Gut microbiota, metabolism and psychopathology:A critical review and novel perspectives

Psychiatric disorders are often associated with metabolic comorbidities. However, the mechanisms through which metabolic and psychiatric disorders are connected remain unclear. Pre-clinical studies in rodents indicate that the bidirectional signaling between the intestine and the brain, the so-called microbiome-gut-brain axis, plays an important role in the regulation of both metabolism and behavior. The gut microbiome produces a vast number of metabolites that may be transported into the host and play a part in homeostatic control of metabolism as well as brain function. In addition to short chain fatty acids, many of these metabolites have been identified in recent years. To what extent both microbiota and their products control human metabolism and behavior is a subject of intense investigation. In this review, we will discuss the most recent findings concerning alterations in the gut microbiota as a possible pathophysiological factor for the co-occurrence of metabolic comorbidities in psychiatric disorders

Exploring neuropsychological effects of a self-monitoring intervention for ADHD-symptoms in school

Children who have symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) often experience disruptive and off-task behavior and lower school performance than would be expected based on their cognitive abilities. These behavior and achievement difficulties are a challenge to teachers, who often provide inclusive education for children with ADHD. This study explored whether a self-monitoring intervention can help children with ADHD-symptoms to reduce off-task behavior as well as improve their cognition. The participating children were seven boys in special needs education with an age between nine and twelve. The students used an interval timer to remind themselves to monitor whether they were still on task. During math classes, observations, teacher ratings and neuropsychological tests were assessed. The results showed that off-task behavior was significantly reduced during the period the interval timer was used compared to baseline (reduction from 46.8 to 27.3%), as measured by observations (effect size: η2p = .83) and this was confirmed by teacher ratings (effect size: η2p = .69). With respect to cognition, children only showed significant improvements in inhibition (effect sizes: Cohen's d = 2.62 and 1.24). The teachers as well as students evaluated the intervention mainly as positive. In line with previous studies, we found that that a self-monitoring intervention can be beneficial for children with ADHD-symptoms. Larger studies including a control group and blind observers are necessary to establish these results and to investigate the underlying mechanisms

Reward Sensitivity at Age 13 Predicts the Future Course of Psychopathology Symptoms

BACKGROUND: There are numerous observations of reward sensitivity being associated with different psychiatric disorders. Nonetheless, most studies investigating this relationship have been cross-sectional. Additionally, current knowledge is fragmentary as studies often investigate only one disorder at a time. The present study addresses these gaps by investigating whether reward sensitivity at age 13 predicts the course of nine psychopathology domains (attention and hyperactivity, autism spectrum, reactive aggression, proactive aggression, mood, anxiety, smoking, alcohol use, and cannabis use) over a 14-year follow-up period. METHODS: We used dimensional outcomes on 2,523 individuals over five measurement waves between ages 13 and 26 of the Dutch Tracking Adolescents' Individual Lives Survey (TRAILS). Reward sensitivity was measured with the Behavioral Activation System (BAS) scale. The longitudinal associations between reward sensitivity and psychopathology were examined using growth curve analysis within a multilevel framework. RESULTS: Reward sensitivity at age 13 was associated with changes in psychopathology over time. Reward sensitivity had a stable main effect on the future course of reactive and proactive aggression problems and anxiety problems. The effect of reward sensitivity increased over time for alcohol and cannabis use. Post-hoc analyses showed that reward sensitivity also had a stable effect on attention problems and hyperactivity and smoking when based on the fun-seeking subscale for both domains and when changing the informant who reported on attention problems and hyperactivity. No evidence was found for a longitudinal association between reward sensitivity and autism spectrum problems and mood problems. CONCLUSION: The current study provides evidence for the long-lasting effects of reward sensitivity on the course of different domains of psychopathology

Increased Resting-State Perfusion after Repeated Encoding Is Related to Later Retrieval of Declarative Associative Memories

Electrophysiological studies in animals have shown coordinated reactivation of neuronal ensembles during a restricted time period of behavioral inactivity that immediately followed active encoding. In the present study we directly investigated off-line processing of associative memory formation in the human brain. Subjects' regional cerebral blood flow (rCBF) as a surrogate marker of neural activity during rest was measured by MR-based perfusion imaging in a sample of 14 healthy male subjects prior to (Pre2) and after (Post) extensive learning of 24 face-name associations within a selective reminding task (SR). Results demonstrated significant Post-Pre2 rCBF increases in hippocampal and temporal lobe regions, while in a control comparison of two perfusion scans with no learning task in-between (Pre2-Pre1) no differences in rCBF emerged. Post perfusion scanning was followed by a surprise cued associative recall task from which two types of correctly retrieved names were obtained: older names already correctly retrieved at least once during one of the SR blocks, and recent names acquired during the last SR block immediately prior to the Post scan. In the anterior hippocampus individual perfusion increases were correlated with both correct retrievals of older and recent names. By contrast, older but not recently learned names showed a significant correlation with perfusion increases in the left lateral temporal cortex known to be associated with long-term memory. Recent, but not older names were correlated with dopaminergic midbrain structures reported to contribute to the persistence of memory traces for novel information. Although the direct investigation of off-line memory processing did not permit concomitant experimental control, neither intentional rehearsal, nor substantial variations in subjects' states of alertness appear to contribute to present results. We suggest that the observed rCBF increases might reflect processes that possibly contribute to the long-term persistence of memory traces

