Basolateral Amygdala Functional Connectivity in Alexithymia: Linking Interoceptive Sensibility and Cognitive Empathy.

Emotions rely on bodily states, and perceiving the emotions of others depends on awareness of one's own emotional state. However, the intercorrelations among interoception, alexithymia, and empathy are not well understood, and the neural mechanisms behind this connection are also largely unknown. To address these issues, 297 college students participated in this study, completing measures of interoceptive sensibility (IS), empathy and alexithymia and undergoing resting-state fMRI scans. The functional connectivity of the amygdala was analysed to identify the neural substrates of alexithymia, and mediation analyses were conducted to examine the mediation effect of alexithymia and alexithymia-specific amygdala functional connectivity on the relationship between IS and empathy. The results showed that higher levels of IS were associated with increased cognitive empathy through weakened alexithymia. Functional connectivity analysis indicated that right basolateral amygdala (BLA)-left precuneus connectivity was negatively related to alexithymia, while right BLA-left precentral gyrus connectivity was positively related to alexithymia. Furthermore, right BLA-left precuneus connectivity was found to mediate the impact of interoception on cognitive empathy. In conclusion, this study provides valuable insights into the relationships among IS, alexithymia, and empathy. The right BLA-left precuneus connectivity may serve as a shared neural substrate between interoception and cognitive empathy.

Neural correlates of perceptual switching and their association with empathy and alexithymia in individuals with and without autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) often show limited empathy (poor recognition of others' emotions) and high alexithymia (poor recognition of own emotions and external thinking), which can negatively impact their social functioning. Previous experimental studies suggest that alterations in cognitive flexibility play key roles in the development of these characteristics in ASD. However, the underlying neural mechanisms that link cognitive flexibility and empathy/alexithymia are still largely unknown. In this study, we examined the neural correlates of cognitive flexibility via functional magnetic resonance imaging during perceptual task-switching in typical development (TD) adults and adults with ASD. We also investigated associations between regional neural activity and psychometric empathy and alexithymia scores among these populations. In the TD group, stronger activation of the left middle frontal gyrus was associated with better perceptual switching and greater empathic concern. Among individuals with ASD, stronger activation of the left inferior frontal gyrus was associated with better perceptual switching, greater empathy, and lower alexithymia. These findings will contribute to develop a better understanding of social cognition, and could be informative for the development of new ASD therapies.

The relationship between alexithymia, interoception, and neural functional connectivity during facial expression processing in autism spectrum disorder.

Neural processing differences of emotional facial expressions, while common in autism spectrum disorder (ASD), may be related to co-occurring alexithymia and interoceptive processing differences rather than autism per se. Here, we investigate relationships between alexithymia, interoceptive awareness of emotions, and functional connectivity during observation of facial expressions in youth (aged 8-17) with ASD (n = 28) compared to typically developing peers (TD; n = 37). Behaviorally, we found no significant differences between ASD and TD groups in interoceptive awareness of emotions, though alexithymia severity was significantly higher in the ASD group. In the ASD group, increased alexithymia was significantly correlated with lower interoceptive sensation felt during emotion. Using psycho-physiological interaction (PPI) analysis, the ASD group showed higher functional connectivity between the left ventral anterior insula and the left lateral prefrontal cortex than the TD group when viewing facial expressions. Further, alexithymia was associated with reduced left anterior insula-right precuneus connectivity and reduced right dorsal anterior insula-left ventral anterior insula connectivity when viewing facial expressions. In the ASD group, the degree of interoceptive sensation felt during emotion was positively correlated with left ventral anterior insula-right IFG connectivity when viewing facial expressions. However, across all participants, neither alexithymia nor interoceptive awareness of emotions predicted connectivity between emotion-related brain regions when viewing emotional facial expressions. To summarize, we found that in ASD compared to TD: 1) there is stronger connectivity between the insula and lateral prefrontal cortex; and 2) differences in interhemispheric and within left hemisphere connectivity between the insula and other emotion-related brain regions are related to individual differences in interoceptive processing and alexithymia. These results highlight complex relationships between alexithymia, interoception, and brain processing in ASD.

Emotional recognition across the adult lifespan: Effects of age, sex, cognitive empathy, alexithymia traits, and amygdala subnuclei volumes.

