Psychiatric Etiology Research Articles

Recurrent noncirrhotic hyperammonemia causing acute metabolic encephalopathy in a patient with a continent ileocecal pouch: a case report

IntroductionAcute encephalopathy, while a common presentation in the emergency department, is typically caused by a variety of metabolic, vascular, infectious, structural, or psychiatric etiologies. Among metabolic causes, hyperammonemia is relatively common and typically occurs in the setting of cirrhosis or liver dysfunction. However, noncirrhotic hyperammonemia is a rare occurrence and poses unique challenges for clinicians.Case presentationHere we report a rare case of a 50-year-old Caucasian female with history of bladder cancer status post chemotherapy, radical cystectomy, and ileocecal diversion who presented to the emergency department with severe altered mental status, combativeness, and a 3-day history of decreased urine output. Her laboratory tests were notable for hyperammonemia up to 289 μmol/L, hypokalemia, and hyperchloremic nonanion gap metabolic acidosis; her liver function tests were normal. Urine cultures were positive for Enterococcus faecium. Computed tomography imaging showed an intact ileoceal urinary diversion with chronic ileolithiasis. Upon administration of appropriate antibiotics, lactulose, and potassium citrate, she experienced rapid resolution of her encephalopathy and a significant reduction in hyperammonemia. Her hyperchloremic metabolic acidosis persisted, but her hypokalemia had resolved.ConclusionThis case is an example of one of the unique consequences of urinary diversions. Urothelial tissue is typically impermeable to urinary solutes. However, when bowel segments are used, abnormal absorption of solutes occurs, including exchange of urinary chloride for serum bicarbonate, leading to a persistent hyperchloremic nonanion gap metabolic acidosis. In addition, overproduction of ammonia from urea-producing organisms can lead to abnormal absorption into the blood and subsequent oversaturation of hepatic metabolic capacity with consequent hyperammonemic encephalopathy. Although this is a rare case, prompt identification and treatment of these metabolic abnormalities is critical to prevent severe central nervous system complications such as altered mental status, coma, and even death in patients with urinary diversions.

Clinicoepidemiological profile and practices to manage dizziness in primary care setting: results from an Indian registry

<p class="abstract"><strong>Background:</strong> Dizziness is a common symptom encountered in primary care settings by general physicians and specialists. This study evaluated the clinicoepidemiological profile and management practices in patients with dizziness in an Indian primary care setting.</p><p class="abstract"><strong>Methods:</strong> This prospective, multicentric, observational study was conducted between November 2018 and June 2019. Patients aged≥18 years presenting with clinical features of dizziness were eligible. The study data included demographics and socioeconomic details, complete medical history, medication and concomitant medication use, and the cause and pattern of dizziness. Patients had a baseline visit and two follow-up visits at weeks 1 and 4. </p><p class="abstract"><strong>Results:</strong> Overall, 1000 patients with a mean age of 45.1 years were included (women: 51.5%; men: 48.5%). Of these, 762 reported dizziness as a primary complaint; whereas, 238 reported it as a complaint associated with nausea, vomiting and light-headedness on visit 1, which reduced on subsequent visits. Around 34% of the patients were unemployed and 59% belonged to the upper-middle class. The most common co-morbidities were hypertension and diabetes mellitus (n=132, each). More than 50% of the patients presented with vestibular cause (n=577), followed by neurologic (n=179), metabolic (n=84) and psychiatric (n=61) etiologies. Betahistine (n=581) and prochlorperazine (n=312) were the commonly prescribed medicines for primary and associated complaints. The most commonly used concomitant medications were telmisartan (n=53), glimepiride plus metformin (n=40), metformin (n=32) and ondansetron (n=29). </p><p class="abstract"><strong>Conclusions:</strong> Dizziness has a multifactorial origin necessitating a multifactorial treatment approach. Betahistine and prochlorperazine were the most commonly prescribed drugs in the primary care setting (CTRI/2018/11/016408). </p>

Psychiatric manifestations of anti-N-methyl-D-aspartate receptor encephalitis: A case report.

