Understanding empathy deficits and emotion dysregulation in psychopathy: The mediating role of alexithymia.

Psychopathy is a severe personality disorder marked by a wide range of emotional deficits, including a lack of empathy, emotion dysregulation, and alexithymia. Previous research has largely examined these emotional impairments in isolation, ignoring their influence on each other. Thus, we examined the concurrent interrelationship between emotional impairments in psychopathy, with a particular focus on the mediating role of alexithymia. Using path analyses with cross-sectional data from a community sample (N = 315) and a forensic sample (N = 50), our results yielded a statistically significant mediating effect of alexithymia on the relationship between psychopathy and empathy (community and forensic) and between psychopathy and emotion dysregulation (community). Moreover, replacing psychopathy with its three dimensions (i.e., meanness, disinhibition, and boldness) in the community sample revealed that boldness may function as an adaptive trait, with lower levels of alexithymia counteracting deficits in empathy and emotion dysregulation. Overall, our findings indicate that psychopathic individuals' limited understanding of their own emotions contributes to their lack of empathy and emotion dysregulation. This underscores the potential benefits of improving emotional awareness in the treatment of individuals with psychopathy.

Disentangling the relationship between sensory processing, alexithymia and broad autism spectrum: A study in parents' of children with autism spectrum disorders and sensory processing disorders.

BACKGROUND: Autistic features and sensory processing difficulties and their phenotypic co-expression with alexithymia share a transdiagnostic vulnerability. In this work, we explored whether the current concept of broad autism phenotype rather translates altered sensory processing (non-specific to autism), meaning that the characteristics of altered sensory processing should be overexpressed among individuals with heightened vulnerability to sensory processing atypicalities (parents of children with sensorial processing disorder, or SPD parents) and individuals with heightened vulnerability to autistic traits (parents of children with autism spectrum disorders, or ASD parents). In addition, the association between altered sensory processing and alexithymia was inspected. METHOD: The Adolescent/Adult Sensory Profile, Autism Spectrum Quotient, and Toronto Alexithymia Scale were completed by 31 parents of children with ASD, 32 parents of children with SPD, and 52 parents of typically developed (TD) children. RESULTS: Extreme sensory patterns were overexpressed both in parents of children with SPD and parents of children with ASD when compared to parents of TD children. In addition, extreme sensory patterns were significantly associated with alexithymia scores. Specifically, sensory avoidance, low registration, and sensory sensitivity were positively correlated with alexithymia. No significant differences were found regarding the proportion of autistic traits and alexithymia between ASD and SPD groups of parents. CONCLUSIONS: These results challenge the specificity of broad autism phenotype and suggest a neurodevelopmental atypicity with roots in altered sensory and emotional processing.

Dynamic Associations Among Sleep, Emotion Dysregulation, and Desire to Live in a Perinatal Sample.

OBJECTIVE: The present study prospectively examined dynamic associations among sleep, emotion dysregulation, and desire to live during the perinatal transition, as it was theorized that these factors may contribute to the emergence of postpartum suicide risk. METHOD: Ninety-four women ( Mage = 29.2 years; 23.4% Latina) wore wrist actigraphs and completed twice daily surveys for 7 days during the third trimester of pregnancy, 6 weeks postpartum, and 4 months postpartum. Multilevel, change-as-outcome models were built to examine changes in attractor dynamics among sleep, emotion dysregulation, and desire to live, as well as if sleep-emotion dysregulation dynamics differed based on participants' desires to live. RESULTS: From pregnancy to 6 weeks postpartum, emotion dysregulation ( B = -0.09, p = .032) and desire to live ( B = -0.16, p < .001) exhibited more stable temporal patterns around higher emotion dysregulation and lower desire to live. Compared to women who reported consistently high desires to live, those who experienced fluctuations in their desires to live exhibited lower, more stable sleep efficiency during pregnancy ( B = -0.90, p < .001). At 4 months postpartum, those with fluctuating desires to live exhibited a coupling dynamic whereby low sleep efficiency predicted increases in emotion dysregulation ( B = -0.16, p = .020). CONCLUSIONS: This study was the first to examine nonlinear dynamics among risk factors for postpartum suicide, which may be evident as early as pregnancy and 6 weeks postpartum. Sleep health, in particular, warrants further exploration as a key susceptibility factor in the emergence of postpartum suicide risk. PREREGISTRATION: Open Science Framework ( https://osf.io/qxb75/?view_only=799ffe5c048842dfb89d3ddfebaa420d ).

