Prediction of estimated risk for bipolar disorder using machine learning and structural MRI features.

BACKGROUND: Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features. METHODS: Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar). RESULTS: For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11-0.361) and a balanced accuracy of 63.1% (95% CI 55.9-70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI -0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6-67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance. CONCLUSIONS: Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.

Acute experimental inflammation in healthy women attenuates empathy for psychological pain.

Administration of low-dose lipopolysaccharide (LPS) to healthy humans is a translational approach to analyze the effects of acute systemic inflammation and sickness behavior. Although studies documented that LPS-induced inflammation can alter social behavior, its impact on empathy remains poorly understood. In this double-blind, placebo-controlled study, 52 healthy female volunteers received an intravenous injection of either LPS (0.4 ng/kg body weight) or placebo and completed the Social Interaction Empathy Task (SIET) two hours after injection. Physiological responses (blood pressure, heart rate, body temperature, cytokines, cortisol) were analyzed along with sickness symptoms and mood before and after LPS or placebo administration. LPS application led to significant increases in plasma cytokines and sickness symptoms as well as low mood. Moreover, volunteers receiving LPS showed significantly less empathy for other's psychological pain than those who received placebo. Furthermore, LPS-injected volunteers with more severe sickness symptoms displayed higher pain ratings in the first-person perspective. Thus, low-grade inflammation reduces empathy for other's psychological pain which might reflect an adaptive strategy to save energy by not responding empathetically when sick oneself.

Microbiome composition and central serotonergic activity in patients with depression and type 1 diabetes.

The role of gut-brain axis functioning gains growing attention in research on the pathophysiology of major depressive disorders. Here, especially consequences of altered microbiota composition on tryptophan metabolism resulting in altered serotonergic neurotransmission in the central nervous system (CNS) have reached a central position. Previous research, however, mainly focused on either microbiota and peripheral serotonin levels or central serotonergic neurotransmission. The present study aimed to combine the analysis of microbiota composition and central serotonergic activity using a valid neurophysiological indicator. We recruited 19 adult patients with type 1 diabetes and depression (D + D; 7 males), 19 patients with type 1 diabetes (D-; 7 male), and 20 healthy participants (HC; 7 males). Next to the analysis of fecal microbiota regarding α- and ß-diversity, the loudness dependence of auditory evoked potential (LDAEP) was investigated, a non-invasive measurement of central serotonergic activity. High α-diversity was associated with high LDAEP, i.e., low serotonergic activity, in patients with diabetes and additional depression. Furthermore, relative abundances of bacterial families belonging to Bacteroidetes, Proteobacteria and Firmicutes were shown to have an impact on central serotonergic activity. This finding was supported by a tendency indicating an association of central serotonergic activity with the Bacteroidetes-Firmicutes ratio in both patients' groups. Together, this data suggests that the guts' microbiota composition might play an important role in regulating the central serotonergic activity in the brain.

Is your pain my pain? A study exploring the relation between pain sensitivity, pain thresholds and empathy for somatic and psychological pain.

OBJECTIVES: Research has shown that empathy for both somatic and psychological pain recruits affective components of the so-called pain matrix, a set of brain regions that is activated during the perception of somatic pain. In addition, the subjective evaluation of experimentally induced somatic pain is related to empathy for somatic pain. In contrast, it is unclear whether or not the subjective sensitivity to somatic pain impacts on empathy for psychological pain. METHODS: In the present study, 55 healthy participants conducted a pain-pressure-test (PPT) and a cold-pressor test (CPT) in order to assess pain thresholds, pain tolerance and evaluation of pain during the task. They further conducted the social interaction empathy task (SIET), which investigates empathy for somatic as well as psychological pain. All participants completed the interpersonal-reactivity index (IRI) and the pain-sensitivity questionnaire (PSQ). RESULTS: Participants who are in general more sensitive to somatic pain, as indicated by high-PSQ scores, showed higher empathy, that is, higher pain ratings, for both somatic and psychological painful situations observed in others as compared to those with low-PSQ scores. High-PSQ scores and high pain and unpleasantness ratings during the CPT were correlated with empathy for pain (both pain conditions), whereas pain thresholds (PPT) and pain tolerance thresholds (CPT) did not correlate with empathy. The IRI subscore 'personal distress' correlated with psychological pain ratings. CONCLUSIONS: Thus, empathy for both somatic and psychological pain were related to the subjective evaluation of somatic pain and general pain sensitivity.