Psychiatric manifestations of anti-N-methyl-D-aspartate receptor encephalitis: A case report.

SATB2‐LEMD2 interaction links nuclear shape plasticity to regulation of cognition‐related genes

SATB2 is a schizophrenia risk gene and is genetically associated with human intelligence. How it affects cognition at molecular level is currently unknown. Here, we show that interactions between SATB2, a chromosomal scaffolding protein, and the inner nuclear membrane protein LEMD2 orchestrate the response of pyramidal neurons to neuronal activation. Exposure to novel environment in vivo causes changes in nuclear shape of CA1 hippocampal neurons via a SATB2‐dependent mechanism. The activity‐driven plasticity of the nuclear envelope requires not only SATB2, but also its protein interactor LEMD2 and the ESCRT‐III/VPS4 membrane‐remodeling complex. Furthermore, LEMD2 depletion in cortical neurons, similar to SATB2 ablation, affects neuronal activity‐dependent regulation of multiple rapid and delayed primary response genes. In human genetic data, LEMD2‐regulated genes are enriched for de novo mutations reported in intellectual disability and schizophrenia and are, like SATB2‐regulated genes, enriched for common variants associated with schizophrenia and cognitive function. Hence, interactions between SATB2 and the inner nuclear membrane protein LEMD2 influence gene expression programs in pyramidal neurons that are linked to cognitive ability and psychiatric disorder etiology.

424 - Using the Montreal cognitive assessment in a memory clinic setting for triaging after initial assessment

Objectives: More and more referrals to memory clinics are expected, but diagnostic routes are already challenged. In order to be able to follow the advice to diagnose dementia more often and earlier in the process, but also to be able to handle the increasing numbers of referrals, a fast but reliable triage test is needed.According to the Cochrane review, “the MoCA can help identify people who need specialist assessment and treatment for dementia”. It has been validated in multiple institutions and languages. However, many of these studies are designed with a case-control design using healthy, community-based individuals as controls, which can lead to spectrum bias.Our cohort of referrals to a memory clinic with patients suspected of having cognitive disorders (mild dementia and MCI) after initial assessment in an old age psychiatric clinic, needs to be validated because different settings can give different results.Design: our reference standard consisted of a consensus-based diagnosis according to international criteria for detecting MCI and MD, and this was compared with patients suspected of MCI/MD - but excluded from cognitive disorders (NoCI)- from the same cohort.Results: The mean MoCA scores differ significantly between the groups: 24 in NoCI, 21 in MCI and 16.5 in MD. The AUC of MD against non-demented (MCI+NoCI) was 0.83 resulting in 90% sensitivity, 65% specificity, 50% PPV and 94% NPV at a best cut-off of <21 according the Younden index. For CI (MD+MCI) against NoCI the results were respectively 0.77AUC, 95%sens, 47%spec, 88%PPV, 68%NPV at a cut-off <26.On an individual basis, as a box plot of DSM IV diagnoses showed, the MoCA score has limitations and clinical aspects need to be taken into account: FTD, high education to the upside; MCI including psychiatric etiology to the downside.Conclusions: by using a cut-off score of <21, 90% of people with positive MoCA have CI, while 94% of people with negative MoCA (≥21) will not have dementia. The MoCA can significantly reduce referrals (50%) by excluding patients for further diagnostic work-up at a memory clinic, even if they are suspected of CI after initial assessment.

