Anhedonia In Major Depressive Disorder Research Articles

Behavioral anhedonia in Major Depressive Disorder (MDD)

Introduction: Depression is a major public health problem, with existing pharmacological and non-pharmacological treatments not equally effective in all patients. The complex etiology and pathogenesis of depression pose a challenge that requires different approach strategies to effectively alleviate this mental symptom. Anhedonia, or loss of interest and pleasure in commonly enjoyed activities, is one of the main diagnostic criteria for depressive disorders in the psychiatric diagnostic systems of the Diagnostic Statistical Manual (DSM) and International Statistical Classification of Diseases (ICD). Major depressive disorder indicates a depressive condition that does not solely rely on reports of sad mood but the presence of anhedonia behavior. The review of these studies aims to determine changes in anhedonia behavior in depressive disorders. Methods: This research review was prepared using the literature review method by collecting valid scientific literature, namely Google Scholar, PubMed and Scientific Direct. Discussion: Anhedonia behavior is related to several factors, including social interaction is the most complex and ambiguous human environment. Hence the existence of rules that are fraught with misunderstandings. It requires complex examination to determine exactly what the rewarding components of social interaction are.

Association of anhedonia with brain-derived neurotrophic factor and interleukin-10 in major depressive disorder

BackgroundAnhedonia, a core symptom of major depressive disorder (MDD), manifests in two forms: anticipatory and consummatory, reflecting a diminished capacity to anticipate or enjoy pleasurable activities. Prior studies suggest that brain-derived neurotrophic factor (BDNF) and interleukin-10 (IL-10) may play key roles in the emergence of anhedonia in MDD. The specific relationships between these biomarkers and the two forms of anhedonia remain unclear. This study investigated the potential links between BDNF, IL-10, and both forms of anhedonia in MDD patients. MethodsThis study included 43 participants diagnosed with MDD and 58 healthy controls. It involved detailed assessments of depression and anxiety levels, anticipatory and consummatory pleasure, cognitive functions, and a broad spectrum of plasma biomarkers, such as C-reactive protein, various interleukins, and BDNF. Using partial correlation, variables related to pleasant experiences were identified. Stepwise multiple linear regression analysis was applied to pinpoint the independent predictors of anhedonia in the MDD group. ResultsDemographically, both groups were comparable in terms of age, sex, body mass index, educational year, and marital status. Individuals with MDD displayed markedly reduced levels of anticipatory and consummatory pleasure, higher anxiety, and depression scores compared to healthy controls. Additionally, cognitive performance was notably poorer in the MDD group. These patients also had lower plasma diamine oxidase levels. Analysis linked anhedonia to impaired delayed memory. Regression results identified IL-10 and BDNF as independent predictors of anticipatory and consummatory anhedonia, respectively. ConclusionThese findings demonstrate that anticipatory and consummatory anhedonia are influenced by independent factors, thereby providing critical insights into the distinct neuroimmunological mechanisms that underlie various forms of anhedonia.Clinicl Trial Registration Number: NCT03790085

259. Nucleus Accumbens and Global Cortical Connectivity May be Important Neural Correlates of Anhedonia in Major Depressive Disorder

259. Nucleus Accumbens and Global Cortical Connectivity May be Important Neural Correlates of Anhedonia in Major Depressive Disorder

A Delphi consensus on clinical features, diagnosis and treatment of major depressive disorder patients with anhedonia amongst psychiatrists in the Asia-Pacific.

