Microorganisms in the human intestine (i.e. the gut microbiome) have an increasingly recognized impact on human health, including brain functioning. Attention-deficit/hyperactivity disorder (ADHD) is ...a neurodevelopmental disorder associated with abnormalities in dopamine neurotransmission and deficits in reward processing and its underlying neuro-circuitry including the ventral striatum. The microbiome might contribute to ADHD etiology via the gut-brain axis. In this pilot study, we investigated potential differences in the microbiome between ADHD cases and undiagnosed controls, as well as its relation to neural reward processing.
We used 16S rRNA marker gene sequencing (16S) to identify bacterial taxa and their predicted gene functions in 19 ADHD and 77 control participants. Using functional magnetic resonance imaging (fMRI), we interrogated the effect of observed microbiome differences in neural reward responses in a subset of 28 participants, independent of diagnosis.
For the first time, we describe gut microbial makeup of adolescents and adults diagnosed with ADHD. We found that the relative abundance of several bacterial taxa differed between cases and controls, albeit marginally significant. A nominal increase in the Bifidobacterium genus was observed in ADHD cases. In a hypothesis-driven approach, we found that the observed increase was linked to significantly enhanced 16S-based predicted bacterial gene functionality encoding cyclohexadienyl dehydratase in cases relative to controls. This enzyme is involved in the synthesis of phenylalanine, a precursor of dopamine. Increased relative abundance of this functionality was significantly associated with decreased ventral striatal fMRI responses during reward anticipation, independent of ADHD diagnosis and age.
Our results show increases in gut microbiome predicted function of dopamine precursor synthesis between ADHD cases and controls. This increase in microbiome function relates to decreased neural responses to reward anticipation. Decreased neural reward anticipation constitutes one of the hallmarks of ADHD.
Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the ...possible mechanisms underlying these relations is limited. In the present paper, we review the most often proposed mechanism, namely that involving the HPA axis and cortisol, as well as other less well-studied but possibly relevant and complementary mechanisms. We present evidence for a role of the following mechanisms: compromised placental functioning, including the 11β-HSD2 enzyme, increased catecholamines, compromised maternal immune system and intestinal microbiota, and altered health behaviors including eating, sleep, and exercise. The roles of (epi)genetics, the postnatal environment and the fetus are also discussed. We conclude that maternal prenatal psychosocial stress is a complex phenomenon that affects maternal emotions, behavior and physiology in many ways, and may influence the physiology and functioning of the fetus through a network of different pathways. The review concludes with recommendations for future research that helps our understanding of the mechanisms by which maternal prenatal stress exerts its effect on the fetus.
We proposed ICA-AROMA as a strategy for the removal of motion-related artifacts from fMRI data (Pruim et al., 2015). ICA-AROMA automatically identifies and subsequently removes data-driven derived ...components that represent motion-related artifacts. Here we present an extensive evaluation of ICA-AROMA by comparing our strategy to a range of alternative strategies for motion-related artifact removal: (i) no secondary motion correction, (ii) extensive nuisance regression utilizing 6 or (iii) 24 realignment parameters, (iv) spike regression (Satterthwaite et al., 2013a), (v) motion scrubbing (Power et al., 2012), (vi) aCompCor (Behzadi et al., 2007; Muschelli et al., 2014), (vii) SOCK (Bhaganagarapu et al., 2013), and (viii) ICA-FIX (Griffanti et al., 2014; Salimi-Khorshidi et al., 2014), without re-training the classifier. Using three different functional connectivity analysis approaches and four different multi-subject resting-state fMRI datasets, we assessed all strategies regarding their potential to remove motion artifacts, ability to preserve signal of interest, and induced loss in temporal degrees of freedom (tDoF). Results demonstrated that ICA-AROMA, spike regression, scrubbing, and ICA-FIX similarly minimized the impact of motion on functional connectivity metrics. However, both ICA-AROMA and ICA-FIX resulted in significantly improved resting-state network reproducibility and decreased loss in tDoF compared to spike regression and scrubbing. In comparison to ICA-FIX, ICA-AROMA yielded improved preservation of signal of interest across all datasets. These results demonstrate that ICA-AROMA is an effective strategy for removing motion-related artifacts from rfMRI data. Our robust and generalizable strategy avoids the need for censoring fMRI data and reduces motion-induced signal variations in fMRI data, while preserving signal of interest and increasing the reproducibility of functional connectivity metrics. In addition, ICA-AROMA preserves the temporal non-artifactual time-series characteristics and limits the loss in tDoF, thereby increasing statistical power at both the subject- and the between-subject analysis level.
