No evidence from a negative mood induction fMRI task for frontal functional asymmetry as a suitable neurofeedback target.

Frontal functional asymmetry (FA) has been proposed as a potential target for neurofeedback (NFB) training for mental disorders but most FA NFB studies used electroencephalography while the investigations of FA NFB in functional magnetic resonance imaging (fMRI) are rather limited. In this study, we aimed at identifying functional asymmetry effects in fMRI and exploring its potential as a target for fMRI NFB studies by re-analyzing an existing data set containing a resting state measurement and a sad mood induction task of n = 30 participants with remitted major depressive disorder and n = 30 matched healthy controls. We applied low-frequency fluctuations (ALFF), fractional ALFF, and regional homogeneity and estimated functional asymmetry in both a voxel-wise and regional manner. We assessed functional asymmetry during rest and negative mood induction as well as functional asymmetry changes between the phases, and associated the induced mood change with the change in functional asymmetry. Analyses were conducted within as well as between groups. Despite extensive analyses, we identified only very limited effects. While some tests showed nominal significance, our results did not contain any clear identifiable patterns of effects that would be expected if a true underlying effect would be present. In conclusion, we do not find evidence for FA effects related to negative mood in fMRI, which questions the usefulness of FA measures for real-time fMRI neurofeedback as a treatment approach for affective disorders.

Effects of Rumination and Mindful Self-Focus Inductions During Daily Life in Patients With Remitted Depression: An Experimental Ambulatory Assessment Study.

Rumination has been proposed as an important risk factor for depression, whereas mindful attention is considered a protective form of self-focusing. Experimental studies have demonstrated differential effects of these modes when induced in the lab. However, their impact on daily life processes is poorly understood, particularly in individuals vulnerable to depressive relapses. The aim of our study was to examine short- and longer-term effects of repeated brief rumination and mindful self-focus inductions during daily life on momentary mood, cognitions, and cortisol in patients with remitted depression (rMDD) as well as in healthy individuals, and to identify their potential differential effects in these groups. The study involved repeated short ambulatory inductions of a ruminative or a mindful self-focus during daily life with additional assessments of momentary mood, rumination, self-acceptance, and cortisol over 4 consecutive days in a sample of patients with rMDD (n = 32, ≥2 lifetime episodes, age 19-55 years) and matched healthy controls (n = 32, age 21-54 years). Multilevel models revealed differential immediate effects of the two induction modes on all momentary mood and cognitive outcomes (all p's < .001), but not on cortisol. Detrimental effects of rumination over mindful self-focus inductions were particularly strong for cognitions in the patient group. Longer-term effects of the inductions over the day were lacking. This study underlines immediate deteriorating effects of an induced ruminative compared to a mindful self-focus on momentary mood and cognitions during daily life in patients with rMDD and in healthy individuals. The observed stronger rumination-related reactivity in patients suggests heightened cognitive vulnerability. Understanding rumination- and mindfulness-based mechanisms of action in real-life settings can help to establish mechanism-based treatment options for relapse prevention in depression.

SLC6A4 polymorphisms modulate the efficacy of a tryptophan-enriched diet on age-related depression and social cognition.

BACKGROUND & AIMS: In a placebo controlled study we sought to determine if a four-weeks tryptophan-enriched diet is able to improve age-related depression or social cognitive impairment, depending on polymorphisms located in the promoter region of Solute Carrier Family 6 Member 4 (SLC6A4), also known as serotonin transporter (SERT1) gene. METHODS: 91 young volunteers (age: 21 ± 2 yrs) and 127 above 50 years old (58 ± 6 yrs) healthy volunteers completed the study. Participants from the placebo and tryptophan group followed the same protocol. Before starting the study blood samples, to measure serotonin-transporter-linked polymorphic region (5-HTTLPR) and rs25531 polymorphisms, were collected. In addition, before and after completing the study urine samples (to measure 5-hydroxyindolacetic acid (5-HIAA) were taken, while psychological questionnaires (to assess depression and social cognition levels), and a one week dietary record (to calculate the tryptophan (TRP) intake) were assessed. RESULTS: The triallelic approach of SLC6A4 showed that in S'S´ subjects there was a positive correlation between TRP intake and 5-HIAA levels. Age of participants, SLC6A4 genotype, and experimental condition were important factors contributing to the outcome of depression and social cognition. CONCLUSIONS: 5-HTTLPR and rs25531 polymorphisms play a key role in the response to the TRP- based nutritional intervention, improving only age-related depressive symptoms and empathy in S'S´ subjects who have a higher risk to show signs of depression during their lifetime.

