Anhedonia Group Research Articles

Anhedonia as a Potential Transdiagnostic Phenotype With Immune-Related Changes in Recent-Onset Mental Health Disorders

BackgroundChronic low-grade inflammation is observed across mental disorders and is associated with difficult-to-treat-symptoms of anhedonia and functional brain changes, reflecting a potential transdiagnostic dimension. Previous investigations have focused on distinct illness categories in people with enduring illness, but few have explored inflammatory changes. We sought to identify an inflammatory signal and the associated brain function underlying anhedonia among young people with recent-onset psychosis and recent-onset depression. MethodsResting-state functional magnetic resonance imaging, inflammatory markers, and anhedonia symptoms were collected from 108 (mean [SD] age = 26.2 [6.2] years; female = 50) participants with recent-onset psychosis (n = 53) and recent-onset depression (n = 55) from the European Union/Seventh Framework Programme–funded PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Time series were extracted using the Schaefer atlas, defining 100 cortical regions of interest. Using advanced multimodal machine learning, an inflammatory marker model and a functional connectivity model were developed to classify participants into an anhedonic group or a normal hedonic group. ResultsA repeated nested cross-validation model using inflammatory markers classified normal hedonic and anhedonic recent-onset psychosis/recent-onset depression groups with a balanced accuracy of 63.9% and an area under the curve of 0.61. The functional connectivity model produced a balanced accuracy of 55.2% and an area under the curve of 0.57. Anhedonic group assignment was driven by higher levels of interleukin 6, S100B, and interleukin 1 receptor antagonist and lower levels of interferon gamma, in addition to connectivity within the precuneus and posterior cingulate. ConclusionsWe identified a potential transdiagnostic anhedonic subtype that was accounted for by an inflammatory profile and functional connectivity. Results have implications for anhedonia as an emerging transdiagnostic target across emerging mental disorders.

Sex-specific immune-inflammatory markers and lipoprotein profile in patients with anhedonia with unipolar and bipolar depression

BackgroundAnhedonia is a core symptom in patients with unipolar and bipolar depression. However, sex-specific markers reflecting biological heterogeneity are lacking. Emerging evidence suggests that sex differences in immune-inflammatory markers and lipoprotein profiles are associated with anhedonia.MethodsThe demographic and clinical data, immune-inflammatory markers (CD3, CD4, and CD8), and lipoprotein profiles [TC, TG, LDL-C, HDL-C, lipoprotein(a) Lp (a)] of 227 patients with unipolar and bipolar depression were collected. The Hamilton Depression Rating Scale (HAMD) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess depression and anhedonia symptoms. Data were analyzed using ANOVA, logistic regression, and receiver operating characteristic curves.ResultsMale patients in the anhedonia group had higher levels of CD3, CD4, and CD8, and lower levels of Lp (a) than the non-anhedonia group, while no significant difference was identified in female patients with and without anhedonia. Logistic regression analysis showed that CD3, CD4, CD8, and Lp (a) levels were associated with anhedonia in male patients. Furthermore, the combination of CD3, CD4, CD8, and Lp (a) had the strongest predictive value for distinguishing anhedonia in male patients than individual parameters.ConclusionsWe identified sex-specific associations between immune-inflammatory markers, lipoprotein profiles, and anhedonia in patients with unipolar and bipolar depression. The combination of CD3, CD4, CD8, and Lp (a) might be a possible biomarker for identifying anhedonia in male patients with unipolar and bipolar depression.

Dysfunction of visual novelty detection in physical but not social anhedonia in a non-clinical sample

Background/objectiveDespite its obvious motivational impairment, anhedonia as a transdiagnostic psychopathological construct is accompanied by deficits in attention function. Previous studies have identified voluntary attention anomalies in anhedonia, but its involuntary attention has received less study. MethodUsing a visual novelty oddball task, the current event-related potential study assessed electrophysical correlates underlying mismatch detection in anhedonia with a non-clinical sample. Well-matched healthy control (N = 28; CNT), social anhedonia (N = 27; SA), and physical anhedonia (N = 26; PA) groups were presented standard, target, and perceptually novel stimuli while their EEG was recording. ResultsThe PA group relative to the CNT group exhibited a reduced N2 to novel stimuli but not to target stimuli. In contrast, the SA group as compared to the other two groups showed comparable N2 responses to both target and novel stimuli. Control analyses indicated that these patterns were unaffected by depression symptoms. ConclusionsThese findings suggest that anhedonia is a heterogenous construct associated with impairments in early detection of visual novelty in physical but not social anhedonia, highlighting that dysfunction in involuntary attention may play a mediating role in the development, maintenance, and consequences of anhedonia-related psychopathology.