Anhedonia, a core diagnostic feature for major depressive disorder (MDD), is defined as the loss of pleasure and interest in daily activities. Its prevalence in MDD patients vary from 35 to 70%. Anhedonia in MDD negatively impacts functioning and is associated with treatment resistance and poorer prognosis for various clinical outcomes. Owing to its complexity, there remains considerable heterogeneity in the conceptualization, diagnosis and clinical management of anhedonia in MDD. This modified Delphi panel was conducted to elicit expert opinion and establish consensus on concepts relating to clinical features, diagnosis and treatment of MDD with anhedonia (MDDwA) amongst psychiatrists in the Asia-Pacific region. Seven themes were covered. A three-stage process was adopted for consensus generation (two online survey rounds, followed by a moderated consensus meeting). Statements were developed based on a literature review and input from a steering committee of six regional experts. The panel included 12 psychiatrists practicing in Australia, China, Hong Kong, Japan, South Korea and Taiwan with ≥5 years of specialist clinical experience, including assessment or management of patients with MDDwA. Overall, consensus was achieved (median ≥8) on 89/103 statements (86%). About half of the statements (55/103, 53%) achieved consensus in Round 1, and 29/36 modified statements achieved consensus in Round 2. At the moderated consensus meeting, five modified statements were discussed by the steering committee and consensus was achieved on all statements (5/5). The findings highlighted a lack of clear and practical methods in clinical practice for assessing anhedonia in MDD patients and limited physician awareness of anhedonia in Asia-Pacific. Insights from this Delphi consensus provide a reference point for psychiatrists in Asia-Pacific to optimize their strategies for personalized diagnosis and management of patients with MDDwA. Identification of distinct and clinically relevant subtypes in MDD may be valuable for guiding personalized diagnosis and management approaches, including type-specific therapies.

Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study

BackgroundSocial 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. Methods85 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. ResultsA 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. ConclusionsBased 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.

Uncovering the Neural Correlates of Anhedonia Subtypes in Major Depressive Disorder: Implications for Intervention Strategies.

Major depressive disorder (MDD) represents a serious public health concern, negatively affecting individuals' quality of life and making a substantial contribution to the global burden of disease. Anhedonia is a core symptom of MDD and is associated with poor treatment outcomes. Variability in anhedonia components within MDD has been observed, suggesting heterogeneity in psychopathology across subgroups. However, little is known about anhedonia subgroups in MDD and their underlying neural correlates across subgroups. To address this question, we employed a hierarchical cluster analysis based on Temporal Experience of Pleasure Scale subscales in 60 first-episode, drug-naive MDD patients and 32 healthy controls. Then we conducted a connectome-wide association study and whole-brain voxel-wise functional analyses for identified subgroups. There were three main findings: (1) three subgroups with different anhedonia profiles were identified using a data mining approach; (2) several parts of the reward network (especially pallidum and dorsal striatum) were associated with anticipatory and consummatory pleasure; (3) different patterns of within- and between-network connectivity contributed to the disparities of anhedonia profiles across three MDD subgroups. Here, we show that anhedonia in MDD is not uniform and can be categorized into distinct subgroups, and our research contributes to the understanding of neural underpinnings, offering potential treatment directions. This work emphasizes the need for tailored approaches in the complex landscape of MDD. The identification of homogeneous, stable, and neurobiologically valid MDD subtypes could significantly enhance our comprehension and management of this multifaceted condition.

Volume changes of the subcortical limbic structures in major depressive disorder patients with and without anhedonia

Anhedonia is a core feature of major depressive disorder (MDD) and the limbic system has been indicated to be associated with anhedonia in MDD due to its crucial role within the reward circuit. However, the relationship between different regions of the limbic system and MDD, particularly anhedonic symptoms, remains unclear. Therefore, the purpose of this study was to investigate volume changes of various parts of the subcortical limbic (ScLimbic) system in MDD with and without anhedonia. A total of 120 individuals, including 30 MDD patients with anhedonia, 43 MDD patients without anhedonia, and 47 healthy controls (HCs) were enrolled in this study. All subjects underwent structural magnetic resonance imaging scans. After that, ScLimbic system segmentation was performed using the FreeSurfer pipeline ScLimbic. Analysis of covariance (ANCOVA) was performed to identify brain regions with significant volume differences among three groups, and then, post hoc tests were calculated for inter-group comparisons. Finally, correlations between volumes of different parts of the ScLimbic and clinical characteristics in MDD patients were further analyzed. The ANCOVA revealed significant volume differences of the ScLimbic system among three groups in the bilateral fornix (Fx), and the right basal forebrain (BF). As compared with HCs, both groups of MDD patients showed decreased volume in the right Fx, meanwhile, MDD patients with anhedonia further exhibited volume reductions in the left Fx and right BF. However, no significant difference was found between MDD patients with and without anhedonia. No significant association was observed between subregion volumes of the ScLimbic system and clinical features in MDD. The present findings demonstrated that MDD patients with and without anhedonia exhibited segregated brain structural alterations in the ScLimbic system and volume loss of the ScLimbic system might be fairly extensive in MDD patients with anhedonia.

