Altered reward network responses to social touch in major depression.

BACKGROUND: Social touch is an integral part of social relationships and has been associated with reward. Major depressive disorder (MDD) is characterized by severe impairments in reward processing, but the neural effects of social touch in MDD are still elusive. In this study, we aimed to determine whether the neural processing of social touch is altered in MDD and to assess the impact of antidepressant therapy. METHODS: Before and after antidepressant treatment, 53 MDD patients and 41 healthy controls underwent functional magnetic resonance imaging (fMRI) while receiving social touch. We compared neural responses to social touch in the reward network, behavioral ratings of touch comfort and general aversion to interpersonal touch in patients to controls. Additionally, we examined the effect of treatment response on those measures. RESULTS: Clinical symptoms decreased after treatment and 43.4% of patients were classified as responders. Patients reported higher aversion to interpersonal touch and lower comfort ratings during the fMRI paradigm than controls. Patients showed reduced responses to social touch in the nucleus accumbens, caudate nucleus and putamen than controls, both before and after treatment. Contrary to our hypotheses, these effects were independent of touch velocity. Non-responders exhibited blunted response in the caudate nucleus and the insula compared to responders, again irrespective of time. CONCLUSIONS: These findings suggest altered striatal processing of social touch in MDD. Persistent dysfunctional processing of social touch despite clinical improvements may constitute a latent risk factor for social withdrawal and isolation.

Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response.

Obsessive-compulsive disorder (OCD) is a prevalent mental disorder affecting ~2-3% of the population. This disorder involves genetic and, possibly, epigenetic risk factors. The dynamic nature of epigenetics also presents a promising avenue for identifying biomarkers associated with symptom severity, clinical progression, and treatment response in OCD. We, therefore, conducted a comprehensive case-control investigation using Illumina MethylationEPIC BeadChip, encompassing 185 OCD patients and 199 controls recruited from two distinct sites in Germany. Rigorous clinical assessments were performed by trained raters employing the Structured Clinical Interview for DSM-IV (SCID-I). We performed a robust two-step epigenome-wide association study that led to the identification of 305 differentially methylated CpG positions. Next, we validated these findings by pinpointing the optimal set of CpGs that could effectively classify individuals into their respective groups. This approach identified a subset comprising 12 CpGs that overlapped with the 305 CpGs identified in our EWAS. These 12 CpGs are close to or in genes associated with the sweet-compulsive brain hypothesis which proposes that aberrant dopaminergic transmission in the striatum may impair insulin signaling sensitivity among OCD patients. We replicated three of the 12 CpGs signals from a recent independent study conducted on the Han Chinese population, underscoring also the cross-cultural relevance of our findings. In conclusion, our study further supports the involvement of epigenetic mechanisms in the pathogenesis of OCD. By elucidating the underlying molecular alterations associated with OCD, our study contributes to advancing our understanding of this complex disorder and may ultimately improve clinical outcomes for affected individuals.

Oxytocin-Augmented Modular-Based Group Intervention for Loneliness: A Proof-Of-Concept Randomized Controlled Trial.

INTRODUCTION: Loneliness poses a significant health problem and existing psychological interventions have shown only limited positive effects on loneliness. Based on preliminary evidence for impaired oxytocin signaling in trait-like loneliness, the current proof-of-concept study used a randomized, double-blind, placebo-controlled design to probe intranasal oxytocin (OT) as an adjunct to a short-term modular-based group intervention for individuals suffering from high trait-like loneliness (HL, UCLA Loneliness Scale ≥55). METHODS: Seventy-eight healthy HL adults (56 women) received five weekly group psychotherapy sessions. HL participants received OT or placebo before the intervention sessions. Primary outcomes were trait-like loneliness measured at baseline, after the intervention, and again at two follow-up time points (3 weeks and 3 months), and, assessed at each session, state loneliness (visual analog scale), perceived stress (Perceived Stress Scale, PSS-10), quality of life (World Health Organization Five Well-Being Index, WHO-5), and the therapeutic relationship (Group Questionnaire, GQ-D). RESULTS: The psychological intervention was associated with significantly reduced perceived stress and improved trait-like loneliness across treatment groups, which was still evident at the 3-month follow-up. OT had no significant effect on trait-like loneliness, quality of life, or perceived stress. However, compared to placebo, OT significantly facilitated the decrease in state loneliness within sessions and significantly improved positive bonding between the group members. CONCLUSION: Despite significantly improved trait-like loneliness after the intervention, OT did not significantly augment this effect. Further studies are needed to determine optimal intervention designs to translate the observed acute effects of OT into long-term benefits.