Young-onset dementia with Lewy Bodies presenting with apathy and alexithymia.

A diagnosis of young-onset dementia can pose a significant challenge for the clinician. We present a young patient with a very unusual presentation of Dementia with Lewy Bodies. The lack of motor symptoms and his marked apathy delayed his diagnosis. His symptoms were thought to be due to depression based on normal structural imaging and the psychiatric nature of his presentation. An extensive work-up was performed. Evidence of a structural neurodegenerative process was provided by the HMPAO-SPECT. Cardiac MIBG confirmed the diagnosis.

Personality traits related to cognitive functioning in patients with functional neurological disorder.

Cognitive symptoms are prevalent in patients with functional neurological disorder (FND). Several studies have suggested that personality traits such as neuroticism may play a pivotal role in the development of FND. FND has also been associated with alexithymia: patients with FND report difficulties in identifying, analyzing, and verbalizing emotions. Whether or not alexithymia and other personality traits are associated with cognitive symptomatology in patients with FND is unknown. In the current study, we explored whether the Big Five personality model factors (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and alexithymia were associated with cognitive functioning in FND. Twenty-three patients with FND were assessed using a neuropsychological assessment and questionnaire assessment to explore personality traits (Neuroticism-Extraversion-Openness Five-Factor Inventory) and alexithymia (Bermond-Vorst Alexithymia Questionnaire). The results indicated that high conscientiousness was associated with lower planning scores (ρ = -0.52, p = .012) and high scores on alexithymia were associated with lower scores on verbal memory scores (ρ = -0.46, p = .032) and lower sustained attention scores (ρ = -0.45, p = .046). The results did not remain significant after controlling for multiple testing. The preliminary results of our study suggest that personality and cognitive symptomatology in patients with FND are topics that should be further explored in future studies, as cognitive symptomology can affect treatment results.

Associations among autistic traits, cognitive and affective empathy, and personality traits in adults with autism spectrum disorder and no intellectual disability.

Reported empathy deficits in autism spectrum disorder (ASD) could be attributable to other ASD-related features. We evaluated 28 ASD adults with no intellectual disability and 24 age-matched non-ASD control subjects using the Autism-Spectrum Quotient (AQ), Questionnaire of Cognitive and Affective Empathy (QCAE), Interpersonal Reactivity Index (IRI), and NEO Personality Inventory-Revised (NEO). Compared to the controls, ASD participants showed lower scores for perspective taking, online simulation, cognitive empathy, and peripheral responsivity on the QCAE, and lower scores for perspective taking and empathic concern on the IRI. Within the ASD group, the AQ scores showed significant relationships with perspective taking, online simulation and cognitive empathy on the QCAE, and perspective taking on the IRI. The ASD group also showed higher scores for neuroticism and lower scores for extraversion on the NEO compared to the controls. However, there were no relationships between AQ scores and NEO factors within the ASD group. Multiple regression analysis with stepwise linear regression demonstrated that perspective taking score on the QCAE and extraversion score on the NEO were good predictor variables to autistic traits on the AQ. These findings help us to understand empathy and personality traits in ASD adults with no intellectual disability.

Psychotherapy for Functional Neurological (Conversion) Disorder: A Case Bridging Mind, Brain, and Body.