The ability to recognize others' emotions is vital to everyday life. The goal of this study was to assess which emotions show age-related decline in recognition accuracy of facial emotional expressions across the entire adult lifespan and how this process is related to cognitive empathy (Theory of Mind [ToM]), alexithymia traits, and amygdala subnuclei volumes in a large cohort of healthy individuals. We recruited 140 healthy participants 18-85 years old. Facial affect processing was assessed with the Penn Emotion Recognition task (ER40) that contains images of the five basic emotions: Neutral, Happy, Sad, Angry, and Fearful. Structural magnetic resonance imaging (MRI) datasets were acquired on a 4.7T MRI system. Structural equation modeling was used to test the relationship between studied variables. We found that while both sexes demonstrated age-related reduction in recognition of happy emotions and preserved recognition of sadness, male participants showed age-related reduction in recognition of fear, while in female participants, age-related decline was linked to recognition of neutral and angry facial expressions. In both sexes, accurate recognition of sadness negatively correlated with alexithymia traits. On the other hand, better ToM capabilities in male participants were associated with improvement in recognition of positive and neutral emotions. Finally, none of the observed age-related reductions in emotional recognition were related to amygdala and its subnuclei volumes. In contrast, both global volume of amygdala and its cortical and centromedial subnuclei had significant direct effects on recognition of sad images.

White matter tracts associated with alexithymia and emotion regulation: A diffusion MRI study.

BACKGROUND: Alexithymia is a cognitive-affective impairment, suggested to be associated with emotion regulation. Herein, we investigated white matter (WM) tracts with Diffusion Magnetic Resonance Imaging (DMRI) connectometry approach using quantitative anisotropy (QA) tractography to discover possible associations between the emotion identification and regulation patterns and WM tracts. METHODS: DMRI data were acquired from 218 healthy subjects aging 39.15 ± 20.19 who filled the Toronto Alexithymia Scale (TAS) and emotion regulation questionnaire (ERQ) from the LEMON dataset. Connectometry analysis was applied on WM tracts in DMRI images. RESULTS: DMRI connectometry analysis revealed a significant correlation between TAS identification score and increased microstructural connectivity in WM pathways, including the body of corpus callosum (CC), bilateral fornix, and left arcuate fasciculus (AF) in males (FDR = 0.028), and corticospinal and cingulum tracts in females (FDR = 0.026). Furthermore, we found a significant positive correlation between overall TAS score and fornix properties in men (FDR = 0.026) and corticospinal tracts in women (FDR = 0.028). Middle cerebellar peduncle negatively correlated with describing emotion (FDR = 0.025) and the splenium of the CC and corticospinal tracts negatively correlated with this subscale (FDR = 0.049) in male group. However, the splenium of the CC, corticospinal tracts, and left AF positively associated with this subscale (FDR = 0.029). The splenium of the CC was negatively related to externally-oriented thinking among men (FDR = 0.038). Our results showed marginally associations between ERQ and similar WM tracts. CONCLUSION: Certain WM microstructures significantly correlate with emotion identification and regulation. These tracts are associated with specific somatosensory areas, language processing areas, and limbic area.

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.

White matter microstructural integrity correlates of emotion dysregulation in children with ADHD: A diffusion imaging tractography study.

BACKGROUND: Emotion dysregulation (ED) is prevalent in youths with attention-deficit hyperactivity disorder (ADHD) and causes more social impairment and poor adaptive function. Alterations in the integrity of white matter (WM) tracts might have important implications for affective processing related to ED. However, little is known about the WM correlates underpinning ED in ADHD. METHODS: Using diffusion spectrum image tractography, we obtained generalized fractional anisotropy (GFA) values of 76 WM tracts in 77 children with ADHD and 105 typically developing controls (TDC). ED severity was defined by the dysregulation profile from the child behavior checklist. Canonical correlation analysis (CCA) was performed to identify modes that relate WM microstructural property to ED severity and cognitive measures. RESULTS: The application of CCA identified one significant mode (r = 0.638, FWE-corrected p = 0.046) of interdependencies between WM property patterns and diagnosis, ADHD total symptom levels, dysregulation by diagnosis interaction, and full-scale intellectual quotient (FIQ). GFA values of 19 WM tracts that were linked to affective-processing, sensory-processing and integration, and cognitive control circuitry were positively correlated with ED severity in TDC but negatively correlated with ED severity in ADHD. ADHD symptom severity and diagnosis were negatively associated with the GFA patterns of this set of tract bundles. In contrast, FIQ was positively correlated with this set of tract bundles. CONCLUSIONS: This study used the CCA to show that children with ADHD and TDC had distinct multivariate associations between ED severity (diagnosis by ED interaction) and microstructural property in a set of WM tracts. These tracts interconnect the cortical regions that are principally involved in emotion processing, integration, and cognitive control in multiple brain systems. The WM microstructure integrity impairment might be an essential correlate of emotion dysregulation in ADHD.