Neural Correlates of Anhedonia in Major Depressive Disorder: Insights from Concurrent Analysis of Feedback-Related Negativity and Stimulus-Preceding Negativity.

Anhedonia, a core symptom of major depressive disorder (MDD), is explored in this study, focusing on the neural underpinnings through the examination of two event-related potential (ERP) components: feedback-related negativity (FRN) and stimulus-preceding negativity (SPN). This cross-sectional study was conducted in China from March 2022 to March 2023. It involved 35 MDD patients and 31 healthy controls (HC) participating in a modified 2-door task with simultaneous EEG recordings. Depression severity and anhedonia were assessed using the Hamilton Depression Scale (HAMD) and the Temporal Experience of Pleasure Scale (TEPS-CV), respectively. FRN and SPN metrics, along with correlations with each other and clinical assessments, were examined. In comparison to the HC group, the MDD group exhibited significantly lower scores in TEPS-CV (t = 2.854, p = 0.006) and its subscales (t = -3.596, p = 0.001 and t = 2.434, p = 0.018, respectively), along with consistently reduced amplitudes of FRN (F 1.64= 4.726, p = 0.033) and SPN (F 1.64= 4.195, p = 0.045) across all conditions. Limited correlations were observed between ERP metrics and clinical indicators, except for positive correlations between FRN amplitudes (loss minus win) and HAMD scores (r = 0.392, p = 0.020), and SPN amplitudes after losing (SPN-L) and TEPS-CV consumption subscale scores (r = 0.357, p = 0.035). Notably, while the HC group displayed no significant FRN-SPN correlations, the MDD group exhibited positive FRN-SPN correlations under distinct conditions (r = 0.376, p = 0.026 and r = 0.355, p = 0.037, respectively). Our data reveal subjective and objective anhedonia in both consumption and anticipation, suggesting a shared impairment in reward feedback processing and anticipatory neural mechanisms in individuals with MDD. These findings deepen our understanding of anhedonia's neural foundations and may guide targeted interventions for this core symptom.

The sex differences in anhedonia in major depressive disorder: A resting-state fMRI study

ObjectiveThe 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). MethodThe 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. ResultsFor 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. ConclusionOur 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.

Altered hippocampal subfield volumes in major depressive disorder with and without anhedonia