The structure and subtypes of gambling activities: Genetic, psychiatric and behavioral etiologies of gambling frequency

The multitude of gambling activities has given rise to heterogeneous ways of analyzing these behaviors and may partially underlie the lack of replication in gambling research. The current study used complementary analyses to investigate the structure, typology and etiology of gambling behaviors in a discovery sample of 2,116 twins (54.86% female; Mage = 24.90) and a replication sample of 619 siblings (30.37% female; Mage = 28.00). Our approach was twofold. First, we used confirmatory factor analyses to investigate the structure across the frequency of eight gambling activities. Second, we used factor mixture models to identify gambling frequency subtypes. We assessed associations with gambling frequency as well as conducted genetically informed analyses to estimate the role of genetic and environmental influences. Across samples, a two-factor model fit the data best, with a Common Gambling factor influencing all activities and a separate factor for Skill Gambling. Our study identified four gambling frequency subtypes, which resembled the typology from the Pathways Model. We found distinct demographic, psychiatric, behavioral and genetic risk profiles for the different gambling factors and subtypes with robust associations observed for male sex, risk-taking, sensation seeking, alcohol dependence and problem gambling. Controlling for shared genetic and environmental influences (via co-twin control modeling), we found that sensation seeking directly increased Common Gambling frequency. In sum, we illustrated the utility of multi-dimensional statistical techniques for disentangling the structure and typology from complex multivariate gambling data.

Redefining phenotypes to advance psychiatric genetics: Implications from hierarchical taxonomy of psychopathology.

Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorders, and to studying psychiatric etiology, than current diagnostic categories. Specifically, genes are expected to operate at different levels of the HiTOP hierarchy, with some highly pleiotropic genes influencing higher order psychopathology (e.g., the general factor), whereas other genes conferring more specific risk for individual spectra (e.g., internalizing), subfactors (e.g., fear disorders), or narrow symptoms (e.g., mood instability). We propose that the HiTOP model aligns well with the current understanding of the higher order genetic structure of psychopathology that has emerged from a large body of family and twin studies. We also discuss the convergence between the HiTOP model and findings from recent molecular studies of psychopathology indicating broad genetic pleiotropy, such as cross-disorder SNP-based shared genetic covariance and polygenic risk scores, and we highlight molecular genetic studies that have successfully redefined phenotypes to enhance precision and statistical power. Finally, we suggest how to integrate a HiTOP approach into future molecular genetic research, including quantitative and hierarchical assessment tools for future data-collection and recommendations concerning phenotypic analyses. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The Ghrelin-AgRP Neuron Nexus in Anorexia Nervosa: Implications for Metabolic and Behavioral Adaptations.

Anorexia Nervosa (AN) is viewed as primarily a psychiatric disorder owing to the considerable behavioral and genetic overlap with mood disorders and other psychiatric traits. However, the recent reconceptualization of AN as one of both psychiatric and metabolic etiology suggests that metabolic circuits conveying hunger, or sensitive to signals of hunger, may be a critical nexus linking metabolic dysfunction to mood disturbances. Within the brain, hunger is primarily percieved by Agouti-related (AgRP) neurons and hunger increases plasma concentrations of the hormone ghrelin, which targets ghrelin receptors on AgRP neurons to facilitate metabolic adaptations to low energy availability. However, beyond the fundamental role in maintaining hunger signaling, AgRP neurons regulate a diverse range of behaviors such as motivation, locomotor activity, negative reinforcement, anxiety, and obsession and a key factor involved in the manifestation of these behavioral changes in response to activation is the presence or absence of food availability. These changes can be considered adaptive in that they promote affective food-seeking strategies in environments with limited food availability. However, it also suggests that these neurons, so well-studied for their metabolic control, shape mood-related behaviors in a context-dependent manner and dysfunctional control leads not only to metabolic problems but also potentially mood-related problems. The purpose of this review is to underline the potential role of AgRP neurons and ghrelin signaling in both the metabolic and behavioral changes observed in anorexia nervosa. We aim to highlight the most recent studies on AgRP neurons and ghrelin signaling and integrate their metabolic and behavioral roles in normal function and highlight how dysfunction may contribute to the development of AN.