Subgroups of depressive symptoms in Korean police officers: A latent class analysis

The prevalence of depressive symptoms is common among police officers; however, studies that identify the patterns of depressive symptoms in police officers and occupational characteristics related to the specific subgroups of depressive symptoms are scarce. A total of 493 police officers in South Korea participated in this descriptive cross-sectional study between October and December 2019. Depressive symptoms were measured using the Patient Health Questionnaire-9. Latent class analysis was used to identify the subgroups of depressive symptoms. To identify the characteristics and predictors of the subgroup, χ2 tests, analysis of variance, and multinomial logistic regression analysis were performed. Four latent classes of depressive symptoms were identified: “at-risk” (10.8%), “anhedonic” (21.5%), “somatic” (17.2%), and “minimal” (50.5%). Compared to the minimal group, drinking behaviors were higher in the at-risk group (odds ratio [OR] = 1.10, 95% confidence interval [CI] [1.03, 1.11]), and working hours were greater in the somatic group (OR = 1.01, 95% CI [1.00, 1.02]). Additionally, sleep quality (OR = 1.35, 95% CI [0.82, 2.22]) and fatigue (OR = 1.02, 95% CI [1.00, 1.04]) were found to be related in the anhedonic group. This study identified the heterogeneity of depressive symptoms among police officers. It is necessary to accurately identify the factors associated with the depression subgroups of police officers to develop support strategies and prevent an increase in their depression severity. The association between risk factors such as working hours and drinking behaviors might inform strategies to reduce depression in police offers.

Striatal dopamine in anhedonia: A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation

BackgroundAnhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample. MethodsParticipants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [11C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors. ResultsRelative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC. ConclusionsResults provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.

Objective measures of reward sensitivity and motivation in people with high v. low anhedonia.

Anhedonia - a diminished interest or pleasure in activities - is a core self-reported symptom of depression which is poorly understood and often resistant to conventional antidepressants. This symptom may occur due to dysfunction in one or more sub-components of reward processing: motivation, consummatory experience and/or learning. However, the precise impairments remain elusive. Dissociating these components (ideally, using cross-species measures) and relating them to the subjective experience of anhedonia is critical as it may benefit fundamental biology research and novel drug development. Using a battery of behavioural tasks based on rodent assays, we examined reward motivation (Joystick-Operated Runway Task, JORT; and Effort-Expenditure for Rewards Task, EEfRT) and reward sensitivity (Sweet Taste Test) in a non-clinical population who scored high (N = 32) or low (N = 34) on an anhedonia questionnaire (Snaith-Hamilton Pleasure Scale). Compared to the low anhedonia group, the high anhedonia group displayed marginal impairments in effort-based decision-making (EEfRT) and reduced reward sensitivity (Sweet Taste Test). However, we found no evidence of a difference between groups in physical effort exerted for reward (JORT). Interestingly, whilst the EEfRT and Sweet Taste Test correlated with anhedonia measures, they did not correlate with each other. This poses the question of whether there are subgroups within anhedonia; however, further work is required to directly test this hypothesis. Our findings suggest that anhedonia is a heterogeneous symptom associated with impairments in reward sensitivity and effort-based decision-making.

Neural correlates of posttraumatic anhedonia symptoms: Decreased functional connectivity between ventral pallidum and default mode network regions

Anhedonia is common in individuals with traumatic experience. Anhedonia symptoms play an important role in posttraumatic psychopathology, and are related to various adverse outcomes. The current study is a preliminary neuroimaging study of the neural correlates of posttraumatic anhedonia symptoms. Resting-state fMRI data were acquired from 88 Chinese earthquake survivors. Whole brain analyses and exploratory ROI-to-ROI analyses were performed to examine the relationship between posttraumatic anhedonia symptoms and resting-state functional connectivity (rsFC) of reward-related subcortical nucleus including nucleus accumbens and ventral pallidum. The rsFC between left ventral pallidum and areas of bilateral posterior cingulate cortex (PCC) and precuneus cortex were found lower in the high posttraumatic anhedonia group, after controlling for sex, age and other posttraumatic stress symptoms. The rsFC between left ventral pallidum and PCC and the rsFC between left ventral pallidum and lateral parietal cortex were significantly lower in the high anhedonia group. Our findings suggest that decreased functional connectivity between the ventral pallidum and the brain default mode network (DMN) regions could be the neural correlates of posttraumatic anhedonia symptoms.