Exploring the Relationship between Adherence to Therapy, Treatment Acceptability, and Clinical Outcomes in Adults with Attention-Deficit/Hyperactivity Disorder: Results from the COMPAS Multicenter Randomized Controlled Trial.

INTRODUCTION: Cognitive behavioral therapy and dialectical behavior therapy (DBT) can be effective in treating adults with ADHD, and patients generally consider these interventions useful. While adherence, as measured by attendance at sessions, is mostly sufficient, adherence to therapy skills has not been assessed. Furthermore, the relationship between patient evaluation of therapy effectiveness, treatment adherence, and clinical outcomes is understudied. OBJECTIVE: This study aimed to examine treatment acceptability and adherence in relation to treatment outcomes in a large randomized controlled trial comparing a DBT-based intervention with a nonspecific active comparison, combined with methylphenidate or placebo. METHOD: A total of 433 adult patients with ADHD were randomized. Participants reported how effective they found the therapy, and adherence was measured by attendance at therapy sessions and by self-reports. Descriptive, between-groups, and linear mixed model analyses were conducted. RESULTS: Participants rated psychotherapy as moderately effective, attended 78.40-94.37% of sessions, and used skills regularly. The best-accepted skills were sports and mindfulness. Groups receiving placebo and/or nonspecific clinical management rated their health condition and the medication effectiveness significantly worse than the psychotherapy and methylphenidate groups. Improvements in clinical outcomes were significantly associated with treatment acceptability. Subjective (self-reported) adherence to psychotherapy was significantly associated with improvements in ADHD symptoms, clinical global efficacy and response to treatment. DISCUSSION: These results further support the acceptability of DBT for adult ADHD and suggest the need to address adherence to treatment to maximize clinical improvements. Results may be limited by the retrospective assessment of treatment acceptability and adherence using an ad hoc instrument.

Treatment of adult attention-deficit hyperactivity disorder (ADHD) with transcranial direct current stimulation (tDCS): study protocol for a parallel, randomized, double-blinded, sham-controlled, multicenter trial (Stim-ADHD).

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment used as an alternative or complementary treatment for various neuropsychiatric disorders, and could be an alternative or add-on therapy to psychostimulants in attention-deficit hyperactivity disorder (ADHD). Previous studies provided some evidence for improvements in cognition and clinical symptoms in pediatric and adult ADHD patients. However, data from multi-center randomized controlled trials (RCTs) for this condition are lacking. Thus, our aim is to evaluate short- and mid-term effects of tDCS in this multi-center, randomized, double blind, and sham-controlled, parallel group clinical trial with a 1:1 randomization ratio. Primary endpoint is the total score of DSM-IV scale of the internationally established Conners' Adult ADHD Rating Scales (German self-report screening version, CAARS-S-SR), at day 14 post-intervention (p.i.) to detect short-term lasting effects analyzed via analyses of covariance (ANCOVAs). In case of significant between-groups differences at day 14 p.i., hierarchically ordered hypotheses on mid-term lasting effects will be investigated by linear mixed models with visit (5 time points), treatment, treatment by visit interaction, and covariates as fixed categorical effects plus a patient-specific visit random effect, using an unstructured covariance structure to model the residual within-patient errors. Positive results of this clinical trial will expand the treatment options for adult ADHD patients with tDCS and provide an alternative or add-on therapy to psychostimulants with a low risk for side effects.Trial Registration The trial was registered on July 29, 2022 in the German Clinical Trials Register (DRKS00028148).

A distinct intra-individual suppression subnetwork in the brain's default mode network across cognitive tasks.

Suppression of the brain's default mode network (DMN) during external goal-directed cognitive tasks has been consistently observed in neuroimaging studies. However, emerging insights suggest the DMN is not a monolithic "task-negative" network but is comprised of subsystems that show functional heterogeneity. Despite considerable research interest, no study has investigated the consistency of DMN activity suppression across multiple cognitive tasks within the same individuals. In this study, 85 healthy 15- to 25-year-olds completed three functional magnetic resonance imaging tasks that were designed to reliably map DMN suppression from a resting baseline. Our findings revealed a distinct suppression subnetwork across the three tasks that comprised traditional DMN and adjacent regions. Specifically, common suppression was observed in the medial prefrontal cortex, the dorsal-to-mid posterior cingulate cortex extending to the precuneus, and the posterior insular cortex and parietal operculum. Further, we found the magnitude of suppression of these regions were significantly correlated within participants across tasks. Overall, our findings indicate that externally oriented cognitive tasks elicit common suppression of a distinct subnetwork of the broader DMN. The consistency to which the DMN is suppressed within individuals suggests a domain-general mechanism that may reflect a stable feature of cognitive function that optimizes external goal-directed behavior.