Tryptophan-rich diet is negatively associated with depression and positively linked to social cognition.

The essential amino acid tryptophan (TRP) is discussed as a potential protective factor for physical and mental health. Besides positive effects via the microbiota of the gut on many physiological processes, TRP is the precursor of the neurotransmitter serotonin (5-HT), thereby playing a role for affective disorders. The present study investigated the effects of a TRP-rich diet on depressiveness and on one of its endophenotypes, impaired social cognition, in a population based sample. N = 482 subjects participated in an online study, assessing the ability to properly recognize emotional states from the eye region of faces (Reading the Mind in the Eye Test, RMET) and asking for subjective ratings of condemnability in a moral judgment task. Moreover, the habitual TRP intake was measured. It was hypothesized that a low-TRP diet is associated with higher depressiveness and worse performance in the social cognition tasks. The main hypotheses could be supported. However, contrary to the expectations, the effect of TRP on social cognition was not mediated by depressiveness. Results show that a tryptophan-rich diet is a potential protective factor against depression and is positively related to functioning in social cognition.

Genetic and epigenetic serotonergic markers predict the ability to recognize mental states.

The serotonergic (5-HT) system is related to affective and cognitive processes and explains behavioral variability in the normal and psychopathological range. For this reason, the hypothesis was put forward that genetic and epigenetic markers related to 5-HT metabolism predict individual differences in social cognitive functioning. Social cognitions are complex mental processes necessary for perceiving, interpreting and reacting to the behaviors of others. In order to test this hypothesis one of the most prominent theory of mind tasks, the reading the mind in the eye test (RMET), was administered to N = 435 participants and measures of performance were related to the functional MAO-A VNTR polymorphism (relevant for 5-HT catabolism) and to epigenetic markers in the promoter of the TPH-2 gene (relevant for 5-HT synthesis). It was postulated that genetic and epigenetic markers of high 5-HT activity are positively related to RMET performance. Results show that the MAO-A high activity allele, together with the degree of methylation at a promoter CpG site on the TPH-2 gene explain significant proportions of variance in the RMET performance even after controlling for age and sex effects. Present findings yield evidence for the importance of 5-HT for social cognition. Based on additional findings, the role of a TRP-rich diet for theory of mind functions is discussed.

Modulation of respiration pattern variability and its relation to anxiety symptoms in remitted recurrent depression.

BACKGROUND: Depression is related to default mode network (DMN) connectivity and higher respiration pattern variability (RPV). In addition, DMN connectivity and RPV are interrelated and predict a poorer clinical course of depression. The association of RPV and depression might further be boosted by anxiety levels. Aim of the present study was to investigate whether a mindfulness-based training in emotionally challenged remitted depressed participants (rMDD) leads to reduced DMN connectivity and lower RPV, and if RPV interacts with anxiety levels. METHODS: To challenge participants, sad mood was induced with keywords of personal negative life events in 49 rMDD during fMRI before and after a 4-week mindfulness-based attention training (MBAT) or progressive muscle relaxation. Respiration was measured by means of a built-in respiration belt. RESULTS: After both trainings, rMDD showed no significant changes in DMN connectivity. However, MBAT was effective in reducing the RPV which was related to lower anxiety levels especially in high anxious individuals. CONCLUSIONS: RPV can be influenced by training which may hint to an underlying biological pathway of training effects. Importantly, these effects seem to be associated with anxiety levels. Therefore, respiration focused training might be an important tool assisting the treatment of depression and anxiety.