The relationship between ambivalence, alexithymia, and salience network dysfunction in schizophrenia.

Ambivalence in schizophrenia is worth investigating its association with salience processing and alexithymia using functional MRI. Twenty-two patients with schizophrenia and 22 healthy controls were scanned during the ambivalence task of matching picture (ambivalent, positive and negative) and word (positive and negative) stimuli, and the Toronto Alexithymia Scale (TAS) was rated. Patients exhibited decreased activity in the anterior cingulate cortex (ACC) and insula compared to controls, and ACC activity in the ambivalent condition was negatively correlated with the TAS score in patients. Ambivalence in schizophrenia may be based on salience network dysfunction, and this disturbance may be related to alexithymia.

Opposing relationships of childhood threat and deprivation with stria terminalis white matter.

While stress may be a potential mechanism by which childhood threat and deprivation influence mental health, few studies have considered specific stress-related white matter pathways, such as the stria terminalis (ST) and medial forebrain bundle (MFB). Our goal was to examine the relationships between childhood adversity and ST and MFB structural integrity and whether these pathways may provide a link between childhood adversity and affective symptoms and disorders. Participants were young adults (n = 100) with a full distribution of maltreatment history and affective symptom severity. Threat was determined by measures of childhood abuse and repeated traumatic events. Socioeconomic deprivation (SED) was determined by a measure of childhood socioeconomic status (parental education). Participants underwent diffusion spectrum imaging. Human Connectome Project data was used to perform ST and MFB tractography; these tracts were used as ROIs to extract generalized fractional anisotropy (gFA) from each participant. Childhood threat was associated with ST gFA, such that greater threat was associated with less ST gFA. SED was also associated with ST gFA, however, conversely to threat, greater SED was associated with greater ST gFA. Additionally, threat was negatively associated with MFB gFA, and MFB gFA was negatively associated with post-traumatic stress symptoms. Our results suggest that childhood threat and deprivation have opposing influences on ST structural integrity, providing new evidence that the context of childhood adversity may have an important influence on its neurobiological effects, even on the same structure. Further, the MFB may provide a novel link between childhood threat and affective symptoms.

Emotion processing and regulation in major depressive disorder: A 7T resting-state fMRI study.

Dysfunctions in bottom-up emotion processing (EP), as well as top-down emotion regulation (ER) are prominent features in pathophysiology of major depressive disorder (MDD). Nonetheless, it is not clear whether EP- and ER-related areas are regionally and/or connectively disturbed in MDD. In addition, it is yet to be known how EP- and ER-related areas are interactively linked to regulatory behavior, and whether this interaction is disrupted in MDD. In our study, regional amplitude of low frequency fluctuations (ALFF) and whole-brain functional connectivity (FC) of meta-analytic-driven EP- and ER-related areas were compared between 32 healthy controls (HC) and 20 MDD patients. Then, we aimed to investigate whether the EP-related areas can predict the ER-related areas and regulatory behavior in both groups. Finally, the brain-behavior correlations between the EP- and ER-related areas and depression severity were assessed. We found that: (a) affective areas are regionally and/or connectively disturbed in MDD; (b) EP-ER interaction seems to be disrupted in MDD; overburden of emotional reactivity in amygdala may inversely affect cognitive control processes in prefrontal cortices, which leads to diminished regulatory actions. (c) Depression severity is correlated with FC of affective areas. Our findings shed new lights on the neural underpinning of affective dysfunctions in depression.