Does it matter what we eat for our mental health? Accumulating data suggests that this may indeed be the case and that diet and nutrition are not only critical for human physiology and body ...composition, but also have significant effects on mood and mental wellbeing. While the determining factors of mental health are complex, increasing evidence indicates a strong association between a poor diet and the exacerbation of mood disorders, including anxiety and depression, as well as other neuropsychiatric conditions. There are common beliefs about the health effects of certain foods that are not supported by solid evidence and the scientific evidence demonstrating the unequivocal link between nutrition and mental health is only beginning to emerge. Current epidemiological data on nutrition and mental health do not provide information about causality or underlying mechanisms. Future studies should focus on elucidating mechanism. Randomized controlled trials should be of high quality, adequately powered and geared towards the advancement of knowledge from population-based observations towards personalized nutrition. Here, we provide an overview of the emerging field of nutritional psychiatry, exploring the scientific evidence exemplifying the importance of a well-balanced diet for mental health. We conclude that an experimental medicine approach and a mechanistic understanding is required to provide solid evidence on which future policies on diet and nutrition for mental health can be based.
•Epidemiological data highlight the association between nutrition and mental health but do not provide information about causality or underlying mechanism.•Emerging findings from intervention studies suggest that diet (often combined with lifestyle) modification has potential in the prevention and treatment of mental health and may modify drug treatment effects.•Dietary intervention studies are informative but often limited methodologically due to: heterogeneity in population characteristics, lack of biomarkers to adequately stratify within and across populations, small sample sizes, lack of blinding of participants to treatment allocation and/or lack of blinded observers.•Progress will require mechanistic insight into the impact of different diets and dietary components at various levels: metabolic and cellular processes, neural circuits, core cognitive and emotional processes, whole organism and disease (models).•Genetic background can be used to strengthen hypotheses on the effects of specific nutrients on mental disorders, which can subsequently be tested in randomized controlled trials.•High quality and adequately powered experimental medicine studies will enable the identification of interventions that have a higher probability of succeeding when tested in large randomized controlled trials.•Sensitivity to mental health issues vary across the lifespan and between individuals and is influenced by genetic background, cultural setting and the environment. Nutritional needs also differ across the lifespan. To provide dietary recommendations for improving mental health, a major challenge is to advance knowledge from population-based observations towards personalized nutrition.
Head motion during functional MRI (fMRI) scanning can induce spurious findings and/or harm detection of true effects. Solutions have been proposed, including deleting ('scrubbing') or regressing out ...('spike regression') motion volumes from fMRI time-series. These strategies remove motion-induced signal variations at the cost of destroying the autocorrelation structure of the fMRI time-series and reducing temporal degrees of freedom. ICA-based fMRI denoising strategies overcome these drawbacks but typically require re-training of a classifier, needing manual labeling of derived components (e.g. ICA-FIX; Salimi-Khorshidi et al. (2014)). Here, we propose an ICA-based strategy for Automatic Removal of Motion Artifacts (ICA-AROMA) that uses a small (n=4), but robust set of theoretically motivated temporal and spatial features. Our strategy does not require classifier re-training, retains the data's autocorrelation structure and largely preserves temporal degrees of freedom. We describe ICA-AROMA, its implementation, and initial validation. ICA-AROMA identified motion components with high accuracy and robustness as illustrated by leave-N-out cross-validation. We additionally validated ICA-AROMA in resting-state (100 participants) and task-based fMRI data (118 participants). Our approach removed (motion-related) spurious noise from both rfMRI and task-based fMRI data to larger extent than regression using 24 motion parameters or spike regression. Furthermore, ICA-AROMA increased sensitivity to group-level activation. Our results show that ICA-AROMA effectively reduces motion-induced signal variations in fMRI data, is applicable across datasets without requiring classifier re-training, and preserves the temporal characteristics of the fMRI data.
Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor cognitive control/attention and hypofunctioning of the dorsal anterior cingulate cortex (dACC). In the current study, we ...investigated for the first time whether real-time fMRI neurofeedback (rt-fMRI) training targeted at increasing activation levels within dACC in adults with ADHD leads to a reduction of clinical symptoms and improved cognitive functioning. An exploratory randomized controlled treatment study with blinding of the participants was conducted. Participants with ADHD (n = 7 in the neurofeedback group, and n = 6 in the control group) attended four weekly MRI training sessions (60-min training time/session), during which they performed a mental calculation task at varying levels of difficulty, in order to learn how to up-regulate dACC activation. Only neurofeedback participants received continuous feedback information on actual brain activation levels within dACC. Before and after the training, ADHD symptoms and relevant cognitive functioning was assessed. Results showed that both groups achieved a significant increase in dACC activation levels over sessions. While there was no significant difference between the neurofeedback and control group in clinical outcome, neurofeedback participants showed stronger improvement on cognitive functioning. The current study demonstrates the general feasibility of the suggested rt-fMRI neurofeedback training approach as a potential novel treatment option for ADHD patients. Due to the study's small sample size, potential clinical benefits need to be further investigated in future studies.
