Bostwick, John

Since the discovery of the first psychoactive medications, their psychiatric and medical uses have overlapped. Designating a medication psychiatric or psychotropic is thus arbitrary, based on its most common usage, but labeling it so obscures the full range of its pharmacologic activity and clinical utility. Psychotropic medications (PMs) are frequently used to treat medical conditions or symptoms in the areas of neurology (e.g., migraine, seizure disorder), dermatology (e.g., itching), gastroenterology, and chronic pain, among many others. It is important for both primary care and specialty physicians to be aware of the potential non-psychiatric indications for the use of common PMs such as antidepressants, antipsychotics, and anxiolytics. This review examines the potential benefits and risks of PMs when used for non-psychiatric indications, highlighting how their pharmacologic effects on neurotransmitters contribute to both therapeutic outcomes and adverse effects. It also provides guiding principles for prescribers, including the importance of adjusting doses based on the specific indication, monitoring for harmful side effects, considering age-related factors, and addressing the risks associated with polypharmacy.

Fundamental to medical education, gross anatomy first introduces medical students to human mortality, often provoking stress. Sense of purpose, a key aspect of well-being, may serve as a protective factor. We studied students’ sense of purpose during an anatomy course, examining its links to performance, spirituality, and belief in an afterlife. Fifty medical students who took a 7-week gross anatomy course in 2022 or 2023 completed the Life Engagement Test at the beginning, middle, and end of the course. We collected other data including demographics, religious/spiritual beliefs, and previous exposure to body donors. Practical and final examinations assessed course performance. Strong sense of purpose at the three measurement points was positively correlated with practical exam performance (r = 0.40, P = .004; r = 0.44, P = .003; r = 0.30, P = .047, respectively) but not National Board of Medical Examiners’ anatomy subject exam performance. Staunch believers and non-believers in an afterlife maintained a stable sense of purpose, while students uncertain about the afterlife experienced a decline from the beginning to the middle of the course and even more to the end ( P = .046; P = .008, respectively). These students also had significantly lower practical examination performance as compared to other students (95% CI [−10.84, −0.52]). In conclusion, a strong sense of purpose predicts better performance in a 7-week anatomy course. Both believers and non-believers in an afterlife do well, but students wavering in their beliefs experience a declining sense of purpose and lower grades. Supporting these students when they confront human mortality, including in other contexts such as palliative care/hospice settings, may be beneficial.

ImportanceThe rates of suicide and suicide attempts are rising precipitously among early adolescents aged 10 to 14 years in the US. While suicide attempts in this age group are more common and associated with lower lethality than in older age groups, very little is known about these individuals’ long-term social and psychiatric outcomes.ObjectivesTo examine the adult outcomes of individuals making index suicide attempts that came to medical attention between the ages of 10 and 14 years.Design, Setting, and ParticipantsThis population-based cohort constitutes a subsample (n = 164) of a previously reported retrospective-prospective study examining individuals who made index suicide attempts during a 22-year period (1986-2007) in Olmsted County, Minnesota.Main Outcomes and MeasuresTo collect outcome measures, the medical records of all individuals were queried until March 31, 2023, comprising up to 36 years of follow-up data after the index attempt. Measures included current social, psychiatric, and mortality outcomes as well as lifetime measures of psychiatric hospitalizations and repeat suicide attempts. K-means clustering generated adult groupings based on aggregates of psychiatric hospitalizations and repeat attempts. Multivariable logistic regression identified index attempt factors associated with poor adult outcomes.ResultsOf 164 individuals aged 10 to 14 years who made index attempts (128 [78.0%] female; mean [SD] age at index attempt, 13.7 [1.1] years), 3 (1.8%) died on the index attempt. In the follow-up period, no individuals died by suicide. K-means clustering generated a 2-group solution reflecting low (120 [80%]) and high (30 [20%]) rates of adult psychopathology. While a minority of the sample belonged to the high-rate group, characterized by multiple repeat attempts and hospitalizations, the majority had favorable social indicators and fewer reattempts and hospitalizations. Poor adult outcomes were associated with being male (odds ratio, 2.44; 95% CI, 1.00-5.80; P = .04) and having a psychiatric diagnosis prior to the index attempt (odds ratio, 3.27; 95% CI, 1.42-8.07; P = .007).Conclusions and RelevanceIn this sample of early adolescents with index suicide attempts followed into adulthood, all who died by suicide did so on the index attempt. While a small number of individuals went on to develop chronic severe psychopathology, the majority demonstrated little evidence of long-term impairment. Given this discrepancy, future studies should focus on using risk stratification after index attempts to direct postvention resources toward adolescents more susceptible to poor outcomes.