[Is Physical Activity a Treatment Option for ADHD?] / Körperliche Aktivität als Therapieoption bei ADHS?

Is Physical Activity a Treatment Option for ADHD? Abstract: Physical activity as an option for the prevention and treatment of psychiatric disorders is increasingly becoming the focus of research. In particular, because of improvements in cognitive functioning, attentional performance, impulsivity, and hyperactivity, physical exercise could be a promising treatment option for attention deficit hyperactivity disorder (ADHD). In this narrative review, we present and evaluate the current state of research on exercise effects in children and adolescents as well as in adults with ADHD. While studies of the short-term effects of a single bout of physical activity indicate robust effects on attention and inhibitory control, results on the impact on further symptoms of ADHD as well as in adults are mixed. Randomized controlled trials of longer-term physical activity are scarce and show high heterogeneity. Nevertheless, they are encouraging for further research in this area.

The effects of creatine supplementation on cognitive performance-a randomised controlled study.

BACKGROUND: Creatine is an organic compound that facilitates the recycling of energy-providing adenosine triphosphate (ATP) in muscle and brain tissue. It is a safe, well-studied supplement for strength training. Previous studies have shown that supplementation increases brain creatine levels, which might increase cognitive performance. The results of studies that have tested cognitive performance differ greatly, possibly due to different populations, supplementation regimens, and cognitive tasks. This is the largest study on the effect of creatine supplementation on cognitive performance to date. METHODS: Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each. We tested participants on Raven's Advanced Progressive Matrices (RAPM) and on the Backward Digit Span (BDS). In addition, we included eight exploratory cognitive tests. About half of our 123 participants were vegetarians and half were omnivores. RESULTS: Bayesian evidence supported a small beneficial effect of creatine. The creatine effect bordered significance for BDS (p = 0.064, η2P = 0.029) but not RAPM (p = 0.327, η2P = 0.008). There was no indication that creatine improved the performance of our exploratory cognitive tasks. Side effects were reported significantly more often for creatine than for placebo supplementation (p = 0.002, RR = 4.25). Vegetarians did not benefit more from creatine than omnivores. CONCLUSIONS: Our study, in combination with the literature, implies that creatine might have a small beneficial effect. Larger studies are needed to confirm or rule out this effect. Given the safety and broad availability of creatine, this is well worth investigating; a small effect could have large benefits when scaled over time and over many people. TRIAL REGISTRATION: The trial was prospectively registered (drks.de identifier: DRKS00017250, https://osf.io/xpwkc/ ).

Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany.

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study's aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as "probable psychiatric AE (pAE)," if well-characterized neuronal IgG autoantibodies were detected or "possible pAE" (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.

Gaze-based attention refocusing training in virtual reality for adult attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is characterized by substantial interindividual heterogeneity that challenges the systematic assessment and treatment. Considering mixed evidence from previous neurofeedback research, we present a novel feedback system that relies on gaze behavior to detect signs of inattention while performing a neuropsychological attention task in a virtual seminar room. More specifically, an audiovisual feedback was given whenever participants averted their gaze from the given task. METHODS: Eighteen adults with ADHD and 18 healthy controls performed a continuous performance task (CPT) in virtual reality under three counterbalanced conditions in which either gaze-based feedback, sham feedback, or no feedback was provided. In all conditions, phases of high and low virtual distraction alternated. CPT errors and reaction times, proportions of gaze dwell times (e.g., task focus or distraction focus), saccade characteristics, EEG theta/beta ratios, head movements, and an experience sampling of ADHD symptoms were analyzed. RESULTS: While patients can be discriminated well from healthy controls in that they showed more omission errors, higher reaction times, higher distraction-related dwell times, and more head movements, the feedback did not immediately improve task performance. It was also indicated that sham feedback was rather associated with an aggravation of symptoms in patients. CONCLUSIONS: Our findings demonstrate sufficient suitability and specificity for this holistic ADHD symptom assessment. Regarding the feedback, a single-session training was insufficient to achieve learning effects based on the proposed metacognitive strategies. Future longitudinal, multi-session trials should conclusively examine the therapeutic efficacy of gaze-based virtual reality attention training in ADHD. TRIAL REGISTRATION: drks.de (identifier: DRKS00022370).