Aetiologies and therapies of nodding syndrome: a systematic review and meta-analysis

# Background Nodding syndrome (NS) is a childhood epileptic disorder of unknown aetiology confined to parts of South Sudan, Uganda and the United Republic of Tanzania. Patients suffer from atonic seizures that result in characteristic head nodding, and may develop other neurological, endocrinological and psychiatric manifestations. The objective of this study was to adopt a non-judgemental approach to review the hypothesised aetiologies and therapeutic options available for NS. To explore the reported association between NS and *Onchocerca volvulus* (OV) a meta-analysis of the prevalence of OV among NS cases and controls was performed. # Methods Systematic searching of five electronic databases yielded 26 articles that addressed potential aetiologies of NS and 12 that explored the treatment of NS. # Results Nine articles contained data about the prevalence of OV in NS cases that was suitable for inclusion in the meta-analysis. Four broad aetiological themes were identified. 1) Nutritional associations included biomarkers of malnutrition and conflicting reports regarding the consumption of some foodstuffs. 2) Regional conflict and the associated psychological trauma have led to consideration of psychiatric aetiologies. 3) There is a strong epidemiological association between NS and *Onchocerca volvulus*. The meta-analysis in this study revealed that 68.0% (95% confidence interval (CI)=45.2-87.0) of 416 NS patients were OV+, compared to 46.6% (95% CI=16.4-78.1) of 321 controls. Heterogeneity among both cases (*I^2^*=95.5%, 95% CI=93.3-97.0) and controls (*I^2^*=97.1%, 95% CI=95.5-98.2) was high. The difference of 21.4% in OV prevalence between the pooled populations was significant (*P*\<0.0001). It is thought that NS represents a form of onchocerciasis-associated epilepsy, however there are also reported associations with *Mansonella pestans* and measles virus. 4) Autoantibodies against leiomodin-1 and the voltage-gated potassium channel have been associated with NS. Molecular mimicry between leiomodin-1 and *O. volvulus* tropomyosin is a recently suggested aetiology. Without a clear aetiology treatment is symptomatic and patients have been shown to improve with a combination of anti-epileptic medication and supportive therapy. # Conclusions The aetiology of NS remains unclear. The leading theory is that NS represents a form of onchocerciasis-associated epilepsy secondary to autoimmunity driven by molecular mimicry. Alternatively, it has been suggested that NS may represent a post-infectious sequelae of measles virus infection. However, each theory currently leaves some questions unanswered. It remains important to understand the aetiology of NS to better prevent or treat future outbreaks.

6.12 COMPARISON OF 18F-FDG-PET FINDINGS IN CASES IDENTIFIED AS SEROPOSITIVE, SERONEGATIVE, POSSIBLE AUTOIMMUNE ENCEPHALITIS, AND PRIMARY MENTAL ILLNESS IN CHILDREN AND ADOLESCENTS PRESENTING WITH ATYPICAL PSYCHIATRIC SYMPTOMS

[18F]Fluoro-deoxy-glucose positron emission tomography (FDG-PET) may aid in the diagnosis of autoimmune encephalitis (AE), which is challenging particularly when mental illness symptoms predominate the clinical presentation or objective markers are negative, yet timely treatment improves outcomes. We aim to compare FDG-PET findings between individuals who are found to be: 1) seropositive for antibodies (SP); 2) seronegative but with probable autoimmune encephalitis (SN); 3) possible autoimmune encephalitis but not meeting diagnostic criteria (PAE); and 4) primary psychiatric etiology (PP). We hypothesize that FDG-PET will demonstrate metabolic patterns consistent with AE in all groups, with the exception of PP.

&lt;p&gt;A patient with Korsakoff syndrome of psychiatric and alcoholic etiology presenting as DSM-5 mild neurocognitive disorder [Corrigendum]&lt;/p&gt;

A patient with Korsakoff syndrome of psychiatric and alcoholic etiology presenting as DSM-5 mild neurocognitive disorder [Corrigendum] Nikolakaros G, Kurki T, Myllymäki A, Ilonen T. Neuropsychiatr Dis Treat. 2019;15:1311–1320. The author has advised that four errors have been detected in the reference list. Some of these issues were introducedthroughout the production process of this paper. The issues are outlined as follows: Read the original article

