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WEEK 3

Reading 1: 

The Hallmarks of Aging

Carlos Lo´pez-Otı´n, Maria A. Blasco, Linda Partridge, Manuel Serrano, and Guido Kroemer 

The full article can be found here. WSJ story featuring this article:  WSJ article

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WEEK 2

Reading 1: 

Gastrointestinal syndromes preceding a diagnosis of Parkinson’s disease: testing Braak’s hypothesis using a nationwide database for comparison with Alzheimer’s disease and cerebrovascular diseases

Bo Konings, Luisa Villatoro, Jef Van den Eynde, Guillermo Barahona, Robert Burns, Megan McKnight, Ken Hui, Gayane Yenokyan, Jan Tack, Pankaj Jay Pasricha

The full article can be found here. BBC story featuring this paper:  https://www.bbc.com/news/health-66604155

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WEEK 1

Reading 1: 

Biomarker-guided neuromodulation aids memory in traumatic brain injury

Michael J. Kahana, Youssef Ezzyat, Paul A. Wanda, Robert E. Gross, Kan Ding, Ramon R. Diaz-Arrastia

The full article can be found here. NPR story featuring this article:  Brain stimulation may help TBI patients with memory recall problems : Shots - Health News : NPR

Patients who have experienced a traumatic brain injury can presents with a wide array of neuropsychiatric and behavioral symptoms.  For some patients, it is their cognitive and psychiatric symptoms that cause the greatest impairment and disability long after they have otherwise physically recovered from the injury sustaining event. 

Studies have demonstrated that direct electrical stimulation of the temporal cortex helped improve memory in patients with epilepsy.   The authors of this paper looked a eight patients with a history of intractable epilepsy and a history of moderate to severe TBI who underwent invasive electricocorticography monitoring and localization using implanted intracranial electrodes.   The study sought to determine if closed-loop stimulation of the lateral temporal cortex in subjects with a history of TBI and memory dysfunction would improve recall on an episodic memory task compared to trials without stimulation.  Of note, each subject served as their own control and was blinded to which specific trials involved stimulation.

The authors found that stimulation did enhance memory, with an average of a 19% improvement in memory and recall performance, with overall positive results in seven out of eight subjects.  Although the study featured a small number of subjects and with the unique feature of undergoing a procedure that allows for direct brain stimulation, it does offer direction for future targets for the treatment of memory loss in TBI patients.

Reading 2: 

Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study

Stephanie Knatz Peck, Samantha Shao, Tessa Gruen, Kevin Yang , Alexandra Babakanian, , Julie Trim, Daphna M. Finn, Walter H. Kaye

The full article can be found here. 

Anorexia nervosa is notable amongst psychiatric disorders for its significant physical morbidity and overall mortality.  Furthermore, there currently are no treatments that reverse core symptoms nor are there any approved pharmacological treatments.  For this study, the authors investigated the safety and tolerability of psilocybin therapy in anorexia nervosa. 

The study was an open-label feasibility study involving 10 adult female subjects with a history of anorexia nervosa.  Subjects received a single 25 mg dose of psilocybin in conjunction with psychological support. The results showed no clinically significant changes in ECG, vital signs or suicidality.  Two subjects did develop asymptomatic hypoglycemia.  Most participants endorsed that the experience was meaningful and had an overall positive effect. 

The results of this preliminary study suggest that psilocybin was well-tolerated and safe in a small cohort of subjects with anorexia and could potentially help in the treatment of adults with anorexia nervosa. 

WEEK 4

Reading 1: 

Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study

Meredith Castro, Samuel T. Wilkinson, Rayan K. Al Jurdi, Mary Pat Petrillo, Naim Zaki, Stephane Borentain, Dong Jing Fu, Ibrahim Turkoz, Liping Sun, Brianne Brown, Patricia Cabrera

The full article can be found here.

In this reading we review results of the Phase III study: ‘Long-term Safety Study of Esketamine Nasal Spray in Treatment-resistant Depression (SUSTAIN-3).’ Esketamine is the (S) enantiomer of ketamine that is FDA-approved for the treatment of treatment- resistant depression (TRD). It is a self-administered nasal spray that is delivered twice a week in clinic during treatment induction, with subsequent weekly maintenance treatment and tapering. It is highly effective and yields similar response and remission rates to repetitive transcranial magnetic stimulation (rTMS)- another interventional treatment. There are outstanding clinical questions as to how to approach multiple inductions and longterm maintenance therapy for esketamine, which is why this study was conducted.

In this Janssen funded open-label study, authors treated patients suffering from TRD with a second induction of esketamine treatment after relapse from an initial induction in a previous study (SUSTAIN-1). SUSTAIN-3 included 96 patients overall, of which the majority were on a placebo esketamine maintenance treatment as part of the previous study (SUSTAIN-1 demonstrated that maintenance esketamine is superior to placebo maintenance). For all patients in SUSTAIN-3, esketamine was given in conjunction with oral antidepressant treatment. There were no significant new safety concerns that developed during this study. While the majority of patients (~70%) achieved response (a >50% improvement) during the esketamine induction, the response rates dropped to ~40% by 24 and 52 weeks out- these are good numbers, but clearly not a panacea treatment. See below for a figure showing depression scores over time in this study.

Overall, this study demonstrates that retrial of esketamine is effective for patients who responded to esketamine and subsequently relapsed. This is true for both patients on esketamine maintenance and those solely on oral antidepressants. However, many patients in this study do appear to relapse during the maintenance phase, and so other treatments should be considered in these situations, such as rTMS or ECT.

Thankfully, esketamine, rTMS and ECT are all available through our Interventional Psychiatry program here at UCSD. Feel free to refer any appropriate patients through EPIC and/or reach out to Dr. Cory Weissman if you have any questions (cweissman@health.ucsd.edu).

Reading 2: 

Sensitivity of Schizophrenia Endophenotype Biomarkers to Anticholinergic Medication Burden

Yash B. Joshi, M.D., Ph.D., Juan L. Molina, M.D., David L. Braff, M.D., Michael F. Green, Ph.D., Ruben C. Gur, Ph.D., Raquel E. Gur, M.D., Ph.D., Keith H. Nuechterlein, Ph.D., William S. Stone, Ph.D., Tiffany A. Greenwood, Ph.D., Laura C. Lazzeroni, Ph.D., Allen D. Radant, M.D., Jeremy M. Silverman, Ph.D., Joyce Sprock, B.A., Catherine A. Sugar, Ph.D., Debby W. Tsuang, M.D., Ph.D., Ming T. Tsuang, M.D., Ph.D., Bruce I. Turetsky, M.D., Neal R. Swerdlow, M.D., Ph.D., Gregory A. Light, Ph.D.

The full Am. J. Psychiatry article can be found here.

Patients with schizophrenia experience cognitive symptoms as part of their illness.  Unfortunately, many of the medications used to treat schizophrenia can further contribute to cognitive impairment as well, thus compounding the problem.  There is literature supporting the increased risk of dementia with increasing anticholinergic medication burden (ACMB) in healthy older adults.  Having objective, biomarker-based means of measuring MCAB could improve treatment outcomes.   

Mismatch negativity (MMN) and p3a are sequentially evoked neurophysiological biomarkers of early auditory information processing that are widely studied in schizophrenia research.   MMN is felt to indicate automatic sensory discrimination and P3a is believed to index the rapid involuntary redirection of attention and subsequent transitions to higher order attention-dependent cognitive processing.    The authors sought to evaluate if MMN and P3a are associated with the degree of ACMB in a large schizophrenia cohort.  The study included 1,062 normal controls and 1,475 subjects with schizophrenia/schizoaffective disorder, with complete data on N= 555 schizophrenia patients.  

The results demonstrated that "higher ACMB score was associated with a reduction in magnitude of both MMN and P3a, driven by ACB-associated effects on deviant stimuli, but not standards."  In particular, an ACB>6 may impact early auditory information processing  (EAIP) biomarker relationships in schizophrenia.  The linkage of medication side-effects to neurophysiological biomarkers can help shape further research into assessing the cognitive impairing effects of medications with high ACB and ultimately influence clinical practice for the better for our patients.

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WEEK 3

Reading 1: 

Zuranolone for the Treatment of Postpartum Depression

Kristina M. Deligiannidis, M.D., Samantha Meltzer-Brody, M.D., M.P.H., Bassem Maximos, M.D., E. Quinn Peeper, M.D., Marlene Freeman, M.D., Robert Lasser, M.D., M.B.A., Amy Bullock, Ph.D., Mona Kotecha, M.D., Sigui Li, M.S., Fiona Forrestal, M.Sc., Nilanjana Rana, M.B.B.S., Manny Garcia, M.D., Bridgette Leclair, Pharm.D., James Doherty, Ph.D.

The full Am. J. Psychiatry article can be found here.WSJ.com article featuring the author of this paper. https://www.wsj.com/articles/first-pill-for-postpartum-depression-is-approved-by-fda-62376e41?reflink=integratedwebview_share

 We normally view the birth of a new child as a joyous occasion with cause for celebration.  Unfortunately for patients with postpartum depression, it strikes at one of the most challenging and potentially vulnerable moments for new moms/parents.  Prior to the approval of brexanolone, there were no treatments specifically approved by FDA to treat postpartum depression.  Unfortunately, brexanolone requires IV infusion which can be challenging and time consuming for patients.  Thus, one can imagine the hope and excitement over a new treatment option that comes as a once-a-day pill.

The authors conducted a double-blind, placebo-controlled, parallel-group phase 3 trial with women diagnosed with severe postpartum depression (PPD).  Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic GABA_A receptors and neuoractive steriod.  It has been hypothesized that dysregulated GABA_A  receptor functioning in the perinatal period might serve as a potential mechanism in PPD.  The study included a screening period of up to 28 days, a 14-day course of treatment (zuranolone 50 mg/day or placebo) and follow-up through day 45.  Medication was administered orally once a day in the evening with fat-containing food.  A total of 196 subjects received blinded study drug.