Severe anhedonia among adolescents with bipolar disorder is common and associated with increased psychiatric symptom burden

BackgroundAnhedonia, a deficit in the ability to experience pleasure, is a cardinal symptom of major depressive episodes. In contrast to adolescent major depressive disorder, there is limited research examining anhedonia in the context of depression among adolescents with bipolar disorder (BD). We therefore examined clinical characteristics of anhedonia in a large sample of adolescents with BD. MethodsParticipants were 197 adolescents, aged 13–20 years old, with BD type I, II or not otherwise specified. Diagnoses were determined using a semi-structured interview. Anhedonia severity was rated from one to six on the Depression Rating Scale (DRS). Adolescents were divided into “severe” and “non-severe” anhedonia groups based on the DRS item scoring. The association of anhedonia with clinical and demographic variables was evaluated in univariate analyses followed by logistic regression analyses for variables with p ≤ 0.1. ResultsThreshold anhedonia was evident among 90.9% during their most severe depressive episode. Significant factors associated with severe most severe lifetime anhedonia (“lifetime anhedonia”) included: female sex, lifetime history of self-injurious behavior, physical abuse, affective lability, higher lifetime depression severity, comorbid anxiety disorders, family history of ADHD, and second-generation antipsychotic use. In regression analyses, severe lifetime anhedonia was independently associated with female sex, comorbid anxiety disorders, most severe lifetime mania severity, and lifetime second-generation antipsychotic use. ConclusionThe vast majority of adolescents with BD experience anhedonia. More severe anhedonia is associated with indicators of greater illness severity. Future research is warranted to evaluate the neurobiological underpinnings of anhedonia among adolescents with BD.

Depressive Anhedonia and Creative Self‐concepts, Behaviors, and Achievements

AbstractIn the large literature on creativity and mental illness, relatively few studies have explored anhedonia—impairments in anticipating, seeking, and experiencing rewards. This project explored self‐reported creativity in a sample of adults who differed in depressive anhedonia, determined via face‐to‐face structured clinical interviews. Participants completed measures of everyday creativity (engaging in common creative behaviors and hobbies), creative self‐concepts (creative self‐efficacy, creative personal identity, and self‐rated creativity in different domains), and creative achievements. Compared to the control group (n = 52), people in the anhedonia group (n = 22) had significantly higher engagement in little‐c creative activities (medium effect size). Effect sizes for self‐rated creativity and creative achievement were either small or near‐zero. Taken together, the findings suggest that anhedonia deserves more attention in future research on motivational aspects of creativity.

Neural dynamics of monetary and social reward processing in social anhedonia.

Being characterized by reduced pleasure from social interaction, social anhedonia constitutes a transdiagnostic marker for various psychiatric disorders. However, the neural portrait of social anhedonia remains elusive because of heterogeneities of reward type and reward dynamics in previous studies. The present event-related potential study investigated neural dynamics in response to monetary and social rewards in social anhedonia. Event-related potential responses were examined when a high social anhedonia (HSA, N = 23) group and a low social anhedonia (LSA, N = 26) group were anticipating and consuming social and monetary rewards. LSA but not HSA participants showed an increased stimulus-preceding negativity (anticipatory phase) and and increased reward positivity (consummatory phase) for monetary as compared with social rewards. This group difference could spring from an increased relevance of social rewards or a general decline in affective responding due to a potential association between social anhedonia and depression. Our findings provide preliminary evidence for neural aberrations of the reward system in social anhedonia, which is contingent upon reward type and reward dynamics.

Impaired perceptual processing of facial expression categorization in social anhedonia.

The current event-related potential study investigated the perceptual processing of the categorization advantage of happy over sad faces in social anhedonia with a nonclinical sample. A high social anhedonia (HSA, N=25) group and a low social anhedonia (LSA, N=27) group performed a facial expression categorization task during which they classified facial expressions (happy, neutral, sad), irrespective of face orientation (upright, upside-down). Behaviorally, happy faces were identified more quickly than sad ones in the upright but not inverted orientation. Electrophysiologically, the LSA group showed earlier N170 latencies for happy than for sad faces in the upright but not upside-down orientation, whereas the HSA group did not show any expression effect on N170 latencies. Moreover, N170 and P2 amplitude results revealed that HSA relative to LSA individuals showed delayed neural discrimination between happy and sad faces. These results suggest that social anhedonia is associated with a deficit of perceptual processing during facial expression categorization.

