Geriatric Psychiatry Across the Spectrum: Medical Student, Resident, and Fellow Education.

The older adult population in the United States is poised to reach 83.7 million by 2050, and up to 20% will suffer from cognitive and mental illnesses. We do not have the workforce available to meet this need; therefore, general psychiatrists will care for many older psychiatric patients. Enhancing learning opportunities during general medical education and residency could improve the knowledge of general psychiatrists and encourage recruitment into geriatric psychiatry. This article outlines geriatric psychiatry education in medical school, residency, and geriatric psychiatry fellowship with suggestions for recruitment into the field, along with recommendations for enhanced learning for general psychiatrists.

Human neurons from Christianson syndrome iPSCs reveal mutation-specific responses to rescue strategies.

Christianson syndrome (CS), an X-linked neurological disorder characterized by postnatal attenuation of brain growth (postnatal microcephaly), is caused by mutations in SLC9A6, the gene encoding endosomal Na+/H+ exchanger 6 (NHE6). To hasten treatment development, we established induced pluripotent stem cell (iPSC) lines from patients with CS representing a mutational spectrum, as well as biologically related and isogenic control lines. We demonstrated that pathogenic mutations lead to loss of protein function by a variety of mechanisms: The majority of mutations caused loss of mRNA due to nonsense-mediated mRNA decay; however, a recurrent, missense mutation (the G383D mutation) had both loss-of-function and dominant-negative activities. Regardless of mutation, all patient-derived neurons demonstrated reduced neurite growth and arborization, likely underlying diminished postnatal brain growth in patients. Phenotype rescue strategies showed mutation-specific responses: A gene transfer strategy was effective in nonsense mutations, but not in the G383D mutation, wherein residual protein appeared to interfere with rescue. In contrast, application of exogenous trophic factors (BDNF or IGF-1) rescued arborization phenotypes across all mutations. These results may guide treatment development in CS, including gene therapy strategies wherein our data suggest that response to treatment may be dictated by the class of mutation.

Understanding the Role of Knowledge in Advance Care Planning Engagement.

CONTEXT: Advance care planning remains underutilized. A better understanding of the role of education in promoting engagement is needed. OBJECTIVES: To examine advance care planning knowledge and its relationship to engagement in middle-aged and older adults. METHODS: This cross-sectional study utilized baseline data from 921 participants age ≥55 years enrolled in the STAMP randomized controlled trial, including a knowledge scale consisting of seven questions regarding the purpose and mechanisms of advance care planning and measures of participation. RESULTS: Only 11.9% of participants answered all 7 questions correctly, and 25.6% of participants answered ≤3 correctly (defined as "low knowledge"). Low knowledge was independently associated with male gender (odds ratio [OR] 2.1, 95% confidence interval [CI]: 1.5, 3.0), non-white race (OR 1.5, 95% CI: 1.1, 2.2), older age (OR 2.2, 95% CI: 1.4, 3.4), lower income (OR 1.5, 95% CI: 1.1, 2.1), and lower education level (OR 2.9, 95% CI: 2.0, 4.1). Higher knowledge was independently associated with communicating with a loved one about quality versus quantity of life (OR 1.7, 95% CI: 1.2, 2.4) and with living will completion (OR 1.6, 95% CI: 1.0, 2.5), but not with healthcare agent assignment. Factors including race and education remained associated with engagement after accounting for knowledge. CONCLUSION: Knowledge deficits regarding advance care planning are common and associated with the same sociodemographic factors linked to other healthcare disparities. While improving knowledge is an important component of intervention, it is unlikely sufficient in and of itself to increase engagement.

Combating Heightened Social Isolation of Nursing Home Elders: The Telephone Outreach in the COVID-19 Outbreak Program.

OBJECTIVE: Social isolation and loneliness-common concerns in older adults-are exacerbated by the COVID-19 pandemic. To address social isolation in nursing home residents, the Yale School of Medicine Geriatrics Student Interest Group initiated a Telephone Outreach in the COVID-19 Outbreak (TOCO) Program that implements weekly phone calls with student volunteers. METHODS: Local nursing homes were contacted; recreation directors identified appropriate and interested elderly residents. Student volunteers were paired with elderly residents and provided phone call instructions. RESULTS: Three nursing homes opted to participate in the program. Thirty elderly residents were paired with student volunteers. Initial reports from recreation directors and student volunteers were positive: elderly residents look forward to weekly phone calls and express gratitude for social connectedness. CONCLUSIONS: The TOCO program achieved initial success and promotes the social wellbeing of nursing home residents. We hope to continue this program beyond the COVID-19 pandemic in order to address this persistent need in a notably vulnerable patient population.