The results showed statistically significant improvement in depression symptoms on the primary endpoint, as assessed by the change in HAM-D score at day 15 from baseline in the zuranolone vs. placebo group.  Response in the active drug group was also quite rapid, with a median time to first HAM-D response of 9 days versus 43 days in placebo group.  It should be noted that the study group was racially and ethnically diverse, including 38.3% Hispanic/Latina and 21.9% African-American participants.  The study medication was well tolerated, with side-effects comparable to other antidepressants.  

Overall, this study shows the efficacy of a novel agent for the treatment of PPD.  With new agents available, it is hoped that more patients can receive effective, life-saving treatment.

Reading 2:

Safety of Antipsychotic Polypharmacy Versus Monotherapy in a Nationwide Cohort of 61,889 Patients With Schizophrenia

Heidi Taipale, Ph.D., Antti Tanskanen, Ph.D., Jari Tiihonen, M.D., Ph.D

Am J. Psychiatry 180:5, May 2023

The full Am J. Psychiatry can be found here. 

Commentary by Dr. Kyle Hendrie, PGY 5 geriatric psychiatry fellow:

Psychiatric prescribing guidelines typically recommend against the use of multiple antipsychotic agents in favor of monotherapy. Trainees are commonly taught that use of multiple antipsychotic agents increases risk of adverse events and doesn't lead to better symptom improvement compared with monotherapy. This article from American Journal of Psychiatry describes an observational study of 61,889 patients identified as having schizophrenia using a nationwide hospital discharge register in Finland from 1972 to 2014. The identified aims were to (1) evaluate the safety of antipsychotic polypharmacy compared to monotherapy in terms of nonpsychiatric hospitalizations and hospitalizations for cardiovascular reasons and (2) determine risk of relapse in each treatment category as determined by psychiatric hospitalizations. Investigators subcategorized study participants by specified total dosage categories.

Authors report that in patients who had periods of both monotherapy and polypharmacy, risk of nonpsychiatric hospitalizations was significantly lower during polypharmacy treatment over dosage categories above 1.1 DDDs/day (for 1.1–<1.4 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.87–0.95; for 1.4–<1.6 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.86–0.96; and for >/= 1.6 DDDs/day, adjusted hazard ratio=0.87, 95% CI=0.84–0.89). Additionally, in the highest dosage category, risk of cardiovascular hospitalization was lower with polypharmacy (-18%, adjusted hazard ratio=0.82, 95% CI=0.72–0.94). For the secondary aim, authors report any antipsychotic polypharmacy was associated with 6% lower risk of psychiatric hospitalization (adjusted hazard ratio=0.94, 95% CI=0.92–0.95).

Results from this study demonstrate that the common psychiatric practice of avoiding prescribing multiple antipsychotics in favor of monotherapy is worth reevaluating in some cases. Of note, this study specifically looks at schizophrenia while antipsychotics are also prescribed for treatment of other psychiatric disorders. Additionally, prospective data in the form of a prospective cohort study or clinical trial would further support use of polypharmacy in treating schizophrenia over single antipsychotic therapy.

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WEEK 2

No reading of the week.

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WEEK 1

No reading of the week.

WEEK 4

No reading of the week. 

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WEEK 3

Reading 1: 

Donanemab in Early Symptomatic Alzheimer Disease The TRAILBLAZER-ALZ 2 Randomized Clinical Trial

John R. Sims, MD; Jennifer A. Zimmer, MD; Cynthia D. Evans, PhD; Ming Lu, MD, MS, MPH; Paul Ardayfio, PhD; JonDavid Sparks, PhD; Alette M. Wessels, PhD; Sergey Shcherbinin, PhD; Hong Wang, PhD; Emel Serap Monkul Nery, MD; Emily C. Collins, PhD; Paul Solomon, PhD; Stephen Salloway, MD; Liana G. Apostolova, MD; Oskar Hansson, MD, PhD; Craig Ritchie, MD, PhD; Dawn A. Brooks, PhD; Mark Mintun, MD; Daniel M. Skovronsky, MD, PhD

JAMA, Published on-line July 17, 2023

The full JAMA article can be found here. NPR story featuring this study: https://www.npr.org/sections/health-shots/2023/07/17/1188075646/donanemab-experimental-alzheimers-drug-outperforms-lecanemab-leqembi

Reading 2: 

Clinical Services for problematic internet usage

Amanda Roberts, Steve Sharman, and Henrietta Bowden-Jones

Current Opinion in Behavioral Sciences 46(2022)

 The full Current Opinion in Behavioral Sciences article can be found here.  Maclean's story discussing internet gaming addiction and a clinical program at CAMH that offers counseling and support groups:  https://macleans.ca/longforms/fortnite-addiction-video-games-mental-health/?utm_source=pocket-newtab

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WEEK 2

Reading 1:

Wearable movement-tracking data identify Parkinson’s disease years before clinical diagnosis

Ann-Kathrin Schalkamp , Kathryn J. Peall, Neil A. Harrison & Cynthia Sandor

Nature Medicine (2023) Published online July 3, 2023

The full Nature Medicine article can be found here. BBC article featuring this study:  https://www.bbc.co.uk/news/health-66088110

By the time patients with Parkinson’s disease present clinically, there is significant neuron loss, functional impairment, and at times serious psychiatric co-morbidity.  Thus, the ability to intervene with disease modifying or even disease reversing agents is limited.  If there was a means of predicting those at greatest risk of developing PD, it could aid the development of neuroprotective treatments.

The authors investigated the predictive value of accelerometry in identifying prodromal PD in the general population and compared this with models based on genetics, lifestyle, blood biochemistry or prodromal symptoms data.   The study examined data from the UK Biobank, a large, prospective population-based cohort of over 500,000 subjects aged 40-69 years for whom data has been collected since 2006 along with ongoing passive follow-up of clinical status.  Accelerometry data were obtained from a subset of this cohort.   The authors hoped to determine if accelerometry data can serve as a prodromal marker for PD.  Data was compared from subjects with a diagnosis of PD with both matched and unmatched unaffected controls.  Diagnoses of PD within the UKBB cohort were obtained via self-reported diagnosis, hospital records, death records, and primary care data.  The prevalence and incidence of PD in the UKBB cohort closely resembled that which would be expected from a comparable population.

The results showed that acceleration was reduced during daytime hours several years prior to clinical diagnosis of PD.  Depression was the only other disease amongst those examined (including Alzheimer’s disease) that showed a reduction in acceleration following diagnosis but not prior.  Compared to the other potential predictive markers, accelerometry was better at predicting future PD diagnoses. 

“Machine learning models trained using accelerometry data achieved better test performance in distinguishing both clinically diagnosed Parkinson’s disease (n = 153) (area under precision recall curve (AUPRC) 0.14 ± 0.04) and prodromal Parkinson’s disease (n = 113) up to 7 years pre-diagnosis (AUPRC 0.07 ± 0.03) from the general population (n = 33,009) compared with all other modalities tested (genetics: AUPRC = 0.01 ± 0.00, P = 2.2 × 10−3; lifestyle: AUPRC = 0.03 ± 0.04, P = 2.5 × 10−3; blood biochemistry: AUPRC = 0.01 ± 0.00, P = 4.1 × 10−3; prodromal signs: AUPRC = 0.01 ± 0.00, P = 3.6 × 10−3).”

The results indicate the potential utility in using accelerometry data as a predictive biomarker for PD screening.  By identifying those at greatest risk of developing PD, it hopeful that such information can assist with the development of preventative and disease modifying treatments.

Reading 2:

Cannabis Use Disorder and Subsequent Risk of Psychotic and Nonpsychotic Unipolar Depression and Bipolar Disorder

Oskar Hougaard Jefsen, MD; Annette Erlangsen, PhD; Merete Nordentoft, DMSc; Carsten Hjorthøj, PhD

JAMA Psychiatry Published online May 24, 2023

The full JAMA article can be found here. The WSJ article featuring this study can be found here. 

Although illegal under US federal law, a seemingly ever-growing (no pun intended) number of states have legalized either medicinal and/or recreational cannabis.  Despite its increased use, social acceptance, and potential therapeutic uses, the public health impact of the greater availability of cannabis, especially outside of a medically supervised setting, warrants consideration. 

The authors of this study sought to examine if cannabis use disorder (CUD) is associated with an increased risk of psychotic and nonpsychotic major depression (unipolar) and bipolar depression and to look at the association of CUD with psychotic and nonpsychotic subtypes of these disorders.  The study was a population-based cohort study using a national register of all individuals born in Denmark between January 1, 1995 and December 31, 2021. 

The results showed that:

“Cannabis use disorder was associated with an increased risk of unipolar depression (HR, 1.84; 95%CI, 1.78-1.90), psychotic unipolar depression (HR, 1.97; 95%CI, 1.73-2.25), and nonpsychotic unipolar depression (HR, 1.83; 95%CI, 1.77-1.89). Cannabis use was associated with an increased risk of bipolar disorder in men (HR, 2.96; 95%CI, 2.73-3.21) and women (HR, 2.54; 95%CI, 2.31-2.80), psychotic bipolar disorder (HR, 4.05; 95%CI, 3.52-4.65), and nonpsychotic bipolar disorder in men (HR, 2.96; 95%CI, 2.73-3.21) and women (HR, 2.60; 95%CI, 2.36-2.85). Cannabis use disorder was associated with higher risk for psychotic than nonpsychotic subtypes of bipolar disorder (relative HR, 1.48; 95%CI, 1.21-1.81) but not unipolar depression (relative HR, 1.08; 95%CI, 0.92-1.27).”

This study suggests that there is a need for health care providers and policy makers to be mindful of the potential role of cannabis as a risk factor for developing mood disorders.

Reading 3:

A fire destroyed millions of veterans’ records. 50 years later, families are still seeking answers​

Allen G. Breed and Randy Herschaft

Associated Press, July 2023

The full Associated Press article can be found here.