Functional neurologic (conversion) disorder (FND) is a core neuropsychiatric condition directly at the intersection of psychiatry and neurology. Over the past several decades, renewed interest in FND has been catalyzed by use of a "rule-in" diagnostic approach leveraging positive clinical signs specific for the diagnosis. In parallel, advances have occurred in identifying mechanisms, etiologic factors, and evidence-based treatments for this population. While "one size fits all" formulations of the "conversion" of psychological distress into physical symptoms are no longer widely accepted, emotion processing and related psychological constructs (eg, alexithymia, dissociation, threat avoidance) remain central to the conceptual understanding of FND. Furthermore, the biopsychosocial model (foundational to psychiatry) is the prevailing model through which to guide longitudinal treatment, with psychotherapy as an emerging first line intervention for FND. Nonetheless, there is a striking dearth of psychotherapists and mental health providers more broadly that feel well versed in the clinical assessment and management of patients with FND. In this article, we seek to address this gap by presenting the psychotherapy treatment narrative of a woman experiencing paroxysmal functional speech and gait disorder symptoms who had a positive clinical outcome. Our goal with this case presentation and related discussion is to increase the proficiency of psychotherapists in providing treatment to patients with FND.

Dose-dependent opposite effects of nortriptyline on affective-like behavior in adolescent rats: Comparison with adult rats.

Antidepressant drugs elicit different behavioral and neurochemical responses with age. In fact, the use of antidepressants during adolescence is associated with an increased risk of suicidal thinking, being the best pharmacological treatment during this critical period a matter of constant debate in terms of its risk-benefit outcome. In this regard, the present study compared the effects of nortriptyline (3-10 mg/kg, 7 days) on regulating different aspects of affective-like behavior by screening adolescent and adult Sprague-Dawley rats through several consecutive tests (forced-swim, open field, sucrose preference). Brains were later collected to evaluate hippocampal neurogenesis and mBDNF protein content as potential molecular correlates of the observed behavioral responses. The main results in adolescent rats showed that nortriptyline induced dose-dependent opposite effects: while 3 mg/kg decreased immobility and increased mBDNF (indicative of an antidepressant-like response), 10 mg/kg decreased exploratory time in the open field and mBDNF (suggestive of an anxiogenic-like response). These effects were not associated with changes in neurogenesis regulation. In adult rats, nortriptyline failed to modulate affective-like behavior or the neuroplasticity markers evaluated at the doses tested. In conclusion, clear behavioral and neurochemical differences were observed between adolescent and adult rats in response to nortriptyline treatment. Interestingly, while nortriptyline displayed an antidepressant-like potential at the lowest dose examined in adolescence, a higher dose shifted these results towards a negative outcome, thus reinforcing the need to extreme caution when considering this treatment for our younger population.

Alexithymia Is Associated With Internalizing Disorders in a Clinical Adolescent Outpatient Sample.

ABSTRACT: The aim of this study was to investigate alexithymic traits in an adolescent clinical sample with internalizing and externalizing disorders. The study group consisted of 125 adolescents aged between 12 and 17 years who applied at our outpatient unit and diagnosed with an internalizing or externalizing disorder. The healthy control group consisted of 53 adolescents with no psychiatric disorder. All subjects fulfilled the Alexithymia Questionnaire for Children (AQC). Total AQC scores were higher in the study group than in the control group. When we divided the study group into two groups as internalizing and externalizing disorders, total AQC scores, AQC-difficulty identifying feelings, and AQC-difficulty describing feelings were significantly higher in the internalizing disorder group than in the externalizing disorder group. AQC-externally oriented thinking scores were significantly higher in the externalizing disorder group than in the internalizing disorder group. In future research, it would be useful to further increase understanding of alexithymia and its association with psychiatric disorders in adolescence.

Structural atrophy of the right superior frontal gyrus in adolescents with severe irritability.

Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. One hundred and eight adolescents (46 youths with severe irritability and 62 healthy youths, average age = 14.08 years, standard deviation = 2.36) were scanned with a T1-weighted MRI sequence. The severity of irritability was measured using the affective reactivity index. In youths with severe irritability, there was decreased CT, GMV, and LGI in the right superior frontal gyrus (SFG) compared to healthy youths, and negative correlations between these indices of the SFG and irritability. Our findings suggest that structural deficits in the SFG, potentially related to its role in inhibitory control, may be critical for the neurobiology of irritability.

Insula reactivity mediates subjective isolation stress in alexithymia.

The risk for developing stress-related disorders is elevated in individuals with high alexithymia, a personality trait characterized by impaired emotional awareness and interpersonal relating. However, it is still unclear how alexithymia alters perceived psychosocial stress and which neurobiological substrates are mechanistically involved. To address this question, we examined freshmen during transition to university, given that this period entails psychosocial stress and frequently initiates psychopathology. Specifically, we used a functional magnetic resonance imaging emotional face matching task to probe emotional processing in 54 participants (39 women) at the beginning of the first year at university and 6 months later. Furthermore, we assessed alexithymia and monitored perceived psychosocial stress and loneliness via questionnaires for six consecutive months. Perceived psychosocial stress significantly increased over time and initial alexithymia predicted subjective stress experiences via enhanced loneliness. On the neural level, alexithymia was associated with lowered amygdala responses to emotional faces, while loneliness correlated with diminished reactivity in the anterior insular and anterior cingulate cortex. Furthermore, insula activity mediated the association between alexithymia and loneliness that predicted perceived psychosocial stress. Our findings are consistent with the notion that alexithymia exacerbates subjective stress via blunted insula reactivity and increased perception of social isolation.

Chronic unpredictable stress during adolescence protects against adult traumatic brain injury-induced affective and cognitive deficits.

Pre-clinical early-life stress paradigms model early adverse events in humans. However, the long-term behavioral consequences of early-life adversities after traumatic brain injury (TBI) in adults have not been examined. In addition, endocannabinoids may protect against TBI neuropathology. Hence, the current study assessed the effects of adverse stress during adolescence on emotional and cognitive performance in rats sustaining a TBI as adults, and how cannabinoid receptor 1 (CB1) activation impacts the outcome. On postnatal days (PND) 30-60, adolescent male rats were exposed to four weeks of chronic unpredictable stress (CUS), followed by four weeks of no stress (PND 60-90), or no stress at any time (Control), and then anesthetized and provided a cortical impact of moderate severity (2.8 mm tissue deformation at 4 m/s) or sham injury. TBI and Sham rats (CUS and Control) were administered either arachidonyl-2'-chloroethylamide (ACEA; 1 mg/kg, i.p.), a CB1 receptor agonist, or vehicle (VEH; 1 mL/kg, i.p.) immediately after surgery and once daily for 7 days. Anxiety-like behavior was assessed in an open field test (OFT) and learning and memory in novel object recognition (NOR) and Morris water maze (MWM) tasks. No differences were revealed among the Sham groups in any behavioral assessment and thus the groups were pooled. In the ACEA and VEH-treated TBI groups, CUS increased exploration in the OFT, enhanced NOR focus, and decreased the time to reach the escape platform in the MWM, suggesting decreased anxiety and enhanced learning and memory relative to the Control group receiving VEH (p < 0.05). ACEA also enhanced NOR and MWM performance in the Control + TBI group (p < 0.05). These data suggest that 4 weeks of CUS provided during adolescence may provide protection against TBI acquired during adulthood and/or induce adaptive behavioral responses. Moreover, CB1 receptor agonism produces benefits after TBI independent of CUS protection.

BNST and amygdala connectivity are altered during threat anticipation in schizophrenia.

