Kratom use and mental health: A systematic literature review and case example.

OBJECTIVE: This review aims to synthesize and critically evaluate the existing literature on kratom use and its possible association with induction of psychotic and manic symptoms, in order to identify potential areas for future research that would improve our understanding of the risks of kratom consumption. METHODS: An electronic search was performed using five major databases: including PubMed, Scopus, Google Scholar, Web of Science, and PsycINFO. keywords such as kratom, Mitragyna speciosa, mania, psychosis, bipolar disorder, schizophrenia, schizoaffective, case report, and case series. The retrieved articles on initial search were screened based on predefined inclusion and exclusion criteria for this study, and then data synthesis was performed to analyze relevant information from the included studies. RESULTS: Six prior papers were found using (1 case series and 5 case reports). These included 10 cases, involving kratom use association with mania and psychosis. The ages of patients ranged from 28 to 55 years mean age was 38, and (SD 13.74), the majority were males (8 out of 11). Patients had durations of kratom use ranging from 2 wk to 15 years. Significant association was found between kratom use and the worsening of psychotic and manic symptoms in individuals with psychiatric conditions. CONCLUSIONS: Our research highlights the possibility of worsening preexisting psychiatric conditions in the context of kratom use. This study emphasizes the need for clinical evaluation of patients for kratom use. Additional research is required to gain a deeper understanding of the potential mental health implications of kratom use, especially among vulnerable populations.

Vitamin D levels among adult psychiatric inpatients and the association with psychosis.

BACKGROUND: The association between low vitamin D levels and mental illness has been described in earlier research. The aim of our study was to examine the association between vitamin D levels with psychotic symptoms among hospitalized patients. METHODS: A total of 1,456 patient records from an academic psychiatric hospital were examined. Vitamin D levels were classified as normal (>30 ng/mL); insufficient (20 to 30 ng/mL); and deficient (<20 ng/mL). We then analyzed the association among vitamin D groups and symptoms of psychosis. RESULTS: The average vitamin D level in our sample was 23.59 ng/mL, with 76.2% of patients presenting with vitamin D levels <30 ng/mL. There was a significant association between vitamin D levels <20 ng/mL and symptoms of psychosis (P < .05). African American patients had lower mean vitamin D levels than White patients (15.6 ± 0.2 ng/mL vs 25.8 ± 0.4 ng/mL, P < .001). There was no sex difference in vitamin D levels (females: 23.3 ± 11.5 ng/mL; males: 23.9 ± 11.0 ng/mL). CONCLUSIONS: Patients with vitamin D levels <30 ng/mL were 1.5 times more likely to have symptoms of psychosis. Patients who were African American, Hispanic, Asian, or biracial had lower vitamin D levels than patients who were White. Multivariate analysis found that after adjusting for age, sex, and race, the association between vitamin D and psychosis was not statistically significant. Possible explanations could include the known tendency to overdiagnose psychosis among individuals who are African American, referral bias, subgroup effect, or an epiphenomenon.

Posttraumatic stress disorder comorbidity in patients undergoing ECT for major depressive disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is not recognized as an indication for electroconvulsive therapy (ECT). However, research indicates promise for this treatment modality. To elucidate the effects of ECT for treating PTSD, prospective research is needed. The first step in assessing the feasibility of such research is to determine if many patients being treated with ECT have comorbid PTSD. This study examined the PTSD comorbidity rates and compared demographic data among patients with major depressive disorder (MDD) who were treated with ECT vs patients with MDD who were not treated with ECT. METHODS: Data from patients with MDD were obtained from the Nationwide Inpatient Sample. RESULTS: Approximately 10% of patients undergoing ECT for MDD also had PTSD. The difference in comorbidity of PTSD in those treated with ECT vs those not treated with ECT was approximately 1%. CONCLUSIONS: Prospective naturalistic studies that examine the response of PTSD to ECT are feasible because a sizable number of patients with PTSD are receiving ECT.

Electroconvulsive therapy in individuals with dementia/major NCD presenting with behavioral symptoms: a systematic review.