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WEEK 1

Reading 1:

Transgender Identity and Suicide Attempts and Mortality in Denmark

The full article is linked here. CNN article featuring this paper:  https://www.cnn.com/2023/06/28/health/transgender-suicide-risk

Reading 2:

MDMA: Australia begins world-first psychedelic therapy

Journal of Clinical Pharmacology, 2022, 62(4) 463–471

The full Journal of Clinical Pharmacology article can be found here. BBC article:  https://www.bbc.com/news/world-australia-66049989

In the United States, psychedelics such as MDMA and psilocybin are currently listed a schedule 1:  "drugs, substances or chemicals...defined as drugs with no currently accepted medical use and a high potential of abuse" (dea.gov)  In other words, psychiatrists cannot legally prescribe either drug in this country.   However, regulators in Australia recently approved the use of MDMA and psilocybin by specifically authorized psychiatrists for PTSD (MDMA) and treatment resistant depression(psilocybin).  Effective July 1, 2023, patients in Australia can access treatment with these agents.   This is a significant development that will hopefully open the door to other jurisdictions allowing access to psychedelics for psychiatric patients.  

The Australian government has published guidelines regarding access and treatment with MDMA and psilocybin:  https://www.tga.gov.au/resources/publication/scheduling-decisions-final/notice-final-decision-amend-or-not-amend-current-poisons-standard-june-2022-acms-38-psilocybine-and-mdma/re-scheduling-psilocybin-and-mdma-poisons-standard-questions-and-answers 

No readings of the month for June 2023

WEEK 4

Reading 1:  

Comparing Physician and Artificial Intelligence Chatbot Responses to Patient Questions Posted to a Public Social Media Forum

John W. Ayers, PhD, MA; Adam Poliak, PhD; Mark Dredze, PhD; Eric C. Leas, PhD, MPH; Zechariah Zhu, BS; Jessica B. Kelley, MSN; Dennis J. Faix, MD; Aaron M. Goodman, MD; Christopher A. Longhurst, MD, MS; Michael Hogarth, MD; Davey M. Smith, MD, MAS

The full article is linked here.

s AI going to render physicians obsolete?  That may not be the exact question this paper poses, but it might be the fear many of us have.   As the reading shows, AI might serve as a tool to help physicians with managing patient communication and mitigate some of the risk for burnout that EMR and patient communication portals can cause.  

As for this series, the following summary is provided courtesy of Perplexity, an AI program https://www.perplexity.ai  Your AI can let my AI know what it thinks!

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WEEK 3

Reading 1:  

A Traitlike Dimension of Subjective Memory Concern Over 30 Years Among Adult Male Twins

Tyler R. Bell, PhD; Asad Beck, BA; Nathan A. Gillespie, PhD; Chandra A. Reynolds, PhD; Jeremy A. Elman, PhD; McKenna E. Williams, MS; Daniel E. Gustavson, PhD; Michael J. Lyons, PhD; Michael C. Neale, PhD; William S. Kremen, PhD; Carol E. Franz, PhD

The full article is linked here.

The risk of developing dementia is a worry expressed by many older adults, especially those who present with subjective memory complaints.  Subjective memory concern is associated with decreased quality of life, mental health challenges, and an increased risk of Alzheimer’s dementia.  Subjective memory concern is viewed as an indicator of impending cognitive impairment preceding the progression to dementia.  Research has shown that for some individuals, subjective memory concern may have a traitlike component that is persistent over time.  Thus, some people may be characterologically disposed to exhibit high levels worry about their memory.  The authors investigated the traitlike dimension of subjective memory concern over 30 years among adult male twins.   The study involved subjects from the Vietnam Era Twin Study of Aging and examined measures of subjective memory concern at four time points, objective memory, depression and anxiety symptoms, trait neuroticism, polygenic risk scores for neuroticism, depression, and Alzheimer’s disease, APOE genotype, and parental history of dementia. 

The results demonstrated that subjective memory concern is a stable trait that persists over time and is influenced by genetic and environmental factors.   The study also found that subjective memory concern is associated with depressive symptoms, anxiety, and neuroticism polygenic risk scores, but no association between subjective memory concern and objective memory decline was found.  

In many Alzheimer’s research programs, cognitively unimpaired adults with subjective memory concern are categorized as a specific subgroup due the belief that they are at an elevated risk for near term progression to mild cognitive impairment or dementia.  The results of this study, demonstrating a heritable, traitlike component of subjective memory concern with its persistence from age 38, suggest the need to re-evaluate the use of subjective memory concern as a means of assessing those at risk of dementia.

Reading 2:  

Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal

Leslie W. Young, M.D., Songthip T. Ounpraseuth, Ph.D., Stephanie L. Merhar, M.D., Zhuopei Hu, M.S., Alan E. Simon, M.D., Andrew A. Bremer, M.D., Ph.D., Jeannette Y. Lee, Ph.D., Abhik Das, Ph.D., Margaret M. Crawford, B.S., Rachel G. Greenberg, M.D., P. Brian Smith, M.D., Brenda B. Poindexter, M.D., et al., for the ACT NOW Collaborative

The full article is linked here. CNN story featuring this study:  New approach for newborns in opioid withdrawal gets them out of the hospital faster and with less medication | CNN

For infants with in utero opioid exposure and experiencing neonatal opioid withdrawal, the means of assessing the severity of their symptoms and need for treatment has relied the same assessment tool, the Finnegan Neonatal Abstinence Scoring Tool, for nearly 50 years.  In 2014, Grossman and colleagues proposed the Eat, Sleep, Console approach for assessing neonates experiencing opioid withdrawal. 

“The Eat, Sleep, Console Care Tool relies on a function-based assessment of withdrawal severity that is focused on an infant’s ability to eat, sleep, and be consoled, along with the use of nonpharmacologic interventions (e.g., low-stimulation environment, skin-to-skin contact, clustered care, and breast-feeding) as the first line of treatment and empowerment of families and caregivers in the care of their infants.”  Despite its increasing use, thus far there is limited data to support its safety and efficacy.  This study looked at the time from birth until medical readiness for discharge and composite safety outcomes for infants with neonatal opioid withdrawal syndrome assessed using the Eat, Sleep, Console method versus the Finnegan tool.

The authors found that for the infants in the Eat, Sleep, Console group, the number of days from birth until readiness for hospital discharge was 8.2 compared to 14.9 in the Finnegan group (mean adjusted difference, 6.7 days, 95% CI).   This study demonstrates that the Eat, Sleep, Console method significantly decreased the number of days infants with neonatal opioid withdrawal syndrome required hospitalization compared to infants assessed using the Finnegan without increasing adverse outcomes. 

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 WEEK 2

Reading 1:  

J Clin Psychiatry 2023;84(3):22com14575

The full article can be found here:

https://www.psychiatrist.com/jcp/depression/insurance-rtms-for-treatment-resistant-depression-mismatch-of-evidence-and-policies/

Major depression is one of the most common psychiatric disorders, with an estimated 12- month prevalence of 8.9 million US adults.  Roughly one third of these patients have treatment resistant depression (TRD).  The criteria for TRD include a minimum of 2 antidepressant failures of different classes at an adequate dose and duration.  Repetitive transcranial magnetic stimulation (rTMS) is a proven safe and effective treatment modality for major depression.  Despite its demonstrated efficacy, insurance coverage for rTMS can be limited and often requires satisfying strict and onerous treatment guidelines.    These can include failure of four antidepressants plus a course of psychotherapy.  This in effect makes rTMS only available for the sickest, most treatment resistant patients.   The Clinical TMS Society suggest coverage guidelines that include a diagnosis of moderate to severe depression, with failure of at least one antidepressant at an adequate dose for a 6-8 week duration. 

The authors examine the impact of such coverage limitations and requirements and how they are contradictory to the evidence for treatment with rTMS.   This paper highlights the barriers that exist to accessing safe and effective mental health care for our patients. 

 Reading 2:  

Clinical impact of reducing the frequency of clozapine monitoring: controlled mirror-image cohort study

Ebenezer Oloyede, Olubanke Dzahini, Zadro Abolou, Siobhan Gee, Eromona Whiskey, Diksha Malhotra, Masuma Hussain, Ian Osborne, Cecilia Casetta, Philip McGuire, James H. MacCabe and David Taylor

The British Journal of Psychiatry (2023) Pg 1-7

The full article is linked here.

Despite its proven benefits in the treatment of psychosis, clozapine is usually considered a treatment of last resort and even then many psychiatrists and patients are still reluctant to use it.  A major reason is the rigorous monitoring program to which patients must adhere while taking clozapine.  The monitoring, which includes weekly CBC’s for the first six months with eventual progression to every month, can be discouraging to some patients who might otherwise benefit from clozapine therapy. 

Within the setting of the COVID-19 pandemic, there have been calls to reconsider the monitoring requirements for clozapine.  In this paper, the authors asked if an extended monitoring schedule for patients on clozapine would have adverse effects on clinical and safety outcomes. 

This study looked at patients who were receiving clozapine treatment with an extended (every 12 weeks) monitoring program (EM) and compared them with a group receiving standard monitoring (SM).   There were a total of 569 subjects in the study (459 received extended monitoring).  Rates of hematological events, psychiatric hospital admissions, and clozapine doses for one year prior to the index study date and during the one year study duration were compared.  

The authors found that:

1.      Hematological events:  Two subjects in the EM group had mild to moderate neutropenia vs one in the SM group- all during the post-mirror phase.  There were no such incidents in the pre-mirror phase and no cases of severe neutropenia in either study group.

2.      Clozapine treatment:  The RR for treatment discontinuation with EM versus SM was 0.48 (95% CI 0.04-5.23, P=0.54)

3.      Admission rates:  For both groups, there was no change in the median number of psychiatric admissions per patient in the post-mirror compared to the pre-mirror period for both EM and SM groups.  The RR for hospital admissions during the follow-up period with EM compared to SM was 0.5 (95% CI 0.17-1.37, P=0.17)

This study showed that there were no differences in hematological events and hospitalization between patients receiving standard versus extended monitoring, suggesting that such a change in clozapine monitoring does not compromise patient safety.  One limitation of this study was that it only included patients who were already on clozapine and had not any history of severe neutropenia.  Thus, larger studies, looking at clozapine naïve patients would be helpful, but this study is an important step in determining if reducing monitoring burdens for patients on clozapine is feasible.

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 WEEK 1

No reading this week. 

