Reduction In Anhedonia Research Articles

Anhedonia and depression severity measures during ketamine administration in treatment-resistant depression.

Anhedonia is a core symptom of depression characterized by a diminished ability to experience pleasure. Currently available treatments for depression often fall short in adequately addressing anhedonia that often presents as a chronic and debilitating symptom. Ketamine is known to possess antianhedonic properties. This post-hoc analysis of a naturalistic observational study of treatment-resistant depression inpatients (n=28) analyzed antianhedonic response patterns measured by Snaith-Hamilton Pleasure Scale and changes in Inventory of Depressive Symptomatology in responders (n=6) and non-responders (n=22) stratified per Montgomery-Åsberg Depression Rating Scale during short-term ketamine treatment. Results show that responders significantly improve in anhedonia over time (p=0.0084) and at the 7th infusion and follow-up (both p<0.05). Non-responders reported significant reduction in anhedonia over time (p=0.0011) and at the 5th, 7th infusion and at the follow-up (all p's<0.05). Non-responders were also observed to improve significantly in self-reported depression at the 7th infusion (p=0.0219) but not at the follow-up. There is no complete overlap between change in depressive symptoms and anhedonia. Therefore, it might be assumed ketamine alleviates anhedonia as an individual symptom domain regardless of formal treatment outcome.

Immune cells as a potential therapeutic agent in the treatment of depression

IntroductionThere are sufficient amount data on the immune cells and their biologically active products leading role in the pathogenesis of depression, which allows viewing modulated immune cells as model objects for developing new approaches to depression immunotherapy.ObjectivesWe first demonstrated the ability of immune cells modulated outside the body by caffeine to edit depression-like behavior and showed the central cytokines-mediated mechanisms of this effect. Considering theimportant role of the peripheral immune system in the pathogenesis of depression, we investigated the main parameters of its functional activity after transplantation of modulated immunocytes.Methods(CBAxC57Bl/6) F1 depressive-like male mice, developed under the long-term social stress, were undergoing the transplantation of syngeneic immune cells with in vitro caffeine-modulated functional activity. Recipient’s behavior and immune systems functional activity parameters were studied.ResultsWe showed earlier significant positive psychoneuromodulatory effect of caffeine-treated immune cells in depressive-like recipients which manifests itself in the behavioral editing (anhedonia reduction, stimulation of exploratory behavior and activity in forced swimming test); hippocampal neurogenesis stimulation against the background of increased BDN and modulation of brain cell’s cytokines production. Transplantation of caffeine-modulated immune cells in syngeneic depressive-like recipients also leads to positive changes in the immune system functional activity as evidenced by enhanced immune response, splenocytes proliferation stimulation on the background of modulation of cell’s cytokines production and decreased tryptophan catabolism, reducing systemic inflammation.ConclusionsResults demonstrated that in vitro caffeine-modulated immune cells caused positive psychoneuroimmunomodulating effect in depressive-like recipients. So, its may be considered as a potential therapeutic agent in the treatment of depression.DisclosureNo significant relationships.

Ropanicant (SUVN-911), an α4β2 nicotinic acetylcholine receptor antagonist intended for the treatment of depressive disorders: pharmacological, behavioral, and neurochemical characterization.

Ropanicant (SUVN-911) (3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo (3.1.0) hexane hydrochloride) is a novel α4β2 nicotinic acetylcholine receptor (nAChR) antagonist being developed for the treatment of depressive disorders. Pharmacological and neurochemical characterization of Ropanicant to support a potential molecule for the treatment of depressive disorders. Ropanicant was assessed for antidepressant-like activity using the rat forced swimming test (FST) and differential reinforcement of low rate -72s (DRL-72s). Alleviation of anhedonia was assessed in chronic mild stressmodel using sucrose preference test. To understand the mechanism of action, serotonin levels, ionized calcium-binding adaptor molecule 1 (Iba1), and brain-derived neurotrophic factor (BDNF) were determined. The onset of antidepressant-like activity was determined using the reduction in submissive behavior assay. The effects on cognition and sexual functions were assessed using the object recognition task and sexual dysfunction assay respectively. Interaction of Ropanicant, TC-5214, and methyllycaconitine (MLA) with citalopram was investigated individually in mice FST. Ropanicant exhibited antidepressant like properties in the FST and DRL-72s. A significant reduction in anhedonia was observed in the sucrose preference test. Oral administration of Ropanicant produced a significant increase in serotonin and BDNF levels, with a reduction in the Iba1 activity. The onset of antidepressant like effect with Ropanicant was within a week of treatment, and was devoid of cognitive dulling and sexual dysfunction. While Ropanicant potentiated the effect of citalopram in FST, such an effect was not observed with MLA or TC-5214. Preclinical studies with Ropanicant support the likelihood of its therapeutic utility in the treatment of depressive disorders.

Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression

BackgroundEarly childhood depression is associated with anhedonia and reduced event-related potential (ERP) responses to rewarding or pleasant stimuli. Whether these neural measures are indicators of target engagement or treatment outcome is not yet known. MethodsWe measured ERP responses to win and loss feedback in a guessing task and to pleasant versus neutral pictures in young (4.0–6.9 years of age) depressed children before and after randomization to either 18 weeks of Parent-Child Interaction Therapy–Emotion Development (PCIT-ED) or waitlist. ResultsAnalyses included reward positivity (RewP) data from 118 children randomly assigned to PCIT-ED (n = 60) or waitlist (n = 58) at baseline and late positive potential (LPP) data from 99 children (44 assigned to PCIT-ED vs. 55 assigned to waitlist) at baseline. Children undergoing PCIT-ED showed a greater reduction in anhedonia (F1,103 = 10.32, p = .002, partial η2 = .09). RewP reward responses increased more (F1,86 = 5.98, p = .02, partial η2 = .07) for PCIT-ED, but a greater change in RewP was not significantly associated with a greater reduction in major depressive disorder symptoms (r = −.12, p > .4). Baseline RewP did not predict treatment change. LPPs to positive pictures did not change across treatment, but greater baseline LPPs to positive pictures predicted a higher likelihood of remission from major depressive disorder in children undergoing PCIT-ED (B = 0.14; SE = 0.07; odds ratio = 1.15; p = .03). ConclusionsThe ERP reward response improved in young children with depression during a treatment designed to enhance emotion development, providing evidence of target engagement of the neural systems associated with reward. Further, greater baseline LPP responses to positive pictures was associated with a greater likelihood of depression remission, suggesting that this ERP measure can predict which children are most likely to respond to treatment.

Interaction of the immune-inflammatory and the kynurenine pathways in rats resistant to antidepressant treatment in model of depression

The kynurenine pathway (KP), a major route of tryptophan catabolism, may be associated with the pathophysiology of depressive disorders. KP is responsible for ca. 99% of brain tryptophan metabolism via its degradation to kynurenine (KYN) catalyzed by indoleamine 2,3-dioxygenase (IDO). Some cytokines, such as interferon-γ (IFN-γ) and interleukin (IL)-6 are potent inducers of IDO. KYN is further converted by kynurenine aminotransferase (KAT) to the more neuroprotective kynurenic acid or by kynurenine 3-monooxygenase (KMO) to neurotoxic 3-hydroxykynurenine. The aim of the present study was to delineate whether the administration of imipramine (IMI) to rats subjected to chronic mild stress (CMS) may reverse behavioral changes induced by CMS in association with changes in immune-inflammatory markers and KP. We confirmed that the CMS procedure modeled one of the main symptoms of depression, i.e. anhedonia, and administration of IMI for 5 weeks resulted in a significant reduction in anhedonia in a majority of animals (CMS IMI-R animals), whereas 20% of animals did not respond to IMI treatment (CMS IMI-NR animals). We established that CMS procedure increased IFN-γ and IDO mRNA and decreased KAT II mRNA expression in the rat cortex. In the cortex and hippocampus, IMI treatment and non-responsiveness to IMI (in CMS IMI-NR animals) were associated with increased IL-6 mRNA expression. In the spleen, CMS increased production of IFN-γ and IL-6 proteins, while these cytokines were decreased by IMI in CMS IMI-R animals. Chronic IMI administration to CMS rats decreased IDO and KMO mRNA and protein expression and increased KAT II/KMO mRNA and protein ratio in IMI responders (CMS IMI-R) in comparison to CMS rats. In CMS IMI-NR rats, a significant increase in IDO mRNA expression and protein level in comparison with IMI responders was observed. Our findings indicate that resistance to therapeutic action of IMI could be explained by a deficiency of the inhibitory properties of IMI on IDO, KMO and KYN synthesis in the cortex. We conclude that the antidepressant activity of IMI may, at least in part, be explained by modulatory activities on the KAT II/KMO ratio in brain areas.