Common and dissociable effects of oxytocin and lorazepam on the neurocircuitry of fear.

Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs share similar effects on the neural circuitry of fear is unclear. Therefore, the rationale of this ultra-high-field functional MRI (fMRI) study was to test OXT against the clinical comparator lorazepam (LZP) with regard to their neuromodulatory effects on local and network responses to fear-related stimuli. One hundred twenty-eight healthy male participants volunteered in this randomized double-blind, placebo-controlled, between-group study. Before scanning using an emotional face-matching paradigm, participants were randomly administered a single dose of OXT (24 IU), LZP (1 mg), or placebo. On the behavioral level, LZP, but not OXT, caused mild sedation, as evidenced by a 19% increase in reaction times. On the neural level, both OXT and LZP inhibited responses to fearful faces vs. neutral faces within the centromedial amygdala (cmA). In contrast, they had different effects on intra-amygdalar connectivity; OXT strengthened the coupling between the cmA and basolateral amygdala, whereas LZP increased the interplay between the cmA and superficial amygdala. Furthermore, OXT, but not LZP, enhanced the coupling between the cmA and the precuneus and dorsomedial prefrontal cortex. These data implicate inhibition of the cmA as a common denominator of anxiolytic action, with only OXT inducing large-scale connectivity changes of potential therapeutic relevance.

Multimodal assessment of adult attention-deficit hyperactivity disorder: A controlled virtual seminar room study.

In the assessment of adult attention-deficit hyperactivity disorder (ADHD) symptoms, the diagnostic value of neuropsychological testing is limited. Partly, this is due to the rather low ecological validity of traditional neuropsychological tests, which usually present abstract stimuli on a computer screen. A potential remedy for this shortcoming might be the use of virtual reality (VR), which enables a more realistic and complex, yet still standardized test environment. The present study investigates a new VR-based multimodal assessment tool for adult ADHD, the virtual seminar room (VSR). Twenty-five unmedicated ADHD patients, 25 medicated ADHD patients, and 25 healthy controls underwent a virtual continuous performance task (CPT) in the VSR with concurrent visual, auditive, and audiovisual distractions. Simultaneously, head movements (actigraphy), gaze behaviour (eye tracking), subjective experience, electroencephalography (EEG), and functional near-infrared spectroscopy (fNIRS) were recorded. Significant differences between unmedicated patients with ADHD and healthy controls were found in CPT performance, head actigraphy, distractor gaze behaviour, and subjective experience. Moreover, CPT performance parameters demonstrated potential utility for assessing medication effects within the ADHD population. No group differences were found in the Theta-Beta-Ratio (EEG) or dorsolateral-prefrontal oxy-haemoglobin (fNIRS). Overall, the results are very promising regarding the potential of the VSR as an assessment tool for adult ADHD. In particular, the combined assessment of CPT, actigraphy, and eye tracking parameters appears to be a valid approach to more accurately capture the heterogeneous symptom presentation of the disorder.

[Prescription-based digital interventions in psychiatry : Methodology, possible areas of application, and legal framework of digital tools for panic disorder and agoraphobia available in Germany]. / Digitale Gesundheitsanwendungen mit psychotherapeutischem Fokus : Therapieprinzipien, Einsatzmöglichkeiten, rechtlicher Rahmen und Verordnungspraxis am Beispiel der Anwendungen für die Panikstörung und Agoraphobie.

In 2020, prescription-based digital interventions were introduced in Germany. These digital courses have to meet safety and data privacy requirements and must prove positive effects on symptoms and/or other outcome parameters. Interventions are available for a range of mental disorders. For patients with panic disorder and agoraphobia, several applications based on cognitive behavioral therapy have been developed. Within these digital courses, patients can typically access psychoeducational content and practice psychotherapeutic strategies such as exposure therapy. Recent meta-analyses prove the effectiveness of such interventions when compared with waitlist control conditions. According to current German guidelines, digital courses can be used to prepare psychotherapy and as an accompanying tool during psychotherapy. In Germany, physicians and psychotherapist can prescribe digital interventions for outpatients and as a post-hospital treatment..

[Attention deficit hyperactivity disorder and substance use in adulthood-Guideline-conform diagnostics and treatment]. / Aufmerksamkeitsdefizit­/Hyperaktivitätsstörung und Substanzkonsum im Erwachsenenalter ­ leitliniengerechte Diagnostik und Behandlung.

