Causes of Death in the Presence of Law Enforcement in Johnson County, Iowa, 2011-2020.

Objectives. To examine sudden and unexpected or trauma-related deaths that occurred in the presence of law enforcement in Johnson County, Iowa, between 2011 and 2020. Methods. We identified deaths in the presence of law enforcement using definitions from the National Association of Medical Examiners. We obtained data, including demographics, cause and manner of death, toxicology results, and circumstances and location of event leading to death, from comprehensive medical examiner investigative reports. Results. There were 165 deaths that occurred in the presence of law enforcement: 114 were from a known disease, and 51 were either trauma related or the sudden, unexpected initial presentation of a previously unrecognized disease. Three deaths occurred in the context of physical restraint by law enforcement. Suicide was the leading manner of death among trauma-related deaths; the means of suicide was predictable based on in-custody (hanging) or precustody (firearm) circumstances. Conclusions. Our findings highlight the potential role of medical examiners and coroners in improving completeness of data on reporting death in the presence of law enforcement to public health agencies. (Am J Public Health. Published online ahead of print April 4, 2024:e1-e9. https://doi.org/10.2105/AJPH.2024.307616).

Fatal Vertebral Artery Dissection Following Self-Manipulation of the Cervical Spine.

ABSTRACT: Cervical spine manipulation is a known risk factor for vertebral artery dissection. In this report, we present a case of fatal vertebral artery dissection that occurred as the result of self-manipulation of the cervical spine. The decedent was a 40-year-old man with no significant past medical history. He was observed to "crack his neck" while at work. Soon after, he began experiencing neck pain, then developed strokelike symptoms and became unresponsive. He was transported to a local medical center, where imaging showed bilateral vertebral artery dissection. His neurological status continued to decline, and brain death was pronounced several days later. An autopsy examination showed evidence of cerebellar and brainstem infarcts, herniation, and diffuse hypoxic-ischemic injury. A posterior neck dissection was performed to expose the vertebral arteries, which showed grossly visible hemorrhage and dilation. There was no evidence of traumatic injury to the bone or soft tissue of the head or neck. Bilateral dissection tracts were readily appreciated on microscopic examination. Death was attributed to self-manipulation of the neck, which in turn led to bilateral vertebral artery dissection, cerebellar and brainstem infarcts, herniation, hypoxic-ischemic injury, and ultimately brain death.

Rare variant of large pediatric glioneuronal tumor with novel MYO5A::NTRK3 fusion: illustrative case.

BACKGROUND: Glioneuronal tumors (GNTs) comprise a rare class of central nervous system (CNS) neoplasms with varying degrees of neuronal and glial differentiation that predominately affect children and young adults. Within the current 2021 World Health Organization (WHO) classification of CNS tumors, GNTs encompass 14 distinct tumor types. Recently, the use of whole-genome DNA methylation profiling has allowed more precise classification of this tumor group. OBSERVATIONS: A 3-year-old male presented with a 3-month history of increasing head circumference, regression of developmental milestones, and speech delay. Magnetic resonance imaging of the brain was notable for a large left hemispheric multiseptated mass with significant mass effect and midline shift that was treated with near-total resection. Histological and molecular assessment demonstrated a glioneuronal tumor harboring an MYO5A::NTRK3 fusion. By DNA methylation profiling, this tumor matched to a provisional methylation class known as "glioneuronal tumor kinase-fused" (GNT kinase-fused). The patient was later started on targeted therapy with larotrectinib. LESSONS: This is the first report of an MYO5A::NTRK3 fusion in a pediatric GNT. GNT kinase-fused is a provisional methylation class not currently included in the WHO classification of CNS tumors. This case highlights the impact of thorough molecular characterization of CNS tumors, especially with the increasing availability of novel gene targeting therapies.

Neuropathologic Features in Chronic Methamphetamine Use.

ABSTRACT: Methamphetamine is a psychostimulant that exerts its euphoric and stimulant effects by increasing cytosolic monoamine concentration at the nerve terminal. In addition to its known systemic cardiovascular effects, there is compelling evidence to suggest a direct neurotoxic effect of methamphetamine; however, the existing body of literature includes very few human tissue studies. This exploratory analysis used postmortem human brain specimens to examine histologic and immunohistochemical features associated with chronic methamphetamine use. This retrospective cohort study included 60 decedents who were autopsied at the University of Iowa Hospitals and Clinics between the years 2015 and 2021. Logistic regression models demonstrated no definite pathologic changes in the hippocampi of individuals with a history of chronic methamphetamine use. Decedents with a history of methamphetamine use had a marginally increased odds of basal ganglia arteriosclerosis, which did not reach statistical significance (odds ratio, 3.33; 95% confidence interval, 0.6-19.2; P = 0.17), which may be independent of the systemic hypertensive effects of methamphetamine. Future studies that include targeted examination of brain regions of interest, such as the basal ganglia and specifically the striatum, may prove revealing.