Anhedonia Reduction and the Association Between Left Ventral Striatal Reward Response and 6-Month Improvement in Life Satisfaction Among Young Adults

Anhedonia is a symptom of multiple psychiatric conditions in young adults that is associated with poorer mental health and psychosocial function and abnormal ventral striatum reward processing. Aberrant function of neural reward circuitry is well documented in anhedonia and other psychiatric disorders. Longitudinal studies to identify potential biomarkers associated with a reduction in anhedonia are necessary for the development of novel treatment targets. To identify neural reward-processing factors associated with improved psychiatric symptoms and psychosocial function in a naturalistic, observational context. A longitudinal cohort follow-up study was conducted from March 1, 2014, to June 5, 2018, at the University of Pittsburgh Medical Center after baseline functional magnetic resonance imaging in 52 participants between the ages of 18 and 25 years who were experiencing psychological distress. Participants were evaluated at baseline and 6 months. At baseline, participants underwent functional magnetic resonance imaging during a card-guessing monetary reward task. Participants completed measures of affective symptoms and psychosocial function at each visit. Neural activation during reward prediction error (RPE), a measure of reward learning, was determined using Statistical Parametric Mapping software. Neural reward regions with significant RPE activation were entered as regions associated with future symptoms in multiple linear regression models. A total of 52 young adults (42 women and 10 men; mean [SD] age, 21.4 [2.2] years) completed the study. Greater RPE activation in the left ventral striatum was associated with a decrease in anhedonia symptoms during a 6-month period (β = -6.152; 95% CI, -11.870 to -0.433; P = .04). The decrease in anhedonia between baseline and 6 months mediated the association between left ventral striatum activation to RPE and improvement in life satisfaction between baseline and 6 months (total [c path] association: β = 0.245; P = .01; direct [c' path] association: β = 0.133; P = .16; and indirect [ab path] association: 95% CI, 0.026-0.262). Results were not associated with psychotropic medication use. Greater left ventral striatum responsiveness to RPE may serve as a biomarker or potential target for novel treatments to improve the severity of anhedonia, overall mental health, and psychosocial function.

T92. Reduction in Anhedonia Mediates the Relationship Between Left Ventral Striatal Reward Response and 6-Month Improvement in Life Satisfaction in Young Adults

T92. Reduction in Anhedonia Mediates the Relationship Between Left Ventral Striatal Reward Response and 6-Month Improvement in Life Satisfaction in Young Adults

RETRACTED: Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression

Early childhood depression is associated with anhedonia and reduced event-related potential (ERP) responses to rewarding or pleasant stimuli. Whether these neural measures are indicators of target engagement or treatment outcome is not yet known. We measured ERP responses to win and loss feedback in a guessing task and to pleasant versus neutral pictures in young (4.0-6.9 years of age) depressed children before and after randomization to either 18 weeks of Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) treatment or waitlist (WL) control condition. Analyses included reward positivity (RewP) data from 118 children randomized to PCIT-ED treatment (n= 60) or WL control condition (n= 58) at baseline and late positive potential (LPP) data from 99 children (44 PCIT-ED treatment vs. 55 WL control condition) at baseline. Children in the PCIT-ED group showed a greater reduction in anhedonia (F1,103= 10.32, p= .002, partial η2= .09). RewP reward responses increased more (F1,87= 5.45, p= .02, partial η2= .06) for PCIT-ED and a greater change in RewP was associated with a greater reduction in major depressive disorder symptoms (r=-.24, p= .05). Baseline RewP did not predict treatment change. LPPs to positive pictures did not change across treatment, but greater baseline LPPs to positive pictures predicted a higher likelihood of remission from major depressive disorder in the PCIT-ED group (B= 0.14; SE= 0.07; odds ratio= 1.15; p= .03). The ERP reward response improved in young children with depression during a treatment designed to enhance emotion development, providing evidence of target engagement of the neural systems associated with reward. Further, greater baseline LPP responses to positive pictures were associated with a greater reduction in depression, suggesting that this ERP measure can predict which children are most likely to respond to treatment.

Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

RationaleDepressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome.ObjectivesThe objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients’ emotional processing biases.MethodsSeventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin.ResultsWe found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010).ConclusionsPsilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.

Use of Deep Brain Stimulation in Depression?- Opportunities and Risks. Conclusions Based On the Results of Author's Research.

