Anhedonia reflects an encoding deficit for pleasant stimuli in schizophrenia: Evidence from the emotion-induced memory trade-off eye-tracking paradigm.

OBJECTIVE: The present study explored the hypothesis that anhedonia reflects an emotional memory impairment for pleasant stimuli, rather than diminished hedonic capacity in individuals with schizophrenia (SZ). METHOD: Participants included 30 SZ and 30 healthy controls (HCs) subjects who completed an eye-tracking emotion-induced memory trade-off task where contextually relevant pleasant, unpleasant, or neutral items were inserted into the foreground of neutral background scenes. Passive viewing and poststimulus elaboration blocks were administered to assess differential encoding mechanisms, and immediate and 1-week recognition testing phases were completed to assess the effects of delay interval. Participants also made self-reports of positive emotion, negative emotion, and arousal in response to the stimuli. RESULTS: Results indicated that SZ experienced stimuli similarly to HC. Both groups demonstrated the typical emotion-induced memory trade-off during the passive viewing and poststimulus elaboration encoding blocks, as indicated by more hits for emotional than neutral items and fewer hits for backgrounds paired with emotional than neutral items. Eye-tracking data also indicated that both groups were more likely to fixate earlier and have longer dwell time on emotional than neutral items. At the 1-week delay, the emotion-induced memory trade-off was eliminated in both groups, and SZ showed fewer overall hits across valence conditions. Greater severity of anhedonia was specifically associated with impaired recognition for pleasant stimuli at the immediate recognition phase. CONCLUSIONS: Findings suggest that anhedonia in SZ is associated with emotional memory impairment, particularly a deficit in encoding positive stimuli. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Environmental context predicts state fluctuations in negative symptoms in youth at clinical high risk for psychosis.

BACKGROUND: Negative symptoms (avolition, anhedonia, asociality) are a prevalent symptom in those across the psychosis-spectrum and also occur at subclinical levels in the general population. Recent work has begun to examine how environmental contexts (e.g. locations) influence negative symptoms. However, limited work has evaluated how environments may contribute to negative symptoms among youth at clinical high risk for psychosis (CHR). The current study uses Ecological Momentary Assessment to assess how four environmental contexts (locations, activities, social interactions, social interaction method) impact state fluctuations in negative symptoms in CHR and healthy control (CN) participants. METHODS: CHR youth (n = 116) and CN (n = 61) completed 8 daily surveys for 6 days assessing negative symptoms and contexts. RESULTS: Mixed-effects modeling demonstrated that negative symptoms largely varied across contexts in both groups. CHR participants had higher negative symptoms than CN participants in most contexts, but groups had similar symptom reductions during recreational activities and phone call interactions. Among CHR participants, negative symptoms were elevated in several contexts, including studying/working, commuting, eating, running errands, and being at home. CONCLUSIONS: Results demonstrate that negative symptoms dynamically change across some contexts in CHR participants. Negative symptoms were more intact in some contexts, while other contexts, notably some used to promote functional recovery, may exacerbate negative symptoms in CHR. Findings suggest that environmental factors should be considered when understanding state fluctuations in negative symptoms among those at CHR participants.

Negative symptoms in schizophrenia differ across environmental contexts in daily life.

A recent environmental theory of negative symptoms posits that environmental contexts (e.g., location, social partner) play a significant-yet often unaccounted for-role in negative symptoms of schizophrenia (SZ). "Gold-standard" clinical rating scales offer limited precision for evaluating how contexts impact symptoms. To overcome some of these limitations, Ecological Momentary Assessment (EMA) was used to determine whether there were state fluctuations in experiential negative symptoms (anhedonia, avolition, and asociality) in SZ across contexts (locations, activities, social interaction partner, social interaction method). Outpatients with SZ (n = 52) and healthy controls (CN: n = 55) completed 8 daily EMA surveys for 6 days assessing negative symptom domains (anhedonia, avolition, and asociality) and contexts. Multilevel modeling demonstrated that negative symptoms varied across location, activity, social interaction partner, and social interaction method. For the majority of contexts, SZ and CN did not report significantly different levels of negative symptoms, with SZ only reporting higher negative symptoms than CN while eating, resting, interacting with a significant other, or being at home. Further, there were several contexts where negative symptoms were similarly reduced (e.g., recreation, most social interactions) or elevated (e.g., using the computer, working, running errands) in each group. Results demonstrate that experiential negative symptoms dynamically change across contexts in SZ. Some contexts may "normalize" experiential negative symptoms in SZ, while other contexts, notably some used to promote functional recovery, may increase experiential negative symptoms.

