Short-term effects of an elimination diet and healthy diet in children with attention-deficit/hyperactivity disorder: a randomized-controlled trial.

An Elimination Diet (ED) may be effective in reducing symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), but has never been compared to an active control condition [i.e., Healthy Diet (HD)]. In a two-armed RCT, a total of N = 165 children (5-12 years) with ADHD were randomized by means of minimization (1:1) to either an ED (N = 84) or HD (N = 81) within two Dutch child and adolescent psychiatry centers. The design included a non-randomized comparator arm including N = 58 children being treated with Care as Usual (CAU). Treatment allocation was unblinded. The primary outcome was a 5-point ordinal measure of respondership based on a combination of parent and teacher ratings on ADHD and emotion regulation, determined after 5 weeks of treatment. Ordinal regression analyses were done on an intention-to-treat basis. Fewer ED (35%) than HD (51%) participants showed a partial to full response, despite overall good-to-excellent treatment adherence (> 88%) and comparable high parental prior believes. A younger age and higher problem severity predicted a better respondership. CAU-preferring participants responded more often favorably (56%) compared to ED-but not HD-participants. Small-to-medium improvements in physical health (blood pressure, heart rate, and somatic complaints) were found in response to ED/HD versus decrements in response to CAU (74% received psychostimulants). The lack of superiority of the ED versus HD suggests that for the majority of children, dietary treatment response is not rooted in food-allergies/-sensitivities. The comparable results for treatment with HD and CAU are remarkable given that CAU participants were probably 'easier to treat' than HD (and ED) participants with proportionally fewer with a (suboptimal/non-response to) prior treatment with medication (4% versus 20%). Further assessment of long-term effects is needed to evaluate the potential place of dietary treatment within clinical guidelines. The trial is closed and registered in the Dutch trial registry, number NL5324 ( https://www.onderzoekmetmensen.nl/en/trial/25997 ).

A boost in self-esteem after positive social evaluation predicts social and non-social learning.

Fluctuations in self-esteem resulting from social acceptance and rejection could guide social behaviour by putting us in a state that is more or less open to social experiences. However, it remains unclear whether social acceptance and rejection may shape learning from social information depending on individual differences in self-esteem changes. Here we used a social feedback paradigm to manipulate social acceptance and rejection in a between-subjects design. Subsequently, we administered a behavioural task that enables the assessment of how well individuals learn on the basis of own experiences versus social information. Participants receiving positive (N = 43) versus negative (N = 44) social evaluation demonstrated an increase in subjective self-esteem. Importantly, the effect of the social evaluation on social learning was moderated by self-esteem changes. Specifically, an increase in self-esteem, as induced by positive evaluation, was associated with increased learning from social, but decreased learning from individual information. A decrease in self-esteem in response to negative evaluation was associated with decreased learning from individual information. These data suggest that increases in self-esteem in response to positive evaluation can induce a shift in the inclination to use social versus non-social information and may open one up to constructive learning from others.

Academic stress, mindfulness-related skills and mental health in international university students.

This study investigated the relationships between academic stress, mindfulness-related constructs (ie, mindfulness, self-compassion and psychological flexibility) and anxiety and depressive symptoms in a sample of 190 international university students. Participants filled in an online questionnaire. Multiple Regression Analyses showed that anxiety and depressive symptoms were significantly related to higher levels of perceived academic stress, and to lower levels of acting with (mindful) awareness, lower self-compassion and lower psychological flexibility. None of the mindfulness-related constructs was found to moderate the relationship between perceived academic stress and anxiety and depressive symptoms. The results provide possible targets for mental health interventions in international university students. Especially the training of mindfulness-related skills could be a promising path.

Stress-sensitive inference of task controllability.