AbstractBackgroundIsotretinoin treatment for acne can reduce adverse psychiatric outcomes in adults, but there has been little investigation of the incidence of psychiatric outcomes in treated adolescents.MethodsThis retrospective cohort study using the Rochester Epidemiology Project identified 606 patients aged 12–18 prescribed isotretinoin over a 10‐year period between January 1, 2008 and December 31, 2017. Medical records were reviewed to identify psychiatric diagnoses before and during isotretinoin therapy, as well as psychiatric symptoms not captured by formal diagnoses and changes to isotretinoin dosing because of psychiatric diagnoses or symptoms.ResultsOne hundred seventy‐seven (29.2%) had a psychiatric diagnosis prior to isotretinoin initiation, but 98 (16.2%) had a new psychiatric diagnosis or psychiatric symptom while taking isotretinoin. Patients with a psychiatric history were no more likely than those without to receive a new psychiatric diagnosis during treatment (4.5% vs. 3.7%; p = .650), but did experience more psychiatric symptoms, primarily low mood and mood swings (23.7% vs. 7.7%; p < .001). Only 25.5% of the 98 with a new psychiatric diagnosis or psychiatric symptom had a subsequent dose change. A dose change was more likely if patients received a new psychiatric diagnosis (41.7% vs. 20.3%; p = .037) or patients did not have a psychosocial explanation for psychiatric symptoms (34.4% vs. 10.8%; p = .009).ConclusionsA substantial proportion of adolescent patients prescribed isotretinoin had a prior psychiatric diagnosis. This predicts more psychiatric symptoms during isotretinoin treatment. Adolescents with a psychiatric history who have worsening symptoms and those with new‐onset psychiatric symptoms would benefit from close monitoring while taking isotretinoin.

Abstract Background: Elevated urine cortisol (&lt;1% of urinary steroid metabolome) was reported to predict future development of dementia. Our objective was to determine the association of urine steroid metabolome and its diurnal variation with cognitive function in men and women. Methods: Cross-sectional study of community-dwelling adults ≥ 50 years. Participants with adrenal disorders, end-stage renal or liver disease, on exogenous steroids or drugs affecting steroid metabolism were excluded. All participants completed day and night separate urine collection. A series of seven IPad-based tests using the National Institute of Health Toolbox Cognition Battery were administered to evaluate five key domains; performance was reported using fully corrected T-scores for age, sex, education, and race with a national normative mean of 50. T-scores were generated for the two summary measures: 1) fluid cognition (includes executive function, episodic memory, working memory, and processing speed), and 2) total composite (composite of fluid and language score). Urine samples were analyzed with the liquid-chromatography, high-resolution, accurate-mass mass spectrometry for 25 urine steroid metabolites. Results: Of 109 participants, 56 (51%) were women, and age and educational status were similar in men and women. On cognitive assessment, men and women had similar median composite cognition (T-score of 53 vs 54, p=0.74) and fluid cognition (T-score of 53 vs 51, p-value 0.96). Urine steroid metabolome analysis demonstrated 21/25 steroids were higher in men vs women. In both women and men, the ratio of total cortisol metabolites/total androgen metabolites (TCM/TAM) was associated with lower fluid cognition (women: ρ= -0.34, p=0.01, men: ρ= -0.43, p=0.001) and composite cognition (women: ρ= -0.27, p=0.04, men: ρ= -0.39, p=0.004). Higher ratio of day to night TCM were associated with a better fluid cognition in men (ρ= 0.35, p=0.01), but not in women (ρ= -0.11, p=0.41). Steroid ratios suggesting a relative enzymatic deficiency of 5α-Reductase type 2 was associated with lower fluid cognition in women (ρ= -0.29, p=0.03). In men, the fluid composite score was associated with a relative deficiency in 21-Hydroxylase (ρ= 0.42, p=0.002), 3β-Hydroxysteroid dehydrogenase (ρ= 0.43, p=0.001), and P450oxidoreductase (ρ= -0.35, p=0.01). Conclusion: We showed that a higher glucocorticoid to androgen ratio and a flattened circadian steroid variation were associated with lower global and fluid cognition score. Steroid ratios reflecting steroidogenesis enzymatic activity demonstrated sex differences in relation to cognition. Additional studies should examine whether the steroid fingerprint associated with lower cognition is predictive of a future dementia onset.