Temporally and sex-specific effects of maternal perinatal stress on offspring cortical gyrification and mood in young adulthood.

Maternal stress during pregnancy and shortly thereafter is associated with altered offspring brain development that may increase risk of mood and anxiety disorders. Cortical gyrification is established during the prenatal period and the first 2 years of life and is altered in psychiatric disorders. Here, we sought to characterize the effects of perinatal stress exposure on offspring gyrification patterns and mood dysregulation in young adulthood. Participants included 85 young adults (56.5% women; 23-24 years) from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) with perinatal stress data across four distinct timepoints and structural MRI data from young adulthood. Perinatal stress exposure was measured as maternal stress during first and second half of pregnancy, first 6 months, and 6-18 months after birth. Cortical gyrification and mood dysregulation were quantified using local gyrification index (LGI), computed with Freesurfer, and the Profile of Mood States questionnaire, respectively. Perinatal stress predicted cortical gyrification in young adulthood, and its timing influenced location, direction, and sex-specificity of effects. In particular, whereas early prenatal stress was associated with sex-dependent medium-to-large effects in large temporal, parietal, and occipital regions (f2 = 0.19-0.38, p < .001), later perinatal stress was associated with sex-independent small-to-medium effects in smaller, more anterior regions (f2 = 0.10-0.19, p < .003). Moreover, in females, early prenatal stress predicted higher LGI in a large temporal region, which was further associated with mood disturbance in adulthood (r = 0.399, p = .006). These findings point out the long-term implications of perinatal stress exposure for cortical morphology and mood dysregulation.

Neural basis of shame and guilt experience in women with borderline personality disorder.

Borderline personality disorder (BPD) is characterized by instability of affect, emotion dysregulation, and interpersonal dysfunction. Especially shame and guilt, so-called self-conscious emotions, are of central clinical relevance to BPD. However, only few experimental studies have focused on shame or guilt in BPD and none investigated their neurobiological underpinnings. In the present functional magnetic resonance imaging study, we took a scenario-based approach to experimentally induce feelings of shame, guilt, and disgust with neutral scenarios as control condition. We included 19 women with BPD (age 26.4 ± 5.8 years; DSM-IV diagnosed; medicated) and 22 healthy female control subjects (age 26.4 ± 4.6 years; matched for age and verbal IQ). Compared to controls, women with BPD reported more intense feelings when being confronted with affective scenarios, especially higher levels of shame, guilt, and fear. We found increased amygdala reactivity in BPD compared to controls for shame and guilt, but not for disgust scenarios (p = 0.05 FWE corrected at the cluster level; p < 0.0001 cluster defining threshold). Exploratory analyses showed that this was caused by a diminished habituation in women with BPD relative to control participants. This effect was specific to guilt and shame scenarios as both groups showed amygdala habituation to disgust scenarios. Our work suggests that heightened shame and guilt experience in BPD is not related to increased amygdala activity per se, but rather to decreased habituation to self-conscious emotions. This provides an explanation for the inconsistencies in previous imaging work on amygdala involvement in BPD as well as the typically slow progress in the psychotherapy of dysfunctional self-conscious emotions in this patient group.

Distinct associations of DSM-5 Somatic Symptom Disorder, the Diagnostic Criteria for Psychosomatic Research-Revised (DCPR-R) and symptom severity in patients with irritable bowel syndrome.

OBJECTIVE: The clinical management of high symptom severity is a challenging task with patients with functional somatic disorders. We investigated the extent to which DCPR-revised (DCPR-R) syndromes and the DSM-5 category of Somatic Symptom Disorder (SSD) were able to predict symptom severity in 203 consecutive tertiary care patients with irritable bowel syndrome (IBS). METHOD: Semistructured interview were used for assessing DCPR-R and validated scales for SSD (combining PHQ-12 and WI-7), severity of symptoms (IBS-SSS), psychological distress (HADS), and psychosocial functioning (SF-12). RESULTS: Compared to moderate severity (IBS-SSS = 175-300), patients in the high range of severity (IBS-SSS > 300) had significantly more DCPR-R syndromes (particularly alexithymia and persistent somatization), higher psychological distress, and poorer psychosocial functioning, but showed no difference for SSD. DCPR-R, particularly alexithymia and persistent somatization, significantly and independently predicted IBS severity by explaining 18.5% of the IBS-SSS variance with large effect size (d = 1.18), after controlling for covariables. Conversely, SSD was not able to significantly predict IBS severity. CONCLUSIONS: This study highlights the need of an integrative approach in the medical setting. Psychosomatic factors play a relevant role in the individual perception of symptom severity and should be carefully evaluated for clinical management of functional syndromes.

