Psychedelic resting-state neuroimaging: a review and perspective on balancing replication and novel analyses

Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research articles published to date, based on the 17 unique studies evaluating psychedelic effects on rs-fMRI, focusing on methodological variation. Prominently, we observe that nearly all studies vary in data processing and analysis methodology, two datasets are the foundation of over half of the published literature, and there is lexical ambiguity in common outcome metric terminology. We offer guidelines for future studies that encourage coherence in the field. Psychedelic rs-fMRI will benefit from the development of novel methods that expand our understanding of the brain mechanisms mediating its intriguing effects; yet, this field is at a crossroads where we must also consider the critical importance of consistency and replicability to effectively converge on stable representations of the neural effects of psychedelics

Genetic Dissection of Acute Ethanol Responsive Gene Networks in Prefrontal Cortex: Functional and Mechanistic Implications

Background Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain) across a highly diverse family of 27 isogenic mouse strains (BXD panel) before and after treatment with ethanol. Results Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol\u27s effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b,Gria1, Sncb and Nell2. Conclusions The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol response of gene networks could have important implications for future studies regarding the mechanisms and treatment of alcohol use disorders

The use of the development and well-being assessment (DAWBA) in clinical practice: a randomized trial

Background: The Development and Well-Being Assessment (DAWBA) has been used in various epidemiological studies whereas the clinical value of the instrument needs support from further studies. In particular, it is important to document how the use of the DAWBA influences clinical decision making. Methods: The present study employed the DAWBA in a consecutive series of 270 new referrals to a large public child and adolescent psychiatric service in Zurich, Switzerland. ICD-10 based diagnoses were obtained from clinicians for all patients and reliability of DAWBA expert raters was calculated. DAWBA diagnoses were randomly disclosed (N=144) or not disclosed (N=126) before clinical decision making. Results: The reliability of DAWBA expert diagnoses was very satisfactory and the agreement under the disclosed vs. the non-disclosed condition amounted to 77% vs. 68% for internalizing disorders and to 63% vs. 71% for externalizing disorders. The increment in agreement due to disclosure of the DAWBA diagnosis was significant for internalizing disorders. Access to DAWBA information was more likely to prompt clinicians to add an extra diagnosis. Professional background and degree of clinical experience did not affect diagnostic agreement. Conclusions: Overall, diagnostic agreements between DAWBA expert diagnoses and clinical diagnoses were in the fair to moderate range and comparable to previous studies with other structured diagnostic interviews. The inclusion of the DAWBA into the clinical assessment process had an impact on diagnostic decision making regarding internalizing disorders but not regarding externalizing disorders