The effects of the COVID-19 pandemic on hallucinations and delusions in youth at clinical high-risk for psychosis and outpatients with schizophrenia.

Although the COVID-19 pandemic has had detrimental effects on mental health in the general population, the impact on those with schizophrenia-spectrum disorders has received relatively little attention. Assessing pandemic-related changes in positive symptoms is particularly critical to inform treatment protocols and determine whether fluctuations in hallucinations and delusions are related to telehealth utilization and treatment adherence. In the current longitudinal study, we evaluated changes in the frequency of hallucinations and delusions and distress resulting from them across three-time points. Participants included: (1) outpatients with chronic schizophrenia (SZ: n = 32) and healthy controls (CN: n = 31); (2) individuals at clinically high risk for psychosis (CHR: n = 25) and CN (n = 30). A series of questionnaires were administered to assess hallucination and delusion severity, medication adherence, telehealth utilization, and protective factors during the pandemic. While there were no significant increases in the frequency of hallucinations and delusions in SZ and CHR, distress increased from pre-pandemic to early pandemic in both groups and then decreased at the third time point. Additionally, changes in positive symptom severity in SZ were related to psychiatric medication adherence. Findings suggest that positive symptoms are a critical treatment target during the pandemic and that ongoing medication services will be beneficial.

Adjunct treatment with ketamine enhances the therapeutic effects of extinction learning after chronic unpredictable stress.

Post-traumatic stress disorder (PTSD) is a debilitating illness characterized by dysfunction in the medial prefrontal cortex (mPFC). Although both pharmacological and cognitive behavioral interventions have shown some promise at alleviating symptoms, high attrition and persistence of treatment-resistant symptoms pose significant challenges that remain unresolved. Specifically, prolonged exposure therapy, a gold standard intervention to treat PTSD, has high dropout rates resulting in many patients receiving less than a fully effective course of treatment. Administering pharmacological treatments together with behavioral psychotherapies like prolonged exposure may offer an important avenue for enhancing therapeutic efficacy sooner, thus reducing the duration of treatment and mitigating the impact of attrition. In this study, using extinction learning as a rat model of exposure therapy, we hypothesized that administering ketamine as an adjunct treatment together with extinction will enhance the efficacy of extinction in reversing stress-induced deficits in set shifting, a measure of cognitive flexibility. Results showed that combining a sub-effective dose of ketamine with a shortened, sub-effective extinction protocol fully reversed stress-induced cognitive set-shifting deficits in both male and female rats. These effects may be due to shared molecular mechanisms between extinction and ketamine, such as increased neuronal plasticity in common circuitry (e.g., hippocampus-mPFC), or increased BDNF signaling. This work suggests that fast-acting drugs, such as ketamine, can be effectively used in combination with behavioral interventions to reduce treatment duration and potentially mitigate the impact of attrition. Future work is needed to delineate other pharmacotherapies that may complement the effects of extinction via shared or independent mechanisms.

Infralimbic BDNF signaling is necessary for the beneficial effects of extinction on set shifting in stressed rats.

Current pharmacotherapies for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are ineffective for many patients, and often do not restore cognitive dysfunction associated with these disorders. Behavioral therapies, such as exposure therapy, can be effective for treatment-resistant patients. The mechanisms underlying exposure therapy are not well-understood. Fear extinction as an intervention after chronic stress can model the beneficial effects of exposure therapy in rats. Extinction requires neuronal activity and protein synthesis in the infralimbic (IL) cortex for its beneficial effects. We hypothesized that extinction requires Brain-Derived Neurotrophic Factor (BDNF) activity in the IL cortex to reverse stress-induced cognitive flexibility impairments. Extinction learning reversed set-shifting deficits induced by Chronic Unpredictable Stress (CUS), tested 24 h after extinction. Blocking BDNF signaling in the IL cortex during extinction by local administration of a neutralizing antibody prevented the beneficial effects of extinction on set shifting after stress. Extinction induced activation of the BDNF TrkB receptor, and signaling pathways associated with BDNF (Akt and Erk). Administration of exogenous BDNF into IL cortex in the absence of extinction was sufficient to reverse the effects of stress on set shifting. The effects of extinction were prevented by blocking either Erk or Akt signaling in the IL cortex, whereas the effects of exogenous BDNF were dependent on Erk, but not Akt, signaling. Our observations suggest that BDNF-Erk signaling induced by extinction underlies plastic changes that can reverse or counteract the effects of chronic stress in the IL cortex.

Machine Learning Identifies Digital Phenotyping Measures Most Relevant to Negative Symptoms in Psychotic Disorders: Implications for Clinical Trials.

BACKGROUND: Digital phenotyping has been proposed as a novel assessment tool for clinical trials targeting negative symptoms in psychotic disorders (PDs). However, it is unclear which digital phenotyping measurements are most appropriate for this purpose. AIMS: Machine learning was used to address this gap in the literature and determine whether: (1) diagnostic status could be classified from digital phenotyping measures relevant to negative symptoms and (2) the 5 negative symptom domains (anhedonia, avolition, asociality, alogia, and blunted affect) were differentially classified by active and passive digital phenotyping variables. METHODS: Participants included 52 outpatients with a PD and 55 healthy controls (CN) who completed 6 days of active (ecological momentary assessment surveys) and passive (geolocation, accelerometry) digital phenotyping data along with clinical ratings of negative symptoms. RESULTS: Machine learning algorithms classifying the presence of a PD diagnosis yielded 80% accuracy for cross-validation in H2O AutoML and 79% test accuracy in the Recursive Feature Elimination with Cross Validation feature selection model. Models classifying the presence vs absence of clinically significant elevations on each of the 5 negative symptom domains ranged in test accuracy from 73% to 91%. A few active and passive features were highly predictive of all 5 negative symptom domains; however, there were also unique predictors for each domain. CONCLUSIONS: These findings suggest that negative symptoms can be modeled from digital phenotyping data recorded in situ. Implications for selecting the most appropriate digital phenotyping variables for use as outcome measures in clinical trials targeting negative symptoms are discussed.

Age-related changes in myelin of axons of the corpus callosum and cognitive decline in common marmosets.

Executive control is a higher-level cognitive function that involves a range of different processes that are involved in the planning, coordination, execution, and inhibition of responses. Many of the processes associated with executive control, such as response inhibition and mental flexibility, decline with age. Degeneration of white matter architecture is considered to be the one of the key factors underlying cognitive decline associated with aging. Here we investigated how white matter changes of the corpus callosum were related to cognitive aging in common marmosets (Callithrix jacchus). We hypothesized that reduction in myelin thickness, myelin density, and myelin fraction of axonal fibers in the corpus callosum would be associated with performance on a task of executive function in a small sample of geriatric marmosets (n = 4) and young adult marmosets (n = 2). Our results indicated declines in myelin thickness, density, and myelin fraction with age. Considerable variability was detected on these characteristics of myelin and cognitive performance assessed via the detoured reach task. Age-related changes in myelin in Region II of the corpus callosum were predictive of cognitive performance on the detoured reach task. Thus the detoured reach task appears to also measure aspects of corticostriatal function in addition to prefrontal cortical function.