P300 and delay-discounting in obsessive-compulsive disorder.

Previous research showed that dysfunctions of fronto-striatal neural networks are implicated in the pathophysiology of obsessive-compulsive disorder (OCD). Accordingly, patients with OCD showed altered performances during decision-making tasks. As P300, evoked by oddball paradigms, is suggested to be related to attentional and cognitive processes and generated in the medial temporal lobe and orbitofrontal and cingulate cortices, it is of special interest in OCD research. Therefore, this study aimed to investigate P300 in OCD and its associations with brain activity during decision-making: P300, evoked by an auditory oddball paradigm, was analysed in 19 OCD patients and 19 healthy controls regarding peak latency, amplitude and source density power in parietal cortex areas by sLORETA. Afterwards, using a fMRI paradigm, Blood-oxygen-level-dependent (BOLD) contrast imaging was conducted during a delay-discounting paradigm. We hypothesised differences between groups regarding P300 characteristics and associations with frontal activity during delay-discounting. The P300 did not differ between groups, however, the P300 latency over the P4 electrode correlated negatively with the NEO-FFI score openness to experience in patients with OCD. In healthy controls, P300 source density power correlated with activity in frontal regions when processing rewards, a finding which was absent in OCD patients. To conclude, associations of P300 with frontal brain activation during delay-discounting were found, suggesting a contribution of attentional or context updating processes. Since this association was absent in patients with OCD, the findings could be interpreted as being indeed related to dysfunctions of fronto-striatal neural networks in patients with OCD.

Pareidolias and Creativity in Patients with Mental Disorders.

OBJECTIVE: Pareidolias are ilusionary misjudgments and are seen as the result of deliberately or unconsciously caused misinterpretations by the human brain, which tends to complete diffuse and apparently incomplete perceptual images. The psychopathological value of pareidolia in the context of neuropsychiatric diseases has, however, been little researched so far. METHODS: In this pilot study, a total of 25 patients (mean age 43.3 years, SD 16.2) with an affective disorder or schizophrenic disease (ICD-10: F3.X or F2.X) and 25 healthy volunteers (mean age 46.1 years, SD 15.4) were compared for sociodemographic factors and psychometric findings, as well as pareidolias and creativity. RESULTS: We found that the patients identified significantly fewer pareidolias than healthy controls (p = 0.002) and that patients with schizophrenia, in particular, had a significantly lower hit rate (p = 0.005). Across the whole group, there were clear positive correlations between pareidolia and high creativity, as well as personality traits such as impulsiveness/spontaneity, extraversion, and conscientiousness. CONCLUSIONS: Unexpectedly, having less nosology-specific features than individual specific properties such as creativity and extraversion, and especially openness and verbal intelligence, in patients with affective disorder or schizophrenia promotes the recognition of pareidolia as a specific form of illusionary misperception.

Childhood trauma and dissociative symptoms predict frontal EEG asymmetry in borderline personality disorder.

Frontal EEG asymmetry (FEA) has been studied as both state and trait parameter in emotion regulation and affective disorders. Its significance in borderline personality disorder (BPD) remains largely unknown. Twenty-six BPD patients and 26 healthy controls underwent EEG before and after mood induction using aversive images. A slight but significant shift from left- to right-sided asymmetry over prefrontal electrodes occurred across all subjects. In BPD baseline FEA over F7 and F8 correlated significantly with childhood trauma and functional neurological "conversion" symptoms as assessed by respective questionnaires. Regression analysis revealed a predictive role of both childhood trauma and dissociative neurological symptoms. FEA offers a relatively stable electrophysiological correlate of BPD psychopathology that responds only minimally to acute mood changes. Future studies should address whether this psychophysiological association is universal for trauma- and dissociation-related disorders, and whether it is responsive to psychotherapy.

Proximodistal segregation of nonspatial information in CA3: preferential recruitment of a proximal CA3-distal CA1 network in nonspatial recognition memory.