Estimating the controllability of the environment enables agents to better predict upcoming events and decide when to engage controlled action selection. How does the human brain estimate controllability? Trial-by-trial analysis of choices, decision times and neural activity in an explore-and-predict task demonstrate that humans solve this problem by comparing the predictions of an 'actor' model with those of a reduced 'spectator' model of their environment. Neural blood oxygen level-dependent responses within striatal and medial prefrontal areas tracked the instantaneous difference in the prediction errors generated by these two statistical learning models. Blood oxygen level-dependent activity in the posterior cingulate, temporoparietal and prefrontal cortices covaried with changes in estimated controllability. Exposure to inescapable stressors biased controllability estimates downward and increased reliance on the spectator model in an anxiety-dependent fashion. Taken together, these findings provide a mechanistic account of controllability inference and its distortion by stress exposure.

How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants.

Over the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (N = 272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (N = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared with full in-person psychiatric screening), recruited at least partly from convenience samples (compared with community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias.

A two arm randomized controlled trial comparing the short and long term effects of an elimination diet and a healthy diet in children with ADHD (TRACE study). Rationale, study design and methods.

BACKGROUND: Food may trigger Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Therefore, an elimination diet (ED) might be an effective treatment for children with ADHD. However, earlier studies were criticized for the nature of the control group, potential confounders explaining the observed effects, unsatisfactory blinding, potential risks of nutritional deficiencies and unknown long term and cost-effectiveness. To address these issues, this paper describes the rationale, study design and methods of an ongoing two arm randomized controlled trial (RCT) comparing the short (5 week) and long term (1 year) effects of an elimination diet and a healthy diet compared with care as usual (CAU) in children with ADHD. METHODS: A total of N = 162 children (5-12 years) with ADHD will be randomized to either an ED or a healthy diet. A comparator arm including N = 60 children being solely treated with CAU (e.g. medication) is used to compare the effects found in both dietary groups. The two armed RCT is performed in two youth psychiatry centers in the Netherlands, with randomization within each participating center. The primary outcome measure is response to treatment defined as a ≥ 30% reduction on an ADHD DSM-5 rating scale (SWAN) and/or on an emotion dysregulation rating scale (SDQ: dysregulation profile). This is assessed after 5 weeks of dietary treatment, after which participants continue the diet or not. Secondary outcome measures include the Disruptive Behavior Diagnostic Observational Schedule (DB-DOS), parent and teacher ratings of comorbid symptoms, cognitive assessment (e.g. executive functions), school functioning, physical measurements (e.g. weight), motor activity, sleep pattern, food consumption, nutritional quality of the diet, adherence, parental wellbeing, use of health care resources and cost-effectiveness. Assessments take place at the start of the study (T0), after five weeks (T1), four months (T2), eight months (T3) and 12 months of treatment (T4). T0, T1 and T4 assessments take place at one of the psychiatric centers. T2 and T3 assessments consist of filling out online questionnaires by the parents only. DISCUSSION: This RCT will likely contribute significantly to clinical practice for ADHD by offering insight into the feasibility, nutritional quality, (cost-)effectiveness and long term effects of dietary treatments for ADHD. TRIAL REGISTRATION: www.trialregister.nl, NTR5434. Registered at October 11th, 2015.

A Reward-Based Framework of Perceived Control.

Perceived control can be broadly defined as the belief in one's ability to exert control over situations or events. It has long been known that perceived control is a major contributor toward mental and physical health as well as a strong predictor of achievements in life. However, one issue that limits a mechanistic understanding of perceived control is the heterogeneity of how the term is defined in models in psychology and neuroscience, and used in experimental settings across a wide spectrum of studies. Here, we propose a framework for studying perceived control by integrating the ideas from traditionally separate work on perceived control. Specifically, we discuss key properties of perceived control from a reward-based framework, including choice opportunity, instrumental contingency, and success/reward rate. We argue that these separate reward-related processes are integral to fostering an enhanced perception of control and influencing an individual's behavior and well-being. We draw on select studies to elucidate how these reward-related elements are implicated separately and collectively in the investigation of perceived control. We highlight the role of dopamine within corticostriatal pathways shared by reward-related processes and perceived control. Finally, through the lens of this reward-based framework of perceived control, we consider the implications of perceived control in clinical deficits and how these insights could help us better understand psychopathology and treatment options.