An Interesting Case of Severe Hyponatremia.

ABSTRACT: In this report, we present an unusual and multifactorial case of severe hyponatremia with important clinical implications. The decedent was a 42-year-old woman who was discovered at her place of residence with altered mental status and profuse watery diarrhea. The scene was significant for numerous empty water bottles. She was transported to the emergency department of a local medical center and rapidly became obtunded. Imaging demonstrated cerebral edema with impending herniation. Serum chemistry was significant for severe hyponatremia (116 mEq/L) with decreased serum osmolality (245 mOsm/kg), suggestive of water overload. Over a brief course of hospitalization, she continued to deteriorate and brain death was pronounced. After brain death, she underwent organ donation. Subsequent autopsy examination demonstrated global cerebral edema with evidence of herniation. Toxicology examination of antemortem blood was positive for methamphetamine (1900 ng/mL) and amphetamine (100 ng/mL). An incidentally identified colon polyp was submitted for microscopic evaluation, which revealed the presence of Cryptosporidium , the likely cause of her diarrheal illness. Death was attributed to severe hyponatremia through the combined effects of excessive water consumption and loss of fluid and electrolytes from cryptosporidiosis, in turn leading to cerebral edema and brain herniation. Acute methamphetamine intoxication was a contributing condition.

Symptoms of mania and anxiety do not contribute to suicidal ideation or behavior in the presence of bipolar depression.

Bipolar disorder is typified by episodes of manic/hypomanic and depressive symptoms, either distinctly or concurrently as mixed symptoms. While depressive symptoms are the major driver of risk, it is unclear whether specific combinations of manic and anxiety symptoms contribute differentially to suicidal ideation and behavior in individuals with bipolar disorder during a depressive state. This study uses a quantitative application of Rothman's theoretical framework of causation, or 'causal pies' model. Data were obtained from the National Network of Depression Centers Mood Outcomes Program for 1028 visits from 626 individuals with bipolar disorder with current moderate-to-severe depressive symptoms, operationalized as a Patient Health Questionnaire-8 (PHQ-8) score ≥10. Mania symptoms were captured using the Altman Self-Rating Mania scale (ASRM) and anxiety symptoms were captured using the Generalized Anxiety Disorder-7 scale (GAD-7). The outcome of suicidal ideation or behavior was captured using the Columbia Suicide Severity Rating Scale (C-SSRS). In this cohort of individuals with bipolar disorder and at least moderate depressive symptoms, we found no increased risk of suicidal ideation or behavior attributable to manic and anxiety symptom clusters in individuals with bipolar disorder during depressive state. A small amount (4%) of risk was attributable to having severe depressive symptoms. These findings, however, may be influenced by limitations in sample size and measurement instruments. Future studies would benefit from larger samples and more rigorous assessments, including clinician-rated measures.

Moderators of the association between depressive, manic, and mixed mood symptoms and suicidal ideation and behavior: An analysis of the National Network of Depression Centers Mood Outcomes Program.

BACKGROUND: It has not been established that suicide risk with mixed symptoms is any greater than the depressive component or if there is synergy between depressive and manic symptoms in conveying suicide risk. METHODS: The National Network of Depression Centers Mood Outcomes Program collected data from measurement-based care for 17,179 visits from 6,105 unique individuals with clinically diagnosed mood disorders (998 bipolar disorder, 5,117 major depression). The Patient Health Questionaire-8 (PHQ-8) captured depressive symptoms and the Altman Self-Rating Mania scale (ASRM) measured hypomanic/manic symptoms. Generalized linear mixed models assessed associations between depressive symptoms, manic symptoms, and their interaction (to test for synergistic effects of mixed symptoms) on the primary outcome of suicidal ideation or behavior (secondarily suicidal behavior only) from the Columbia-Suicide Severity Rating Scale (C-SSRS). Moderation was assessed. RESULTS: PHQ-8 scores were strongly associated with suicide-related outcomes across diagnoses. ASRM scores showed no association with suicidal ideation/behavior in bipolar disorder and an inverse association in major depression. There was no evidence of synergy between depressive and manic symptoms. There was no moderation by sex, race, or mood disorder polarity. Those over 55 years of age showed a protective effect of manic symptoms, which was lost when depressive symptoms were also present (mixed symptoms). DISCUSSION: Mixed depressive and manic symptoms convey no excess risk of suicidal ideation or behavior beyond the risk conveyed by the depressive symptoms alone. Depressive symptoms are strongly linked to suicidal ideation and suicidal behavior and represent an important and potentially modifiable risk factor for suicide.