Deciphering the neural underpinnings of alexithymia in multiple sclerosis.

OBJECTIVES: Alexithymia is a personality construct that could occur in up to 53 % of patients with multiple sclerosis (MS). It entails difficulties in identifying and describing one's feelings and an externally oriented thinking. The current work aims to assess the neural underpinnings of alexithymia in this population. METHODS: Forty-five patients with MS filled in the Toronto Alexithymia Scale (n = 17 with high alexithymia and n = 28 with low alexithymia). Brain magnetic resonance imaging was obtained for each patient and a morphometry algorithm (MorphoBox) was applied to calculate regional brain volumes. All patients underwent a clinical and neuropsychological evaluation which included measures for anxiety, depression, fatigue, daytime sleepiness, and basic and social cognition. RESULTS: Compared to patients with low alexithymia, patients with high alexithymia had significantly higher fatigue and depression ratings, and lower empathy scores. In addition, they had lower volumes of corpus callosum, deep white matter, pallidum bilaterally, and left thalamus. In the whole cohort, alexithymia scores were inversely correlated with gray matter (thalamus and pallidum bilaterally) and white matter volumes (corpus callosum and bilateral deep white matter) after controlling for covariates (ps<0.05). CONCLUSION: This study offers insights on the neuropsychological and neural substrates of alexithymia in MS. The current findings are consistent with alexithymia reports in other clinical populations, and suggest an association between alexithymia and atrophy of thalami, pallidum, corpus callosum and deep white matter in MS. Further research is needed to enhance the understanding of alexithymia mechanisms in this clinical context.

Alexithymia Is Associated with Altered Cortical Thickness Networks in the General Population.

BACKGROUND: Alexithymia is a personality trait characterized by difficulties in identifying and describing emotions and associated with various psychiatric disorders. Neuroimaging studies found evidence for morphological and functional brain alterations in alexithymic subjects. However, the neurobiological mechanisms underlying alexithymia remain incompletely understood. METHODS: We study the association of alexithymia with cortical correlation networks in a large community-dwelling sample of the Study of Health in Pomerania. Our analysis includes data of n = 2,199 individuals (49.4% females, age = 52.1 ± 13.6 years) which were divided into a low and high alexithymic group by a median split of the Toronto Alexithymia Scale. Cortical correlation networks were constructed based on the mean thicknesses of 68 regions, and differences in centralities were investigated. RESULTS: We found a significantly increased centrality of the right paracentral lobule in the high alexithymia network after correction for multiple testing. Several other regions with motoric and sensory functions showed altered centrality on a nominally significant level. CONCLUSIONS: Finding increased centrality of the paracentral lobule, a brain area with sensory as well as motoric features and involvement in bowel and bladder voiding, may contribute to explain the association of alexithymia with functional somatic disorders and chronic pain syndromes.

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

BACKGROUND: Affective 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. METHODS: Individuals with social anhedonia (n = 40) and healthy controls (n = 46) completed a social affective forecasting task and underwent resting-state fMRI scanning. RESULTS: Compared 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. CONCLUSIONS: These 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.

Insula Activity to Visceral Stimulation and Endocrine Stress Responses as Associated With Alexithymia in Patients With Irritable Bowel Syndrome.