A prevailing view in memory research is that CA3 principally supports spatial processes. However, few studies have investigated the contribution of CA3 to nonspatial memory function. Interestingly, the proximal part of CA3 (close to the dentate gyrus) predominantly projects to distal CA1 (away from the dentate gyrus), which preferentially processes nonspatial information. Moreover, the cytoarchitecture and connectivity patterns in the proximal and distal parts of CA3 strongly differ, suggesting a functional segregation in this area. Here, we tested whether CA3 is recruited during nonspatial recognition memory, and whether nonspatial information is differentially represented along the proximodistal axis of CA3. Furthermore, we investigated whether the pattern of activation within CA3 would mirror that of CA1. We used a high-resolution imaging technique specifically designed to analyze brain activity in distant areas that is based on the detection of the expression of the immediate-early gene Arc, used as a marker of neuronal activation. We showed that proximal CA3 is strongly recruited during a nonspatial delayed nonmatching-to-sample recognition memory task in rats, while distal CA3 is not. In addition, distal CA1 was more activated than proximal CA1 in the same task. These findings suggest a functional segregation of CA3 that mirrors that of CA1, and potentially indicate the existence of a proximal CA3-distal CA1 hippocampal subnetwork that would preferentially process nonspatial information during recognition memory.

Heartbeat evoked potentials and autonomic arousal during dissociative seizures: insights from electrophysiology and neuroimaging.

Introduction: Dissociative seizures often occur in the context of dysregulated affective arousal and entail dissociative symptoms such as a disintegration of bodily awareness. However, the interplay between affective arousal and changes in interoceptive processing at the onset of dissociative seizures is not well understood. Methods: Using retrospective routine data obtained from video-electroencephalography telemetry in a university hospital epilepsy monitoring unit, we investigate ictal changes in cardiac indices of autonomic arousal and heartbeat evoked potentials (HEPs) in 24 patients with dissociative seizures. Results: Results show autonomic arousal during seizures with increased heart rate and a shift towards sympathetic activity. Compared with baseline, ictal HEP amplitudes over central and right prefrontal electrodes (F8, Fz) were significantly less pronounced during seizures, suggesting diminished cortical representation of interoceptive information. Significant correlations between heart rate variability measures and HEPs were observed at baseline, with more sympathetic and less parasympathetic activity related to less pronounced HEPs. Interestingly, these relationships weakened during seizures, suggesting a disintegration of autonomic arousal and interoceptive processing during dissociative seizures. In a subgroup of 16 patients, MRI-based cortical thickness analysis found a correlation with HEP amplitudes in the left somatosensory association cortex. Conclusions: These findings possibly represent an electrophysiological hint of how autonomic arousal could negatively impact bodily awareness in dissociative seizures, and how these processes might be related to underlying brain structure.

Effects of human and animal-assisted skills training on oxytocin und cortisol levels in patients with borderline personality disorder.

OBJECTIVE: Borderline Personality Disorder (BPD) is characterised, among other symptoms, by emotional instability and difficulties in regulating proximity to significant others. Many with BPD have difficulties in establishing a trustful therapeutic relationship, which often develop before a background of adverse childhood experiences with caregivers. One way to facilitate therapeutic interaction in psychotherapy incorporates pet animals as "door openers". No study exists, however, that has examined the effect of animal-assisted versus human-guided skills training on neurobiological correlates of affiliation and stress regulation, i.e. oxytocin and cortisol. METHODS: Twenty in-patients diagnosed with BPD were recruited to participate in an animal-assisted skills-training. Another 20 in-patients participated in a human-guided skills-training. Salivary samples of both groups were taken for determining oxytocin and cortisol before and immediately after 3 therapeutic sessions at least one week apart from one another. In addition, borderline symptom severity (BSL-23), impulsivity (BIS-15), alexithymia (TAS-20), and fear of compassion (FOCS) were determined by self-rating questionnaires before and after the 6-week interventions. RESULTS: Both therapeutic interventions led to a significant reduction in cortisol and an (non-significant) increase in oxytocin, respectively. Importantly, there was a statistically significant interaction between changes in cortisol and oxytocin, independent of group. Both groups further showed clinical improvement as measured using the above-listed questionnaires. CONCLUSION: Our findings suggest that both animal-assisted and human-guided interventions have measurable short-term effects on affiliative and stress hormones, with no approach being superior to the other in this regard.

Narcissism and central serotonergic neurotransmission in depression.