Somatization disorder and the issue of stigmatization among psychiatric patients

Background: The somatic accusations disorder represents those somatic complaints which affects deeply the mental state of the patient being accompanied by an affective allure which deteriorates the relationship between the physician, family and the patient, the source of these complaints being unable to be found after the numerous medical investigations the patient demands. Purpose and methods: The purpose of the presentation is to highlight the relationship between the multitude of investigations to which the patient is subjected and the evolution of the somatoform disorders and to describe the psycho-emotional implications in this type of pathology by describing a clinical case met in our clinic diagnosed as Somatoform Disorder according to ICD-10 and DSM-IV. Description of the case: D.O. is a 58 years-old woman which came for the first time in a psychiatry unit with the purpose of hospital admission. The first impression on this patient was made of the various somatic complaints with occipital and cervical pain, thorax lumbar pain and various accusations of paresthesia at the extremities of the inferior limbs accompanied by a melodramatic and profoundly affective expression of the poor general condition. For almost 17 years, numerous medical investigations with negative results and consultations with doctors from various specialties and from different cities in the country, as well as alternatives methods of treatment such as massage ,spa, alternative medicine and even local healers were used because of the fear of stigma the patient may felt searching for psychiatric help. Unsatisfied and constantly affected by his current state , the patient has finally recognized that it may be reasonable a psychiatric approach towards his condition and required specialized medical service. Following hospitalization which consisted of psychotherapy, psychotropic antidepressant, anxiolytic and brain neurotrophic treatment, the somatic complaints decreased in intensity to the patient`s tolerable threshold. Conclusions: Somatic complaints and the denial of a possible psychiatric etiology creates a psycho-familial picture difficult to accept and with its numerous investigations and presentations in various medical services and a purposeless and unintended journey in the identification of the somatic complaints while the material, moral and affective costs are up to date.

A patient with Korsakoff syndrome of psychiatric and alcoholic etiology presenting as DSM-5 mild neurocognitive disorder.

Background: Wernicke’s encephalopathy (WE) and Korsakoff syndrome (KS) are underdiagnosed. The DSM-5 has raised the diagnostic threshold by including KS in the major neurocognitive disorders, which requires that the patient needs help in everyday activities.Methods: We report clinical, neuropsychological, and radiological findings from a patient who developed Wernicke-Korsakoff syndrome as a result of alcohol use and weight loss due to major depression. We assess the diagnosis in the context of the scientific literature on KS and according to the DSM-IV and the DSM-5.Results: The patient developed ataxia during a period of weight loss, thus fulfilling current diagnostic criteria of WE. WE was not diagnosed, but the patient partially improved after parenteral thiamine treatment. However, memory problems became evident, and KS was considered. In neuropsychological examination, the Logical Memory test and the Word List test were abnormal, but the Verbal Pair Associates test was normal (Wechsler Memory Scale-III). There were intrusions in the memory testing. The Wisconsin Card Sorting Test was broadly impaired, but the other test of executive functions (difference between Trail Making B and Trail Making A tests) was normal. There was atrophy of the mammillary bodies, the thalamus, the cerebellum, and in the basal ganglia but not in the frontal lobes. Diffusion tensor imaging showed damage in several tracts, including the uncinate fasciculi, the cinguli, the fornix, and the corona radiata. The patient remained independent in everyday activities. The patient can be diagnosed with KS according to the DSM-IV. According to the DSM-5, the patient has major neurocognitive disorders.Conclusions: Extensive memory testing is essential in the assessment of KS. Patients with a history of WE and typical clinical, neuropsychological, and radiological KS findings may be independent in everyday activities. Strict use of the DSM-5 may worsen the problem of Wernicke-Korsakoff syndrome underdiagnosis by excluding clear KS cases that do not have very severe functional impairment.