ISRCTN12390961.
Objective: To date, treatment programs for adult domestic violence (DV) or intimate partner violence (IPV) have had minimal impact. To make treatment more effective, programs should be adjusted to ...psychopathology of the offender. As emotional lability and poor emotional self-regulation and self-control are common features of ADHD, it may play a pivotal role as a predictor for adult DV/IPV. Method: This systematic review synthesizes the available evidence for childhood and/or adult ADHD being a risk factor for DV/IPV. Results: Four case control studies and three cohort studies were included in the review. Although three case control studies showed positive associations between childhood and/or adult ADHD and adult DV/IPV, two did insufficiently control for the presence of comorbid Conduct Disorder (CD) or Antisocial Personality Disorder (ASPD). Conclusion: Cohort studies identified hyperactive, impulsive, and inattention symptoms as risk factors for adult IPV. CD and ASPD were regarded as mediators in three studies.
Psychiatric disorders are increasingly being recognised as having a biological basis, but their diagnosis is made exclusively behaviourally. A promising approach for 'biomarker' discovery has been ...based on pattern recognition methods applied to neuroimaging data, which could yield clinical utility in future. In this review we survey the literature on pattern recognition for making diagnostic predictions in psychiatric disorders, and evaluate progress made in translating such findings towards clinical application. We evaluate studies on many criteria, including data modalities used, the types of features extracted and algorithm applied. We identify problems common to many studies, such as a relatively small sample size and a primary focus on estimating generalisability within a single study. Furthermore, we highlight challenges that are not widely acknowledged in the field including the importance of accommodating disease prevalence, the necessity of more extensive validation using large carefully acquired samples, the need for methodological innovations to improve accuracy and to discriminate between multiple disorders simultaneously. Finally, we identify specific clinical contexts in which pattern recognition can add value in the short to medium term.
The present paper presents a fundamentally novel approach to model individual differences of persons with the same biologically heterogeneous mental disorder. Unlike prevalent case-control analyses, ...that assume a clear distinction between patient and control groups and thereby introducing the concept of an 'average patient', we describe each patient's biology individually, gaining insights into the different facets that characterize persistent attention-deficit/hyperactivity disorder (ADHD).
Using a normative modeling approach, we mapped inter-individual differences in reference to normative structural brain changes across the lifespan to examine the degree to which case-control analyses disguise differences between individuals.
At the level of the individual, deviations from the normative model were frequent in persistent ADHD. However, the overlap of more than 2% between participants with ADHD was only observed in few brain loci. On average, participants with ADHD showed significantly reduced gray matter in the cerebellum and hippocampus compared to healthy individuals. While the case-control differences were in line with the literature on ADHD, individuals with ADHD only marginally reflected these group differences.
Case-control comparisons, disguise inter-individual differences in brain biology in individuals with persistent ADHD. The present results show that the 'average ADHD patient' has limited informative value, providing the first evidence for the necessity to explore different biological facets of ADHD at the level of the individual and practical means to achieve this end.
To compare findings across species, neuroscience relies on cross-species homologies, particularly in terms of brain areas. For cingulate cortex, a structure implicated in behavioural adaptation and ...control, a homologous definition across mammals is available – but currently not employed by most rodent researchers. The standard partitioning of rodent cingulate cortex is inconsistent with that in any other model species, including humans. Reviewing the existing literature, we show that the homologous definition better aligns results of rodent studies with those of other species, and reveals a clearer structural and functional organisation within rodent cingulate cortex itself. Based on these insights, we call for widespread adoption of the homologous nomenclature, and reinterpretation of previous studies originally based on the nonhomologous partitioning of rodent cingulate cortex.
Cingulate cortex is a hub of cognitive and emotional control, and it is highly preserved across mammals. As such, much of our knowledge on cingulate cortex relies on a synthesis of findings across species.One crucial obstacle to such cross-species comparisons is a striking discrepancy in anatomical definitions. In most mammals, the border between subregions of the cingulate cortex is drawn along the rostrocaudal axis, but in mice and rats it has been routinely drawn perpendicularly to this axis.This rarely discussed discrepancy has given rise to apparent inconsistencies in cingulate cortex structure and function, within and across species.A homologous nomenclature of cingulate cortex across species was proposed in 2005, but has so far been rarely used in relevant studies.We argue that applying the homologous definition aligns the structure and function of rodent cingulate cortex with that of other species. It also better reflects the inherent structure of rodent cingulate cortex itself.
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