Anxiety, C-reactive protein, and obesity in NHANES 1999-2004.

The inflammatory marker C-reactive protein has been linked to anxiety across a number of studies. This paper uses data for 1,439 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2004 to examine the association between anxiety and C-reactive protein (CRP), and the potential for moderation by body mass index. No association was found between anxiety or depression and CRP in unadjusted or multivariable-adjusted logistic regression analyses, nor was there evidence of moderation by continuous BMI, BMI class, or obesity. Future studies on the relationship between anxiety and CRP should utilize larger general population samples or populations with a high prevalence of anxiety. There is also a need for prospective studies in this area to better discern the temporal relationships between anxiety and inflammation.

Depressive symptoms carry an increased risk for suicidal ideation and behavior in bipolar disorder without any additional contribution of mixed symptoms.

OBJECTIVES: To determine whether the risk of suicidal ideation or behavior during mixed states exceeds that attributable to the depressive components of these states alone in bipolar disorder. METHODS: We utilized real-world, longitudinal clinical data collected on 290 patients with bipolar disorders (bipolar I, bipolar II, and bipolar not otherwise specified (NOS)) from the National Network of Depression Centers (NNDC) Clinical Care Registry (CCR) seen for 891 visits over a mean of 27.5 weeks. Depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9), manic symptoms with the Altman Self-Rating Mania (ASRM), and suicidal ideation and behavior with the Columbia-Suicide Severity Rating Scale (C-SSRS), obtained as part of the routine, measurement-based care provided across the NNDC. The relations between depressive symptoms, manic symptoms, and the interaction thereof (mixed symptoms) on coinciding suicidal ideation and behavior were modeled in generalized linear mixed models. RESULTS: Depressive symptoms, as measured by the PHQ-9, were strongly associated with suicidal ideation and behavior (p < 0.0001), while there was no significant association with manic symptoms as measured by the ASRM or the interaction between depressive and manic symptoms. Similar results were observed when the outcome was restricted to suicidal behavior and when mood was modeled categorically. There was evidence of a gender by ASRM interaction (p = 0.011) and risk of suicidal ideation or behavior was significant for women, but not men with manic symptoms. LIMITATIONS: Diagnoses were based on clinician assessment and not structured interview. Mood assessments were self-reported rather than clinician-administered. Suicidal ideation was more frequently observed than suicidal behavior (23/272 visits where outcome positive). CONCLUSIONS: Depression represents the primary mood state accounting for suicide risk in bipolar disorder. Co-occurring symptoms of mania (mixed symptoms) do not appear to convey an elevated risk for suicidal ideation or behavior beyond that explained by the depressive symptoms alone.

Mixed state and suicide: Is the effect of mixed state on suicidal behavior more than the sum of its parts?

OBJECTIVE: To assess whether suicidal behavior during mixed states exceeds that expected from the manic or depressive components alone. METHODS: This study included 429 participants with bipolar disorder from the National Institute of Mental Health Collaborative Depression Study (CDS). Mood and suicidal behavior were captured using the Longitudinal Interval Follow-up Evaluation and the Schedule of Affective Disorders and Schizophrenia. Suicidal behavior during each mood state, relative to euthymia, was analyzed using Cox regression to allow for repeated events, with a frailty term to account for intra-participant correlation. Mixed states were modeled as a depression-by-mania interaction. RESULTS: Individuals with a history of mixed states were at higher risk of suicidal behavior and spent more time depressed, compared to subjects with no such history. In bipolar I disorder, risk increased during episodes of mania (hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.28-2.99, P = .0019) and depression (HR: 5.49, 95% CI: 4.01-7.51, P < .0001) and there was a less than additive effect of mixed states. In bipolar II disorder, risk was increased during episodes of depression (HR: 3.66, 95% CI: 2.51-5.35, P < .0001) and there was no excess risk during mixed states beyond that attributable to the depressed component. Most of the excess risk (71%) among those with a history of mixed states was attributable to a depression predominant course of illness. CONCLUSIONS: Individuals with mixed states are at high risk of suicidal behavior, largely due to more time spent depressed. Clinicians should aggressively treat depression to mitigate suicide risk for patients with or without mixed states.