BackgroundPrevious neuroimaging findings have demonstrated the association between anhedonia and the hippocampus. However, few studies have focused on the structural changes in the hippocampus in major depressive disorder (MDD) patients with anhedonia. Meanwhile, considering that multiple and functionally specialized subfields of the hippocampus have their own signatures, the present study aimed to investigate the volumetric alterations of the hippocampus as well as its subfields in MDD patients with and without anhedonia.MethodsA total of 113 subjects, including 30 MDD patients with anhedonia, 40 MDD patients without anhedonia, and 43 healthy controls (HCs), were recruited in the study. All participants underwent high-resolution brain magnetic resonance imaging (MRI) scans, and the automated hippocampal substructure module in FreeSurfer 6.0 was used to evaluate the volumes of hippocampal subfields. We compared the volumetric differences in hippocampal subfields among the three groups by analysis of variance (ANOVA, post hoc Bonferroni), and partial correlation was used to explore the association between hippocampal subregion volumes and clinical characteristics.ResultsANOVA showed significant volumetric differences in the hippocampal subfields among the three groups in the left hippocampus head, mainly in the cornu ammonis (CA) 1, granule cell layer of the dentate gyrus (GC-ML-DG), and molecular layer (ML). Compared with HCs, both groups of MDD patients showed significantly smaller volumes in the whole left hippocampus head. Interestingly, further exploration revealed that only MDD patients with anhedonia had significantly reduced volumes in the left CA1, GC-ML-DG and ML when compared with HCs. No significant difference was found in the volumes of the hippocampal subfields between MDD patients without anhedonia and HCs, either the two groups of MDD patients. However, no association between hippocampal subfield volumes and clinical characteristics was found in either the subset of patients with anhedonia or in the patient group as a whole.ConclusionsThese preliminary findings suggest that MDD patients with anhedonia exhibit unique atrophy of the hippocampus and that subfield abnormalities in the left CA1 and DG might be associated with anhedonia in MDD.

Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H.

Anhedonia is a trans-diagnostic symptom in schizophrenia and MDD. Our recent work indicated that increased plasma level of complement factor H (CFH) is associated with anhedonia in major depressive disorder. This study hypothesized that CFH is likely to be a biomarker of anhedonia in schizophrenia. A 12-week prospective study is performed to observe the effects of olanzapine on anhedonia and CFH. We used the Chinese version of Snaith-Hamilton Pleasure Scale (SHAPS) to evaluate anhedonic phenotype in patients with schizophrenia. Plasma levels of C-reactive protein (CRP), C3, C4 and CFH were measured. Of the recruited 152 samples, patients with anhedonia were found in 99/152 (65.13%). Patients with anhedonia had notably higher PANSS negative subscores, SHAPS total score and higher level of plasma CFH than those without anhedonia (Ps<0.05). Stepwise multivariate linear regression analysis showed that increasing level of plasma CFH was a risk factor for SHAPS total score (β = 0.18, p = 0.03). Of the 99 patients with anhedonia, 74 completed the 12-week follow-up. We observed significantly reduced scores of PANSS, SHAPS and decreased plasma CFH level, when the patients completed this study. The change of SHAPS total score is positively correlated with the level of CFH decrease (p = 0.02). Our results implied that plasma CFH levels may be a biomarker for anhedonia in schizophrenia, and the effect of olanzapine on treating anhedonia is through decreasing plasma CFH levels.

Sexual health and serotonin 4 receptor brain binding in unmedicated patients with depression—a NeuroPharm study

Sexual dysfunction is prominent in Major Depressive Disorder (MDD) and affects women with depression more than men. Patients with MDD relative to healthy controls have lower brain levels of the serotonin 4 receptor (5-HT4R), which is expressed with high density in the striatum, i.e. a key hub of the reward system. Reduced sexual desire is putatively related to disturbed reward processing and may index anhedonia in MDD. Here, we aim to illuminate plausible underlying neurobiology of sexual dysfunction in unmedicated patients with MDD. We map associations between 5-HT4R binding, as imaged with [11C]SB207145 PET, in the striatum, and self-reported sexual function. We also evaluate if pre-treatment sexual desire score predicts 8-week treatment outcome in women. From the NeuroPharm study, we include 85 untreated MDD patients (71% women) who underwent eight weeks of antidepressant drug treatment. In the mixed sex group, we find no difference in 5-HT4R binding between patients with sexual dysfunction vs normal sexual function. However, in women we find lower 5-HT4R binding in the sexual dysfunctional group compared to women with normal sexual function (β = −0.36, 95%CI[−0.62:−0.09], p = 0.009) as well as a positive association between sexual desire and 5-HT4R binding (β = 0.07, 95%CI [0.02:0.13], p = 0.012). Sexual desire at baseline do not predict treatment outcome (ROC curve AUC = 52%[36%:67%]) in women. Taken together, we find evidence for a positive association between sexual desire and striatal 5-HT4R availability in women with depression. Interestingly, this raises the question if direct 5-HT4R agonism can target reduced sexual desire or anhedonia in MDD.