WEEK 4

Reading 1: (Submitted by Dr. Jeff Daskalakis) 

High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation

A. Wang, et. al.

PNAS April 24, 2023 120(18) 

 The full article is linked here.

CNN Article Referencing Study: 

https://www.cnn.com/2023/04/24/health/fried-food-anxiety-depression-risk-wellness

We are what we eat or so the saying goes, but perhaps it is more like we become what we eat.  It is well known that diets high in fat and sugar, commonly referred to as "Western diets," pose a number of long-term health risks.  What is unique about this study is that the authors looked specifically at the mechanistic effects on mental health of consumption of a large ammounts of fried food.  This article focused acrylamide, a food processing contaminant in fried foods, and its contribution to anxiety and depressive-like behaviors via oxidative stress mediated neuroinflammation and disordered lipid metabolism.    The authors looked at the impact of fried food and acrylamide in humans and zebrafish and found that:

1.     Fried Food Consumption Is Associated with the Occurrence of Anxiety and Depression Symptoms.

2.     Long-Term Exposure to Acrylamide Induces Anxiety- and Depressive-Like Behaviors by Reducing Exploration Ability and Impairing Sociality of Zebrafish.

3.     Chronic Exposure to Acrylamide Induces Cerebral Lipid Metabolism Disturbance and Immune Response.

4.     Cerebral Lipid Metabolism Disturbance Links to Acrylamide-Induced Anxiety and Depression Symptoms.

5.     Chronic Exposure to Acrylamide Dysregulates Sphingolipid and Phospholipid Metabolism.

6.     Chronic Exposure to Acrylamide Impairs Blood–Brain Barrier and Induces Neuroinflammation.

7.     Chronic Exposure to Acrylamide Induces Anxiety and Depression Symptoms via Disturbing Lipid Metabolism and Inflammatory Response.

This interesting study contributes to the understanding of the “causative link and underlying mechanisms “ that fried foods and acrylamide exposure have on human and zebrafish mental health and brain functioning.  Such research can help us uncover how the food we eat contributes to or deters from our physical and emotion health.

Reading 2: 

Suspected Suicidal Cannabis Exposures Reported to US Poison Centers, 2009-2021

Janessa M. Graves, PhD, MPH; Julia A. Dilley, PhD, MES; Tracy Klein, PhD, ARNP; Erica Liebelt, MD

JAMA Network Open 2023; 6(4)

 The full article is linked here.

As more states legalize cannabis for medical and recreational use, the public health consequences of such legislation must be considered.  In the US, suicide is a leading cause of death and studies have shown an association between cannabis use and suicidal ideation and acts in adolescent and younger adults.  The authors examined data from the National Poison Data System (NPDS) for intentional, suspected suicidal cannabis exposures reported to US poison control centers. 

What they found was an increase in intentional, suicidal cannabis exposures reported to US poison centers from 2009 – 2021.  The increases were particularly noteworthy amongst children and females.   Given the expanding access to legal cannabis products in the US, it is important to understand the potential impact on mental health, especially for youth, that such policies might have.

Reading 1: 

The Safety and Efficacy of Psychedelic-Assisted Therapies for Older Adults: Knowns and Unknowns

C. Bree Johnston, MD, MPH, Maria Mangini, FNP, PhD, Charles Grob, MD, Brian Anderson, MD, MSc

 American Journal of Geriatric Psychiatry 31:1 January 2023

 The full article is linked here.

Comments by Dr. Kush Bhatt:

This review article discusses the current state of research on the use of psychedelic-assisted therapy in older adults. In summary, the article reports that many of the illnesses for which psychedelics appear to show promise are prevalent in older adults; however, studies have included very few older adults and have not addressed many of the possible medical complications that more often afflict older patients. The article calls for more research to study the safety and efficacy of psychedelic-assisted therapy in older adults. 

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 WEEK 3

No reading this week.

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 WEEK 2

Reading 1:  

Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomised trial (EULAST)

Inge Winter-van Rossum, Mark Weiser, Silvana Galderisi, Stefan Leucht, Istvan Bitter, Birte Glenthøj, Alkomiet Hasan, Jurjen Luykx, Marina Kupchik, Georg Psota, Paola Rocca, Nikos Stefanis, Alexander Teitelbaum, Mor Bar Haim, Claudia Leucht, Georg Kemmler, Timo Schurr, Michael Davidson, Reneì S Kahn, W Wolfgang Fleischhacker

Lancet Psychiatry 2023; 10: 197–208

The full article is linked here.

Patients with schizophrenia can experience relapse of psychotic symptoms when medications are discontinued.  Although effective, antipsychotic medications have side-effects which can lead to discontinuation and ultimately the re-emergence of symptoms.  Successful treatment of schizophrenia requires on-going treatment.  A number of antipsychotics are available in both oral and long-acting injectable formulations.  The authors seek to determine if long-acting injectable antipsychotics are more efficacious at preventing medication discontinuation. 

This paper presents data from the EULAST study:

“EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done.”

The results of the study showed that there was no significant difference in time to discontinuation amongst subjects taking oral aripiprazole or oral paliperidone versus those taking long-acting formulations of the same medications.  One limitation was that this was an open-label trial rather than a blinded one.  The findings suggest that while long-acting antipsychotics may not offer benefit in terms of time to discontinuation, treatment needs to be individualized to take patient needs into account.

Reading 2:  

What is Computational Psychiatry Good For?

Michael Browning, Martin Paulus, Quentin Huys

Biological Psychiatry Volume 93, Issue 8, P658-660, April 15, 2023 

The full article is linked here.

In this reading, the authors discuss how computational psychiatry can assist not only with finding hidden answers to clinically relevant questions but may also guide us on what questions might be most useful to ask in the first place.   The paper illustrates this by looking at the matter of how do depressed patients learn from rewarding experiences and the finding from the literature that when presented with two choices, one less rewarding than the other, patients with depression will choose the more rewarding option with less consistency than those without depression. 

The authors describe two possible ways to explain this behavior:  “either an effect of how patients use information when they make decisions or as a consequence of reduced estimates of the reward value of the reinforcer.”  A second, more sophisticated model designed to differentiate between these two was unable to do so.  Despite this, the authors note that the second model has utility in helping to formulate what questions might be able to address reward choice in depression.  Thus, computational models can assist with finding biologically derived clinical measures.

Reading 3:  

Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial

Edouard G. Mills, MD, PhD; Natalie Ertl, MSci; Matthew B.Wall, PhD; Layla Thurston, MD, PhD; Lisa Yang,MD, PhD; Sofiya Suladze, BSc; Tia Hunjan, MD; Maria Phylactou, MD, PhD; Bijal Patel, MD; Beatrice Muzi, MSc; Dena Ettehad, MD; Paul A. Bassett, MSc; Jonathan Howard, PhD; Eugenii A. Rabiner, MD;

Paul Bech, PhD; Ali Abbara, MD, PhD; David Goldmeier, MD; Alexander N. Comninos, MD, PhD; Waljit S. Dhillo,MD, PhD

 JAMA Network Open. 2023;6(2):

The full article is linked here.

CNN article discussing the results of this study is at:  https://www.cnn.com/2023/04/11/health/male-low-sex-drive-treatment-wellness

Hypoactive sexual desire disorder (HSDD) affects about 8% of men.  This condition is thought to be caused by decreased activation of brain areas regulating sexual desire and increased activation of areas involved in self-referential processing.  This leads to a shift in focus from sexual stimuli to self-monitoring and a subsequent decline in sexual desire and an increase in associated feelings of distress.  Despite the significant impact HSDD can have on emotional well-being, there are no approved medication treatments.  Animal models have suggested that the neuropeptide kisspeptin plays a role in modulating reproductive behavior and sexual desire. 

This paper presents the results of a trial of kisspeptin on the effects of sexual brain processing and penile tumescence in men with HSDD. 

“In this double-blind, 2-way crossover, placebo-controlled randomized clinical trial, participants

completed 2 study visits each (kisspeptin and placebo) at least 7 days apart.  Participants had 2 intravenous cannulas sited for blood sampling and for kisspeptin or placebo administration. Blood sampling for hormonal measurements took place at 15-minute intervals from 30 minutes before commencement of the kisspeptin or placebo infusion to the end of the 75-minute infusion. At 0 minutes, a 75-minute infusion of kisspeptin-54 (1 nmol/kg/h) or commenced. Participants completed psychometric questionnaires before and toward the end of kisspeptin or placebo administration.

Between 30 and 60 minutes of the kisspeptin or placebo infusion, fMRI scanning was

performed with participants completing 2 tasks involving watching videos with sexually explicit and non-sexual content.”  Penile tumescence and subjective level of arousal were also recorded during the second task. 

The results demonstrated that kisspeptin infusion in men with HSDD significantly modulated sexual-processing brain region activity and increased sexual behavior and penile tumescence in response to visual sexual content compared to placebo.  This study suggests that kisspeptin may be a pharmacological target of treatment for HSDD in men.

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WEEK 1

Reading 1:  

“Association of Age at Menopause and Hormone Therapy Use With Tau and β-Amyloid Positron Emission Tomography” 

Gillian T. Coughlan, MS, PhD; Tobey J. Betthauser, PhD; Rory Boyle, PhD; Rebecca L. Koscik, PhD; Hannah M. Klinger, MS; Lori B. Chibnik, PhD, MPH; Erin M. Jonaitis, PhD, MS; Wai-Ying Wendy Yau, MD; Allen Wenzel, BS; Bradley T. Christian, PhD; Carey E. Gleason, PhD; Ursula G. Saelzler, PhD; Michael J. Properzi, BEng, BCompSci; Aaron P. Schultz, PhD; Bernard J. Hanseeuw, MD, PhD; JoAnn E. Manson, MD, DrPH, MACP; Dorene M. Rentz, PsyD; Keith A. Johnson, MD; Reisa Sperling, MD; Sterling C. Johnson, PhD; Rachel F. Buckley, PhD

JAMA Neurology published online April 3, 2023

The full article is linked here and an accompanying CNN article is available at: Alzheimer's and HRT: Study suggests sweet spot to avoid dementia | CNN .