In schizophrenia, impairments in affect are prominent and anxiety disorders are prevalent. Neuroimaging studies of fear and anxiety in schizophrenia have focused on the amygdala and show alterations in connectivity. Emerging evidence suggests that the bed nucleus of the stria terminalis (BNST) also plays a critical role in anxiety, especially during anticipation of an unpredictable threat; however, previous studies have not examined the BNST in schizophrenia. In the present study, we examined BNST function and connectivity in people with schizophrenia (n = 31; n = 15 with comorbid anxiety) and controls (n = 15) during anticipation of unpredictable and predictable threat. A secondary analysis tested for differences in activation and connectivity of the central nucleus of the amygdala (CeA), which has also been implicated in threat anticipation. Analyses tested for group differences in both activation and connectivity during anticipation of unpredictable threat and predictable threat (p < .05). Relative to controls, individuals with schizophrenia showed stronger BNST-middle temporal gyrus (MTG) connectivity during unpredictable threat anticipation and stronger BNST-MTG and BNST-dorsolateral prefrontal connectivity during predictable threat anticipation. Comparing subgroups of individuals with schizophrenia and a comorbid anxiety disorder (SZ+ANX) to those without an anxiety disorder (SZ-ANX) revealed broader patterns of altered connectivity. During unpredictable threat anticipation, the SZ+ANX group had stronger BNST connectivity with regions of the salience network (insula, dorsal anterior cingulate cortex). During predictable threat anticipation, the SZ+ANX group had stronger BNST connectivity with regions associated with fear processing (insula, extended amygdala, prefrontal cortex). A secondary CeA analysis revealed a different pattern; the SZ+ANX group had weaker CeA connectivity across multiple brain regions during threat anticipation compared to the SZ-ANX group. These findings provide novel evidence for altered functional connectivity during threat anticipation in schizophrenia, especially in individuals with comorbid anxiety.

Association between symptoms, affect and heart rhythm in patients with persistent or paroxysmal atrial fibrillation: an ambulatory pilot study.

Symptoms in atrial fibrillation are generally assumed to correspond to heart rhythm; however, patient affect - the experience of feelings, emotion or mood - is known to frequently modulate how patients report symptoms but this has not been studied in atrial fibrillation. In this study, we investigated the relationship between affect, symptoms and heart rhythm in patients with paroxysmal or persistent atrial fibrillation. We found that presence of negative affect portended reporting of more severe symptoms to the same or greater extent than heart rhythm.

A psychoacoustic test for misophonia assessment.

Misophonia is a condition where a strong arousal response is triggered when hearing specific human generated sounds, like chewing, and/or repetitive tapping noises, like pen clicking. It is diagnosed with clinical interviews and questionnaires since no psychoacoustic tools exist to assess its presence. The present study was aimed at developing and testing a new assessment tool for misophonia. The method was inspired by an approach we have recently developed for hyperacusis. It consisted of presenting subjects (n = 253) with misophonic, pleasant, and unpleasant sounds in an online experiment. The task was to rate them on a pleasant to unpleasant visual analog scale. Subjects were labeled as misophonics (n = 78) or controls (n = 55) by using self-report questions and a misophonia questionnaire, the MisoQuest. There was a significant difference between controls and misophonics in the median global rating of misophonic sounds. On the other hand, median global rating of unpleasant, and pleasant sounds did not differ significantly. We selected a subset of the misophonic sounds to form the core discriminant sounds of misophonia (CDSMiso). A metric: the CDS score, was used to quantitatively measure misophonia, both with a global score and with subscores. The latter could specifically quantify aversion towards different sound sources/events, i.e., mouth, breathing/nose, throat, and repetitive sounds. A receiver operating characteristic analysis showed that the method accurately classified subjects with and without misophonia (accuracy = 91%). The present study suggests that the psychoacoustic test we have developed can be used to assess misophonia reliably and quickly.

Individual differences in sensory and expectation driven interoceptive processes: a novel paradigm with implications for alexithymia, disordered eating and obesity.