OBJECTIVES: Based on previous research, it has been proposed that the development of depressive disorders is related to altered functioning of the serotonergic systems as well as the personality style, including narcissism. However, it is unclear to date how personality style, especially narcissism, depressive disorders and serotonergic activity are related. METHODS: We included 74 patients with a depressive disorder (DP) and 74 healthy controls (HC) in the study. All participants completed the Personality Style and Disorder Inventory (PSDI) and the Beck Depression Inventory (BDI II). Moreover, we conducted EEG recordings for analysis of serotonergic neurotransmission by using the so-called intensity or loudness dependence of the auditory evoked potentials (LDAEP). RESULTS: Significantly higher LDAEP results emerged for the DP group compared to the HC group, which indicated lower serotonergic activity in the patient's group. In addition, the positive correlation between ambitious-narcissistic personality and LDAEP reached significance in depressive patients. LIMITATIONS: There was only a monocentric cross-sectional study with only one scale having differences between the two groups due to age and education. CONCLUSIONS: Our data supports the theory of lower serotonergic activity in patients with depressive disorders and further suggests that high narcissistic personality traits are related to lower serotonergic neurotransmission in patients.

Relationships between fear of flying, loudness dependence of auditory evoked potentials and frontal alpha asymmetry.

Previous research has suggested that fear of flying, which is defined as a situational, specific phobia, could overlap with depressive and anxiety disorders. Whether the neuronal dysfunctions including altered serotonergic activity in the brain and altered neural oscillations observed for depressive and anxiety disorders also overlap with alterations in fear of flying is unclear. Here, thirty-six participants with self-reported fear of flying (FF) and forty-one unaffected participants (NFF) were recruited. The participants completed the Beck Depression Inventory (BDI-II), the State-trait Anxiety Inventory (STAI) and the Fear of Flying Scale (FFS). EEG-recording was conducted during resting-state and during presentation of auditory stimuli with varying loudness levels for analysis of the Loudness Dependence of Auditory Evoked Potentials (LDAEP), which is suggested to be inversely related to central serotonergic activity. Participants with fear of flying did not differ from the control group with regard to BDI-II and STAI data. The LDAEP was higher over F4 electrode in the FF group compared to controls, whereas exploratory analysis suggest that differences between groups were conveyed by female participants. Moreover, the FF group showed relatively higher right frontal alpha activity compared to the control group, whereas no difference in frequency power (alpha, beta and theta) was observed. Thus, this study brought the first hint for reduced serotonergic activity in individuals with fear of flying and relatively higher right frontal activity. Thus, based on the preliminary findings, future research should aim to examine the boundaries with anxiety and depressive disorders and to clarify the distinct neural mechanisms.

Machine Learning Prediction of Estimated Risk for Bipolar Disorders Using Hippocampal Subfield and Amygdala Nuclei Volumes.

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve upon the early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (n = 271, 7 sites) to compare volumes of hippocampus, amygdala and their subfields/nuclei between help-seeking subjects divided into risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using a linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2-74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0-71.9) for leave-one-site-out. Structural alterations of the hippocampus and amygdala may not be as pronounced in young people at risk; nonetheless, machine learning can predict the estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value.

Alterations of the gut microbiota in borderline personality disorder.

OBJECTIVE: A growing body of research has shown that people with a wide range of psychiatric disorders, including depression, present with alterations of the gut microbiota, although it is unclear if differences may be caused by the action of psychotropic medication. No data exist for patients with borderline personality disorder (BPD), a psychiatric condition that is frequently comorbidly associated with depression. METHODS: Twenty-four unmedicated patients and twenty-one age- and sex-matched healthy controls were recruited. Stool samples were frozen at -80 °C within ten minutes after defecation. The V4 region of bacterial 16S ribosomal RNA (rRNA) gene was sequenced on an Illumina platform. Operational taxonomic units (OTUs) were used for further analysis of community structure, alpha- and beta-diversity. RESULTS: There was no significant difference in alpha- and beta-diversity between patients and controls. However, the Bacteroidetes/Firmicutes-ratio was higher in patients, approaching significance (p = 0.06, r = 0.23). Four species were significantly less abundant in BPD patients, namely Pseudoflavonifractor phocaensis (p = 0.003, r = 0.41), Eubacterium coprostanoligenes (p = 0.01, r = 0.34), Anaerotaenia torta (p = 0.01, r = 0.35), and (statistically somewhat weaker) Parabacteroides chongii (p = 0.046, r = 0.26), which correlated with various psychometric scores. CONCLUSION: Differences in the taxonomic composition may indicate a potential dysbiosis among SCFA-producing bacteria in BPD. Future research is warranted to replicate these findings in independent and larger samples. If confirmed, the results suggest that microbiota-targeted therapies may be a useful adjunct strategy for BPD.

