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"Biological Psychiatry"
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Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it?
Patients with mental disorders show many biological abnormalities which distinguish them from normal volunteers; however, few of these have led to tests with clinical utility. Several reasons contribute to this delay: lack of a biological ‘gold standard’ definition of psychiatric illnesses; a profusion of statistically significant, but minimally differentiating, biological findings; ‘approximate replications’ of these findings in a way that neither confirms nor refutes them; and a focus on comparing prototypical patients to healthy controls which generates differentiations with limited clinical applicability. Overcoming these hurdles will require a new approach. Rather than seek biomedical tests that can ‘diagnose’ DSM-defined disorders, the field should focus on identifying biologically homogenous subtypes that cut across phenotypic diagnosis—thereby sidestepping the issue of a gold standard. To ensure clinical relevance and applicability, the field needs to focus on clinically meaningful differences between relevant clinical populations, rather than hypothesis-rejection versus normal controls. Validating these new biomarker-defined subtypes will require longitudinal studies with standardized measures which can be shared and compared across studies—thereby overcoming the problem of significance chasing and approximate replications. Such biological tests, and the subtypes they define, will provide a natural basis for a ‘stratified psychiatry’ that will improve clinical outcomes across conventional diagnostic boundaries.
Journal Article
Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental
Background
Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established.
Method
Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians’ opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey.
Results
The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression.
Conclusion
The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.
Journal Article
The other side of normal : how biology is providing the clues to unlock the secrets of normal and abnormal behavior
\"Brilliant Harvard psychiatrist Jordan Smoller reveals the hidden side of our everyday behaviors and addresses one of society's most enduring questions: What do we mean by \"normal?\" And what does this tell us about \"abnormal?\"\"--Provided by publisher.
Book
Understanding the Consequences of Repetitive Subconcussive Head Impacts in Sport: Brain Changes and Dampened Motor Control Are Seen After Boxing Practice
The potential effects of exposure to repetitive subconcussive head impacts through routine participation in sport are not understood. To investigate the effects of repetitive subconcussive head impacts we studied boxers following customary training (sparring) using transcranial magnetic stimulation (TMS), decomposition electromyographic (EMG) and tests of memory.
Twenty amateur boxers performed three 3-min sparring bouts. Parameters of brain function and motor control were assessed prior to sparring and again immediately, 1 h and 24 h post-sparring. Twenty control participants were assessed following mock-sparring.
One hour after sparring boxers showed increased corticomotor inhibition, altered motor unit recruitment strategies, and decreased memory performance relative to controls, with values returning to baseline by the 24 h follow up.
Repetitive subconcussive head impacts associated with sparring resulted in acute and transient brain changes similar to those previously reported in soccer heading, providing convergent evidence that sport-related head impacts produce a GABAergic response. These acute changes in brain health are reminiscent of effects seen following brain injury, and suggest a potential mechanism underlying the damaging long-term effects of routine repetitive head impacts in sport.
Journal Article
Detrended Fluctuation, Coherence, and Spectral Power Analysis of Activation Rearrangement in EEG Dynamics During Cognitive Workload
In the study of human cognitive activity using electroencephalogram (EEG), the brain dynamics parameters and characteristics play a crucial role. They allow to investigate the changes in functionality depending on the environment and task performance process, and also to access the intensity of the brain activity in various locations of the cortex and its dependencies. Usually, the dynamics of activation of different brain areas during the cognitive tasks are being studied by spectral analysis based on power spectral density (PSD) estimation, and coherence analysis, which are
standard tools in quantitative characterization of brain activity. PSD and coherence reflect the strength of oscillations and similarity of the emergence of these oscillations in the brain, respectively, while the concept of stability of brain activity over time is not well defined and less formalized. We propose to employ the detrended fluctuation analysis (DFA) as a measure of the EEG persistence over time, and use the DFA scaling exponent as its quantitative characteristics. We applied DFA to the study of the changes in activation in brain dynamics during mental calculations and united it with PSD and coherence estimation. In the experiment, EEGs during resting state and mental serial subtraction from 36 subjects were recorded and analyzed in four frequency ranges: θ1 (4.1-5.8 Hz), θ2 (5.9-7.4 Hz), β1 (13-19.9 Hz), and β2 (20-25 Hz). PSD maps to access the intensity of cortex activation and coherence to quantify the connections between different brain areas were calculated, the distribution of DFA scaling exponent over the head surface was exploited to measure the time characteristics of the dynamics of brain activity. Obtained arrangements of DFA scaling exponent suggest that normal functioning of the brain is characterized by long-term temporal correlations in the cortex. Topographical distribution of the DFA scaling exponent was comparable for θ and β frequency bands, demonstrating the largest values of DFA scaling exponent during cognitive activation. The study shows that the long-term temporal correlations evaluated by DFA can be of great interest for diagnosis of the variety of brain dysfunctions of different etiology in the future.
Journal Article
Simultaneous Electrophysiology and Fiber Photometry in Freely Behaving Mice
electrophysiology is the gold standard technique used to investigate sub-second neural dynamics in freely behaving animals. However, monitoring cell-type-specific population activity is not a trivial task. Over the last decade, fiber photometry based on genetically encoded calcium indicators (GECIs) has been widely adopted as a versatile tool to monitor cell-type-specific population activity
. However, this approach suffers from low temporal resolution. Here, we combine these two approaches to monitor both sub-second field potentials and cell-type-specific population activity in freely behaving mice. By developing an economical custom-made system and constructing a hybrid implant of an electrode and a fiber optic cannula, we simultaneously monitor artifact-free mesopontine field potentials and calcium transients in cholinergic neurons across the sleep-wake cycle. We find that mesopontine cholinergic activity co-occurs with sub-second pontine waves, called P-waves, during rapid eye movement sleep. Given the simplicity of our approach, simultaneous electrophysiological recording and cell-type-specific imaging provides a novel and valuable tool for interrogating state-dependent neural circuit dynamics
.
Journal Article