Those with disordered eating and/or obesity often express difficulties in sensing or interpreting what is happening in the body (interoception). However, research is hindered by conceptual confusion, concerns surrounding domain specificity, and an inability to distinguish sensory (bottom-up) and expectation driven (top-down) interoceptive processes. A paradigm was therefore developed from an active inference perspective. Novel indices were computed and examined in those with alexithymia: a personality associated with interoceptive deficits and disordered eating. The paradigm successfully identified individuals driven by sensations rather than expectations: alexithymia was characterized by attenuated prior precision (a larger divergence between pre-prandial and post-prandial satiety, and low expectation confidence), and increased prediction error (a higher correlation between changes in hunger and blood glucose, and greater rebound hunger after a sensory incongruent drink). In addition, those with a higher BMI were less confident and had a larger anticipated satiety divergence. These findings demonstrate the need to move beyond existing paradigms such as the Satiety Quotient and Heartbeat Counting Task which may have limited our understanding of eating behaviour.

Emotional and behavioral problems in pediatric patients with migraine and tension-type headache.

OBJECTIVE: This study aimed to investigate the associations between psychopathological characteristics of children and adolescents with primary headache, as measured by the Strengths and Difficulties Questionnaire (SDQ), and treatment outcomes. METHODS: A cohort study was conducted on 124 pediatric patients with primary headache. At the first consultation, the SDQ was completed by the parents. The analysis of treatment efficacy was conducted on 90 patients with a follow-up period of at least one year. Treatment responders were defined as those who showed 50% reduction in the headache frequency. First, an analysis of the SDQ total scores and five subscales, among the migraine and tension-type headache groups, was conducted for 124 participants. Second, the association between the SDQ scores and treatment outcomes in the groups with periods of improvement of less than three months and three months or more were analyzed in 90 patients. RESULTS: Migraine patients displayed more difficulties than strengths in terms of the total score (p = .004) and in the emotional symptoms subscale (p = .012) compared with tension-type headache patients. Migraine patients who required more than three months to show improvement displayed more peer problems (p = .020), while tension-type headache patients who required more than three months to show improvement displayed fewer conduct problems (p = .007). CONCLUSION: Evaluation of patient characteristics using the SDQ at first consultation can predict the treatment outcome. Moreover, it can help provide appropriate initial treatment and improve outcome of primary headache in children.

The Motor Basis for Misophonia.

Misophonia is a common disorder characterized by the experience of strong negative emotions of anger and anxiety in response to certain everyday sounds, such as those generated by other people eating, drinking, and breathing. The commonplace nature of these "trigger" sounds makes misophonia a devastating disorder for sufferers and their families. How such innocuous sounds trigger this response is unknown. Since most trigger sounds are generated by orofacial movements (e.g., chewing) in others, we hypothesized that the mirror neuron system related to orofacial movements could underlie misophonia. We analyzed resting state fMRI (rs-fMRI) connectivity (N = 33, 16 females) and sound-evoked fMRI responses (N = 42, 29 females) in misophonia sufferers and controls. We demonstrate that, compared with controls, the misophonia group show no difference in auditory cortex responses to trigger sounds, but do show: (1) stronger rs-fMRI connectivity between both auditory and visual cortex and the ventral premotor cortex responsible for orofacial movements; (2) stronger functional connectivity between the auditory cortex and orofacial motor area during sound perception in general; and (3) stronger activation of the orofacial motor area, specifically, in response to trigger sounds. Our results support a model of misophonia based on "hyper-mirroring" of the orofacial actions of others with sounds being the "medium" via which action of others is excessively mirrored. Misophonia is therefore not an abreaction to sounds, per se, but a manifestation of activity in parts of the motor system involved in producing those sounds. This new framework to understand misophonia can explain behavioral and emotional responses and has important consequences for devising effective therapies.SIGNIFICANCE STATEMENT Conventionally, misophonia, literally "hatred of sounds" has been considered as a disorder of sound emotion processing, in which "simple" eating and chewing sounds produced by others cause negative emotional responses. Our data provide an alternative but complementary perspective on misophonia that emphasizes the action of the trigger-person rather than the sounds which are a byproduct of that action. Sounds, in this new perspective, are only a "medium" via which action of the triggering-person is mirrored onto the listener. This change in perspective has important consequences for devising therapies and treatment methods for misophonia. It suggests that, instead of focusing on sounds, which many existing therapies do, effective therapies should target the brain representation of movement.