Attention deficit hyperactivity disorder (ADHD) is the most frequent developmental disorder in childhood, adolescence and adulthood. Substance use disorders are a frequent comorbidity in ADHD. The many different forms and severities of these comorbidities necessitate individual strategies in the diagnostics and treatment. Principally, ADHD and addictive disorders should be treated together whenever possible. The more acute or severe the dependence disorder is, the less priority can be given to the topic of ADHD and the lower are the chances of carrying out valid diagnostics and simultaneous treatment at the beginning of the treatment of the addictive disorder. The less severe and acute the addictive disorder is, the quicker the diagnostics and, if necessary, treatment of ADHD can be initiated. In this continuing education article, the customary means for diagnostics and pharmacotherapy as well as the special features that must be considered with respect to comorbidities of both disorders are presented.

Effects and feasibility of psychological interventions to reduce inattention symptoms in adults with ADHD: a systematic review.

BACKGROUND: Adult ADHD is common, highly comorbid, and restricts daily functioning. However, only a minority of patients receive appropriate treatment. AIMS: Primary objective: To identify psychological interventions that diminish inattention symptoms in adults with ADHD. Secondary objective: To evaluate feasibility aspects. METHODS: A search in PubMed, Cochrane Library, PsycInfo, PSYNDEX, and Eric was conducted. Interventions were grouped in: ADHD coaching, neuro feedback, cognitive training, psychoeducation, and behavioral therapy. Inattention symptoms were evaluated using standardized mean differences. Study quality was rated with the Cochrane Risk of Bias tool. Feasibility was assessed by number and time of sessions, setting, and qualification of the provider. RESULTS: A total of N = 2229 results were identified, 19 randomized controlled studies were included in the analysis. Behavioral therapy showed effects on inattention symptoms [SMD: 0.44-1.71] when compared to inactive controls. In terms of feasibility, longer interventions did not outperform shorter ones and individual sessions were not superior to group sessions. No effects were given for neuro feedback, cognitive training, and psychoeducation in comparison to controls. CONCLUSION: For adults with ADHD behavioral therapy seems an effective intervention to reduce inattention symptoms. In terms of feasibility, brief interventions may be valuable for a primary care setting.

Exogenous estradiol and oxytocin modulate sex differences in hippocampal reactivity during the encoding of episodic memories.

Considerable evidence supports sex differences in episodic memory. The hormones estradiol and oxytocin both affect episodic memory and may contribute to these sex differences, but possible underlying hormonal interactions have not been tested in a sample involving both sexes. To this end, we conducted a randomized, placebo-controlled, parallel-group functional magnetic resonance imaging (fMRI) study including healthy free-cycling women (n = 111) and men (n = 115). The fMRI session was conducted under four experimental conditions: 1. transdermal estradiol (2 mg) and intranasal oxytocin (24 IU), 2. transdermal placebo and intranasal oxytocin, 3. transdermal estradiol and intranasal placebo, 4. transdermal placebo and intranasal placebo. Participants were scanned during the encoding of positive, neutral, and negative scenes. Recognition memory was tested three days following the scanning sessions without additional treatments. Under placebo, women showed a significantly better recognition memory and increased hippocampal responses to subsequently remembered items independent of the emotional valence compared to men. The separate treatments with either hormone significantly diminished this mnemonic sex difference and reversed the hippocampal activation pattern. However, the combined treatments produced no significant effect. Collectively, the results suggest that both hormones play a crucial role in modulating sex differences in episodic memory. Furthermore, possible antagonistic interactions between estradiol and oxytocin could explain previously observed opposing hormonal effects in women and men.

Lower fractional anisotropy of the corticothalamic tract and increased response time variability in adult patients with ADHD.

BACKGROUND: Intraindividual intertrial variability has been suggested as an endophenotype of attention-deficit/hyperactivity disorder (ADHD). It is usually evaluated as response time variability (RTV) in reaction time tasks, and RTV has emerged as a robust and stable feature of ADHD. Among attempts to elucidate the neurobiological underpinnings of RTV, it has been suggested that alterations in white matter microstructure may explain RTV. METHODS: We used diffusion tensor imaging (DTI) in a group of 53 adults with ADHD and 50 healthy controls. We obtained RTV parameters from a simple reaction-time task, in which participants were asked to respond to the appearance of white crosses on a screen using button presses. RESULTS: We observed significant between-group differences for the ex-Gaussian parameter τ, indicating that the mean of extremely slow responses was greater for adults with ADHD than controls. Fractional anisotropy (FA) derived from DTI was significantly different between groups in 2 clusters of the corticothalamic tract. In the ADHD group, relatively decreased FA values were significantly associated with the parameter τ, such that lower FA values in the corticothalamic tract predicted greater τ as an index of RTV. We did not observe this association in healthy controls. LIMITATIONS: For comparison with previous studies, we used FA as a dependent variable of interest. However, although this metric is sensitive to white matter structural properties, there are ambiguities in its interpretation. CONCLUSION: Even in a simple reaction-time task, RTV proved again to be a stable feature of ADHD. It was associated with altered white matter structural properties of the corticothalamic tract in adults with ADHD.

