So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

https://bic.berkeley.edu/sites/default/files/Rossi_09_TMS%20safety%20review.pdf

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

The insula is a brain structure implicated in disparate cognitive, affective, and regulatory functions, including interoceptive awareness, emotional responses, and empathic processes. While classically considered a limbic region, recent evidence from network analysis suggests a critical role for the insula, particularly the anterior division, in high-level cognitive control and attentional processes. The crucial insight and view we present here is of the anterior insula as an integral hub in mediating dynamic interactions between other large-scale brain networks involved in externally oriented attention and internally oriented or self-related cognition. The model we present postulates that the insula is sensitive to salient events, and that its core function is to mark such events for additional processing and initiate appropriate control signals. The anterior insula and the anterior cingulate cortex form a “salience network” that functions to segregate the most relevant among internal and extrapersonal stimuli in order to guide behavior. Within the framework of our network model, the disparate functions ascribed to the insula can be conceptualized by a few basic mechanisms: (1) bottom–up detection of salient events, (2) switching between other large-scale networks to facilitate access to attention and working memory resources when a salient event is detected, (3) interaction of the anterior and posterior insula to modulate autonomic reactivity to salient stimuli, and (4) strong functional coupling with the anterior cingulate cortex that facilitates rapid access to the motor system. In this manner, with the insula as its integral hub, the salience network assists target brain regions in the generation of appropriate behavioral responses to salient stimuli. We suggest that this framework provides a parsimonious account of insula function in neurotypical adults, and may provide novel insights into the neural basis of disorders of affective and social cognition.

/pdf/saliency-switching-attention-and-control-a-network-model-of-4nzu8lqybn.pdf

Saliency, switching, attention and control: a network model of insula function

Visual hallucinations and lifetime use of HPPD-related drugs: Results from a large online survey

BACKGROUND AND HYPOTHESIS
Patients with hearing impairment (HI) may experience hearing sounds without external sources, ranging from random meaningless noises (tinnitus) to music and other auditory hallucinations (AHs) with meaningful qualities. To ensure appropriate assessment and management, clinicians need to be aware of these phenomena. However, sensory impairment studies have shown that such clinical awareness is low.


STUDY DESIGN
An online survey was conducted investigating awareness of AHs among clinicians and their opinions about these hallucinations.


STUDY RESULTS
In total, 125 clinicians (68.8% audiologists; 18.4% Ear-Nose-Throat [ENT] specialists) across 10 countries participated in the survey. The majority (96.8%) was at least slightly aware of AHs in HI. About 69.6% of participants reported encountering patients with AHs less than once every 6 months in their clinic. Awareness was significantly associated with clinicians' belief that patients feel anxious about their hallucinations (β = .018, t(118) = 2.47, P < .01), their belief that clinicians should be more aware of these hallucinations (β =.018, t(118) = 2.60, P < .01), and with confidence of clinicians in their skills to assess them (β = .017, t(118) = 2.63, P < .01). Clinicians felt underequipped to treat AHs (Median = 31; U = 1838; PFDRadj < .01).


CONCLUSIONS
Awareness of AHs among the surveyed clinicians was high. Yet, the low frequency of encounters with hallucinating patients and their belief in music as the most commonly perceived sound suggest unreported cases. Clinicians in this study expressed a lack of confidence regarding the assessment and treatment of AHs and welcome more information.

/pdf/hallucinations-in-hearing-impairment-how-informed-are-2rultpml.pdf

Hallucinations in Hearing Impairment: How Informed Are Clinicians?

BACKGROUND AND HYPOTHESIS
Distress associated with auditory (AH) and visual (VH) hallucinations in the general population was found to be predictive of later need for mental healthcare. It is, therefore, important to understand factors relating to the distress individuals experience from their hallucinations. Hallucinations can easily occur under substance-induced states, but recreational drug use is also known as a self-medication strategy. The current study, therefore, investigated whether recreational drug use by individuals from the general population is associated with the degree of distress experienced from AH and/or VH.