Paracingulate Sulcus Length Is Shorter in Voice-Hearers Regardless of Need for Care.

Hallucinations-while often considered an indication of mental illness-are commonly experienced by those without a need for clinical care. These nonclinical voice-hearers offer an opportunity to investigate hallucinations in the absence of confounds inherent to the clinical state. Recent work demonstrates an association between auditory verbal hallucinations (AVH) and structural variability in paracingulate sulcus (PCS) of medial prefrontal cortex in a clinical population. However, before PCS length may be considered a biomarker for clinical hallucination risk, it is necessary to investigate PCS structure in a nonclinical population of voice-hearers with AVH phenomenology similar to those of their clinical counterparts. In the current study, PCS length was measured from T1-weighted structural MRI scans of four groups of participants: (1) voice-hearers with a psychotic disorder (n = 15); (2) voice-hearers without a psychotic disorder (n = 15); (3) nonvoice-hearers with a psychotic disorder (n = 14); and (4) nonvoice-hearers without a psychotic disorder (n = 15). There was a main effect of AVH status-but not psychosis-on right PCS length, with no interaction of AVH and psychosis. Participants with AVH exhibited reduced right PCS length compared to participants without AVH (mean reduction = 8.8 mm, P < 0.05). While past studies have demonstrated decreased PCS length in clinical voice-hearers, ours is the first demonstration that shorter right PCS extends to nonclinical voice-hearers. Our findings support the hypothesis that differences in PCS length are related to the propensity to hear voices and not to illness, consistent with a continuum model of voice-hearing.

Genetic control of postnatal human brain growth.

PURPOSE OF REVIEW: Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here, we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. RECENT FINDINGS: Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, post-mortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. SUMMARY: To understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders.

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms.

Autism spectrum disorder (ASD) is a group of highly genetic neurodevelopmental disorders characterized by language, social, cognitive, and behavioral abnormalities. ASD is a complex disorder with a heterogeneous etiology. The genetic architecture of autism is such that a variety of different rare mutations have been discovered, including rare monogenic conditions that involve autistic symptoms. Also, de novo copy number variants and single nucleotide variants contribute to disease susceptibility. Finally, autosomal recessive loci are contributing to our understanding of inherited factors. We will review the progress that the field has made in the discovery of these rare genetic variants in autism. We argue that mutation discovery of this sort offers an important opportunity to identify neurodevelopmental mechanisms in disease. The hope is that these mechanisms will show some degree of convergence that may be amenable to treatment intervention.

Trait and state corticostriatal dysfunction in bipolar disorder during emotional face processing.

OBJECTIVES: Convergent evidence supports limbic, anterior paralimbic, and prefrontal cortex (PFC) abnormalities in emotional processing in bipolar disorder (BD) and suggests that some abnormalities are mood-state dependent and others persist into euthymia. However, few studies have assessed elevated, depressed, and euthymic mood states while individuals processed emotional stimuli of varying valence to investigate trait- and state-related neural system responses. Here, regional brain responses to positive, negative, and neutral emotional stimuli were assessed in individuals with BD during elevated, depressed, and euthymic mood states. METHODS: One hundred and thirty-four subjects participated in functional magnetic resonance imaging scanning while processing faces depicting happy, fearful, and neutral expressions: 76 with BD (18 in elevated mood states, 19 depressed, 39 euthymic) and 58 healthy comparison (HC) individuals. Analyses were performed for BD trait- and mood state-related features. RESULTS: Ventral anterior cingulate cortex (VACC), orbitofrontal cortex (OFC), and ventral striatum responses to happy and neutral faces were decreased in the BD group, compared to the HC group, and were not influenced by mood state. Elevated mood states were associated with decreased right rostral PFC activation to fearful and neutral faces, and depression was associated with increased left OFC activation to fearful faces. CONCLUSIONS: The findings suggest that abnormal VACC, OFC, and ventral striatum responses to happy and neutral stimuli are trait features of BD. Acute mood states may be associated with additional lateralized abnormalities of diminished right rostral PFC responses to fearful and neutral stimuli in elevated states and increased left OFC responses to fearful stimuli in depressed states.