In the US over 6 million people live with a diagnosis of Alzheimer’s dementia.  In the setting of elevated β-Amyloid, there is evidence that female individuals have greater amounts of neurofibrillary tau tangles than do males.  Additionally, premature or early menopause has been associated with deleterious clinical outcomes related to Alzheimer’s.   Following the publication of data in 2003 demonstrating that hormone therapy (HT) was found to increase incidence rate for probable dementia, use of HT decline by 80% in US.   The authors attempted to see if female sex, earlier age at menopause and hormone therapy are associated with the deposition of tau pathology.  They found that “in this cross-sectional study, female sex, earlier age at menopause, and HT use were significantly associated with higher regional tau in the context of high β-amyloid, as measured on the positron emission tomography signal. Late initiation of HT following menopause onset may underpin the association between HT use and the elevated tau positron emission tomography signal.”

The implications of this study suggest that HT is safe when used close to menopause onset but that later initiation of HT increases the risk of progression to  Alzheimer’s dementia.

Reading 2:  

Manuel Gardea-Resendez , Brandon J. Coombes, Marin Veldic , Susannah J. Tye, Francisco Romo-Nava , Aysegul Ozerdem, Miguel L. Prieto, Alfredo Cuellar-Barboza, Nicolas A. Nunez, Balwinder Singh, Richard S. Pendegraft, Alessandro Miola, Susan L. McElroy, Joanna M. Biernacka, Eva Morava, Tamas Kozicz, and Mark A. Frye

Molecular Psychiatry (2023) 28:1020–1026

The full article is linked here.

The treatment of bipolar depression can be especially challenging.  Antidepressants, while commonly used  in the treatment of bipolar depression, have both high rates of treatment non-response and the potential to cause antidepressant-induced mania.   There is evidence that the neurobiology of bipolar disorder is caused, in part, by mitochondrial dysfunction with reduced expression of electron transport chain genes in the frontal cortex and hippocampus.  Additionally, there is evidence that antidepressants may differentially influence mitochondrial energetics.  The authors seek to examine "the mitochondrial energetics profile of specific antidepressants and its association with the adverse drug related event of treatment-emergent mania."

The paper concludes that:   " TEM+ [treatment emergent mania] was more frequent with use of antidepressants that increase mitochondrial activity versus those that decrease it (Mito+ 24.7% vs. Mito− 13.5%; OR = 2.21; p = 0.000009) after adjusting for age, sex, and BD type.  

The implications for this are important in that mitochondrial activity could potentially serve as a way of evaluating the safety of specific antidepressants for bipolar depression and allow us to move away from the conventional, but perhaps less useful, classification based on drug mechanism of action.

Reading 3:  

 Holly Humphrey, Dana Levison, Keme Carter

JAMA, Published online March 23, 2023

The full article is linked here.

The authors of this article discuss the recent decisions by Harvard and the leadership of at least 14 other medical schools (including medical schools affiliated with two of the nation's historically Black colleges and universities) to opt out of the  US News and World Report survey.   They note that the survey and rankings criteria fail to account for the holistic review practices recommended by the AAMC.  In particular, the authors state that a medical school's pursuit of such rankings has often come at the expense of serving their values and that no one ranking system can adequately account for the variety of missions represented by the medical schools in our nation (including scientific discovery and innovation, training primary physicians to work with selected populations within a state/region, recruiting a diversified physician workforce that reflects a school's community/state, etc.).  

WEEK 4

Reading 1:  

"The New Crisis of Increasing All-Cause Mortality in US Children and Adolescents"

S. Woolf, E. Wolf, F. Rivara

The full article is linked here.

Life expectancy in industrialized countries has lengthened over the past centry but increases in life expectancy ceased after 2010, attributable to inceases in mortality among individuals aged 25-64 years.  Since the COVID-19 pandemic however, pediatric mortality has also increased.  The contribution of COVID-19 to this rise in childhood mortality is limited.  The authors note that injuries accounted for the majority of the increase in childhood mortality.  Deaths from transport, homicide, poisoning, and suicide all increased from 2019-2021.  As the authors note "medicine and public health have made remarkable progress in lowering pediatric mortality rates, but the lives they have saved are now endangered by manmade pathogens. Bullets, drugs, and automobiles are now causing a youth death toll sufficient to elevate all-cause mortality rates, the largest such increase in recent memory. Without bold action to reverse the trend, children’s risk of not reaching adulthood may increase. " 

Reading 2:  

 JAMA Psychiatry. 2023;80(2):156–166

The full article is linked here.

Psychiatric disorders commonly occur in women of reproductive age.  In fact, while many disorders first appear at this stage of life, treating mental illness during pregnancy can be challenging.  Ever since thaliidomide demonstrated the dangers of terratogenicity, prescribers have been wary of the potential for adverse effects of medications on the developing fetus.  As pregnant women are excluded from most clinical trials, the the safety of antipsychotics use during pregnancy is an area where there exists gaps in our knowledge.  This paper  presents a cohort study of over 26,000 antipsychotic-exposed pregnancies from 6 countries and seeks to evaluate the risk of first-trimester exposure to antipsychotics on cognetial malformations.  

The authors found that :  "Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]); however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]."  The take home point from this is that in utero exposure to antipsychotics generally was not "meaningfully associated with an increased risk of malformations."

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WEEK 3

Reading 1:  

“Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression” (Submitted by Dr. Ellen Lee)

E.J. Lenze, B.H. Mulsant, S.P. Roose, H. Lavretsky, C.F. Reynolds III, D.M. Blumberger, P.J. Brown, P. Cristancho, A.J. Flint, M.A. Gebara, T.R. Gettinger, E. Lenard, J.P. Miller, G.E. Nicol, H.A. Oughli, V.T. Pham, B.L. Rollman, L. Yang, and J.F. Karp

N Engl J Med . 2023 Mar 3 

The full article is linked here.

NEJM late-life depression (LLD) clinical trial of aripiprazole augmentation vs bupropion augmentation vs bupropion monotherapy - 619 patients enrolled. ‘The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P=0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation.’ Take away: better to augment than switch – at least in LLD – Dr. Jeff Daskalakis

Reading 2:

“Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape”  (Selected by and commentary from Dr. David Gratzer)

Manish K. Jha and Sanjay J. Mathew

The American Journal of Psychiatry, 1 March 2023  Online First

The full AJP paper can be found here:
https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.20230025

The authors focus on four FDA-approved medications.
 
Aripiprazole
 
“In initial randomized controlled trials (RCTs), 6-week augmentation with aripiprazole (2–20 mg/day) after inadequate response to an 8-week course of antidepressant treatment was associated with higher remission rates than placebo (25.4% compared with 15.2% and 26.0% compared with 15.7%), with a number needed to treat (NNT) of 10. Subsequent similarly designed RCTs had similar results, with NNTs of 9 to 11 for aripiprazole (at dosages of 3 mg/day, 3–15 mg/day, or 3–12 mg/day) compared with placebo. Augmentation with aripiprazole (at 2–15 mg/day) was also associated with higher rates of remission (44%) compared with placebo (29%) (NNT=7) in a study of elderly patients who did not attain remission with 12 weeks of treatment with extended-release venlafaxine.”
 
Brexpiprazole
 
“Initial RCTs found significantly greater reductions in depressive symptoms with adjunctive brexpiprazole at 2 mg/day and 3 mg/day but not at 1 mg/day after inadequate response to 8 weeks of antidepressant treatment. However, remission rates with adjunctive brexpiprazole (14.7%, 14.9%, and 14.1% with 1, 2, and 3 mg/day, respectively) did not differ from placebo (9.0% and 10.8%), with NNTs ranging from 17 to 31. Subsequent acute-phase RCTs had similar reductions in depressive symptoms but no differences in rates of remission (NNTs of 28 and 42). A longer-term (24-week) study found that adjunctive brexpiprazole had similar rates of improvement but higher rates of adverse event–related withdrawal (6.3%) compared with placebo (3.4%).”
 
Extended-release quetiapine
 
“In two phase 3 trials of individuals with MDD who had continuing depressive symptoms after ≥6 weeks of treatment with an adequate dosage of an antidepressant... extended-release quetiapine at 300 mg/day was more effective than placebo in reducing depression severity in both studies, and the 150 mg/day dosage was more effective in one study but not the other. In a pooled analysis, rates of remission were 41.8% (NNT=11) with 150 mg/day and 46.3% (NNT=7) with 300 mg/day of extended-release quetiapine, compared with 32.0% for placebo.”
 
Cariprazine
 
“This issue of the Journal includes a report on a phase 3 trial of cariprazine augmentation in MDD. The trial enrolled 757 patients with MDD with inadequate response (<50% improvement in depressive symptoms) to one to three antidepressants in the current episode (of adequate dosage per prescribing label and of at least 6 weeks’ duration) and randomized them in a 1:1:1 ratio to 6 weeks of augmentation with placebo, cariprazine at 1.5 mg/day, or cariprazine at 3 mg/day. This study used fixed-dose arms... The study found significantly greater improvement in depressive symptoms with cariprazine at 1.5 mg/day (−14.1 points in Montgomery-Åsberg Depression Rating Scale [MADRS] score) compared with placebo (−11.5 points in MADRS score) but not with 3 mg/day (−13.1 points in MADRS score). Remission rates at week 6 did not differ significantly among the treatment arms...”
 
The paper also considers other options, including ketamine. 

Reading 3:  

“From Womb to Neighborhood: A Racial Analysis of Social Determinants of Psychosis in the United States”

Deidre M. Anglin, Ph.D., Sabrina Ereshefsky, Ph.D., Mallory J. Klaunig, Ph.D., Miranda A. Bridgwater, B.S., Tara A. Niendam, Ph.D., Lauren M. Ellman, Ph.D., Jordan DeVylder, Ph.D., Griffin Thayer, M.A., Khalima Bolden, Ph.D., Christie W. Musket, M.S., Rebecca E. Grattan, Ph.D., Sarah Hope Lincoln, Ph.D., Jason Schiffman, Ph.D., Emily Lipner, M.A., Peter Bachman, Ph.D., Cheryl M. Corcoran, M.D., Natália B. Mota, M.D., Els van der Ven, Ph.D

American Journal of Psychiatry Vol 178, issue 7, July 2021

The full article can be found here:   From Womb to Neighborhood: A Racial Analysis of Social Determinants of Psychosis in the United States | American Journal of Psychiatry (psychiatryonline.org)

This article seeks to provide “the first consolidated integration of UC-based work on social determinants of psychosis in there key areas, with a specific focus on race and ethnicity.”   The authors look at neighborhood factors, cumulative trauma and stress, and pre and perinatal complications.  Each of these areas reflect social conditions that may effect psychosis risk and are impacted by structural racism.   