Investigation of the Serotonergic Activity and the Serotonin Content in Serum and Platelet, and the Possible Role of the Serotonin Transporter in Patients with Depression.

According to the monoamine hypothesis, the development of depression is associated with dysfunctions of the serotonergic system. Alterations in the serotonin transporter gene (5-HTTLPR), the serotonergic activity in the brain, and the content of serotonin (5-HT) have been related to depression and were examined separately by previous studies. This study investigates these parameters in 89 depressed patients and 89 healthy participants. We investigated the serotonergic activity measured by the loudness dependence of auditory evoked potentials (LDAEP). In addition to the examination of the serotonin content (serum and platelet), enzyme-linked immunosorbent assays (ELISA) were used and 5-HTTLPR genotypes were analyzed. We observed a lower serotonin content in patients compared to healthy participants. Further, we noticed a correlation between anxiety and depression-associated symptoms with serotonergic activity. Patients treated with SSRI/SNRI showed decreased contents of serum serotonin compared to patients without any psychotropic medication or other psychotropic medications. Since the serotonergic activity, peripheral serotonin content, and 5-HTTLPR were unrelated, the results suggest independent alterations of central and peripheral serotonergic systems in depression. In line with this finding, serotonergic activity was related to anxiety and depression symptoms. Furthermore, the applied medication seems to influence serum serotonin content in patients with depression.

Time experience in patients with schizophrenia and affective disorders.

BACKGROUND: The experience of time, or the temporal order of external and internal events, is essential for humans. In psychiatric disorders such as depression and schizophrenia, impairment of time processing has been discussed for a long time. AIMS: In this explorative pilot study, therefore, the subjective time feeling as well as objective time perception were determined in patients with depression and schizophrenia, along with possible neurobiological correlates. METHODS: Depressed (n = 34; 32.4 ± 9.8 years; 21 men) and schizophrenic patients (n = 31; 35.1 ± 10.7 years; 22 men) and healthy subjects (n = 33; 32.8 ± 14.3 years; 16 men) were tested using time feeling questionnaires, time perception tasks and critical flicker-fusion frequency (CFF) and loudness dependence of auditory evoked potentials (LDAEP) to determine serotonergic neurotransmission. RESULTS: There were significant differences between the three groups regarding time feeling and also in time perception tasks (estimation of given time duration) and CFF (the "DOWN" condition). Regarding the LDAEP, patients with schizophrenia showed a significant negative correlation to time experience in terms of a pathologically increased serotonergic neurotransmission with disturbed time feeling. CONCLUSIONS: Impairment of time experience seems to play an important role in depression and schizophrenia, both subjectively and objectively, and novel neurobiological correlates have been uncovered. It is suggested, therefore, that alteration of experience of time should be increasingly included in the current psychopathological findings.

Impairments of Social Interaction in Depressive Disorder.

OBJECTIVE: Despite the numerous findings on the altered emotion recognition and dysfunctional social interaction behavior of depressive patients, a lot of the relationships are not clearly clarified. METHODS: In this pilot study, 20 depressive patients (mean±SD, 38.4±14.2) and 20 healthy subjects (mean±SD, 38.9±15.3) (each in dyads) were videographed. We then analyzed their social interaction behavior and emotion processing in terms of emotion recognition, their own emotional experience, and the expression of emotions under the conditions of a semi-structured experimental paradigm. RESULTS: Patients showed more significant impairment regarding the dimensions of social interaction behavior (i.e., attention, interest, and activity) and their interaction behavior was characterized by neutral affectivity, silence, and avoidance of direct eye contact. This interactive behavioral style was statistically related to depressive psychopathology. There were no differences concerning emotion recognition. CONCLUSION: Impairments of non-verbal and verbal social interaction behavior of depressive patients seem to be less associated with disturbances of basic skills of emotion recognition.

Association between childhood maltreatment, psychopathology and DNA methylation of genes involved in stress regulation: Evidence from a study in Borderline Personality Disorder.