Emotionally Aversive Cues Suppress Neural Systems Underlying Optimal Learning in Socially Anxious Individuals.

Learning and decision-making are modulated by socio-emotional processing and such modulation is implicated in clinically relevant personality traits of social anxiety. The present study elucidates the computational and neural mechanisms by which emotionally aversive cues disrupt learning in socially anxious human individuals. Healthy volunteers with low or high trait social anxiety performed a reversal learning task requiring learning actions in response to angry or happy face cues. Choice data were best captured by a computational model in which learning rate was adjusted according to the history of surprises. High trait socially anxious individuals used a less-dynamic strategy for adjusting their learning rate in trials started with angry face cues and unlike the low social anxiety group, their dorsal anterior cingulate cortex (dACC) activity did not covary with the learning rate. Our results demonstrate that trait social anxiety is accompanied by disruption of optimal learning and dACC activity in threatening situations.SIGNIFICANCE STATEMENT Social anxiety is known to influence a broad range of cognitive functions. This study tests whether and how social anxiety affects human value-based learning as a function of uncertainty in the learning environment. The findings indicate that, in a threatening context evoked by an angry face, socially anxious individuals fail to benefit from a stable learning environment with highly predictable stimulus-response-outcome associations. Under those circumstances, socially anxious individuals failed to use their dorsal anterior cingulate cortex, a region known to adjust learning rate to environmental uncertainty. These findings open the way to modify neurobiological mechanisms of maladaptive learning in anxiety and depressive disorders.

Incident experience predicts freezing-like responses in firefighters.

Freezing is a defensive response to acute stress that is associated with coping and alterations in attentional processing. However, it remains unclear whether individuals in high risk professions, who are skilled at making rapid decisions in emergency situations, show altered threat-induced freezing. Here we investigated the effect of incident experience in a high risk profession on freezing. Additionally, we explored whether any effect of incident experience on freezing would be different for profession-related and -unrelated threat. Forty experienced and inexperienced firefighters were presented neutral, pleasant, related-unpleasant, and unrelated-unpleasant pictures in a passive viewing task. Postural sway and heart rate were assessed to determine freezing. Both postural and heart rate data evidenced reduced freezing upon unpleasant pictures in the experienced versus the inexperienced group. Relatedness of the unpleasant pictures did not modulate these effects. These findings indicate that higher incident experience relates to decreased threat-induced freezing, at least in a passive task context. This might suggest that primary defense responses are malleable through experience. Finally, these findings demonstrate the potential of using animal to human translational approaches to investigate defensive behaviors in relation to incident experience in high risk professions and stimulate future research on the role of freezing in resilience and coping.

Elimination diets' efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder.

Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and autism spectrum disorder, with a focus on the efficacy of the food additives exclusion diet, gluten-free/casein-free diet and oligoantigenic diet. Furthermore, we discuss the potential mechanisms of elimination diets' effects in these neurodevelopmental disorders. The main candidate mechanism is the microbiome-gut-brain axis possibly involving complex interactions between multiple systems, including the metabolic, immune, endocrine, and neural system. We conclude with practical implications and future directions into the investigation of an elimination diet's efficacy in the treatment of attention deficit hyperactivity disorder and autism spectrum disorder.

Reduced transfer of affective value to instrumental behavior in violent offenders.