OBJECTIVE: This study aims to systematically review the literature on using electroconvulsive therapy (ECT) in patients with dementia/major NCD (Neuro cognitive disorder) presenting with behavioral symptoms. DESIGN: We conducted a PRISMA-guided systematic review of the literature. We searched five major databases, including PubMed, Medline, Embase, Cochrane, and registry (ClinicalTrials.gov), collaborating with "ECT" and "dementia/major NCD" as our search terms. MEASUREMENTS: Out of 445 published papers and four clinical trials, only 43 papers and three clinical trials met the criteria. There were 22 case reports, 14 case series, 4 retrospective chart reviews, 1 retrospective case-control study, 1 randomized controlled trial, and 2 ongoing trials. We evaluated existing evidence for using ECT in dementia/major NCD patients with depressive symptoms, agitation and aggression, psychotic symptoms, catatonia, Lewy body dementia/major NCD, manic symptoms, and a combination of these symptoms. SETTINGS: The studies were conducted in the in-patient setting. PARTICIPANTS: Seven hundred and ninety total patients over the age of 60 years were added. RESULTS: All reviewed studies reported symptomatic benefits in treating behavioral symptoms in individuals with dementia/major NCD. While transient confusion, short-term memory loss, and cognitive impairment were common side effects, most studies found no serious side effects from ECT use. CONCLUSION: Current evidence from a systematic review of 46 studies indicates that ECT benefits specific individuals with dementia/major NCD and behavioral symptoms, but sometimes adverse events may limit its use in these vulnerable individuals.

Electroconvulsive therapy plus lithium is associated with less cognitive impairment and drug-induced delirium in bipolar depression compared to unipolar depression.

BACKGROUND: Although major depressive disorder (MDD) and bipolar depression can present with similar symptoms, biological differences exist. One difference is the possible variance in adverse effects associated with treatment. This study examined the association of cognitive impairment and delirium in patients treated with electroconvulsive therapy (ECT) plus lithium for MDD or bipolar depression. METHODS: The Nationwide Inpatient Sample included 210 adults receiving ECT plus lithium. Descriptive statistics and a Chi-square test were used to evaluate the differences between mild cognitive impairment and drug-induced delirium for those with MDD or bipolar depression. We calculated the odds ratio (OR) for drug-induced delirium in inpatients with MDD (compared to inpatients with bipolar depression) using a binomial logistic regression model. RESULTS: Mild cognitive impairment was observed in 9.1% of patients with MDD (n = 110), compared to 0 in bipolar depression (n = 100) (P = .002). Drug-induced delirium was more prevalent in MDD (OR 1.19; 95% CI, 1.11 to 1.30). CONCLUSIONS: ECT plus lithium is associated with less cognitive impairment and drug-induced delirium in bipolar depression compared to MDD. This study may also support biological differences between the 2 types of depression.

A randomized, double-blind, clinical pilot trial of adjunct ketone supplement compared to placebo for treating posttraumatic stress disorder.

BACKGROUND: Despite some evidence of the helpful role of ketones in some neuropsychiatric disorders, there are no clinical trials that examine these agents for posttraumatic stress disorder (PTSD). Our aim was to investigate whether ketone salt supplementation can improve PTSD symptoms in a randomized, placebo-controlled trial. METHODS: A total of 21 participants were recruited and randomized to placebo or ketone supplement. Each dose of ketone supplement included 7 g of ketones in the form of beta-hydroxybutyrate for a total of 14 g/d. Data were collected through questionnaires to assess PTSD symptoms. We used Fisher's exact tests for categorical variables and 2-sample t tests for continuous variables to examine differences in baseline values between treatment groups. Mixed models were employed to examine changes over time between groups on the PTSD Checklist for DSM-5 (PCL-5). RESULTS: There were no statistically significant differences in PCL-5 medians between the ketone and control groups at pretest (P = 1.0000) or post-test (P = .6020). The ketone group had a statistically significant decrease in median PCL-5 scores from 58.5 (pretest) to 54.0 (posttest; P = .0003) but the control group did not change (34 at pretest and at posttest; P = .4418). CONCLUSIONS: The ketone group showed a significant decrease in PCL-5 score at posttest compared with pretest that was not seen in the control group, although these changes were not statistically significant between groups. The small sample size limited the study and likely contributed to the lack of significance. Larger trials are needed to more definitively examine these findings.

Electroconvulsive Treatment Utilization for Inpatient Management of Catatonia in Adolescents With Schizophrenia Spectrum Disorders.