Just a very expensive breathing training? Risk of respiratory artefacts in functional connectivity-based real-time fMRI neurofeedback.

Real-time functional magnetic resonance imaging neurofeedback (rtfMRI NFB) is a promising method for targeted regulation of pathological brain processes in mental disorders. But most NFB approaches so far have used relatively restricted regional activation as a target, which might not address the complexity of the underlying network changes. Aiming towards advancing novel treatment tools for disorders like schizophrenia, we developed a large-scale network functional connectivity-based rtfMRI NFB approach targeting dorsolateral prefrontal cortex and anterior cingulate cortex connectivity with the striatum. In a double-blind randomized yoke-controlled single-session feasibility study with N â€‹= â€‹38 healthy controls, we identified strong associations between our connectivity estimates and physiological parameters reflecting the rate and regularity of breathing. These undesired artefacts are especially detrimental in rtfMRI NFB, where the same data serves as an online feedback signal and offline analysis target. To evaluate ways to control for the identified respiratory artefacts, we compared model-based physiological nuisance regression and global signal regression (GSR) and found that GSR was the most effective method in our data. Our results strongly emphasize the need to control for physiological artefacts in connectivity-based rtfMRI NFB approaches and suggest that GSR might be a useful method for online data correction for respiratory artefacts.

Mindfulness-based focused attention training versus progressive muscle relaxation in remitted depressed patients: Effects on salivary cortisol and associations with subjective improvements in daily life.

Major Depression is a stress-related disorder characterized by altered hypothalamic-pituitary-adrenal axis function. Mindfulness-based interventions have shown to improve subjective parameters of stress and to reduce relapse rates in depressed patients. However, research on their effects on diurnal patterns of cortisol and associations with subjective outcomes is lacking. The present Ambulatory Assessment study investigated possible changes in daily rhythm cortisol parameters (cortisol awakening response (CAR), daily slope, total cortisol) in currently remitted individuals with recurrent depression who were randomized to a four-week mindfulness-based focused attention training (MBAT, n = 39) or a progressive muscle relaxation training (PMR, n = 39). A second aim was to investigate whether changes in cortisol were linked to improvements in affective and cognitive daily life states. On three weekdays before and after the intervention, seven saliva cortisol samples per day were collected. For analysis, multilevel models were applied. Results revealed no group-specific or general change in CAR and daily slopes from pre- to postintervention. In contrast, total cortisol increased across groups, which was however moderated by group and subjective improvement status. While cortisol increased irrespective of subjective improvement in PMR participants, MBAT participants with larger reductions in negative affect and rumination maintained their initial cortisol levels, whereas those with lower improvement paralleled the PMR group. Thereby, MBAT appeared to buffer an increase in overall cortisol secretion over time, but only in patients showing marked improvements in those affective and cognitive states that constitute core elements for depressive relapses in the vulnerability model of mindfulness-based cognitive therapy.

Respiration pattern variability and related default mode network connectivity are altered in remitted depression.

BACKGROUND: Studies with healthy participants and patients with respiratory diseases suggest a relation between respiration and mood. The aim of the present analyses was to investigate whether emotionally challenged remitted depressed participants show higher respiration pattern variability (RPV) and whether this is related to mood, clinical outcome and increased default mode network connectivity. METHODS: To challenge participants, sad mood was induced with keywords of personal negative life events in individuals with remitted depression [recurrent major depressive disorder (rMDD), n = 30] and matched healthy controls (HCs, n = 30) during functional magnetic resonance imaging. Respiration was measured by means of a built-in respiration belt. Additionally, questionnaires, a daily life assessment of mood and a 3 years follow-up were applied. For replication, we analysed RPV in an independent sample of 53 rMDD who underwent the same fMRI paradigm. RESULTS: During sad mood, rMDD compared with HC showed greater RPV, with higher variability in pause duration and respiration frequency and lower expiration to inspiration ratio. Higher RPV was related to lower daily life mood and predicted higher depression scores as well as relapses during a 3-year follow-up period. Furthermore, in rMDD compared with HC higher main respiration frequency exhibited a more positive association with connectivity of the posterior cingulate cortex and the right parahippocampal gyrus. CONCLUSIONS: The results suggest a relation between RPV, mood and depression on the behavioural and neural level. Based on our findings, we propose interventions focusing on respiration to be a promising additional tool in the treatment of depression.