Effect of Exenatide Use on Cognitive and Affective Functioning in Obese Patients With Type 2 Diabetes Mellitus: Exenatide Use Mediates Depressive Scores Through Increased Perceived Stress Levels.

PURPOSE/BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a molecule used to treat type 2 diabetes mellitus (T2DM). Given their widespread expression in the nervous system, GLP-1 receptors also play a role in regulating mood and cognitive function. Here, we aimed to compare obese patients with T2DM, with or without exenatide (a GLP-1R agonist) use on cognitive and affective functioning. METHODS/PROCEDURES: A total of 43 patients with T2DM (23 on exenatide and 20 without exenatide) were evaluated with the Snaith-Hamilton Pleasure Scale, Cognitive Failures Questionnaire, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7, Childhood Trauma Questionnaire, Perceived Stress Scale (PSS), and Chronic Stress Scale, in addition to laboratory-based measures of reward learning (the probabilistic reward task) and working memory (Letter-N-Back task). FINDINGS/RESULTS: Patients on exenatide had higher body mass index (BMI) (37.88 ± 5.44 vs 35.29 ± 6.30; P = 0.015), PHQ-9 (9.70 ± 4.92 vs 6.70 ± 4.66; P = 0.026), and PSS (29.39 ± 6.70 vs 23.35 ± 7.69; P = 0.015) scores. Other stress scales (Childhood Trauma Questionnaire and Chronic Stress Scale), Generalized Anxiety Disorder-7 scores, response bias, or discriminability as assessed by probabilistic reward task and self-report (Cognitive Failures Questionnaire) and laboratory-based (Letter-N-Back) cognitive measures were not significantly different between groups (both Ps > 0.05). Multivariate linear regression analyses adding BMI and PSS as covariates revealed that although BMI had no effect (P = 0.5), PSS significantly predicted PHQ-9 scores (P = 0.004). Mediation analysis showed that exenatide users reported higher PSS, with greater PSS associated with higher PHQ-9 levels (b = 0.236). There was no evidence on exenatide directly influencing PHQ-9 independent of PSS (c' = 1.573; P = 0.305; 95% bootstrap confidence interval, -1.487 to 4.634). IMPLICATIONS/CONCLUSIONS: Based on previous research and our findings, exenatide use might be mediating depression scores through disrupting stress responses.

Frontotemporal Dementia: A Window to Alexithymia.

Alexithymia is pervasive among psychiatric patients, but its neurobiological mechanism is unclear. Patients with alexithymia cannot "read emotions," a process involving interoception, or the perception of the body's internal state, primarily in the insulae. The frontotemporal dementias are also associated with inability to correctly read emotions; hence, these dementias can provide a window into the mechanism of alexithymia. Patients with behavioral variant frontotemporal dementia (bvFTD) have a weak emotional signal with impaired emotional recognition, hypoemotionality, and decreased physiological arousal. bvFTD affects the insulae, and the weak emotional signal facilitates impaired interoceptive accuracy, resulting in an overreliance on cognitive appraisal rather than on internal sensations. In contrast, patients with semantic dementia, another frontotemporal dementia syndrome, can have intact interoception, but they have disturbed cognitive appraisal of the meaning of their bodily sensations. This "alexisomia" in semantic dementia can lead to misinterpreted somatic symptoms. Together, the findings in alexithymic patients and frontotemporal dementia syndromes support the model of impaired interoceptive accuracy as the mechanism of alexithymia, possibly from dysfunction in the insulae.