OBJECTIVE: The aim of this study was to determine rates of electroconvulsive therapy (ECT) use for catatonia in schizophrenia spectrum disorders, stratified by patient demographics and hospital characteristics, and its impact on inpatient length of stay and cost. METHODS: We found 155 adolescents (aged 12-18 years) with principal discharge diagnosis of schizophrenia spectrum disorders with catatonia from the National Inpatient Sample. They were subgrouped into ECT (n = 20) and non-ECT (n = 135) groups. We used descriptive statistics to evaluate the utilization of ECT for catatonia and independent-sample t test for continuous variables with statistical significance at P ≤ 0.05. RESULTS: The overall utilization rate of ECT in adolescents for catatonia was 12.9%. A high rate of ECT use was evident for Whites (30.8%) compared with the other race/ethnicities and also was seen in private health insurance beneficiaries (20%). The rate of ECT use varied by the region, with highest for the Northeast (20%), followed by the South (18.2%), and the West (14.3%). Adolescent inpatients with catatonia in public and teaching type, and large bed-size hospitals were more likely to receive ECT than their counterparts. The mean number of ECT sessions required during the inpatient stay was 5.2 (range, 1-15), and the mean number of days from admission to initial ECT was 2.5 (range, 0-6). CONCLUSIONS: Electroconvulsive therapy is used for approximately only 13% of adolescents with catatonia when comorbid schizophrenia spectrum disorders are present, suggesting that many patients may not get evidence-based treatment. Future studies in this area are needed.

Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach.

PURPOSE: Posttraumatic Stress Disorder (PTSD) is associated with increased alcohol use and alcohol use disorder (AUD), which are all moderately heritable. Studies suggest the genetic association between PTSD and alcohol use differs from that of PTSD and AUD, but further analysis is needed. BASIC PROCEDURES: We used genomic Structural Equation Modeling (genomicSEM) to analyze summary statistics from large-scale genome-wide association studies (GWAS) of European Ancestry participants to investigate the genetic relationships between PTSD (both diagnosis and re-experiencing symptom severity) and a range of alcohol use and AUD phenotypes. MAIN FINDINGS: When we differentiated genetic factors for alcohol use and AUD we observed improved model fit relative to models with all alcohol-related indicators loading onto a single factor. The genetic correlations (rG) of PTSD were quite discrepant for the alcohol use and AUD factors. This was true when modeled as a three-correlated-factor model (PTSD-AUD rG:.36, p < .001; PTSD-alcohol use rG: -0.17, p < .001) and as a Bifactor model, in which the common and unique portions of alcohol phenotypes were pulled out into an AUD-specific factor (rG with PTSD:.40, p < .001), AU-specific factor (rG with PTSD: -0.57, p < .001), and a common alcohol factor (rG with PTSD:.16, NS). PRINCIPAL CONCLUSIONS: These results indicate the genetic architecture of alcohol use and AUD are differentially associated with PTSD. When the portions of variance unique to alcohol use and AUD are extracted, their genetic associations with PTSD vary substantially, suggesting different genetic architectures of alcohol phenotypes in people with PTSD.

Potential Societal and Cultural Implications of Transgenerational Epigenetic Methylation of Trauma and PTSD: Pathology or Resilience?

Psychological trauma is unique in that it is an environmental event that could induce biological changes and post-traumatic stress disorder (PTSD), depression, or other mood disorders in some patients. On the other hand, there may be no psychopathology (in most cases), or even sometimes post-traumatic growth and resilience. According to the DSM-5, trauma is a prerequisite for PTSD and traumatic stress disorder, but not for depressive episodes or mood disorders, or other psychiatric conditions. This paper brings attention to the preliminary literature on transgenerational inheritance due to trauma exposure and its societal and cultural implications. There is accumulating evidence that exposure to trauma can be passed transgenerationally through epigenetic inheritance leading to changes in gene expression and possible disorders or resilience. The effects of resilience from transgenerational inheritance have not been studied, but should be, for a full understanding not only of the disease risk across generations, but also of its social and cultural implications. The epigenetic pathologic effects across generations also need further studies, as the current research is preliminary; larger replications are needed for definitive and more complete understanding. I present here a glimpse of where we are, a vision of where we should go in terms of future research direction for disease risk transmission, and recommend studies of resilience and post-traumatic growth across generations, as well as other studies related to the societal implications at the population level.