Olfactory Disorder Pattern in Patients With Neurological Diseases Excluding Psychiatric and Traumatic Aetiologies

IntroductionThe most common cause of olfactory ENT disorders are colds and flu, chronic sinusitis, allergies and traumatic brain injury. Rarer aetiologies include certain neurological, psychiatric and metabolic injuries. TargetThe aim of this paper was to check the sort of olfactory disorders found in people who have suffered a brain injury, excluding: cranial traumas, psychiatric diseases, epilepsy, Parkinson's and Alzheimer's disease, and synaesthesia. Material and MethodsA descriptive study based on 61 patients with diagnoses of various neurological injuries, which were tested by BAST-24 olfactometer. The results were compared with those of a control group (n=120). ResultsThe results show major impairment in these patients’ olfactory sense. The neurological injury patients were able to detect from 60% to 77% of the odours, while the control group were able to detect between 98% and 100%. The neurological patients were able, at best, to identify, 11%–32% of the odours correctly, while the control group were able to correctly detect between 59% and 75%. The differences between odour detection and correct identification were statistically significant (P<.05). ConclusionsWe concluded: (a) Neurological injury, not caused by traumatic brain injury, psychiatric disorders or ENT diseases, ranged from 68% to 89% of the olfactory failures. (b) We must bear in mind that these sorts of injuries can cause olfactory disorders. (c) ENT and Neurologists should collaborate in the treatment of these disorders.

Neuro-otology: at the borders of ear and brain

Vertigo and dizziness are frequent chief complaints in clinical practice. Symptoms may originate from otological, neurological, medical and psychiatric etiologies, which poses an interdisciplinary challenge. Systematic analysis of case history and clinical examination generally allow classification into peripheral-, central- or non-vestibular disorders. The most important criteria for differentiation are the timeline, quality of symptoms, modulating factors and accompanying symptoms. As concerns the clinical examination, the following tests are relevant: head impulse test, test for spontaneous nystagmus, positional nystagmus, central ocular motor signs and the Romberg test. However, neuro-otological disorders with combined peripheral and central vestibular pathology do exist. Occlusion of the anterior inferior cerebellar artery results in ischemia of the labyrinth and cerebellum and therefore causes acute vestibular syndrome and unilateral hearing loss. Repetitive attacks of vertigo or dizziness which are accompanied by ear symptoms and headaches may be due to an overlap syndrome of Menière's disease and vestibular migraine. In this case patients often have to be treated with adual prophylactic medication to control symptoms. In case of chronic dizziness and instability of gait asubsample of patients may suffer from CANVAS, which is acombination of bilateral vestibulopathy, acerebellar syndrome and polyneuropathy. Chronic dizziness with signs of peripheral and central vestibular dysfunction can also originate from tumors of the cerebellopontine angle with compression of central structures. In conclusion, the diagnostic algorithm in the workup of patients with vertigo and dizziness should always include tests for peripheral and central vestibular and ocular motor function.

Evaluation of depression, anxiety, alexithymia, attachment, social support and somatization in functional dyspepsia

AIM: The psychiatric and psychosocial aetiology of Functional dyspepsia is not well known. In the present study, our aim is to determine the relative contributions of psychiatric predictors – i.e. ...

240. Extracellular Free Water and Glutathione in First Episode Schizophrenia and a Non-Human Primate Model of Maternal Immune Activation – Exploring Neuroimmune Mechanisms of Psychiatric Disorders

Recent work highlights an immune-based component of psychiatric disorder etiology, particularly schizophrenia. We evaluated two putative biomarkers of neuroinflammation—diffusion MRI free water (FW) and 1H-MRS Glutathione (GSH)—in a first episode schizophrenia (SZ) sample. Furthermore, we developed a non-human primate (NHP) model of maternal immune activation (MIA) to test that maternal immune response contributes to parallel brain changes in developing NHP offspring.