Reward processing in adolescents with social phobia and depression

ObjectiveImpaired reward processing has been found in individuals with anxiety, but also major depressive disorder (MDD). Here, we studied neural correlates of reward anticipation and processing in a sample of youth with severe social phobia and comorbid depression (SP/MDD) and investigated the specific contribution of SP and MDD symptoms. Methods15 affected, unmedicated and 25 typically developing (TD) youth completed a monetary gambling task, which included a positive, negative and ambiguous reward condition. Event-related potentials representing cue processing (cue P300), reward anticipation (stimulus preceding negativity, SPN), reward sensitivity (feedback related negativity, FRN) and reward processing (reward P300) were analysed. ResultsReduced amplitudes of the right hemispheric (r)SPN and reward P300 were observed in SP/MDD compared to TD. Within the SP/MDD group SP symptoms correlated with larger rSPN, and FRN amplitudes. MDD symptoms correlated with smaller rSPN and smaller FRN positive–negative difference wave. ConclusionsReward anticipation and feedback processing are reduced in SP/MDD. Higher SP symptoms are associated with stronger neural activation during reward anticipation and reward sensitivity. Depressive symptoms are associated with decreased reward anticipation and sensitivity. Findings are in line with the theory of heightened vigilance in anxiety and blunted reward processing due to anhedonia in MDD. SignificanceThe study results can inform behavioural interventions for SP and MDD.

Right amygdala-right precuneus connectivity is associated with childhood trauma in major depression patients and healthy controls.

The present study investigated the effect of childhood trauma (CT) on amygdala and hippocampus functional connectivity (FC) and the association with clinical presentations of major depressive disorder (MDD). Participants included 73 MDD patients (42 with moderate-to-severe CT and 31 with no or low CT) and 64 healthy controls (HC; 30 with moderate-to-severe CT and 34 with no or low CT). Seed-based whole-brain resting-state FC analyses were performed with seeds located in amygdala and hippocampus. Individuals with moderate-to-severe CT, irrespective of MDD diagnosis, had decreased right amygdala-right precuneus connectivity compared to those with no or low CT. Right amygdala-right precuneus connectivity was significantly correlated with physical and social trait anhedonia in MDD. Mediation effects of this FC on relationship between CT (specifically neglect but not abuse) and trait anhedonia in MDD were significant. MDD patients demonstrated increased right amygdala-left middle frontal gyrus FC, decreased right amygdala-right medial superior frontal gyrus (mSFG) FC and decreased right hippocampus-bilateral mSFG FC relative to HC. Findings highlight the effect of CT on right amygdala-right precuneus FC irrespective of MDD diagnosis. FC of right amygdala-right precuneus may be involved in the mechanism linking CT and depression through its association with trait anhedonia.

Aberrant interhemispheric functional connectivity in major depressive disorder with and without anhedonia

ObjectiveAnhedonia is a core feature of major depressive disorder (MDD), and as a subtype of depression, MDD with anhedonia may have exceptional neurobiological mechanisms. However, the neuropathology of anhedonia in MDD remains unclear. Thus, this study aimed to investigate the brain functional differences between MDD with and without anhedonia.MethodsA total of 62 individuals including 22 MDD patients with anhedonia, 20 MDD patients without anhedonia, and 20 healthy controls (HCs) were recruited for this study. All participants underwent 3.0-T functional magnetic resonance imaging scan. Voxel-mirrored homotopic connectivity (VMHC) was employed to quantitatively describe bilateral functional connectivity. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons.ResultsThe ANOVA revealed significant VMHC differences among three groups in the bilateral middle temporal gyrus (MTG), superior frontal gyrus (SFG), and inferior parietal lobule (IPL) (F = 10.47 ~ 15.09, p < 0.05, AlphaSim corrected). Relative to HCs, MDD with anhedonia showed significantly decreased VMHC in the bilateral MTG (t = -5.368, p < 0.05, AlphaSim corrected), as well as increased VMHC in the bilateral SFG (t = -4.696, p < 0.05, AlphaSim corrected). Compared to MDD without anhedonia, MDD with anhedonia showed significantly decreased VMHC in the bilateral MTG and IPL (t = -5.629 ~ -4.330, p < 0.05, AlphaSim corrected), while increased VMHC in the bilateral SFG (t = 3.926, p < 0.05, AlphaSim corrected). However, no significant difference was found between MDD without anhedonia and HCs.ConclusionThe present findings suggest that MDD with and without anhedonia exhibit different patterns of interhemispheric connectivity. Anhedonia in MDD is related to aberrant interhemispheric connectivity within brain regions involved in the frontal–temporal-parietal circuit.