Abstract Background: Adrenal adenomas are incidentally diagnosed in 7% of adults undergoing abdominal imaging. Mild autonomous cortisol secretion is present in 50% of adrenal adenomas, and even “nonfunctioning” adrenal adenomas demonstrate abnormal steroid profile. We aimed to 1) investigate the prevalence of mental and sleep disorders in patients with adrenal adenomas and to 2) determine the risk of mental and sleep disorders after the diagnosis of adrenal adenoma in patients compared to the referent subjects from the same population Methods: Using a medical records linkage system, we identified adult patients living in the Olmsted County, MN diagnosed with an adrenal adenoma during 1995–2017. Patients with overt hormone excess were excluded. Every patient with adenoma was matched by sex and age to a referent subject from the same population. Subjects were followed until death or end of the study. Mental health related comorbidities and sleep disorders were assessed at baseline and during follow up. Results: Our cohort included 1004 patients with adrenal adenomas and 1004 referent subjects (58% women, median age of 63 years). Patients were more likely to smoke (70% vs 54%, p &lt;0.001) and had a higher BMI (30 kg/m2 vs 28 kg/m2, p &lt; 0.001). Within 5 years prior to the index date (diagnosis of adenoma), and after adjusting for BMI and smoking, patients demonstrated a higher prevalence of depression (Odds ratio, OR of 1.3 (CI95% 1.1–1.6), p=0.02), anxiety (OR of 1.4 (CI95% 1.1–1.8, p=0.003), substance abuse disorders (OR of 2.4 (CI 95% 1.7–3.4), p&lt;0.001), but not insomnia (OR of 1.2 (CI95% 0.9–1.7) and sleep related breathing disorders (OR of 1.3 (CI 95% 0.9–1.7). During follow-up, starting 1 year after the diagnosis, patients demonstrated a higher risk of new onset depression (HR of 1.9, CI95%1.5–2.4), anxiety (HR of 1.5,CI95% 1.2–1.9), schizophrenia (HR of 1.7, CI95% 1.2–2.4), and substance abuse disorders (HR of 1.6, CI95% 1.2–2.0). Risk of sleep disorders 1 year after diagnosis was also high for insomnia (HR of 1.4, CI95% 1.1–1.9), sleep-related breathing disorders (HR of 1.8, CI95% 1.4–2.3), hypersomnias of central origin (HR of 2.0, CI95%1.04–3.96), parasomnias (HR of 2.4, CI95%1.2–4.7), and sleep-related movement disorders(HR of 1.9, CI95%1.3–2.6). Conclusion: Patients with adenomas are at increased risk for mental and sleep disorders, possibly explained by the underlying subtle cortisol secretion. Further prospective studies with an in-depth characterization of both hormonal secretion and mental/sleep disorders are needed. Reversibility or improvement of mental health and sleep disorders with adrenalectomy should be investigated.