Impact of Mood on Endothelial Function and Arterial Stiffness in Bipolar Disorder.

BACKGROUND: Previous research in bipolar disorder demonstrates greater than expected vascular dysfunction later in the course of illness, proportionate to the cumulative burden of mood symptoms. However, little is known about the effect of acute mood states on vascular function. Here we examine the relation between vascular function and mood state in individuals with bipolar disorder. METHOD: This prospective study followed 40 individuals with bipolar disorder for up to 6 months. Participants were assessed for mood state and vascular function at baseline, 2 weeks, and 6 months. Mood state was determined using clinician-administered Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. Vascular function was assessed by flow-mediated dilation (FMD) of the brachial artery, forearm vascular resistance (FVR), and arterial stiffness. RESULTS: Participants had a mean age of 30.1 years and 75% were male. Primary outcome measures FMD and nitroglycerine-mediated dilation were not found to have statistically significant associations with depressive or manic symptoms. In unadjusted models, higher manic symptoms were significantly associated with increased FVR nitroprusside-mediated dilation and diastolic blood pressure. In adjusted models, higher depressive symptoms were significantly associated with increases in augmentation index adjusted for heart rate of 75 bpm, and higher manic symptoms remained associated with increases in diastolic blood pressure. CONCLUSION: FMD may have limited sensitivity as a biomarker for measuring short-term effects of mood state. Longer-term prospective studies are needed to clarify the temporal relation between chronic mood symptoms and vascular function in bipolar disorder.

Serum lipid changes following the onset of depressive symptoms in postmenopausal women.

A cross-sectional association between depression and serum low-density lipoprotein cholesterol (LDL-c) has been noted in psychiatric literature, raising the question of temporality: does low LDL-c predict depression, does depression lead to changes in LDL-c levels, or is this relationship bidirectional? In a previous longitudinal analysis of postmenopausal women ages 50-79 who participated in the Women's Health Initiative (WHI), we detected an association between low LDL-c and the subsequent onset of depressive symptoms (HR=1.25, 95% CI 1.05-1.49, p=0.01). This current study uses the WHI cohort to explore the question of temporality in the opposite direction, examining the influence of depressive symptoms on subsequent changes in LDL-c levels. This study provides no evidence to suggest an association between depression and subsequent changes in LDL-c level (-2.78mg/dL, 95% CI=-7.49 to 1.92, p=0.25), nor was any association detected for total cholesterol, HDL, or triglyceride changes over time. Further, this study demonstrates that the relationship between depression and serum LDL changes is not mediated by changes in weight, exercise, or energy intake.

Depression and serum low-density lipoprotein: A systematic review and meta-analysis.

BACKGROUND: A cross-sectional association between depression and serum low-density lipoprotein (LDL) has been noted in the literature. This study aims to employ meta-analytic techniques to clarify the relationship between depression and serum LDL. METHODS: Published articles through April 2015 were identified through systematic query of PubMed with follow-up manual searches. Data from 36 studies reporting mean difference and 7 studies reporting odds ratios were analyzed separately. RESULTS: Meta-analysis of studies modeling serum LDL as a continuous measure demonstrates overall significantly lower serum LDL in depression (Mean difference=-4.29, 95% CI=-8.19, -0.40, p=0.03). Meta-analysis of studies modeling serum LDL as a categorical measure demonstrates a marginally significant lower odds of depression in the presence of low serum LDL relative to high serum LDL (OR=0.90, 95% CI=0.80, 1.01, p=0.08). LIMITATIONS: High heterogeneity was noted across sampled studies, which may be a function of variations in study design, participants sampled, or other factors. The potential for publication bias was also assessed. CONCLUSIONS: This meta-analysis demonstrates a cross-sectional link between depression and low serum LDL.

Longitudinal study of low serum LDL cholesterol and depressive symptom onset in postmenopause.