Epigenetics and first-episode psychosis: A systematic review.

BACKGROUND: Schizophrenia has a large disease burden globally. Early intervention in psychosis, and therefore a decreased duration of untreated psychosis, has a positive clinical impact. There are several recognized risk factors for psychosis, including trauma history and substance use. This systematic review examined the literature for studies related to epigenetic changes in first-episode psychosis, with the goal of identifying future research directions. METHODS: A literature review was conducted from inception to October 3, 2021 using MedLine/PubMed, Web of Science, and PsycInfo searches with the keywords ("first-episode schizophrenia" OR "first-episode psychosis" OR "drug-naive schizophrenia" OR "drug-naive psychosis") AND (epigenetic OR methylation OR hydroxymethylation OR "histone modification" OR "miRNA") as well as a search of the bibliography of the identified papers. RESULTS: Seventeen studies that examined various portions of the genome were included in this systematic review. There were two studies that showed hypomethylation at the LINE-1 portion of the genome and two that showed hypermethylation at LINE-1. Additionally, two studies showed hypomethylation specifically at the GRIN2B promoter (part of LINE-1). CONCLUSIONS: Although sample sizes were small, these studies provide evidence for epigenetic alterations in early psychosis. Further research in this area is warranted for more definitive epigenetic correlations.

Characteristics of patients who had deep brain stimulation for treatment-resistant depression from among 116,890 inpatients with major depressive disorder.

BACKGROUND: The aims of this study were to evaluate the characteristics of patients and the pattern and rate of use of deep brain stimulation (DBS) for major depressive disorder (MDD) in the United States. METHODS: Data from the 2012-2014 Nationwide Inpatient Sample (NIS) included 116,890 patients. Patient variables included age, gender, race, median household income, insurance, primary diagnosis, primary procedure, length of stay, and total cost. Hospital variables included ownership, location, teaching status, bed size, and geographic region. RESULTS: Patients who received DBS for MDD were primarily high- income White females with private insurance. The mean age was 49.1 years (SD 7.85). The length of inpatient stay was 1 to 1.6 days. Total cost was highest in the West and lowest in the Northeast. Deep brain stimulation was mostly used by private nonprofit urban teaching hospitals in the South region of the United States. CONCLUSIONS: Deep brain stimulation was used in .03% of the total inpatient population with a primary diagnosis of MDD. If efficacy is established in definitive trials, DBS could fill a need for patients with treatment-resistant depression who do not respond to standard therapeutics or electro-convulsive therapy.

Artificial intelligence to aid detection and diagnostic accuracy of mood disorders and predict suicide risk: A systematic review.

BACKGROUND: Mood disorders often are diagnosed by clinical interview, yet many cases are missed or misdiagnosed. Mood disorders increase the risk of suicide, making it imperative to diagnose and treat these disorders quickly. Artificial intelligence (AI) has been investigated for diagnosing mood disorders, but the merits of the literature have not been evaluated. This systematic review aims to understand and explain AI methods and evaluate their use in augmenting clinical diagnosis of mood disorders as well as identifying individuals at increased suicide risk. METHODS: We conducted a systematic literature review of all studies until August 1, 2020 examining the efficacy of different AI techniques for diagnosing mood disorders and identifying individuals at increased suicide risk because of a mood disorder. RESULTS: Our literature search generated 13 studies (10 of mood disorders and 3 describing suicide risk) where AI techniques were used. Machine learning and artificial neural networks were most commonly used; both showed merit in helping to diagnose mood disorders and assess suicide risk. CONCLUSIONS: The data shows that AI methods have merit in improving the diagnosis of mood disorders as well as identifying suicide risk. More research is needed for bipolar disorder because only 2 studies explored this condition, and it is often misdiagnosed. Although only a few AI techniques are discussed in detail in this review, there are many more that can be employed, and should be evaluated in future studies.

Predicting Neuropsychiatric Symptoms of Parkinson's Disease with Measures of Striatal Dopaminergic Deficiency.