Appetitive Motivation in Depressive Anhedonia: Effects of Piece-Rate Cash Rewards on Cardiac and Behavioral Outcomes.

Deficits in self-regulation and motivation are central to depression. Using motivational intensity theory (Brehm & Self, 1989), the present research examined how depressive anhedonia influences effort during a piece-rate appetitive task. In piece-rate tasks, people can work at their own pace and are rewarded for each correct response, so they can gain rewards more quickly by expending more effort. A sample of community adults (n = 78) was evaluated for depressive anhedonia using a structured clinical interview, yielding depressive anhedonia and control groups. Participants completed a self-paced cognitive task, and each correct response yielded a cash reward (3 cents or 15 cents, manipulated within-person). Using impedance cardiography, effort-related physiological activity was assessed via the cardiac pre-ejection period (PEP). The results indicated lower reward responsiveness in the anhedonia group. Compared to the control group, the depressive anhedonia group showed significantly less baseline-to-task change in PEP, and they performed marginally worse on the task. The experiment supports the predictions made by applying motivational intensity theory to depression and offers a useful paradigm for evaluating anhedonic effects on effort while people are striving for appealing rewards.

Social anhedonia and clinical outcomes in early adulthood: A three-year follow-up study within a community sample

Social anhedonia has been employed in psychometric high risk studies to identify putative schizotypes. The current study reports three-year longitudinal results from a community study of social anhedonia: the Maryland Longitudinal Study of Schizotypy (MLSS). The initial recruitment for the MLSS involved mailed questionnaire screening of 2434 18-year olds. Baseline and three-year follow-up laboratory assessments were subsequently conducted with individuals identified as being high in social anhedonia (N = 79) and a comparison sample (N = 79). Across the assessments both groups showed maturational improvement on all clinical symptom measures with declining symptom severity at the follow-up compared to baseline and there were no group differences in personality disorder diagnoses at follow-up. However, compared to the control group, over the three-year follow-up individuals in the social anhedonia group were found to have elevated schizophrenia-spectrum personality disorder (Cluster A) characteristics, greater negative symptom characteristics, and lower global functioning. The social anhedonia group also had lower educational attainment, higher unemployment, and higher rates of mental health service utilization than did the control group. Within the social anhedonia group, social support and family relationships were cross-sectionally related to symptom severity at follow-up, although social support and family variables from baseline were not predictive of clinical symptom outcomes at follow-up. Results indicate that social anhedonia is associated with persistent schizophrenia-spectrum symptoms and functional impairment in early adulthood.

Mind-Wandering in Adolescents Predicts Worse Affect and Is Linked to Aberrant Default Mode Network–Salience Network Connectivity

Understanding the fluctuating emotional and cognitive states of adolescents with depressive symptoms requires fine-grained and naturalistic measurements. This study used ecological momentary assessment (EMA) to investigate the affective correlates and consequences of mind-wandering in adolescents with anhedonia (AH) and typically developing (TD) controls. In addition, we examined the association between mind-wandering and resting state functional connectivity between the medial prefrontal cortex (mPFC), a core hub of the default mode network (DMN) linked to internally oriented mentation, and networks linked to attentional control (dorsal attention network [DAN]) and affect/salience detection (salience network [SN]). A total of 65 adolescents, aged 12 to 18 years (TD= 36; AH= 29), completed a resting state functional magnetic resonance imaging scan and subsequently used a smartphone application for ecological momentary assessment (EMA) data collection (2-3 times/d for 5 days). Each survey (N= 678) prompted adolescents to report on their current positive and negative affect (PA and NA), cognition, and activity. The frequency of mind-wandering was higher for AH (70.0% of EMA samples) relative to TD (59.2%) participants, and the participants with AH were more likely to mind-wander to unpleasant content. Mind-wandering was associated with higher concurrent NA, even when controlling for plausible confounds (eg, current activity, social companion, rumination). Time-lagged analyses revealed a bidirectional association between mind-wandering and PA. Greater levels of mind-wandering within the AH group were associated with stronger mPFC-SN/DAN connectivity. Rates of mind-wandering were high, especially among adolescents with anhedonia, and predicted worse affect. The relation between mind-wandering and enhanced mPFC-SN coupling may reflect heightened bottom-up influence of affective and sensory salience on DMN-mediated internally oriented thought.