Robust perceptual-load-dependent audiovisual integration in adult ADHD.

We perceive our daily-life surrounded by different senses (e.g., visual, and auditory). For a coherent percept, our brain binds those multiple streams of sensory stimulations, i.e., multisensory integration (MI). Dependent on stimulus complexity, early MI is triggered by bottom-up or late via top-down attentional deployment. Adult attention-deficit/hyperactivity disorder (ADHD) is associated with successful bottom-up MI and deficient top-down MI. In the current study, we investigated the robustness of the bottom-up MI by adding additional task demand varying the perceptual load. We hypothesized diminished bottom-up MI for high perceptual load for patients with ADHD. 18 adult patients with ADHD and 18 age- and gender-matched healthy controls participated in this study. In the visual search paradigm, a target letter was surrounded by uniform distractors (low load) or by different letters (high load). Additionally, either unimodal (visual flash, auditory beep) or multimodal (audiovisual) flanked the visual search. Linear-mixed modeling was used to investigate the influence of load on reaction times. Further, the race model inequality was calculated. Patients with ADHD showed a similar degree of MI performance like healthy controls, irrespective of perceptual load manipulation. ADHD patients violated the race model for the low load but not for the high-load condition. There seems to be robust bottom-up MI independent of perceptual load in ADHD patients. However, the sensory accumulation might be altered when attentional demands are high.

Molecular and neurocircuitry mechanisms of social avoidance.

Humans and animals live in social relationships shaped by actions of approach and avoidance. Both are crucial for normal physical and mental development, survival, and well-being. Active withdrawal from social interaction is often induced by the perception of threat or unpleasant social experience and relies on adaptive mechanisms within neuronal networks associated with social behavior. In case of confrontation with overly strong or persistent stressors and/or dispositions of the affected individual, maladaptive processes in the neuronal circuitries and its associated transmitters and modulators lead to pathological social avoidance. This review focuses on active, fear-driven social avoidance, affected circuits within the mesocorticolimbic system and associated regions and a selection of molecular modulators that promise translational potential. A comprehensive review of human research in this field is followed by a reflection on animal studies that offer a broader and often more detailed range of analytical methodologies. Finally, we take a critical look at challenges that could be addressed in future translational research on fear-driven social avoidance.

Amygdala reactivity and ventromedial prefrontal cortex coupling in the processing of emotional face stimuli in attention-deficit/hyperactivity disorder.

Impaired emotion recognition is common in individuals with attention-deficit/hyperactivity disorder (ADHD) and may, via deficient emotion self-regulation, relate to the frequently co-occurring affective and social problems. The present study used an emotional face-matching task and functional magnetic resonance imaging (fMRI) to investigate neural responses during the processing of angry and fearful faces and visuo-spatial control stimuli. Additionally, measures for emotion dysregulation, ADHD type, and age were investigated in relation to the behavioral and neural fMRI data. We utilized a sample of 61 adolescents/young adults with ADHD and 51 age-matched healthy controls (age range: 12-28 years). Participants with ADHD had higher emotion dysregulation scores than controls. They also reacted slower and less accurate in response to emotional but not visuo-spatial control stimuli. Neural response differences between emotional and visuo-spatial trials were significantly smaller in cases, particularly in the left amygdala. While coupling between the right amygdala and bilateral ventromedial prefrontal cortex was stronger for emotional than visuo-spatial stimuli in control subjects, levels of positive coupling between the trial types did not significantly differ in participants with ADHD. Neither emotion dysregulation scores, nor ADHD type or age were related to the behavioral and neural processing alterations during the emotional face-matching task. Results indicate that emotion recognition deficits in ADHD are particularly associated with lower amygdala activation to emotional stimuli and alterations in the functional connections of the amygdala to medial prefrontal areas. Emotion recognition deficits and associated neural alterations were unrelated to emotion dysregulation, ADHD type, or age.