The “review of the U.S.-based literature on social determinants reveals a pattern of racial disparities in established risk factors for psychosis. That racism has historically structured U.S. societal systems means that the neighborhood and social context may hold a significant portion of the relative contribution of risk for psychosis. This may occur through individual-level discrimination as well as through collective trauma at the community level (e.g., police and gun violence). The evidence that these multilevel exposures may enhance chronic stress activation across generations through perinatal complications in mothers is considerable.”  The authors advocate for the promotion of research, treatment, and educational initiatives that prioritize mitigating  the impact of structural racism and its contribution to mental illness.

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WEEK 1

Reading 1:  

"Risk of Violent Behavior in Young People at Clinical High Risk for Psychosis from the North American Prodrome Longitudinal Studies Consortium"

Early Interv Psychiatry 2023 Jan 10

The full article link.

Psychiatrists are often asked to predict the potential for violence of patients and unfortunately, concerns about violence or the risk of it help perpetuate stigma against those with mental health conditions.  This article seeks to examine the risk of violence in youth at clinical high risk for psychosis (CHR) and to determine the relationship between Structured Assemement for Violence Risk in Youth (SAVRY) violence risk scores, psychosis risk symptoms, and global functioning.  The hope is that such determinations can assist with providing early interventions to support at risk youth.  The authors found that " the majority of those meeting CHR criteria were at low violence risk per the SAVRY Summary Risk Rating. High scores were extremely rare."    They demonstrated that higher SAVRY risk scores were associated with more severe psychosis and poorer functioning.  Also, CHR participants with co-morbid ADHD, borderline personality disorder, or substance use had higher violence risk scores.  The paper also highlights the importance of protective factors in a CHR population and the possibility of interventions designed to strengthen such factors and resilience.

Reading 2:

"Assessing the Preparedness of the US Health Care System Infrastructure for an Alzheimer's Treatment"

Jodi L. Liu, Jakub P. Hlávka, Richard Hillestad, Soeren Mattke

The RAND Corporation report link.

For the first time, we have two disease-modifying therapies for Alzheimer's disease that have been approved by the FDA.  The controversies surrounding aducanumab's approval notwithstanding, this report examines that challenges faced by the US health care system should disease-modifying treatments for Alzheimer's disease become widely available.  As a geriatric psychiatrist, this report highlights the urgent needs and deficiencies in providing for the mental health care needs of older adults which I see in everyday practice.

Reading 3: (Selected by and commentary from Dr. David Gratzer)

“Looking After Our Own”

Richard M Boulary

The New England Journal of Medicine, 16 February 2023

The full article can be found here:   https://www.nejm.org/doi/full/10.1056/NEJMp2214345

“‘If you follow me, Dr. Boulay, she’s in ICU-10,’ the intensivist began, walking me down the labyrinthine corridors. ‘She remains delirious, but her rigidity is improving. Her head CT, bloodwork, and tox screen are normal. We just sent an LP. She’s still tachy to 180, but her pressure is holding. She’s not any worse in the few hours she’s been here, but she’s no better. Her husband brought in her empty antidepressant bottles. Our working diagnosis is serotonin syndrome.’

3. The New England Journal of Medicine has published important papers and correspondence on physician burnout and mental health in recent years. The Fang et al. letter – tying resident work hours to depression symptoms – was particularly strong. (This wasn’t considered in a past Reading, but we’ve recently interviewed Dr. Srijan Sen, a co-author, for a podcast.) The letter can be found here: https://www.nejm.org/doi/full/10.1056/NEJMc2210365

WEEK 4

Reading 1:

“Targeted Oral Naltrexone for Mild to Moderate Alcohol Use Disorder Among Sexual and Gender Minority Men: A Randomized Trial”

Glenn-Milo Santos, Ph.D., M.P.H., Janet Ikeda, M.A., Phillip Coffin, M.D., M.I.A., John Walker, N.P., Tim Matheson, Ph.D., Arsheen Ali, B.A., Matthew McLaughlin, A.B., Jennifer Jain, Ph.D., M.P.H., Justine Arenander, M.S.W., Eric Vittinghoff, Ph.D., Steven Batki, M.D.

The American Journal of Psychiatry, December 2022

The full article is here.

Here’s a link to coverage of this article by the NYTimes 2/14/23: https://www.nytimes.com/2023/02/14/health/alcohol-binge-drinking-pill-naltrexone.html?smid=em-share

There is older data with a proposed mechanism and some efficacy of using as needed naltrexone (50 mg by mouth) when having cravings to drink alcohol or prior to events with either exposure to alcohol or planned drinking.  The goal is to reducing craving or desire to drink alcohol, or if planning to drink, to reduce the amount imbibed.  Much of the data we have on naltrexone for Alcohol Use Disorder is based on taking the medication consistently once daily or in the once monthly long-acting injectable form.  The article is looking at “targeted naltrexone” in sexual and gender minority men who binge drink and have a mild to moderate alcohol use disorder.  Targeted naltrexone significantly reduced drinking outcomes among SGM with mild to moderate alcohol use disorder during treatment, with sustained effects at 6 months posttreatment. Naltrexone may be an important pharmacotherapy to address binge drinking in populations with mild to moderate alcohol use disorder.  Of note, the generalizability of this study to all AUD and/or all “binge” drinkers may be limited.  In particular, there is some evidence on post-hoc analyses of naltrexone being less effective in females by birth.  It’s also exciting to see sustained behavior change as much as 6 months after treatment.  The findings are more for alcohol reduction than for abstinence.  Naltrexone is cheap and well tolerated (some nausea for some – usually brief and mild).  From a harm reduction standpoint, this is a great option, and it may have better adherence than daily regimens. 

Reading 2:

“Avoiding Unethical Altruism in Global Health:  Revisiting Ethics Guidelines for International Rotations for Medical Residents”

Stephanie Ross, Kenneth Goodman

Journal of Graduate Medical Education, February 2023

The full Journal of Graduate Medical Education article can be found here:  https://doi.org/10.4300/JGME-D-22-00455.1

Having the opportunity as a trainee to rotate overseas can be a transformative learning experience.  Interacting with other cultures and health care systems allows one to gain exposure to diagnoses and situations that are outside of the range of what one might normally encounter in daily practice at home.  Such international rotations should enrich both the visiting trainee and those with whom one is serving and learning from in the host country.  Unfortunately, as the article discusses, such experiences can also cause harm to the local population if done without regard for the needs and resources of the site or a lack of respect for the local culture.  The reading outlines a series of guidelines to follow when participating in such rotations abroad to avoid perpetuating colonialist biases or causing injury.

Reading 3: (Selected by  and commentary from Dr. David Gratzer)

“A Meta-Research of Randomized Controlled Trials in the Field of Mental Health: Comparing Pharmacological to Non-Pharmacological Interventions from 1955 to 2020”

Sheng Chen, Alina Lee, and Wei Wang

The Canadian Journal of Psychiatry, 6 February 2023  Online First

The full article can be found here:  https://journals.sagepub.com/doi/full/10.1177/07067437231154993

“Since the introduction of randomized controlled trials (RCTs) in 1948, tens of thousands of such experimentations have been conducted. The ability of RCTs to control for confounding factors, reduce bias, and elucidate the direction of causation enables a robust evaluation of the efficacy and effectiveness of interventions. RCTs are regarded as the gold standard in the medical/health field and have a vital role in the development of evidence-based treatment interventions.”
 
So begins a paper by Chen et al.
 
Here’s what they did:
 
“This study aimed to provide a general overview of mental health randomized controlled trials (RCTs) and summarize the temporal trends in terms of the number of studies, median sample sizes, and median effect sizes using data collected from the Cochrane Database of Systematic Reviews (CDSR).”
 
Here’s what they found:

·         After eliminating studies with missing information and duplicates, the final dataset included 6,652 RCTs in mental health and psychiatry.

·         Number. “The number of mental health RCTs reported in publications has increased almost exponentially from 1955 to 2020.” See figure below. (The drop in recent years may be due to a delay in reporting.)

·         Types of RCTs. “While pharmacological-RCT comprised a majority of mental health RCTs in the earlier years, the proportion of non-pharmacological-RCTs increased more quickly over time and markedly exceeded [the former] after 2010.”

·         By population. “The proportion of pharmacological-RCTs was more than double that of non-pharmacological-RCTs among patients with schizophrenia (71.5% vs. 28.5%) and mood disorders (69.7% vs. 30.3%). Conversely, the proportions were 33.8% for the pharmacological-RCTs and 66.2% for the non-pharmacological-RCTs for neurotic/stress-related disorders, and 18.3% versus 81.7% in all other mental disorders RCTs.”

·         Sample size. “The median sample size for all 6,652 mental health RCTs was 61… Over time, the median fluctuated, but with an overall increasing trend over the past 60+ years, from less than 50 before the 1990s to around 70 after the 2000s.”

·         Effect size. “The median of the effect size, measured by Pearson’s r, for overall RCTs was 0.18…” 

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WEEK 3

Reading 1: (Submitted by Dr. Ramanathan with editorial)

"Clinical effectiveness of active Apha-Stim AID versus sham Alpha-Stim AID in major depression in primary care in England (Alpha-Stim-D)"

The full Lancet article can be found here:

 "Alpha-stim is a “cranioelectrotherapy” device – a form of non-invasive neuromodulation in which electrical clips are attached to earlobes in an attempt to modulate brain activity. Theoretical advantages to this are they are relatively cheap, able to be used at home, and very low voltage devices (i.e., relatively safe). Veterans occasionally have heard of and ask about this. 