Currently work is underway on the use of DBS in psychiatry, particularly in the population of patients with treatment-resistant depression. Authors summarize the current state of knowledge, risks and benefits associated with the use of DBS and try to specify the position of DBS in the treatment of depression. Conclusions are based on a review of the literature and the results of research conducted in the Department of Neurosurgery in Institute of Psychiatry and Neurology (Warsaw). The study group included 60 patients with Parkinson's disease surgically treated by implantation of subthalamic nucleus stimulator (STN -DBS). The aim of the study was to assess the mental state of patients before and after implantation of STN-DBS, with particular attention to the presence of depression and anhedonia. This study showed an improvement in mental status, which has followed within a month after the start of stimulation and manifested in the improvement of mood, reduction of sadness, apathy and anhedonia. The trend towards improvement was maintained over the following months. The assessment carried out six months after DBS implantation showed reduction in score in HADRS, MADRS, BDI compared to the state before the operation. Anhedonia reduction observed during the first 30 days after initiating the stimulation persisted in the assessment six months after DBS implantation. There is a need of systematic study of population treated with DBS using standardized measures. Data on effectivness and side-effects of DBS would be extremely useful for further research on the use of DBS in psychiatric disorders.

S.15.04 Cytokines as mediators of depression: the involvement of the HPA axis and the serotonergic system

The kynurenine pathway (KP), a major route of tryptophan catabolism, may be associated with the pathophysiology of depressive disorders. KP is responsible for ca. 99% of brain tryptophan metabolism via its degradation to kynurenine (KYN) catalyzed by indoleamine 2,3-dioxygenase (IDO). Some cytokines, such as interferon-γ (IFN-γ) and interleukin (IL)-6 are potent inducers of IDO. KYN is further converted by kynurenine aminotransferase (KAT) to the more neuroprotective kynurenic acid or by kynurenine 3-monooxygenase (KMO) to neurotoxic 3-hydroxykynurenine. The aim of the present study was to delineate whether the administration of imipramine (IMI) to rats subjected to chronic mild stress (CMS) may reverse behavioral changes induced by CMS in association with changes in immune-inflammatory markers and KP. We confirmed that the CMS procedure modeled one of the main symptoms of depression, i.e. anhedonia, and administration of IMI for 5 weeks resulted in a significant reduction in anhedonia in a majority of animals (CMS IMI-R animals), whereas 20% of animals did not respond to IMI treatment (CMS IMI-NR animals). We established that CMS procedure increased IFN-γ and IDO mRNA and decreased KAT II mRNA expression in the rat cortex. In the cortex and hippocampus, IMI treatment and non-responsiveness to IMI (in CMS IMI-NR animals) were associated with increased IL-6 mRNA expression. In the spleen, CMS increased production of IFN-γ and IL-6 proteins, while these cytokines were decreased by IMI in CMS IMI-R animals. Chronic IMI administration to CMS rats decreased IDO and KMO mRNA and protein expression and increased KAT II/KMO mRNA and protein ratio in IMI responders (CMS IMI-R) in comparison to CMS rats. In CMS IMI-NR rats, a significant increase in IDO mRNA expression and protein level in comparison with IMI responders was observed. Our findings indicate that resistance to therapeutic action of IMI could be explained by a deficiency of the inhibitory properties of IMI on IDO, KMO and KYN synthesis in the cortex. We conclude that the antidepressant activity of IMI may, at least in part, be explained by modulatory activities on the KAT II/KMO ratio in brain areas.

Cognitive and psychological correlates of smoking abstinence, and predictors of successful cessation

The neural circuitry implicated in addictive drug use, which appears to be down-regulated in early abstinence, corresponds closely with brain reward pathways. A literature review suggests that responses to incentive stimuli and the ability to inhibit reflexive responses, both of which have been associated with normal functioning in these pathways, might be weakened during acute abstinence from chronic drug use. In an ongoing study, 82 smokers, abstinent overnight before two separate testing occasions, have been assessed after administration of nicotine and placebo lozenges (order of sessions counterbalanced). Nicotine administration is associated with a significant reduction in anhedonia, a near-significant increase in response to financial incentive, enhanced ability to inhibit reflexive eye movements, and increased attentional bias to words with appetitive significance. Fifty-nine participants then initiated a quit attempt and 19 reported relapsing within 7 days. Comparing their performance in the two prequit lozenge assessment sessions, relapsers showed a stronger effect of nicotine on enhancing their ability to inhibit reflexive eye movements and a near-significant trend towards greater nicotine-induced increases in attentional bias toward appetitive words.