Electrophysiological responses to images ranging in motivational salience: Attentional abnormalities associated with schizophrenia-spectrum disorder risk

Individuals at risk for schizophrenia-spectrum disorders display abnormalities related to motivational salience, or the ability of stimuli to elicit attention due to associations with rewards or punishments. However, the nature of these abnormalities is unclear because most focus on responses to stimuli from broad “pleasant” and “unpleasant” categories and ignore the variation of motivational salience within these categories. In two groups at risk for schizophrenia-spectrum disorders—a Social Anhedonia group and a Psychotic-like Experiences group—and a control group, the current study examined event-related potential components sensitive to motivational salience—the Early Posterior Negativity (EPN), reflecting earlier selective attention, and the Late Positive Potential (LPP), reflecting sustained attention. Compared to controls, the Social Anhedonia group showed smaller increases in the EPN in response to erotica and smaller increases in the LPP as the motivational salience of pleasant images increased (exciting<affiliative<erotica). In contrast, the Psychotic-like Experiences group had larger increases in LPP amplitudes as the motivational salience of pleasant images increased. Also, both at-risk groups showed larger increases in the LPP to threatening images but smaller increases to mutilation images. These findings suggest that examining abnormalities beyond those associated with broad categories may be a way to identify mechanisms of dysfunction.

Affective forecasting in individuals with social anhedonia: The role of social components in anticipated emotion, prospection and neural activation

BackgroundAffective forecasting, or the ability to forecast emotional responses to future events, is essential to everyday life adaption. Previous research suggests that individuals with social anhedonia exhibit deficits in affective forecasting, but the pattern of these deficits and their neural correlates are not known. MethodsIndividuals with social anhedonia (n = 40) and healthy controls (n = 46) completed a social affective forecasting task and underwent resting-state fMRI scanning. ResultsCompared with healthy controls, social anhedonia individuals anticipated reduced pleasure especially in social conditions and their prospection contained less visualization, voice, taste, self-referential thoughts, other-referential thoughts and language communication. Moreover, anticipated pleasure (valence and arousal for positive events) was positively associated with effort level, especially in social conditions. The social anhedonia group also exhibited stronger functional connectivity between the retrosplenial cortex and the insula and reduced functional connectivity between the hippocampal formation and the parahippocampus. These altered functional connectivities were correlated with anticipated valence in social, but not non-social, conditions. ConclusionsThese findings suggest that individuals with social anhedonia anticipate less pleasure predominately in social conditions and impaired prospection may contribute to the reduced anticipated pleasure. Reduced anticipated pleasure may be a target to improve social motivation in social anhedonia individuals.

Aberrant reward dynamics in trait anticipatory anhedonia

As a cardinal feature of several psychiatric disorders, anhedonia includes a consummatory component (deficits in hedonic response to rewards) and an anticipatory component (a reduced motivation to pursue them). Although being conceptualized as impairments of reward system, the neural characterization of reward processing in anhedonia is hampered by the enormous heterogeneity in the reward phase (‘wanting’ vs ‘liking’) and comorbidity (inherent to disease states). The current event-related potential (ERP) study examined the reward dynamics of anticipatory anhedonia in a non-clinical sample. Anticipatory and consummatory ERP components were assessed with a monetary incentive delay task in a high anticipatory anhedonia (HAA) group and a low anticipatory anhedonia (LAA) group. HAA vs LAA group showed a diminished reward-related speeding during behavioral performance and reported overall reduced positive affect during anticipation and receipt of outcomes. Importantly, neural dynamics underlying reward processing were negatively associated with anticipatory anhedonia across the anticipatory phase indexed by the contingent negative variation and the consummatory phase indexed by the feedback P3. Our results suggest that anticipatory anhedonia in non-clinical individuals is linked to a poor modulation during both anticipatory and consummatory phases of reward processing.

Mood configurations and their relationship to immune system responses: Exploring the relationship between moods, immune system responses, thyroid hormones, and social support.