[Sensory Inventory (SI): self-assessment of sensory sensitivity for adults and adolescents]. / Sensorik Inventar (SI) ­ Selbstbeurteilung der sensorischen Sensitivität für Erwachsene und Jugendliche.

An adequate perception of the environment is one of the main foundations of adaptive behavior. Furthermore, sensory sensitivity varies from person to person and can play a central role in the development and course of mental disorders. The objective was the development of a questionnaire for the multidimensional assessment of sensory sensitivity. A total of 1417 persons were evaluated with the Sensory Inventory (SI). The factorial validity was tested with exploratory factor analyses and exploratory structural equation modeling. A 6-factorial structure was established. High internal consistency and retest reliability were shown, as well as increased sensory sensitivity and lower body perception in participants with mental disorders. The SI is a short instrument with good test characteristics that can easily be integrated in a clinical or research environment.

Cognitive and affective trait and state factors influencing the long-term symptom course in remitted depressed patients.

BACKGROUND: Major depressive disorder (MDD) is characterized by a high risk for relapses and chronic developments. Clinical characteristics such as residual symptoms have been shown to negatively affect the long-term course of MDD. However, it is unclear so far how trait repetitive negative thinking (RNT) as well as cognitive and affective momentary states, the latter experienced during daily-life, affect the long-term course of MDD. METHOD: We followed up 57 remitted depressed (rMDD) individuals six (T2) and 36 (T3) months after baseline. Clinical outcomes were time to relapse, time spent with significant symptoms as a marker of chronicity, and levels of depressive symptoms at T2 and T3. Predictors assessed at baseline included residual symptoms and trait RNT. Furthermore, momentary daily life affect and momentary rumination, and their variation over the day were assessed at baseline using ambulatory assessment (AA). RESULTS: In multiple models, residual symptoms and instability of daily-life affect at baseline independently predicted a faster time to relapse, while chronicity was significantly predicted by trait RNT. Multilevel models revealed that depressive symptom levels during follow-up were predicted by baseline residual symptom levels and by instability of daily-life rumination. Both instability features were linked to a higher number of anamnestic MDD episodes. CONCLUSIONS: Our findings indicate that trait RNT, but also affective and cognitive processes during daily life impact the longer-term course of MDD. Future longitudinal research on the role of respective AA-phenotypes as potential transdiagnostic course-modifiers is warranted.

Neural correlates of an attentional bias to health-threatening stimuli in individuals with pathological health anxiety.

BACKGROUND: An attentional bias to health-threat stimuli is assumed to represent the primary pathogenetic factor for the development and maintenance of pathological health anxiety (PHA; formerly termed "hypochondriasis"). However, little is known about the neural basis of this attentional bias in individuals with PHA. METHODS: A group of patients with PHA, a group of depressed patients and a healthy control group completed an emotional Stroop task with health-threat (body symptom and illness) words and neutral control words while undergoing functional MRI. RESULTS: We included 33 patients with PHA, 28 depressed patients and 31 controls in our analyses. As reflected in reaction times, patients with PHA showed a significantly stronger attentional bias to health-threat words than both control groups. In addition, patients with PHA showed increased amygdala and rostral anterior cingulate cortex activation for body symptom, but not for illness words. Moreover, only in patients with PHA amygdala activation in response to symptom words was positively associated with higher arousal and more negative valence ratings of the body symptom word material. LIMITATIONS: A control group of patients with an anxiety disorder but without PHA would have helped to define the specificity of the results for PHA. CONCLUSION: The attentional bias observed in patients with PHA is associated with hyperactivation in response to body symptom words in brain regions that are crucial for an arousal-related fear response (e.g., the amygdala) and for resolving emotional interference (e.g., the rostral anterior cingulate cortex). The findings have important implications for the nosological classification of PHA and suggest the application of innovative exposure-based interventions for the treatment of PHA.