Reducing Anhedonia in Major Depressive Disorder with Future Event Specificity Training (FEST): A Randomized Controlled Trial

BackgroundImproving future thinking, such as characteristics of specificity, detail, and use of mental imagery, may be one means to reduce anhedonia, particularly in a Major Depressive Episode (MDE) in which future thinking is impaired. The current study aimed to test this using a validated program, Future Event Specificity Training (FEST).MethodsParticipants (N = 177; 80.8% women; M age = 43.7, SD = 11.8) with a current depressive episode with anhedonia and high symptom severity were randomized to FEST or no FEST. Future thinking, anhedonia-related variables, and other clinical outcomes were assessed at baseline, one- and three-month follow-up.ResultsRelative to the control group, FEST was associated with significantly improved future thinking characteristics, a reduced likelihood of anhedonia (35.1% vs. 61.1%, p = .015), improvements on other anhedonia-related variables such as anticipatory (d = 0.63, p = .004) and anticipated pleasure for future events (d = 0.77, p < .001), and desirable clinical outcomes such as less people meeting criteria for an MDE (37.8% vs. 64.8%, p = .011), higher behavioural activation (d = 0.71, p = .001) and improved global functioning (d = 0.52, p = .017). Changes in future thinking were found to mediate the effect of FEST on anhedonia.ConclusionThe quality of future thinking can be enhanced in Major Depression, and this leads to a substantially reduced likelihood of anhedonia, other significant clinical effects, and functional gains.

Individualized prediction of consummatory anhedonia from functional connectome in major depressive disorder.

Anhedonia is a key symptom of major depressive disorder (MDD) and other psychiatric diseases. The neural basis of anhedonia has been widely examined, yet the interindividual variability in neuroimaging biomarkers underlying individual-specific symptom severity is not well understood. To establish an individualized prediction model of anhedonia, we applied connectome-based predictive modeling (CPM) to whole-brain resting-state functional connectivity profiles of MDD patients. The CPM can successfully and reliably predict individual consummatory but not anticipatory anhedonia. The predictive model mainly included salience network (SN), frontoparietal network (FPN), default mode network (DMN), and motor network. Importantly, subsequent computational lesion prediction and consummatory-specific model prediction revealed that connectivity of the SN with DMN and FPN is essential and specific for the prediction of consummatory anhedonia. This study shows that brain functional connectivity, especially the connectivity of SN-FPN and SN-DMN, can specifically predict individualized consummatory anhedonia in MDD. These findings suggest the potential of functional connectomes for the diagnosis and prognosis of anhedonia in MDD and other disorders.

Reduced Sulcal Depth in Central Sulcus of Major Depressive Disorder.