OBJECTIVE: The aim of this study was to characterize the relationship between serum low-density lipoprotein cholesterol (LDL-c) and subsequent depressive symptoms onset in postmenopausal women. We secondarily assessed serum high-density lipoprotein (HDL-c), total cholesterol, and triglycerides. METHOD: This population-based prospective cohort study utilizes data from 24,216 women between 50 and 79 years of age who were participants of the Women's Health Initiative, which originally ran from 1993 to 2005 and has since incorporated 2 extension studies, with the most recent culminating in 2015. Fasting lipids were measured for all participants at baseline and for a subset through 6 years of follow-up. Depressive symptoms were characterized using the Burnam 8-item scale for depressive disorders (Center for Epidemiologic Studies-Depression/Diagnostic Interview Schedule short form) at baseline and during follow-up, using a cut point of 0.06 to indicate presence of depressive symptoms. RESULTS: The lowest quintile of LDL-c was associated with an increased risk of subsequent depressive symptoms (hazard ratio [HR] = 1.25, 95% CI = 1.05-1.49, P = .01), and follow-up analyses demonstrated that the elevated risk appeared to be confined to the lowest decile (LDL-c < 100 mg/dL). Further, this elevated risk was moderated by lipid-lowering drug treatment. Elevated risk was demonstrated among those who reported no lipid-lowering medication use (HR = 1.23, 95% CI = 1.03-1.47, P = .02), but not among those reporting use (HR = 0.65, 95% CI = 0.18-2.29, P = .50). CONCLUSIONS: Among postmenopausal women, untreated serum LDL-c below 100 mg/dL was associated with an increased risk of developing depressive symptoms. No excess risk was observed in those attaining LDL-c < 100 mg/dL with lipid-lowering therapy. These findings have important implications for risk assessment, treatment considerations, and mechanistic insight.

Rapid adipose deposition with mood disorders.

BACKGROUND: Persons with bipolar disorder represent a high-risk group for obesity, but little is known about the time course by which weight gain occurs in bipolar disorder. METHODS: We prospectively studied changes in fat distribution using dual-energy x-ray absorptiometry in relationship to medication exposure and mood symptom burden in 36 participants with bipolar disorder. We assessed the relationship between prior medication exposure and course of illness with adiposity measures at baseline (N = 36) and at 6-month follow-up (N = 22). RESULTS: At baseline, greater adiposity was associated with advanced age and female sex, not retrospectively assessed symptom course or medication exposure (past 2 years). Over 6 months of prospective follow-up, participants developed greater adiposity (fat mass index +0.82 kg/m(²), P = .007; visceral fat area +8.6 cm(²), P = .02; total percent fat +1.6%, P = .02). Manic symptomatology, not antipsychotic exposure, was related to the increased adiposity. CONCLUSIONS: Acute exacerbations of mood disorders appear to represent high-risk periods for adipose deposition. Obesity prevention efforts may be necessary during acute exacerbations.

Omega-3 fatty acid biomarkers and subsequent depressive symptoms.

OBJECTIVE: We sought to determine the relationship between the omega-3 fatty acid content of red blood cell membranes (RBC), in particular docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and baseline and new-onset depressive symptoms in post-menopausal women. We secondarily sought to characterize the association between dietary omega-3 fatty acid intake and depressive symptomatology. METHODS: Study participants included 7086 members of the Women's Health Initiative Memory Study (aged 63-81 years) who had an assessment of RBC omega-3 fatty acid concentrations at the baseline screening visit. Depressive symptoms at baseline and follow-up were characterized using the Burnam eight-item scale for depressive disorders (Center for Epidemiologic Studies Depression Scale/Diagnostic Interview Schedule short form) and secondarily additionally inferred by antidepressant medication use. RESULTS: In multivariable-adjusted models, our primary exposure, RBC DHA + EPA, was not related to depressive symptoms by any measure at baseline or follow-up, nor were RBC total omega-3, DHA, or EPA (all p > 0.2). In contrast, dietary intake of omega-3 was positively associated with depressive symptoms at baseline (adjusted odds ratio 1.082, 95% confidence interval 1.004-1.166; p = 0.04 for dietary DHA + EPA and Burnam score ≥0.06), although this generally did not persist at follow-up. CONCLUSION: No relationship between RBC omega-3 levels and subsequent depressive symptoms was evident, and associations between dietary omega-3 and depressive symptoms were variable. Biomarkers of omega-3 status do not appear to be related to risk of new depression in post-menopausal women.