Aberrant activity and connectivity of the posterior superior temporal sulcus during social cognition in schizophrenia.

Schizophrenia is associated with significant impairments in social cognition. These impairments have been shown to go along with altered activation of the posterior superior temporal sulcus (pSTS). However, studies that investigate connectivity of pSTS during social cognition in schizophrenia are sparse. Twenty-two patients with schizophrenia and 22 matched healthy controls completed a social-cognitive task for functional magnetic resonance imaging that allows the investigation of affective Theory of Mind (ToM), emotion recognition and the processing of neutral facial expressions. Moreover, a resting-state measurement was taken. Patients with schizophrenia performed worse in the social-cognitive task (main effect of group). In addition, a group by social-cognitive processing interaction was revealed for activity, as well as for connectivity during the social-cognitive task, i.e., patients with schizophrenia showed hyperactivity of right pSTS during neutral face processing, but hypoactivity during emotion recognition and affective ToM. In addition, hypoconnectivity between right and left pSTS was revealed for affective ToM, but not for neutral face processing or emotion recognition. No group differences in connectivity from right to left pSTS occurred during resting state. This pattern of aberrant activity and connectivity of the right pSTS during social cognition might form the basis of false-positive perceptions of emotions and intentions and could contribute to the emergence and sustainment of delusions.

Early Memories of Individuals on the Autism Spectrum Assessed Using Online Self-Reports.

"When I was one and a half years old, I was on a ferry lying on red seats" - while several autobiographical accounts by people with autism reveal vivid memories of early childhood, the vast amount of experimental investigations found deficits in personal autobiographic memory in autism. To assess this contradiction empirically, we implemented an online questionnaire on early childhood events to compare people on the autism spectrum (AS) and non-autistic people with respect to their earliest autobiographical episodic memories and the earliest semantic know event as told by another person. Results indicate that people on the AS do not differ from non-autistic people in the age of their earliest know events but remember events from an earlier age in childhood and with more sensory details, contradicting the assumption of an overall deficit in personal episodic memory in autism. Furthermore, our results emphasize the supporting influence of language for memory formation and give evidence for an important role of sensory features in memories of people on the AS.

Hippocampal-dorsolateral prefrontal coupling as a species-conserved cognitive mechanism: a human translational imaging study.

Hippocampal-prefrontal cortex (HC-PFC) interactions are implicated in working memory (WM) and altered in psychiatric conditions with cognitive impairment such as schizophrenia. While coupling between both structures is crucial for WM performance in rodents, evidence from human studies is conflicting and translation of findings is complicated by the use of differing paradigms across species. We therefore used functional magnetic resonance imaging together with a spatial WM paradigm adapted from rodent research to examine HC-PFC coupling in humans. A PFC-parietal network was functionally connected to hippocampus (HC) during task stages requiring high levels of executive control but not during a matched control condition. The magnitude of coupling in a network comprising HC, bilateral dorsolateral PFC (DLPFC), and right supramarginal gyrus explained one-fourth of the variability in an independent spatial WM task but was unrelated to visual WM performance. HC-DLPFC coupling may thus represent a systems-level mechanism specific to spatial WM that is conserved across species, suggesting its utility for modeling cognitive dysfunction in translational neuroscience.

Increased involvement of the parahippocampal gyri in a sad mood predicts future depressive symptoms.