BACKGROUND: The role of nigrostriatal dopaminergic neurons degeneration is well established in the pathophysiology of Parkinson's disease. However, it is unclear if and how the degeneration of the dopamine pathways affects the manifestation of the neuropsychiatric symptoms (NPS) of Parkinson's Disease (PD). Dopamine transporter (DAT) imaging, a technique to measure the reduction in dopamine transporters is increasingly used as a tool in the diagnosis of PD. METHODS: In this study, we examine if the baseline dopamine transporter density in the striatum measured by the Striatal Binding Ratio (SBR) is associated with the longitudinal onset and/or progression of NPS in PD as measured by part 1 of Movement Disorder Society - Unified Parkinson's Disease Rating Scale, over four years. Data of patients with PD and an abnormal screening present on 123I-ioflupane single-proton emission computed tomography were obtained from Parkinson's Progression Markers Initiative (PPMI) database. Latent Growth Modeling (LGM), a statistical technique that can model the change over time while considering the variability in the rate of change at the individual level, was used to examine the progression of NPS over time. RESULTS: The results indicate the SBR did not correlate with the baseline NPS but did correlate with the rate of change of NPS (p<0.001) over the next four years, even after eliminating age-related variance, which can be a significant confounding factor. CONCLUSION: In conclusion, this study showed gradual worsening in NPS in patients with Parkinson's disease, which inversely correlates with the density of the dopamine transporters as measured by SBR at baseline.

Student leadership in medical school and its implications for health care and policy-making.

BACKGROUND: Approximately 5% of hospital chief executive officers are physicians, and that number is growing. Leadership is a vital skill for future physicians. METHODS: We conducted a narrative review of the literature on student leadership in medical school and its implications for health care and policy-making. RESULTS: Qualities a good leader should possess include accountability, empathy, positivity, teamwork, and organization. Leadership skills need to be taught to students in their formative pre-clinical years so they can build upon this foundation during their clinical and residency years. Leadership is a multifaceted quality because unlike other lessons, it cannot be measured on a scale or under the microscope; it is largely developed through practice. Furthermore, among physicians, psychiatrists are especially well-trained to serve in active leadership roles because psychiatry training emphasizes interpersonal dynamics and emotional intelligence, qualities that are vital to the skill set of an effective leader. CONCLUSIONS: Medical leadership is essential because physicians relate best to other physicians, and those adept in administrative skills can help bridge the gap between administration and clinicians. There is a need for teaching an evidence-based leadership curriculum and training techniques that will fill a recognized educational void in medical student education (as well as for residents and junior faculty).

The Effects of Focal Electrically Administered Seizure Therapy Compared With Ultrabrief Pulse Right Unilateral Electroconvulsive Therapy on Suicidal Ideation: A 2-Site Clinical Trial.

BACKGROUND: Preliminary data suggest that focal electrically administered seizure therapy (FEAST) has antidepressant effects and less adverse cognitive effects than traditional forms of electroconvulsive therapy (ECT). This study compared the impact of FEAST and ultrabrief pulse, right unilateral (UB-RUL) ECT on suicidal ideation. METHODS: At 2 sites, patients in a major depressive episode were treated openly with FEAST or UB-RUL ECT, depending on their preference. The primary outcome measure was scores on the Beck Scale for Suicide Ideation (SSI). Scores on the suicide item of the Hamilton Rating Scale for Depression (HRSD-SI) provided a secondary outcome measure. RESULTS: Thirty-nine patients were included in the intent-to-treat sample (FEAST, n = 20; UB-RUL ECT, n = 19). Scores on both the SSI and HRSD-SI were equivalently reduced with both interventions. Both responders and nonresponders to the interventions showed substantial reductions in SSI and HRSD-SI scores, although the magnitude of improvement was greater among treatment responders. CONCLUSIONS: Although limited by the open-label, nonrandomized design, FEAST showed comparable effects on suicidal ideation when compared with routine use of UB-RUL ECT. These results are encouraging and support the need for further research and a noninferiority trial.

Assessing medical students' knowledge in differentiating the diagnosis and treatment of unipolar vs bipolar depression.