It is unclear the mechanism of action – but probably a best guess, beyond simply stimulation of the earlobes, is that if this therapy does anything, it may work by providing some low level auricular nerve stimulation that indirectly modulates the vagus nerve – but this is highly speculative. Another reasonable speculation is that this device works via activation of placebo. The low current and position of electrodes do not allow for any realistic direct effects on the brain that we might see with TMS, or even other forms of transcranial electrical stimulation which are typically delivered using higher current electrodes directly applied to the brain.  

There was a recent large RCT for this device in the treatment of moderate depression (PHQ-9 between 10-19, see attached pdf above) with very unimpressive results unfortunately – Alpha-stim did not beat sham for  any outcomes (primary or secondary). "

Reading 2:

"An Introduction to ChatGPT"

By Dr. Scott Patten

From Dr. David Gratzer

This essay by Dr. Scott Patten explores the possible future of AI generated scholarship.  The prospect of such publications led JAMA to publish an editorial (https://jamanetwork.com/journals/jama/fullarticle/2801170?resultClick=1) and updated its instructions to authors to include:  “Nonhuman artificial intelligence, language models, machine learning, or similar technologies do not qualify for authorship.”

 ChatGPT is a natural language processing model produced by “Open AI” – an American organization dedicated to developing AI applications and making the code and patents freely available to the public. This organization was founded in 2015 (one of its original founders was Elon Musk). It also has a for-profit subsidiary that is aligned with Microsoft.  
 
But I am wasting my time here. Instead of writing this essay, why not ask ChatGPT to describe itself?
 
SP: “Write a brief history of ChatGPT”
 
ChatGPT responds:
 

ChatGPT is a language model developed by OpenAI, a leading artificial intelligence research organization. The model is based on the transformer architecture, a type of neural network that has revolutionized the field of natural language processing.

ChatGPT was first introduced in 2019 as an improvement over OpenAI's GPT-2, a large language model that was capable of generating human-like text. The development of ChatGPT was a significant step forward in the advancement of AI and its ability to understand and generate human language.

Since its release, ChatGPT has been widely used in a variety of applications, including chatbots, customer service, language translation, and text generation. The model has received recognition for its ability to generate high-quality text, understand context, and answer questions accurately.

In recent years, OpenAI has continued to improve ChatGPT, making it even more powerful and versatile. The model has grown in size, with an increased number of parameters, and has been fine-tuned on a variety of tasks and languages to improve its performance.

In conclusion, ChatGPT is a state-of-the-art language model developed by OpenAI that has been widely adopted in various applications due to its ability to generate human-like text and understand context. The model has a rich history of advancements and improvements, making it a powerful tool in the field of natural language processing.

 
The model represents an advancement over prior versions of this language model – but this one has caused a much greater stir for two reasons. First, it is able to understand the question being asked. Second, the response provided has qualities that we instinctively recognize as a human voice. Like previous versions (and other natural language models), it is likely to be widely used, e.g. serving a customer service role on websites, but the human-like tone of the “speech” it produces has led to widespread concerns. One concern arises from teachers and other educators who note that it could be a tool for plagiarism. For example, asking ChatGPT to write a brief summary of lithium safety one receives information that is consistent with what might be produced by an undergraduate student. It lacks the depth of information that would be expected of an expert, but certainly could have been written by a human:

SP: “Write a brief overview of lithium safety monitoring in psychiatry”

ChatGPT responds:
 

I can provide a brief overview on the topic of lithium safety monitoring in psychiatry:

Lithium is a commonly used mood stabilizer in the treatment of bipolar disorder and major depression. However, its use requires careful monitoring due to its narrow therapeutic index and the potential for toxicity. To ensure the safety and effectiveness of lithium therapy, regular monitoring of serum lithium levels and kidney function is necessary.

The therapeutic range of lithium levels is typically between 0.6-1.2 mMol/L. Levels above 1.5 mMol/L can lead to toxicity, while levels below 0.5 mMol/L may be ineffective. Toxicity can manifest in a variety of symptoms, including nausea, vomiting, diarrhea, tremors, confusion, and seizures. In severe cases, lithium toxicity can lead to coma and death.

To monitor the safety and effectiveness of lithium therapy, it is recommended that patients have their serum lithium levels measured at least every 3-6 months. In addition, regular monitoring of kidney function is necessary as lithium can cause renal impairment. Creatinine clearance, serum creatinine, and electrolyte levels should also be measured to assess kidney function.

It is important to note that there are various factors that can affect lithium levels and kidney function, including changes in medication, diet, fluid intake, and underlying medical conditions. Therefore, it is important for patients to inform their healthcare provider of any changes in their health or medication regimen.

In conclusion, lithium is an effective mood stabilizer for the treatment of bipolar disorder and major depression, but its use requires careful monitoring to ensure safety and effectiveness. Regular monitoring of serum lithium levels and kidney function is necessary to prevent toxicity and ensure the optimal therapeutic response. Patients should inform their healthcare provider of any changes in their health or medication regimen to ensure proper monitoring and management of their lithium therapy.

 
There have also been concerns among academic journal editors that products of this kind of language model could be produced deceptively as a means of producing academic articles. This seems unlikely since ChatGPS is a language model that in its present version doesn’t search the internet and its only content knowledge consists of materials that it collected in 2021 from the internet at that time. When I ask it who won the 2022 Grey Cup, it acknowledges this limitation in a way that still sounds quite human:
 
As my training data only goes up until 2021, I don't have information on the winner of the 2022 Grey Cup. The Grey Cup is the championship game of the Canadian Football League (CFL) and is held annually. I suggest checking current sources such as news websites or the CFL's official website for up-to-date information on the winner of the 2022 Grey Cup.
 
Until recently, universities prohibited the use of computer-generated text in assignments and exams – but many are now giving up the fight because of ChatGPT, acknowledging that this might be a way to quickly produce preliminary drafts of commentaries and essays. Transparency about the use of such tools is now often the stated goal, rather than prohibition.
 
ChatGPT’s responses sometimes include incorrect information. When I asked it questions about myself a few days ago, it incorrectly asserted that I graduated from the University of Toronto. The same question a few days later resulted in a response saying that it can only comment on public figures. Its responses are being refined by user feedback. Instead of providing inaccurate answers, ChatGPT increasingly responds by acknowledging that “as a language model” I cannot answer that question. Similarly, it cannot distinguish misinformation or propaganda from other types of information found on the internet. Consequently, users have been able to elicit racist statements from ChatGPT. However, it is subject to training influences and is open sourced, so its responses improve with feedback, for example: 
 
SP: “Are vaccines safe?”
 
ChatGPT responds:
 

Yes, vaccines are safe. Vaccines have been rigorously tested for safety and effectiveness before being approved for use and continuously monitored for safety after they are on the market. According to the World Health Organization (WHO), vaccines are one of the safest and most effective ways to prevent disease.

Like all medical interventions, vaccines can have side effects, but the benefits of vaccination far outweigh the risks. The side effects of vaccines are generally mild, such as soreness at the injection site, and usually go away on their own within a few days. Serious side effects from vaccines are extremely rare, and the risk of having a serious reaction is much lower than the risk of serious complications from the diseases that the vaccine helps to prevent.

In conclusion, vaccines are safe and play a critical role in protecting people against serious and potentially life-threatening diseases. It's important to rely on credible sources of information, such as the WHO, the Centers for Disease Control and Prevention (CDC), and local public health authorities, when evaluating the safety of vaccines.

 
An interesting feature of ChatGPT is that in addition to natural languages, it can also write code:
 
SP: “How can I fit a logistic regression model in Python”
 
ChatGPT responds:
 

In Python, you can fit a logistic regression model using the scikit-learn library. Here's a basic example of how to fit a logistic regression model in Python:
 
pythonCopy code
import pandas as pd from sklearn.model_selection 
import train_test_split from sklearn.linear_model 
import LogisticRegression 
# Load the data into a Pandas DataFrame
data = pd.read_csv("data.csv") 
# Split the data into training and testing sets
X_train, X_test, y_train, y_test = train_test_split(data.iloc[:, :-1], data.iloc[:, -1], test_size=0.2) 
# Fit the logistic regression model to the training data
model = LogisticRegression() model.fit(X_train, y_train) 
# Predict the response values for the test data
y_pred = model.predict(X_test) 
# Print the model's accuracy
print("Accuracy:", model.score(X_test, y_test)) 
 
In the example above, the data is loaded into a Pandas DataFrame using pd.read_csv("data.csv"). The data is then split into training and testing sets using train_test_split(), which splits the data into 80% training data and 20% testing data by default. The logistic regression model is then fit to the training data using model.fit(X_train, y_train). Finally, the model's accuracy is calculated and printed using model.score(X_test, y_test).
 
Note that this is just a basic example, and you may need to modify the code to fit your specific use case. For example, you may need to perform feature scaling, regularization, or other preprocessing steps to improve the model's performance.

 
The concerns are the same – here, it assumed I wanted to use logistic regression to cross-validate a training dataset. If I didn’t know what this was, I might have been pointed in the wrong direction. However, its code works and is more natural to look at than the help file in Python’s documentation.
 
In summary, ChatGPT is a natural language model that represents a major advance due to the human-like qualities of its responses to questions posed in natural language. However, its AI advances are mostly related to its language processing so it seems human, which seems and feels amazing, but in my opinion, it is actually just regurgitating information from the internet in a human-like way. A recent Nature Commentary (https://www.nature.com/articles/d41586-023-00288-7) basically agrees with this opinion, but states that it is a “premature assumption” that this state of affairs will continue. The Commentary notes that in the not-too-distant future AI may be able to “…summarize literature, draft and improve papers, as well as identify research gaps and write computer code, including statistical analyses.” The concern here is that the natural language used in communicating these activities may make it difficult to clarify the role of AI when a scientific report is published. This concern is enlarged due to the factual errors often made by ChatGPT. These concerns are similar with those that ChatGPT may be used to generate student essays, although plagiarism detectors typically give high scores to ChatGPT content – it has been noted that running the text through grammar-checking software (now widely used by students) lowers those scores a lot. The JAMA Network has stated that ChatGPT should not be listed as an author of papers, and that if it is used as a writing tool this should be clearly stated (https://jamanetwork.com/journals/jama/fullarticle/2801170). Authors retain the responsibility for referencing sources and ensuring factual accuracy. This emphasis on transparency is consistent with current scientific values. A recent editorial identified four papers in which Chat-GPT was listed as an author, but they were all commentaries and were generally not published in credible journals, except for one that escaped the notice of an inattentive editor (https://www.nature.com/articles/d41586-023-00107-z). 
 