Behavioral studies suggest a relationship between autobiographical memory, rumination and depression. The objective of this study was to determine whether remitted depressed patients show alterations in connectivity of the posterior cingulate cortex (PCC, a node in the default mode network) with the parahippocampal gyri (PHG, a region associated with autobiographical memory) while intensively recalling negative memories and whether this is related to daily life symptoms and to the further course of depression. Sad mood was induced with keywords of personal negative life events in participants with remitted depression (n = 29) and matched healthy controls (n = 29) during functional magnetic resonance imaging. Additionally, daily life assessments of mood and rumination and a 6-month follow-up were conducted. Remitted depressed participants showed greater connectivity than healthy controls of the PCC with the PHG, which was even stronger in patients with more previous episodes. Furthermore, patients with increased PCC-PHG connectivity showed a sadder mood and more rumination in daily life and a worsening of rumination and depression scores during follow-up. A relationship of negative autobiographical memory processing, rumination, sad mood and depression on a neural level seems likely. The identified increased connectivity probably indicates a 'scar' of recurrent depression and may represent a prognostic factor for future depression.

Effects of mood and rumination on cortisol levels in daily life: an ambulatory assessment study in remitted depressed patients and healthy controls.

The influence of naturally occurring emotional and cognitive experiences on hypothalamic-pituitary-adrenal axis (HPAA) activity is still underinvestigated, particularly in clinical populations. The present study examined effects of mood and rumination on cortisol levels in daily life in remitted depressed patients with recurrent episodes or a chronic precourse (n=31) and healthy controls (n=32). Ambulatory assessment of subjective variables (valence, calmness, energetic-arousal, ruminative self-focus), daily stressors, and saliva cortisol samples was performed five times a day on two consecutive workdays, whereby cortisol was collected 20min after the subjective assessments. In addition, depressive symptoms and trait rumination (brooding, reflection) were measured retrospectively. Multilevel models revealed that remitted depressed patients showed lower cortisol activity compared to healthy controls. Depressive symptoms and trait rumination did not predict HPAA activity, whereas, by controlling for daily stressors, higher daily means of ruminative self-focus and lower daily means of valence, energetic arousal and calmness were associated with higher daily cortisol levels. Separate analyses per group revealed that mean daily ruminative self-focus predicted higher cortisol in both samples. In contrast, lower daily means of calmness, but also of valence and energetic arousal, were significantly linked to higher cortisol output only in healthy controls, but not in the patient sample. These findings indicate that naturally occurring rumination and low mood are associated with increased activation of the HPAA in daily life. Moreover, our data revealed a potentially reduced mood-cortisol coupling in remitted recurrent depression, possibly indicating that during the course of recurrent depression HPAA activation might become less responsive toward subtle emotional experiences in natural contexts.

Induced ruminative and mindful attention in everyday life: an experimental ambulatory assessment study.

BACKGROUND AND OBJECTIVES: Rumination has been proposed as a risk factor for depression, while mindful attention might be protective. Differential effects of these attention foci have so far only been examined in the laboratory. Therefore, we conducted an experimental ambulatory assessment study using ruminative and mindful attention inductions in everyday life to examine their effects in a natural context. METHODS: Fifty young adults carried palmtops over three weekdays (rumination induction day, mindful attention induction day, noninduction day; randomized cross-over design). Ten times a day, participants rated ruminative self-focus and mood. On the induction days, they were additionally subjected to 3-min inductions of ruminative or mindful attention at each assessment. RESULTS: The two induction modes exhibited differential immediate effects on ruminative self-focus and mood. While induced rumination immediately deteriorated valence and calmness, induced mindful attention specifically enhanced calmness. Depressive symptoms did not moderate these effects. While overall longer term effects of the inductions were missing, the mindful attention day was associated with slightly increasing positive valence over the day. LIMITATIONS: The results need to be replicated in high-risk and patient samples to demonstrate the clinical significance of identified effects. CONCLUSIONS: Results confirm the emotional relevance of rumination and mindful attention in real world settings. Future work may test whether adaptive attention-focusing instructions delivered in daily life can support clinical interventions.