Analyzing data on 2,057 healthy subjects in the Dutch Lifelines database we explore the relationship between immune system responses, thyroid hormone functioning and people’s mood that is expected to be moderated by social support. We focus (1) on the innate immune system cell count: monocytes, eosinophil granulocytes, basophilic granulocytes, neutrophil granulocytes; and thrombocytes; and (2) on the adaptive immune system cell count: lymphocytes (T, B and NK cells). Moods were measured on the positive (PA) and negative (NA) dimensions of the PANAS scale, divided in four groups based on their PA and NA median scores: hedonic, positive mood, negative mood and anhedonic. We focus further on (3) thyroid cells: T3 and T4; and (4) on social support. We found significant differences between mood groups and mean cell counts for basophilic granulocytes and thrombocytes but not for monocytes, eosinophil granulocytes and neutrophil granulocytes in the innate immune system. However, in the adaptive immune system we found mean lymphocyte cell counts to be different in all four mood groups. We also found that T3 and T4 levels differ significantly across all mood groups and work in very close association with lymphocytes to activate the adaptive immune system. These differences were most significant in the hedonic and anhedonic groups. The findings allow us to better understand mood groups, especially the hedonic and anhedonic groups, and open up new avenues for intervention.

Reciprocal associations between positive emotions and motivation in daily life: Network analyses in anhedonic individuals and healthy controls.

Anhedonia reflects a dysfunction in the reward system, which can be manifested in an inability to enjoy pleasurable situations (i.e., lack of positive emotions), but also by a lack of motivation to engage in pleasurable activities (i.e., lack of motivation). Little is known about the interrelations between positive emotions and motivation in daily life, and whether these associations are altered in anhedonic individuals. In the present study, we used a network approach to explore the reciprocal, lagged associations between positive emotions and motivation in anhedonic individuals (N = 66) and controls (N = 68). Participants (aged between 18 and 24 years) filled out momentary assessments of affect 3 times per day for 30 consecutive days. Our results showed that (a) anhedonic individuals and controls had similar moment-to-moment transfer of positive emotions; (b) in the anhedonic network feeling cheerful was the node with the highest outstrength, both within this group and compared with the control group; (c) feeling relaxed had the highest outstrength in the control network, and (d) anhedonic individuals had stronger pathways from positive emotions to motivation than controls. Taken together, our findings suggest that low levels of positive emotions lead to decreased motivation in the anhedonic group, which could instigate a negative spiral of low pleasure and low motivation. On a more positive note, we showed that cheerfulness had the highest outstrength in the network of anhedonic participants. Hence, interventions may focus on increasing cheerfulness in anhedonic individuals, as this will likely have the greatest impact on other positive emotions and motivations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Neurite atrophy in dorsal hippocampus of rat indicates incomplete recovery of chronic mild stress induced depression.

Depression is a leading cause of disability worldwide, and it can often ensue after a chronic mild stress (CMS) exposure. Despite intensive preclinical and clinical research, an objective test to diagnose depression is still not available, causing suboptimal diagnosis and treatment. Recently, the neuronal tracing technique and stereology showed persistent microstructural alterations in the stress‐sensitive brain regions, such as dendritic atrophy in the hippocampus (HP) and prefrontal cortex, (PFC) and hypertrophy in the amygdala (AM). These brain regions also showed consistent gliosis in cadaver brains of patients with depressive disorders as well as in the animal model of depression. Clinically feasible methods to probe these microstructural alterations could be useful in treatment planning and intervention.The present study employed ex vivo diffusion MRI (dMRI) and immunohistochemistry to identify microstructural alterations in stress‐sensitive brain regions of CMS‐induced anhedonic rats after eight weeks of spontaneous recovery in comparison with age‐matched controls. The investigation employs dMRI‐based neurite density model parameters (ν, Deff, and DL), traditional diffusion kurtosis imaging parameters (mean kurtosis, axial kurtosis, and radial kurtosis), kurtosis tensor parameters (mean kurtosis tensor, WL, and WT), and diffusion tensor parameters (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). The neurite density (ν) parameter has shown a significant reduction in dorsal HP in comparison with the control, while immunohistochemistry showed a significant reduction in histological neurite density (Hν) in dorsal HP, ventral HP, and AM. Hν also showed significant correlation with ν, which strengthens the reliability of ν and provides a plausible underpinning of the diffusion signal. However, the correlation was not significant when evaluated in the anhedonic group alone. These stress‐recovery findings are opposite to the changes observed just after the CMS exposure paradigm in our recent in vivo study. The present study revealed long‐term effects of CMS exposure, which may be due to incomplete microstructural normalization or long‐lasting microstructural alterations in dHP.