OBJECTIVE: Few studies have investigated associations between alexithymia and physiological mechanisms in psychosomatic diseases. We examined associations between alexithymia and 1) perception and brain processing of visceral stimulation and 2) the endocrine responses to corticotrophin-releasing hormone (CRH) in healthy individuals and patients with irritable bowel syndrome (IBS). METHODS: The study included 29 patients with IBS and 35 age- and sex-matched healthy controls (HCs). Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20). Brain responses to rectal distention and its anticipation were measured by functional magnetic resonance imaging and analyzed at a voxel-level threshold of puncorrected < .001 combined with a cluster-level threshold of pFWE-corrected < .05. On a different day, plasma adrenocorticotropic hormone and cortisol responses after intravenous CRH administration were measured. RESULTS: TAS-20 scores did not differ significantly between patients with IBS and HCs (p = .18). TAS-20 scores correlated positively with the individual rectal discomfort thresholds (ßrobust = 0.49, p = .03) and negatively with the rating of fear before rectal distention (ßrobust = -1.63, p = .04) in patients with IBS but not in HCs. Brain responses to rectal distention in the right insula and other brain regions were positively associated with TAS-20 scores to a greater extent in patients with IBS than in HCs. Individuals with higher TAS-20 scores (both patients with IBS and HCs) demonstrated stronger adrenocorticotropic hormone responses to CRH administration (F(4,224) = 3.54, p = .008). CONCLUSION: Higher alexithymia scores are associated with stronger physiological responses, but lower anticipatory fear ratings and higher discomfort thresholds, particularly in patients with IBS.

Transdiagnostic Prediction of Affective, Cognitive, and Social Function Through Brain Reward Anticipation in Schizophrenia, Bipolar Disorder, Major Depression, and Autism Spectrum Diagnoses.

The relationship between transdiagnostic, dimensional, and categorical approaches to psychiatric nosology is under intense debate. To inform this discussion, we studied neural systems linked to reward anticipation across a range of disorders and behavioral dimensions. We assessed brain responses to reward expectancy in a large sample of 221 participants, including patients with schizophrenia (SZ; n = 27), bipolar disorder (BP; n = 28), major depressive disorder (MD; n = 31), autism spectrum disorder (ASD; n = 25), and healthy controls (n = 110). We also characterized all subjects with an extensive test battery from which a cognitive, affective, and social functioning factor was constructed. These factors were subsequently related to functional responses in the ventral striatum (vST) and neural networks linked to it. We found that blunted vST responses were present in SZ, BP, and ASD but not in MD. Activation within the vST predicted individual differences in affective, cognitive, and social functioning across diagnostic boundaries. Network alterations extended beyond the reward network to include regions implicated in executive control. We further confirmed the robustness of our results in various control analyses. Our findings suggest that altered brain responses during reward anticipation show transdiagnostic alterations that can be mapped onto dimensional measures of functioning. They also highlight the role of executive control of reward and salience signaling in the disorders we study and show the power of systems-level neuroscience to account for clinically relevant behaviors.

Brain structural correlates of alexithymia in patients with major depressive disorder

Background: Alexithymia is a risk factor for major depressive disorder (MDD) and has been associated with diminished treatment response. Neuroimaging studies have revealed structural aberrations of the anterior cingulate cortex and the fusiform gyrus in healthy controls with high levels of alexithymia. The present study tried to corroborate and extend these results to patients with MDD compared with healthy controls. Methods: We investigated the relationship between alexithymia, depression and grey matter volume in 63 patients with MDD (mean age ± standard deviation = 42.43 yr ± 11.91; 33 female) and 46 healthy controls (45.35 yr ± 8.37; 22 female). We assessed alexithymia using the Toronto Alexithymia Scale. We conducted an alexithymia × group analysis of covariance; we used a region-of-interest approach, including the fusiform gyrus and anterior cingulate cortex, and conducted whole brain analysis using voxelbased morphometry. Results: Our analysis revealed a significant alexithymia × group interaction in the fusiform gyrus (left, pFWE = 0.031; right, pFWE = 0.010). Higher alexithymia scores were associated with decreased grey matter volume in patients with MDD (pFWE = 0.009), but with increased grey matter volume of the fusiform gyrus in healthy controls (pFWE = 0.044). We found no significant main effects in the region-of-interest analysis. Limitations: Owing to the naturalistic nature of our study, patients with MDD and healthy controls differed significantly in their alexithymia scores. Conclusion: Our results showed the fusiform gyrus as a correlate of alexithymia. We also found differences related to alexithymia between patients with MDD and healthy controls in the fusiform gyrus. Our study encourages research related to the transition from risk to MDD in people with alexithymia.