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

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

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

On the transience of stability of subthreshold psychopathology

Symptoms of psychopathology lie on a continuum ranging from mental health to psychiatric disorders. Although much research has focused on progression along this continuum, for most individuals, subthreshold symptoms do not escalate into full-blown disorders. This study investigated how the stability of psychopathological symptoms (attractor strength) varies across severity levels (homebase). Data were retrieved from the TRAILS TRANS-ID study, where 122 at-risk young adults (mean age 23.6 years old, 57% males) monitored their mental states daily for a period of six months (± 183 observations per participant). We estimated each individual’s homebase and attractor strength using generalized additive mixed models. Regression analyses showed no association between homebases and attractor strengths (linear model: B = 0.02, p = 0.47, R(2) < 0.01; polynomial model: B < 0.01, p = 0.61, R(2) < 0.01). Sensitivity analyses where we (1) weighed estimates according to their uncertainty and (2) removed individuals with a DSM-5 diagnosis from the analyses did not change this finding. This suggests that stability is similar across severity levels, implying that subthreshold psychopathology may resemble a stable state rather than a transient intermediate between mental health and psychiatric disorder. Our study thus provides additional support for a dimensional view on psychopathology, which implies that symptoms differ in degree rather than kind

The Associations of Affection and Rejection During Adolescence with Interpersonal Functioning in Young Adulthood:A Macro- and Micro-Level Investigation Using the TRAILS TRANS-ID Study

Affection and rejection in close relationships during adolescence are thought to impact adult interpersonal functioning, but few studies focused on how the quality of adolescents' relationships with different people (e.g. parents, peers, and teachers) impacts the daily, micro-level social experiences as well as general, macro-level interpersonal functioning in young adulthood. The present study investigated the associations between: (i) parental, teacher and peer affection and rejection during adolescence and macro-level (over several months) interpersonal functioning as well as different patterns (i.e. mean, variability and inertia) of micro-level (daily social experiences) during young adulthood; (ii) macro-level interpersonal functioning and the patterns of micro-level social experiences during young adulthood. The sample consisted of N = 122 (43% female) youth. At 11.2 +/- 0.4 and 16.0 +/- 0.6 years old, self- and other-reported parental, peer and teacher affection and rejection were assessed. At 23.7 +/- 0.6 years old, participants reported daily social experiences and interpersonal functioning across six months. The results suggested that: (i) higher teacher-reported peer rejection was associated with lower macro-level interpersonal functioning, higher means and higher variability in negative social experiences during adulthood; (ii) higher macro-level interpersonal functioning during young adulthood was associated with higher means and lower inertia in positive and lower variability in negative daily social experiences. These findings indicate that the affection and rejection during adolescence impact interpersonal functioning at macro- and micro-level during adulthood. The present study also shows distinct associations between macro-level interpersonal functioning and dynamics in daily social experiences

Anticipating Transitions in Mental Health in At-Risk Youths:A 6-Month Daily Diary Study Into Early-Warning Signals

If psychopathology behaves like a complex dynamic system, sudden onset or worsening of symptoms may be preceded by early-warning signals (EWSs). EWSs could thus reflect personalized warning signals for impending psychopathology. We empirically investigated this hypothesis in at-risk youths (N = 122, mean age = 23.6 ± 0.7 years, 57% males) from the clinical cohort of Tracking Adolescents’ Individual Lives Survey (TRAILS-CC), who provided daily emotion assessments for 6 months. We analyzed whether EWSs (rising autocorrelations and standard deviations in emotions) preceded transitions toward psychopathology. Across indicators and a range of analytical options, EWSs had low sensitivity (M = 26%, SD = 11%) and moderate specificity (M = 75%, SD = 14%). Thus, in the present sample, the proposed generic nature and clinical utility of EWSs could not be substantiated. Given this finding, we call for a more nuanced view on the application of complex-dynamic-systems principles to psychopathology and lay out key questions to be addressed in the future

Can we predict the direction of sudden shifts in symptoms?:Transdiagnostic implications from a complex systems perspective on psychopathology

Recently, there has been renewed interest in the application of assumptions from complex systems theory in the field of psychopathology. One assumption, with high clinical relevance, is that sudden transitions in symptoms may be anticipated by rising instability in the system, which can be detected with early warning signals (EWS). Empirical studies support the idea that this principle also applies to the field of psychopathology. The current manuscript discusses whether assumptions from complex systems theory can additionally be informative with respect to the specific symptom dimension in which such a transition will occur (e.g. whether a transition towards anxious, depressive or manic symptoms is most likely). From a complex systems perspective, both EWS measured in single symptom dynamics and network symptom dynamics at large are hypothesized to provide clues regarding the direction of the transition. Challenging research designs are needed to provide empirical validation of these hypotheses. These designs should be able to follow sudden transitions 'live' using frequent observations of symptoms within individuals and apply a transdiagnostic approach to psychopathology. If the assumptions proposed are supported by empirical studies then this will signify a large improvement in the possibility for personalized estimations of the course of psychiatric symptoms. Such information can be extremely useful for early intervention strategies aimed at preventing specific psychiatric problems

Comorbidity between depression and anxiety:assessing the role of bridge mental states in dynamic psychological networks

Background: Comorbidity between depressive and anxiety disorders is common. A hypothesis of the network perspective on psychopathology is that comorbidity arises due to the interplay of symptoms shared by both disorders, with overlapping symptoms acting as so-called bridges, funneling symptom activation between symptom clusters of each disorder. This study investigated this hypothesis by testing whether (i) two overlapping mental states "worrying"and "feeling irritated"functioned as bridges in dynamic mental state networks of individuals with both depression and anxiety as compared to individuals with either disorder alone, and (ii) overlapping or non-overlapping mental states functioned as stronger bridges. Methods: Data come from the Netherlands Study of Depression and Anxiety (NESDA). A total of 143 participants met criteria for comorbid depression and anxiety (65%), 40 participants for depression-only (18.2%), and 37 for anxiety-only (16.8%) during any NESDA wave. Participants completed momentary assessments of symptoms (i.e., mental states) of depression and anxiety, five times a day, for 2 weeks (14,185 assessments). First, dynamics between mental states were modeled with a multilevel vector autoregressive model, using Bayesian estimation. Summed average lagged indirect effects through the hypothesized bridge mental states were compared between groups. Second, we evaluated the role of all mental states as potential bridge mental states. Results: While the summed indirect effect for the bridge mental state "worrying"was larger in the comorbid group compared to the single disorder groups, differences between groups were not statistically significant. The difference between groups became more pronounced when only examining individuals with recent diagnoses (< 6 months). However, the credible intervals of the difference scores remained wide. In the second analysis, a non-overlapping item ("feeling down") acted as the strongest bridge mental state in both the comorbid and anxiety-only groups. Conclusions: This study empirically examined a prominent network-approach hypothesis for the first time using longitudinal data. No support was found for overlapping mental states "worrying"and "feeling irritable"functioning as bridge mental states in individuals vulnerable for comorbid depression and anxiety. Potentially, bridge mental state activity can only be observed during acute symptomatology. If so, these may present as interesting targets in treatment, but not prevention. This requires further investigation

Ten Simple Rules for Effective Computational Research

<p>Ten Simple Rules for Effective Computational Research</p

Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo