonia, avolition and loss of appetite and motivation. The majority of conventional antidepressants are monoaminergic system selective inhibitors, yet the efficacies are not sufficient. Up to 30% of depressed patients are resistant to treatment with available antidepressants, underscoring the urgent need for development of novel therapeutics to meet clinical needs. Recent years, compounds acting on the glutamate system have attracted wide attention because of their strong, rapid and sustained antidepressant effects. Among them, selective inhibitors of metabotropic glutamate receptors 2 and 3 (mGluR2/3) have shown robust antidepressant benefits with fewer side-effects in both preclinical and clinical studies. Thus, we here attempt to summarize the antidepressant effects and underlying mechanisms of these inhibitors revealed in recent years as well as analyze the potential value of mGluR2/3 selective inhibitors in the treatment of depression.
Topics: Humans; Antidepressive Agents; Mental Disorders
PubMed: 36443586
DOI: 10.1007/s10571-022-01310-8 -
BioRxiv : the Preprint Server For... Sep 2023Spatially heterogeneous synapse loss is a characteristic of many psychiatric and neurological disorders, but the underlying mechanisms are unclear. Here, we show that...
Spatially heterogeneous synapse loss is a characteristic of many psychiatric and neurological disorders, but the underlying mechanisms are unclear. Here, we show that spatially-restricted complement activation mediates stress-induced heterogeneous microglia activation and synapse loss localized to the upper layers of the mouse medial prefrontal cortex (mPFC). Single cell RNA sequencing also reveals a stress-associated microglia state marked by high expression of the apolipoprotein E gene (ApoE ) localized to the upper layers of the mPFC. Mice lacking complement component C3 are protected from stress-induced layer-specific synapse loss, and the ApoE microglia population is markedly reduced in the mPFC of these mice. Furthermore, C3 knockout mice are also resilient to stress-induced anhedonia and working memory behavioral deficits. Our findings suggest that region-specific complement and microglia activation can contribute to the disease-specific spatially restricted patterns of synapse loss and clinical symptoms found in many brain diseases.
PubMed: 37425856
DOI: 10.1101/2023.06.28.546889 -
Journal of Personality Oct 2023Social anhedonia is associated with disinterest in social interactions and poor relationship functioning, yet little is known about the specific mechanisms underlying...
OBJECTIVE
Social anhedonia is associated with disinterest in social interactions and poor relationship functioning, yet little is known about the specific mechanisms underlying associations between social anhedonia and romantic relationship behaviors and satisfaction. We examined the links between social anhedonia, perceptions of conflict communication patterns, and marital satisfaction.
METHOD
The current research examined the role of social anhedonia on marital quality and functioning longitudinally across a year in a sample of 100 newlywed couples using an actor-partner interdependence framework.
RESULTS
Social anhedonia was negatively associated with own and partner's marital satisfaction. It was also negatively associated with constructive communication and positively associated with destructive communication. Furthermore, cross-sectional mediation analyses showed that communication patterns mediated the social anhedonia-satisfaction link.
CONCLUSIONS
Taken together, these findings suggest that social anhedonia is likely to lead to lower marital satisfaction, partly through its effect on communication between partners.
Topics: Humans; Interpersonal Relations; Anhedonia; Cross-Sectional Studies; Marriage; Communication; Personal Satisfaction; Spouses
PubMed: 36477834
DOI: 10.1111/jopy.12798