Instrumental or goal-directed aggression is a core feature in violent offenders with psychopathic tendencies. To understand this type of behavior, previous work in the field of aggression has focused on affective processing, with mixed results. We propose that instrumental aggression is best understood in terms of the consequences of affective processing for instrumental behavior rather than affective processing per se. Therefore, we assessed the degree of affective biasing of instrumental action in a group of violent offenders with psychopathic tendencies and healthy controls using a validated affective decision-making task. Participants learned whole body approach-avoidance actions upon instrumental targets based on monetary feedback, while being primed by aversive versus appetitive facial stimuli. Unlike controls, instrumental behavior in violent offenders was not influenced by the affective stimuli. Specifically, violent offenders showed reduced instrumental avoidance in the context of aversive (vs. appetitive) stimuli relative to controls. This finding suggests that reduced affective biasing of instrumental behavior may underlie the behavioral anomalies observed in violent offenders with psychopathic tendencies. More generally, the finding underscores the relevance of examining the interaction between affect and instrumental behavior for a better understanding of dysfunctional behaviors in psychiatric populations. (PsycINFO Database Record

Reduced Affective Biasing of Instrumental Action With tDCS Over the Prefrontal Cortex.

BACKGROUND: Instrumental action is well known to be vulnerable to affective value. Excessive transfer of affective value to instrumental action is thought to contribute to psychiatric disorders. The brain region most commonly implicated in overriding such affective biasing of instrumental action is the prefrontal cortex. OBJECTIVE: The aim of the present study was to reduce affective biasing of instrumental action using transcranial direct current stimulation (tDCS) in young healthy human volunteers. METHODS: In a double-blind, randomized between-group design, 120 participants received anodal, cathodal and sham tDCS while at the same time (online) performing a task that assessed affective biasing of instrumental action. We placed tDCS electrodes over the anterior part of the prefrontal cortex based on evidence from brain stimulation work demonstrating the role of this brain region in controlling affective biasing of instrumental action. RESULTS: We showed that prefrontal tDCS reduced affective biasing of instrumental action. Specifically, prefrontal tDCS reduced the degree to which aversive (versus appetitive) cues potentiated instrumental avoidance and suppressed instrumental approach. Contrary to our hypothesis, this effect was seen for cathodal tDCS rather than anodal tDCS. CONCLUSION: The results demonstrate the potential utility of prefrontal tDCS as a tool for reducing affective biasing of instrumental behavior, thus opening avenues for interventional research on psychiatric disorders that implicate excessive transfer of affective value.

Infant attachment predicts bodily freezing in adolescence: evidence from a prospective longitudinal study.

Early life-stress, particularly maternal deprivation, is associated with long-lasting deviations in animals' freezing responses. Given the relevance of freezing for stress-coping, translational research is needed to examine the relation between insecure infant-parent attachment and bodily freezing-like behavior in humans. Therefore, we investigated threat-related reductions in body sway (indicative of freezing-like behavior) in 14-year-old adolescents (N = 79), for whom attachment security was earlier assessed in infancy. As expected, insecure (vs. secure) attachment was associated with less body sway for angry vs. neutral faces. This effect remained when controlling for intermediate life events. These results suggest that the long-lasting effects of early negative caregiving experiences on the human stress and threat systems extend to the primary defensive reaction of freezing. Additionally, we replicated earlier work in adults, by observing a significant correlation (in adolescents assessed as securely attached) between subjective state anxiety and reduced body sway in response to angry vs. neutral faces. Together, this research opens venues to start exploring the role of freezing in the development of human psychopathology.

Individual differences in bodily freezing predict emotional biases in decision making.

Instrumental decision making has long been argued to be vulnerable to emotional responses. Literature on multiple decision making systems suggests that this emotional biasing might reflect effects of a system that regulates innately specified, evolutionarily preprogrammed responses. To test this hypothesis directly, we investigated whether effects of emotional faces on instrumental action can be predicted by effects of emotional faces on bodily freezing, an innately specified response to aversive relative to appetitive cues. We tested 43 women using a novel emotional decision making task combined with posturography, which involves a force platform to detect small oscillations of the body to accurately quantify postural control in upright stance. On the platform, participants learned whole body approach-avoidance actions based on monetary feedback, while being primed by emotional faces (angry/happy). Our data evidence an emotional biasing of instrumental action. Thus, angry relative to happy faces slowed instrumental approach relative to avoidance responses. Critically, individual differences in this emotional biasing effect were predicted by individual differences in bodily freezing. This result suggests that emotional biasing of instrumental action involves interaction with a system that controls innately specified responses. Furthermore, our findings help bridge (animal and human) decision making and emotion research to advance our mechanistic understanding of decision making anomalies in daily encounters as well as in a wide range of psychopathology.

Aversive disinhibition of behavior and striatal signaling in social avoidance.

Social avoidance is a major factor contributing to the development and maintenance of anxiety and depressive symptoms. Converging evidence suggests that social avoidance is associated with abnormal aversive processing and hyperactive amygdala signaling. However, what are the consequences of such abnormal aversive processing for action and for the neural mechanisms implementing action is unclear. Existing literature is conflicting, pointing at either enhanced or reduced action inhibition. We investigated the interaction between aversion and action in social avoidance by comparing the effects of aversive vs appetitive faces on a go/no-go task and associated striatal signals in 42 high and low socially avoidant individuals. We combined fMRI with a novel probabilistic learning task, in which emotional valence (angry and happy faces) and optimal response (go- and no-go-responses) were manipulated independently. High compared with low socially avoidant individuals showed reduced behavioral inhibition (proportion no-go-responses) for angry relative to happy faces. This behavioral disinhibition correlated with greater striatal signal during no-go-responses for angry relative to happy faces. The results suggest that social avoidant coping style is accompanied by disinhibition of action and striatal signal in the context of social threat. The findings concur with recent theorizing about aversive disinhibition and affective disorders.

Using an experimental medicine model to explore combination effects of pharmacological and cognitive interventions for depression and anxiety.

Selective serotonergic reuptake inhibitors (SSRIs) and cognitive therapies are effective in the treatment of anxiety and depression. Previous research suggests that both forms of treatments may work by altering cognitive biases in the processing of affective information. The current study assessed the effects of combining an SSRI with a cognitive intervention on measures of affective processing bias and resilience to external challenge. A total of 62 healthy participants were randomly assigned to receive either 7 days of citalopram (20 mg) or placebo capsules while also completing either an active or a control version of a computerized cognitive bias training task. After treatment, standard measures of affective processing bias were collected. Participants' resilience to external stress was also tested by measuring the increase in negative symptoms induced by a negative mood induction. Participants who received both citalopram and the active cognitive bias training task showed a smaller alteration in emotional memory and categorization bias than did those who received either active intervention singly. The degree to which memory for negative information was altered by citalopram predicted participants' resistance to the negative mood induction. These results suggest that co-administration of an SSRI and a cognitive training intervention can reduce the effectiveness of either treatment alone in terms of anxiety- and depression-relevant emotional processing. More generally, the findings suggest that pinpointing the cognitive actions of treatments may inform future development of combination strategies in mental health.

Social anxiety and cognitive expectancy of aversive outcome in avoidance conditioning.

Fear conditioning studies have shown that social anxiety is associated with enhanced expectancy of aversive outcome. However, the relation between cognitive expectancy and social anxiety has never been tested in avoidance conditioning paradigms. We compared 48 low (LSA) and high socially anxious individuals (HSA) on subjective expectancy of aversive outcome during an avoidance conditioning task. Displays of neutral faces were coupled with an aversive outcome (US): a shout and a shock. Participants could avoid the US by pressing a correct button from a button box. First, HSA showed higher US expectancy than LSA during the initial phase of avoidance conditioning, supporting the view that socially anxious individuals have an expectancy bias when social situations are ambiguous. Second, when the avoidance response became unavailable, LSA showed lower US expectancy than HSA, suggesting that low socially anxious individuals are prone to a positive bias when perceived threat is high. A lack of such positive bias in socially anxious individuals may lead to higher susceptibility to safety behavior interpretations. Together, these findings support the role of cognitive processes in avoidance conditioning and underscore the relevance to encounter avoidance learning when studying social anxiety.