Major depressive disorder (MDD) is one of the most common psychiatric disorders, and present various symptoms such as the dysregulation of mood, cognition, and behavior. The purpose of the present study was to investigate the morphometric change in MDD patients by voxel-based morphometry (VBM) and sulcal depth analyses. Forty-six MDD patients (mean age, SD; 36.07±14.34), and 23 age- and sex-matched normal controls (NML) (mean age, SD; 36.78±14.42) were included. Coronal 3D T1 magnetic resonance imaging (MRI) was obtained with the resolution of isotropic 1.0 mm. To check morphological changes of brain, T1 MRIs were objectively processed by VBM and sulcal depth methods. In sulcal depth analysis, depressed patients showed reduced sulcal depth in the areas of left posterior ramus of the lateral sulcus, superior frontal sulcus, supramarginal gyrus, central sulcus (Rolando's fissure), and Heschl's gyrus. And right posterior ramus of the lateral sulcus, temporal plane of the superior temporal gyrus, anterior transverse collateral sulcus, and central sulcus (Rolando's fissure) were also reduced compared to NML. But, VBM analyses did not showed significant finding. Reduced sulcal depth in the motor and emotion related areas were found in patients with MDD. Especially reduced sulcal depth in bilateral central sulci which are connecting between primary motor cortex and primary sensory cortex seems to be related with social and physical anhedonia in MDD.

Changes of anhedonia and cognitive symptoms in first episode of depression and recurrent depression, an analysis of data from NSSD

BackgroundAnhedonia and cognitive impairment are core features of major depressive disorder (MDD), and are essential to the treatment and prognosis. Here, we aimed to investigate anhedonia and its cognitive correlates between first episode of depression (FED) and recurrent depression (RD), which was part of the National Survey on Symptomatology of Depression. MethodsIn this study, 1400 drug naïve FED patients and 487 on medicine RD patients were included. Differences of anhedonia, cognitive symptoms and other clinical characteristics between groups were compared via Student's t-test, or the chi-square test as appropriate. Partial correlation analysis was used to analyze the correlations between anhedonia and cognitive symptoms after adjusting for potential confounders. A stepwise logistic regression analysis was performed to identify relapse risk factors among symptomatic variables, demographic factors, clinical characteristics and medication use. ResultsCompared to FED, RD patients displayed more comprehensive depressive, impaired cognitive and anhedonia symptoms. Cognitive symptoms were significantly related with the anhedonia symptoms with varying aspects. Patients taking emotional stabilizers displayed more abnormal cognitive symptoms, followed by benzodiazepines, and finally SSRIs, SNRIs and TCAs. The effect of drug use on anhedonia is not as extensive as that of cognitive symptoms. ConclusionCollectively, the results of this investigation advance the knowledge on changes in anhedonia and cognitive symptoms in MDD. LimitationsAs this is a cross sectional study, it is difficult to draw any causal conclusions between cognitive impairment and anhedonia in MDD, and to ascertain the worse cognitive performances identified here were induced by current drug use.

Combined serum IL-6, C-reactive protein, and cortisol may distinguish patients with anhedonia in major depressive disorder.

Neuroinflammation and anhedonia in major depressive disorder (MDD) are closely connected, though the exact mechanism is unclear. This study aimed to investigate the relationships between cytokines, C-reactive protein (CRP), cortisol, and anhedonia, revealing the potential predictive value in identifying anhedonic MDD. In total, 66 patients with MDD (29 with anhedonia and 37 without anhedonia) and 66 healthy controls (HCs) were included. The severity of depression and anhedonia was evaluated using the Hamilton Rating Scale for Depression-24 (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS), respectively. Serum cytokines were measured using flow cytofluorometric kits, while CRP and cortisol were measured using enzyme-linked immunosorbent assay kits. We found higher serum levels of interleukin-2 (IL-2), IL-6, and cortisol in MDD than in HC where anhedonic MDD was highest. CRP and IL-6 were positively associated with anhedonia, and cortisol levels were related to both anhedonia and depression. A combination of IL-6, CRP, and cortisol had optimal predictive value for distinguishing anhedonic MDD. Anhedonic MDD has unique neuroendocrine-immune characteristics compared with those without anhedonia. The combination of IL-6, CRP, and cortisol might be an early marker to distinguish anhedonic MDD.