Previous research suggests that childhood maltreatment is associated with epigenetic modification of genes involved in hypothalamic-pituitary-adrenal (HPA) functioning, which could cause dysregulation of the stress response system. If pervasive, this may be associated with the development of stress-related disorder in adults, including affective disorders, anxiety disorders, post-traumatic stress disorder (PTSD) or borderline-personality disorder (BPD). The majority of studies have focused on DNA methylation of the glucocorticoid receptor gene (NR3C1) and the FKBP5 encoding gene, which regulates the sensitivity of the glucocorticoid receptor (GR). How methylation of NR3C1 and FKBP5 interferes with childhood adversity and psychopathology as well as empathy is an under-researched issue. Here, we sought to investigate the association of childhood maltreatment in a sample of 89 individuals (44 healthy participants and 45 patients diagnosed with BPD) with the methylation of the 1F promoter region of NR3C1 and the intron 7 of FKBP5 as well as with different measures of psychopathology and empathy. Methylation of FKBP5 (bin 2) correlated with anxiety (SCL-90-R) and the global psychopathological symptom load index (GSI), as well as with lower empathic perspective-taking abilities. Psychopathology and empathy impairments correlated with the level of childhood maltreatment. No difference in FKBP5 methylation was observed between the clinical and the non-clinical group. Methylation of NR3C1 was lower in BPD patients compared to controls, yet with small differences. The results are discussed regarding their biological relevance, including possible evolutionary explanations. In short, the regulation of the GR sensitivity by methylation of FKBP5 correlated with psychopathology and empathy scores, while no correlation emerged with the severity of childhood adversity.

Short-Term Fasting and Ingestion of Caloric Drinks Affect Heartbeat-Evoked Potentials and Autonomic Nervous System Activity in Males.

Central nervous systems receive and process information from the internal and external environment to maintain homeostasis. This includes interoceptive awareness of the organism's nutritional state. Whenever food supply is required, feelings of hunger initiate the search for and the consumption of appropriate amounts of nutrients. How this is physiologically regulated in humans has been subjected to research into interoceptive awareness of body states during fasting and food consumption. However, there is no research on the distinct effects of carbohydrate or protein intake on interoception. Therefore, we aimed to investigate the impact of fasting and consumption of standardized carbohydrate and protein shakes on interoception in a repeated-measures cross-over design in a sample of 37 healthy, normal weight males. As a physiological correlate of interoception, we measured heartbeat-evoked potentials (HEPs), which are suggested to reflect the cortical representation of cardiac signals, during eight-minutes resting state EEG-recordings. After a 16-hour fasting period, the HEP amplitudes were lower over right central and parietal electrodes and increased after ingestion of the nutritional shake. Exploratory analyses indicated that the difference between fasting and satiety was more prominent at carbohydrate compared protein testing days. Correlation analyses with heart rate variability (HRV) suggested that high cardiac sympathetic activity is related to lower HEP amplitudes. Furthermore, cardiac sympathetic activity and stress indices decreased from before to after the intervention, whereas HRV increased. Together, this study shows for the first time that fasting and the intake of a nutritional shake affects cardiac measures of autonomic nervous system functioning and the neural correlates of cardiac interoception. These findings could be relevant for diets and psychosomatic disorders, including eating disorders.

Loudness Dependence of Auditory-evoked Potentials, a Marker of Central Serotonergic Activity, is Affected by Fasting and Selective Uptake of Food.

Serotonin is an important neuromodulator involved in many physiological processes including mood and satiety. In the brain, serotonin is manufactured from tryptophan, as serotonin itself cannot cross the blood-brain barrier. Previous research has shown that blood-tryptophan levels increase upon ingestion of carbohydrates and decrease upon protein consumption. How this translates into serotonin availability is as yet under-researched. Therefore, we examined the effect of fasting versus consuming carbohydrates or protein on central serotonergic activity using a repeated-measures crossover design in a sample of 37 healthy men. The loudness dependence of auditory-evoked potentials (LDAEP) serves as a noninvasive method to study central serotonergic activity. Blood-glucose levels and mood changes were also monitored before and after the nutritional intervention. The intervention had a significant nutrition-specific effect on LDAEP and blood-glucose levels. A significant difference emerged between the fasting condition and satiety, with LDAEP being lower during satiety, irrespective of the type of food. Thus, this indicator of serotonergic activity increased after food consumption, which was further related to mood improvement. Moreover, the LDAEP differed between the 2 measurements only for the carbohydrate testing day, suggesting that LDAEP can be selectively modulated by the type of nutrition consumed. Our data further indicate a high intraindividual stability of LDAEP, as the electrophysiological signals were very similar in the fasting condition across the 2 testing days. Together, these findings demonstrate that the LDAEP can serve as a biological marker for central serotonergic activity, while at the same time being sensitive to nutritional changes.