Gut microbiota, nutrition, and mental health.

The human brain remains one of the greatest challenges for modern medicine, yet it is one of the most integral and sometimes overlooked aspects of medicine. The human brain consists of roughly 100 billion neurons, 100 trillion neuronal connections and consumes about 20-25% of the body's energy. Emerging evidence highlights that insufficient or inadequate nutrition is linked to an increased risk of brain health, mental health, and psychological functioning compromise. A core component of this relationship includes the intricate dynamics of the brain-gut-microbiota (BGM) system, which is a progressively recognized factor in the sphere of mental/brain health. The bidirectional relationship between the brain, gut, and gut microbiota along the BGM system not only affects nutrient absorption and utilization, but also it exerts substantial influence on cognitive processes, mood regulation, neuroplasticity, and other indices of mental/brain health. Neuroplasticity is the brain's capacity for adaptation and neural regeneration in response to stimuli. Understanding neuroplasticity and considering interventions that enhance the remarkable ability of the brain to change through experience constitutes a burgeoning area of research that has substantial potential for improving well-being, resilience, and overall brain health through optimal nutrition and lifestyle interventions. The nexus of lifestyle interventions and both academic and clinical perspectives of nutritional neuroscience emerges as a potent tool to enhance patient outcomes, proactively mitigate mental/brain health challenges, and improve the management and treatment of existing mental/brain health conditions by championing health-promoting dietary patterns, rectifying nutritional deficiencies, and seamlessly integrating nutrition-centered strategies into clinical care.

Primary Care at the Intersection of Lifestyle Interventions and Unhealthy Substance Use.

Primary care physicians are well-positioned to integrate lifestyle interventions into the management of patients with unhealthy substance use, who may also have mental and physical chronic health comorbidities. However, the COVID-19 pandemic exacerbated the U.S.'s poor state of health, revealing that its current approach to chronic disease management is neither effective nor sustainable. Today's full spectrum comprehensive care model requires an expanded toolkit. Lifestyle interventions broaden current treatment approaches and may enhance Addiction Medicine care. Primary care providers have the potential to have the greatest impact on unhealthy substance use care because they are experts in chronic disease management and their frontline accessibility minimizes healthcare barriers. Individuals with unhealthy substance use are at an increased risk of chronic physical conditions. Incorporating lifestyle interventions with unhealthy substance use care at every level of medicine, from medical school through practice, normalizes both as part of the standard care of medicine and will drive evidence-based best practices to support patients through prevention, treatment, and reversal of chronic diseases.

Developmental regulation of gene expression and astrocytic processes may explain selective hippocampal vulnerability.

The hippocampus plays a central role in the brain network that is essential for memory function. Paradoxically, the hippocampus is also the brain structure that is most sensitive to hypoxic-ischemic episodes. Here, we show that the expression of genes associated with glycolysis and glutamate metabolism in astrocytes and the coverage of excitatory synapses by astrocytic processes undergo significant decreases in the CA1 field of the monkey hippocampus during postnatal development. Given the established role of astrocytes in the regulation of glutamate concentration in the synaptic cleft, our findings suggest that a developmental decrease in astrocytic processes could underlie the selective vulnerability of CA1 during hypoxic-ischemic episodes in adulthood, its decreased susceptibility to febrile seizures with age, as well as contribute to the emergence of selective, adultlike memory function.

Neurodevelopmental pathways to aggression: a model to understand and target treatment in youth.

The authors describe a neurodevelopmentally relevant, clinically derived model for understanding and treating aggressive behavior in youth. Based on case experience and literature review, the authors divide aggressive behavior into five symptomatic domains with respective neurobiological/neurodevelopmental underpinnings. These five symptom domains (impulsivity, affective instability, anxious/hyperarousal, cognitive disorganization, and predatory aggression) emerge as logical and clinically useful targets for treatment. The authors aim to establish a relationship between these symptom domains and brain structure and function that offers a clinically relevant approach to the complexities of understanding aggression and its treatment.

Pharmacological intervention for cognitive deficits and aggression in frontal lobe injury.

We present a case that promotes early intervention and pharmacological treatment for the neuropsychiatric sequelae (frontal lobe syndrome, including cognitive impairment and aggressive behavior) associated with traumatic brain injury (TBI) and delirium. The patient, who sustained significant systemic complications related to his trauma, was previously diagnosed with alcohol and drug dependence and antisocial personality disorder. These antecedent conditions and prolonged systemic complications likely played a complicating role in his course of recovery.

An integrated neuropsychiatric approach to diagnosis and management of patients with epileptic seizures.

In patients who present to neurology settings with history of epileptic seizures, psychiatric disorders may be the sole manifestation of apparent neurologic symptoms, or they may coexist. Current challenges for clinicians include distinguishing between two disorders and making the correct diagnoses, interpreting test results, and (co-) managing the disorder(s). Our goal is to provide the clinician with an integrated neuropsychiatric approach for the triage, assessment (history, screening tools, examination, diagnostic tests), and treatment (neurologic and/or psychiatric) of these challenging patients. In particular, use of schemata, tables, and algorithms will offer step-by-step approaches and guidelines for the clinician. Recommendations are made for the indications for psychiatric consultation, and co-management is recommended for patients with emergencies, those who fail routine psychiatric treatments, and those with complex presentations or multiple comorbid conditions.

Development of the specialized AMPA receptors of auditory neurons.

At maturity, the AMPA receptors of auditory neurons exhibit very rapid desensitization kinetics and high permeability to calcium, reflecting the predominance of GluR3 flop and GluR4 flop subunits and the paucity of GluR2. We used mRNA analysis and immunoblotting to contrast the development of AMPA receptor structure in the chick cochlear nucleus [nucleus magnocellularis (NM)] with that of the slowly desensitizing and calcium-impermeable AMPA receptors of brainstem motor neurons in the nucleus of the glossopharyngeal/vagal nerves. The relative abundance of transcripts for GluRs 1-4 changes substantially in auditory (but not motor) neurons after embryonic day (E)10, with large decreases in GluR2 and increases in GluR3 and GluR4. Relative to the motor neurons, NM neurons show a higher abundance of flop isoforms of GluRs 2-4 at E10, suggesting that auditory neurons are already biased toward expression of flop isoforms before the onset of synaptic function at E11. Immunoreactivities in NM show very distinct developmental patterns from E13 onward: GluR2 declines by >90%, GluR3 increases threefold, and GluR4 remains relatively constant. Our results show that there are a series of critical points during normal development, most occurring after the onset of function, when rapid changes in receptor structure (occurring via both transcriptional and post-transcriptional control mechanisms) produce the specialized AMPA receptor functions that enable auditory neurons to accurately encode acoustic information.