BACKGROUND: Depression is one of the leading causes of premature death and disability. However, both unipolar and bipolar depression are underdiagnosed and undertreated. The aims of this study were to assess medical students' level of confidence in and knowledge of diagnosing and treating depression before and after completing a psychiatry clerkship, and their knowledge of differentiating unipolar vs bipolar depression. METHODS: Third-year medical students at Augusta University (Georgia, USA) completed an online questionnaire to assess confidence in and knowledge of diagnosing and treating unipolar and bipolar depression. RESULTS: Students who completed a psychiatry clerkship were statistically significantly more comfortable/confident with diagnosing (P < .0001) and treating (P < .0001) unipolar depression. Regarding bipolar depression, 73% of students who completed a psychiatry clerkship correctly diagnosed bipolar disorder, vs 59% of students who did not complete a psychiatry clerkship. This difference was not statistically significant (P = .181). CONCLUSIONS: Students who completed a psychiatry clerkship were more confident in diagnosing and treating unipolar depression compared with those who did not complete a psychiatry clerkship. However, there was no statistically significant difference between students who had completed a psychiatry clerkship and those who had not completed a psychiatry clerkship in making the correct diagnosis of bipolar depression. Neither group had a very high rate of correct diagnosis.

Should Catatonia Be Conceptualized as a Pathological Response to Trauma?

ABSTRACT: Although catatonia is related to several medical conditions, catatonia as a response to trauma and posttraumatic stress disorder (PTSD) is less clear. The aim of this review is to explore the small emerging body of preliminary evidence that suggests a possible correlation between psychological trauma and catatonia. Initial data suggests a correlation between episodes of intense fear associated with trauma and PTSD and some forms of catatonic responses. Although this relationship is still speculative to be causative, it can have important implications if confirmed. This is especially salient when it is examined alongside existing studies of the response to fear in animals and the phenomenon of tonic immobility, which bears a striking resemblance to catatonia in humans. If prospective studies further support the initial findings, it could change our conceptual understanding of the etiology of a subtype of catatonia substantially while pointing to likely targets of further research to understand the biological mechanisms that underlie the illness.

Safe Administration of ECT in a Suicidal Patient With a Space-Occupying Astrocytoma.

ABSTRACT: Electroconvulsive therapy (ECT) can be lifesaving for patients suffering from treatment-resistant psychiatric conditions, especially acute suicidality or depression. However, space-occupying lesions pose risks associated with ECT use due in part to seizure-induced escalations in blood pressure with corresponding increases in cerebral blood flow and possibly intracranial pressure, subsequently increasing the risk of brain herniation. Here, we present the case of a patient with a left medial temporal lobe astrocytoma, worsening epileptic seizures, and nonepileptic seizures who underwent ECT for major depressive disorder and suicidality. The patient had improvement of depressive symptoms, resolution of suicidality, and brief cessation of nonepileptic seizures. Brief anterograde amnesia contributed to the termination of treatment. This case adds to the growing literature about the feasibility of ECT treatment in cerebral lesions prone to changes in intracranial pressure, such as the usually cystic astrocytomas.

Characteristics of patients who received deep brain stimulation in obsessive-compulsive disorder versus major depressive disorder.

OBJECTIVE: Deep brain stimulation (DBS) is cleared for treatment of obsessive-compulsive disorder (OCD) but is an investigational treatment for major depressive disorder (MDD). The aim of this study is to compare the characteristics of patients who received DBS as part of standard care for OCD versus those who received it a part of a research protocol for MDD. METHODS: The inpatient sample (N = 110) was drawn from the 2012-2014 Nationwide Inpatient Sample (NIS), and included adults with a primary discharge diagnosis of MDD (N = 50) or OCD (N = 60) and primary procedure of DBS. The study compared various patient demographics, clinical, hospital and insurance variables between the 2 groups. RESULTS: DBS recipients with OCD were younger compared to those with MDD. DBS recipients with MDD tended to be from high-income families compared to those with OCD. DBS patients with MDD were in the South region, while DBS patients with OCD were in the Midwest and South regions of the United States (US). The study did not detect a significant difference in the length of stay and total charges among DBS recipients with OCD versus MDD. CONCLUSIONS: DBS patients with MDD are typically older with more financial resources compared to those with OCD. DBS is federally cleared for OCD, but not for MDD, demonstrating the need for further investigation to establish DBS as a federally cleared treatment for difficult to treat MDD if well-powered randomized trials further support its use.