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

Same or different? auditory verbal hallucinations in healthy and psychotic individuals

Background: Auditory verbal hallucinations (AVH) are experienced more frequently by patients with borderline personality disorder (BPD) than previously assumed. However, consensus is lacking on how to treat them. Objective: To provide a systematic review of studies reporting on AVH in patients with BPD, with a focus on the efficacy of treatment of psychotic symptoms. Methods: For this review a systematic search was made in the PubMed and Ovid databases, and mean weighted prevalence rates, adjusted for sample size, were computed. Results: The search yielded 36 studies describing a total of 1,263 patients. Auditory hallucinations (including AVH) were reported in 27% of hospitalized BPD patients; AVH were reported in 25% of all patients and in 24% of outpatients. Of the hallucinating patients, 78% experienced AVH at least once per day, for a duration of several days to many years. On the whole, patients with BPD regarded their voices as malevolent and omnipotent in nature. Compared to patients with schizophrenia, the phenomenological characteristics of AVH were similar and the ensuing distress was equal or even higher, whereas scores for other positive symptoms were lower. The presence of AVH in BPD was associated with an increase of suicide plans and attempts, and more frequent hospitalization. Moreover, AVH in the context of BPD were associated with higher prevalence rates for post-traumatic stress disorder and emotional abuse. The efficacy of antipsychotics was investigated in 21 studies. Based on these studies, we conclude that both typical and atypical antipsychotics tend to have positive effects on AVH experienced in the context of BPD. The efficacy of cognitive-behavioral therapy and non-invasive brain stimulation has not yet been systematically assessed. Conclusions: These findings indicate that AVH experienced in the context of BPD are in need of proper diagnosis and treatment, and that antipsychotics tend to be beneficial in treating these (and other psychotic) symptoms. There is an urgent need for studies assessing the efficacy of cognitive-behavioral therapy and non-invasive brain stimulation in this underdiagnosed and undertreated group.

/pdf/auditory-verbal-hallucinations-in-borderline-personality-4wb8jki8cl.pdf

Auditory Verbal Hallucinations in Borderline Personality Disorder and the Efficacy of Antipsychotics: A Systematic Review

What can psychiatrists learn from SARS and MERS outbreaks

Background: A diagnosis of psychotic disorder is traditionally considered incompatible with borderline personality disorder (BPD), even though patients sometimes fulfill the diagnostic criteria for both disorders. How often this happens is barely known, as is the influence of comorbid psychotic disorders on the outcome of BPD. Since studies on isolated auditory verbal hallucinations in patients with BPD indicate that these perceptual symptoms have severe consequences, and are associated with suicidal behavior and hospitalization, patients with comorbid psychotic disorders are unlikely to fare better. Objective: To examine the point prevalence of psychotic disorders in patients with BPD, their association with the outcome of BPD, and their predictive value for outcome. Methods: In a cross-sectional design, 84 female outpatients diagnosed with BPD were interviewed with the aid of the MINI-International Neuropsychiatric Interview to establish the point prevalence of comorbid psychotic and other comorbid disorders. After termination of their treatment at a specialized outpatient clinic, the type of referral was considered to be a ‘good ‘outcome when they were referred to their general practitioner or to basic psychiatric care for noncomplex patients, and a ‘poor’ outcome when referred to a specialized psychiatric department or to a psychiatric district team for patients with severe psychiatric disorders. Results: Psychotic disorders were present in 38% of the patients with BPD. With a prevalence of 20%, psychotic disorder not otherwise specified (NOS) was the most common subtype; the least common types were schizophrenia (2%), substance-induced psychotic disorder (2%), and brief psychotic disorder (1%). Among six types of comorbid disorders, only psychotic disorders were associated with a poor outcome; they were also predictors for a poor outcome, along with comorbid mood disorders, eating disorders, and somatoform disorders, as well as the severity of BPD, and, counterintuitively, more years of education. Conclusion: Psychotic disorders, notably of the psychotic disorder NOS subtype, are common among patients with BPD, and their presence is associated with a poor outcome. This implies that adequate diagnosis and treatment of both disorders is warranted in this subgroup with a dual diagnosis.

/pdf/comorbid-diagnosis-of-psychotic-disorders-in-borderline-40ny56j3pl.pdf

Comorbid Diagnosis of Psychotic Disorders in Borderline Personality Disorder: Prevalence and Influence on Outcome.

/pdf/the-silent-danger-of-social-distancing-sazllq0u1f.pdf

Iris E. C. Sommer

Papers

Same or different? auditory verbal hallucinations in healthy and psychotic individuals

Auditory Verbal Hallucinations in Borderline Personality Disorder and the Efficacy of Antipsychotics: A Systematic Review

What can psychiatrists learn from SARS and MERS outbreaks

Comorbid Diagnosis of Psychotic Disorders in Borderline Personality Disorder: Prevalence and Influence on Outcome.

The silent danger of social distancing.