Scene complexity modulates degree of feedback activity during object detection in natural scenes

Selective brain responses to objects arise within a few hundreds of milliseconds of neural processing, suggesting that visual object recognition is mediated by rapid feed-forward activations. Yet disruption of neural responses in early visual cortex beyond feed-forward processing stages affects object recognition performance. Here, we unite these discrepant findings by reporting that object recognition involves enhanced feedback activity (recurrent processing within early visual cortex) when target objects are embedded in natural scenes that are characterized by high complexity. Human participants performed an animal target detection task on natural scenes with low, medium or high complexity as determined by a computational model of low-level contrast statistics. Three converging lines of evidence indicate that feedback was selectively enhanced for high complexity scenes. First, functional magnetic resonance imaging (fMRI) activity in early visual cortex (V1) was enhanced for target objects in scenes with high, but not low or medium complexity. Second, event-related potentials (ERPs) evoked by target objects were selectively enhanced at feedback stages of visual processing (from ~220 ms onwards) for high complexity scenes only. Third, behavioral performance for high complexity scenes deteriorated when participants were pressed for time and thus less able to incorporate the feedback activity. Modeling of the reaction time distributions using drift diffusion revealed that object information accumulated more slowly for high complexity scenes, with evidence accumulation being coupled to trial-to-trial variation in the EEG feedback response. Together, these results suggest that while feed-forward activity may suffice to recognize isolated objects, the brain employs recurrent processing more adaptively in naturalistic settings, using minimal feedback for simple scenes and increasing feedback for complex scenes

Specificity of psychopathology across levels of severity:a transdiagnostic network analysis

A prominent hypothesis within the field of psychiatry is that the manifestation of psychopathology changes from non-specific to specific as illness severity increases. Using a transdiagnostic network approach, we investigated this hypothesis in four independent groups with increasing psychopathology severity. We investigated whether symptom domains became more interrelated and formed more clusters as illness severity increased, using empirical tests for two network characteristics: global network strength and modularity-based community detection. Four severity groups, ranging from subthreshold psychopathology to having received a diagnosis and treatment, were derived with a standardized diagnostic interview conducted at age 18.5 (n = 1933; TRAILS cohort). Symptom domains were assessed using the Adult Self Report (ASR). Pairwise comparisons of the symptom networks across groups showed no difference in global network strength between severity groups. Similar number and type of communities detected in the four groups exceeded the more minor differences across groups. Common clusters consisted of domains associated with attention deficit hyperactivity disorder (ADHD) and combined depression and anxiety domains. Based on the strength of symptom domain associations and symptom clustering using a network approach, we found no support for the hypothesis that the manifestation of psychopathology along the severity continuum changes from non-specific to specific

A hierarchical dynamic model used for investigating feed efficiency and its relationship with hepatic gene expression in APOE*3-Leiden.CETP mice

Background: Feed efficiency (FE) is an important trait for livestock and humans. While the livestock industry focuses on increasing FE, in the current obesogenic society it is more of interest to decrease FE. Hence, understanding mechanisms involved in the regulation of FE and particularly how it can be decreased would help tremendously in counteracting the obesity pandemic. However, it is difficult to accurately measure or calculate FE in humans. In this study, we aimed to address this challenge by developing a hierarchical dynamic model based on humanized mouse data. Methods: We analyzed existing experimental data derived from 105 APOE*3-Leiden.CETP (E3L.CETP) mice fed a high-fat high-cholesterol (HFHC) diet for 1 (N = 20), 2 (N = 19), 3 (N = 20), and 6 (N = 46) month. We developed an ordinary differential equation (ODE) based model to estimate the FE based on the longitudinal data of body weight and food intake. Since the liver plays an important role in maintaining metabolic homeostasis, we evaluated associations between FE and hepatic gene expression levels. Depending on the feeding duration, we observed different relationships between FE and hepatic gene expression levels. Results: After 1-month feeding of HFHC diet, we observed that FE was associated with vitamin A metabolism, arachidonic acid metabolism, and the PPAR signaling pathway. After 3- and 6-month feeding of HFHC diet, we observed that FE was associated most strongly with expression levels of Spink1 and H19, genes involved in cell proliferation and glucose metabolism, respectively. Conclusions: In conclusion, our analysis suggests that various biological processes such as vitamin A metabolism, hepatic response to inflammation, and cell proliferation associate with FE at different stages of diet-induced obesity.</p