Despite all of this, if you look at the essay written by ChatGPT about its potential role in psychiatry, it seems to try to sell itself in particular roles, for example, in a possible triage function in clinical settings. This is not based on evidence-based, which doesn’t seem very transparent at all:
 
SP: “Write a presentation on the role of ChatGPT in psychiatry for an audience of psychiatrists and psychiatry residents”
 
ChatGPT responds:
 

Good morning/afternoon everyone. Today, I would like to talk to you about a state-of-the-art technology in the field of language processing: ChatGPT.
ChatGPT is a Generative Pre-trained Transformer-based language model, created and developed by OpenAI. It was fine-tuned on a diverse range of internet text data, making it capable of generating human-like responses to a wide range of topics.

In the context of psychiatry, ChatGPT can be a valuable tool in several ways. First, it can help in triaging patients who need immediate attention. For example, if someone is in a mental health crisis, they can reach out to ChatGPT for support and receive a prompt response. This can be particularly helpful for individuals who may not have access to immediate human support or who may feel uncomfortable speaking to a human.

Second, ChatGPT can be used as a tool to educate patients on mental health topics and provide them with information that can help improve their well-being. For example, if a patient is struggling with depression and doesn't know much about the condition, they can engage in a conversation with ChatGPT and receive helpful information and resources.

Finally, ChatGPT can also be used as a tool for research purposes. By analyzing the conversations it has with patients, researchers can gain valuable insights into patient behaviors and mental health patterns. This information can then be used to improve existing mental health treatments and develop new ones.

In conclusion, ChatGPT is a powerful technology with many applications in the field of psychiatry. Whether it's for triaging patients, educating patients, or conducting research, ChatGPT has the potential to make a significant impact on mental health care.

Thank you for your attention. Are there any questions?

 
Perhaps it is best to use ChatGPT for applications that are purely linguistic rather than truly intelligent, at least at this stage, so I’ve asked it to write a poem about psychiatric residency:
 

Psychiatric training, a journey untold, 
A path filled with challenges, wisdom to hold. 

With each patient’s story, a lesson to learn, 
A journey of healing, a bridge to burn.

In the depths of the mind, lies a world so vast, 
With secrets and fears, from the past. 

As a psychiatry resident, one must be bold, 
To navigate this realm, and find what is untold.

With compassion and care, the healing begins, 
With a listening ear, and a gentle grin. 

For each person is unique, with a story to share, 
And a journey to embark, to find solace and repair.

Through rounds and lectures, the knowledge grows, 
With guidance from mentors, the resident flows. 

Learning to diagnose, and treatments to apply, 
The future is bright, with no room to shy.

So here's to the residents, on this noble quest, 
With hearts full of hope, they'll do their best. 

To bring comfort and peace, to those in need, 

And to make a difference, in this world indeed.

Reading 3: (Submitted by Dr. Jeff Daskalakis)

“Response to acute monotherapy for major depressive disorder in

randomized, placebo controlled trials submitted to the US Food

and Drug Administration: individual participant data analysis”

Marc Stone, Zimri Yaseen, Brian Miller, Kyle Richardville, Shamir Kalaria, Irving Kirsch

BMJ, August 2022

The full BMJ article can be found here:

 https://www.bmj.com/content/378/bmj-2021-067606

Also, please see the attached The Economist article highlighting this paper’s results.

The authors of this article analyzed 232 randomized, double blind, placebo controlled trials of drug monotherapy for major depression submitted to FDA by pharmaceutical companies between 1979 and 2016.  To assess outcome, the authors converted the responses to Hamilton Rating Scale for Depression (HAMD17) equivalent scores when other measures were used to assess efficacy.  The results showed that “the random effects mean difference between drug and placebo favored drug (1.75 points, 95% confidence interval 1.63 to 1.86).”  What was interesting was that the authors found that a trimodal model best explained the response distributions, designated as Large, Non-specific, and Minimal responses (mean improvements from baseline to end of treatment of 16.0, 8.9 and 1.7 points respectively).  Furthermore, they estimate that 15% of patients have a “Large” response with substantial improvement in symptoms.  What this suggests is that determining which patients will fall into this “Large” response category through better predictive models and measurement-based care will help reduce the pitfalls associated with the current trial-and-error approach to antidepressant prescribing.

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WEEK 2

Reading 1:

“Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression”

Guy M. Goodwin, Scott T. Aaronson, Oscar Alvarez, et al.

The New England Journal of Medicine, 3 November 2022

The full NEJM article can be found here:

https://www.nejm.org/doi/full/10.1056/NEJMoa2206443

This paper presents the results of a phase 2 double-blind trial of a single dose of a proprietary synthetic psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control) along with  psychological support for adults with treatment resistant depression.  The administration session lasted 6-8 hours and included having a lead therapist and assistant therapist present.  Participants received two integration sessions following the administration session for the purpose of supporting participants in deriving insights from the psilocybin treatment session.  The authors found that “participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects.”  Serious adverse effects were noted in 9% of subjects in 25 mg group from day 2 to week 3 and included suicidal ideation and self-injurious behavior.   

Reading 2:

“‘I was Close to Helping him but Couldn’t Quite get There’: Psychiatrists’ Experiences of a Patient’s Death by Suicide”​
Zainab Furqan, Rachel Beth Cooper, Andrew Lustig, et al. ​

​The Canadian Journal of Psychiatry, 19 September 2022 First Online

The full Canadian Journal of Psychiatry article can be found here:

https://journals.sagepub.com/doi/full/10.1177/07067437221125300

This article examines the reactions of psychiatrists to a patient's suicide.  The results were obtained by interviewing eighteen psychiatrists about their experiences and had three main objectives:  " (1) understanding the emotional and behavioural impact of a patient's suicide on psychiatrists, (2) exploring if and how the experience of a patient's suicide results in changes in psychiatrist practice patterns, and (3) understanding the tangible steps that psychiatrists and institutions take to manage the emotional and behavioural impact of patient suicide on psychiatrists."  The authors find that there are a number of institutional and educational interventions that can aid psychiatrists who coping with a patient suicide.

Reading 3:

“TikTok and Attention-Deficit/Hyperactivity Disorder: A Cross-Sectional Study of Social Media Content Quality”​
Anthony Yeung, Enoch Ng, Elia Abi-Jaoude​

The Canadian Journal of Psychiatry, December 2022

The full Canadian Journal of Psychiatry article can be found here:

https://journals.sagepub.com/doi/full/10.1177/07067437221082854

TikTok is a popular social media platform that is especially popular with teens.  The platform has contributed to increased awareness of ADHD.  While social media can help reduce stigma and connect patients, it can also provide misinformation about medical conditions. The authors of this article studied the quality of mental health information provided by TikTok videos related to ADHD.  They found that upwards of half of the videos reviewed were misleading (52%).  The article suggests: "It is thus important for clinicians to be aware of the dissemination of misleading videos on TikTok and the potential impact on clinical care."

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WEEK 1

Reading 1:

“Cognitive behavior therapy vs. control conditions, other psychotherapies, pharmacotherapies and combined treatment for depression: a comprehensive meta-analysis including 409 trials with 52,702 patients”

Pim Cuijpers, Clara Miguel, Mathias Harrer, et al.

World Psychiatry, February 2023

The full World Psychiatry paper can be found here:
https://onlinelibrary.wiley.com/doi/10.1002/wps.21069

The authors of this paper present a new meta-analysis examining the evidence for CBT for depression and found the following:

·         3,584 full-text papers were considered with 409 trials selected including 52,702 patients (27,000 in CBT and 25,702 in control groups).

·         Demographics. Patients tended to be female (69.0%), with a mean age of 40.1; many were adults (39.1%).

·         CBT versus control. “CBT had moderate to large effects compared to control conditions such as care as usual and waitlist (g=0.79...), which remained similar in sensitivity analyses and were still significant at 6-12 month follow-up.”

·         CBT versus other psychotherapies. “CBT was significantly more effective than other psychotherapies, but the difference was small (g=0.06...) and became non-significant in most sensitivity analyses.”

·         CBT versus pharmacotherapies and combined treatment. “Combined treatment was more effective than pharmacotherapies alone at the short (g=0.51...) and long term (g=0.32...), but it was not more effective than CBT alone at either time point.”

·         On the quality of the literature. “The quality of the trials was found to have increased significantly over time (with increasing numbers of trials with low risk of bias, less waitlist control groups, and larger sample sizes).

Reading 2:

“The need for a new generation of digital mental health tools to support more accessible, effective and equitable care”

John Torous, Keris Myrick, Adrian Aguilera

World Psychiatry, February 2023

The full World Psychiatry Editorial can be found here:
https://onlinelibrary.wiley.com/doi/10.1002/wps.21058

This article discusses the promise and perils afforded by digital mental health.   The authors note that many of the most vulnerable and at risk patients lack the means/ability to access such interventions.  They also examine the potential biases that can exist with AI and the challenges which "digital disparities" impose upon the uptake and utilization of digital mental health care.

Reading 3:

“Physician-as-Patient—Vulnerabilities and Strengths”

Karla Castro-Frenzel
JAMA, 20 December 2022

The full JAMA paper by found here:

https://jamanetwork.com/journals/jama/fullarticle/2799650

In this moving article, Dr. Castro-Frenzel reflects on being a physician-patient as she faced advanced stage lung cancer.  Dr. Castro-Frenzel elloquently examines the fear that comes with possessing medical training and the hope and support she was able to receive from colleagues.  The culture of medicine makes it challenging for physicians to accept help or acknowledge vulnerability, but this reading provides a revealing portrait of a colleague navigating the health system as both patient and peer.