STUDY DESIGN
Drug use and distress severity associated with AH (N = 3.041) and/or VH (N = 2.218) were assessed by means of an online survey in the general Dutch population (>14 years of age).


STUDY RESULTS
Multiple linear regression revealed that while past month consumption of alcohol was associated with less AH- and VH-related distress, past month cannabis use was associated with more AH- and VH-related distress. Furthermore, past month use of nitrous oxide was associated with more severe VH-related distress.


CONCLUSION
Recreational use of alcohol, cannabis, and nitrous oxide may play important differential roles in the degree of distress associated with AH and VH in individuals from the general population. The consumption of these substances could form a potential risk factor for the development of distressing hallucinations or function as a signal marker for their occurrence. Due to the cross-sectional design of the current study, the causal relation between recreational drug use and distressing hallucinations remains to be elucidated.

/pdf/recreational-drug-use-and-distress-from-hallucinations-in-625se8cy.pdf

Recreational Drug Use and Distress From Hallucinations in the General Dutch Population.

Dit artikel beschrijft een gecombineerde behandelmethode om patienten met auditieve verbale hallucinaties, en bij wie medicatie niet voldoende helpt, beter te leren omgaan met hun stemmen en ze mogelijk doen verdwijnen. Er wordt met name gekeken naar een relatief nieuwe techniek: Competitive Memory Training (COMET). Deze nieuwe methode kan op een soms verrassende manier uitkomst bieden, bijvoorbeeld door te zingen of te springen. Dit wordt geillustreerd aan de hand van drie korte gevalsbeschrijvingen. Resultaten laten zien dat de gecombineerde aanpak, dat wil zeggen psycho-educatie, groepsbijeenkomsten en individuele psychotherapie, effectief is. Door vanuit verschillende invalshoeken te focussen op het stemmen horen, helpt de stemmenpoli van het UMC Utrecht patienten met auditieve verbale hallucinaties om de ervaren last van de stemmen voor een groot deel te verminderen en bij sommigen de stemmen te doen verdwijnen.

Na tien jaar eindelijk minder last van stemmen: COMET bij auditieve verbale hallucinaties

Reports of decreased mortality among patients with schizophrenia who use clozapine may be biased if clozapine is prescribed to relatively healthy patients and if intensive monitoring during its use prevents (under-treatment of) somatic disorder. We aimed to assess whether there is a difference in: (1) somatic comorbidity between patients who start with clozapine and those who start with other antipsychotics and (2) prescribed somatic medication, between patients using clozapine and those using olanzapine. Cohort study based on insurance claims (2010-2015). After selecting new users of antipsychotics and those who subsequently switched to clozapine (N = 158), aripiprazole (N = 295), olanzapine (N = 204) or first-generation antipsychotics (N = 295), we compared the clozapine starters to others on cardiovascular or diabetic comorbidity. Those using clozapine and olanzapine were compared on new prescriptions for cardiovascular or antidiabetic drugs. The OR(adj)of cardiovascular or diabetic comorbidity among other starters compared with clozapine starters was 0.77 [95% confidence interval (CI): 0.43-1.39], that is, a nonsignificantly increased prevalence associated with clozapine was found. Users of clozapine received significantly more new prescriptions for cardiovascular or antidiabetic medication (ORadj: 2.70, 95% CI: 1.43-5.08). Starters with clozapine were not cardiovascular/metabolic healthier than starters with other antipsychotics. During its use, they received more somatic treatment.

Iris E. C. Sommer

Papers

Visual hallucinations and lifetime use of HPPD-related drugs: Results from a large online survey

Hallucinations in Hearing Impairment: How Informed Are Clinicians?

Recreational Drug Use and Distress From Hallucinations in the General Dutch Population.

Na tien jaar eindelijk minder last van stemmen: COMET bij auditieve verbale hallucinaties

Use of cardiovascular and antidiabetic drugs before and after starting with clozapine versus other antipsychotic drugs: a Dutch database study.