T35. DIFFUSION MEASURES OF EXTRACELLULAR FREE WATER IN A NON-HUMAN PRIMATE MODEL OF MATERNAL IMMUNE ACTIVATION: EXPLORING NEUROIMMUNE MECHANISMS OF PSYCHIATRIC DISORDERS

BackgroundEvidence has been accumulating for an immune-based component of psychiatric disorder etiology, particularly schizophrenia. Early epidemiological studies found an increased incidence of schizophrenia in offspring of mothers who had an infection during pregnancy. Recent work has identified genetic links to the MHC complex, pro-inflammatory cytokine elevations in cerebrospinal fluid and plasma. We have developed a non-human primate (NHP) model of maternal immune activation (MIA) using a modified form of the viral mimic polyIC (polyICLC) examine the relationship between altered neuorimmune function may contribute to psychosis risk through effects on the developing brain and behavior of NHP offspring. In a previous cohort of MIA-exposed offspring, our group observed evidence for increased pre-synaptic dopamine levels in the striatum using 6-[18F]fluoro-L-m-tyrosine (FMT) positron emission tomography, in addition to pubertal-onset behavioral abnormalities, which may model part of the neurodevelopmental pathway towards psychosis. This study builds on this model and examines the effect of maternal immune activation on in vivo--extracellular free water--a diffusion magnetic resonance imaging measure obtained with a multi-shell acquisition. We sought to test the hypothesis that offspring of pregnant monkeys who received polyICLC injections at the end of the first trimester would show increased extracellular free water compared to control offspring.MethodsFourteen pregnant rhesus monkeys (Macaca mulatta) receiving polyICLC at the end of the first trimester were compared to 14 controls. The offspring from both groups underwent a multi-shell diffusion MRI scan at 3 Tesla. Diffusion data was collected when the offspring were one month, 6 months, and 12 months of age. Six month preliminary findings are currently presented. Diffusion images were aligned to individual subject MPRAGE scans. Individual subject structural scans were then nonlinearly aligned to generate a common group average template and the group average template was subsequently nonlinearly aligned to a neurodevelopmental rhesus atlas. For this preliminary analysis, the frontal cortex was selected as an a priori region of interest in addition to the more global whole-brain gray and white matter masks.ResultsSix month old MIA-exposed rhesus offspring showed a trend for increased whole-brain white matter extracellular free water (p=.09) with no significant difference in whole-brain gray matter free water (p=.27) compared to control offspring. However, analysis of the frontal ROI revealed significantly increased gray matter free water in the left hemisphere (p=.013) with a trend towards increased gray matter free water in the right hemisphere (p=.081). There were no significant differences between MIA-exposed and control offspring in basic motor and reflex development or growth trajectories.DiscussionThese data suggest that despite the lack of behavioral abnormalities at this early age, extracellular free water values are increased in MIA-exposed offspring, particularly in frontal gray matter. More global whole-brain free water group differences did not reach statistical significance, which may indicate some regional specificity to these changes early in development. The NHP MIA model complements the human schizophrenia literature in which extracellular free water increases have been repeatedly identified. Ultimately, these data provide validation of the clinical relevance of the NHP MIA model and improve our understanding of neuroimmune mechanisms in the development of psychiatric disorders, particularly schizophrenia.

Approach to the Agitated Emergency Department Patient

BackgroundAcute agitation is a common occurrence in the emergency department (ED) that requires rapid assessment and management. ObjectiveThis review provides an evidence-based summary of the current ED evaluation and management of acute agitation. DiscussionAcute agitation is an increasingly common presentation to the ED and has a broad differential diagnosis including metabolic, neurologic, infectious, toxicologic, and psychiatric etiologies. Missed diagnosis of a dangerous etiology of the patient's agitation may result in severe morbidity and mortality. Assessment and management of the agitated patient should occur concurrently. Focused history and physical examination are recommended, though control of the patient's agitation may be required. All patients should receive a point-of-care glucose test, with additional testing depending upon the specific patient presentation. Initial management should involve verbal de-escalation techniques, followed by pharmacologic interventions, with physical restraints reserved as a last resort. Pharmacologic options include first-generation antipsychotics, second-generation antipsychotics, benzodiazepines, and ketamine. Finally, the management of pediatric, pregnant, and elderly patients warrants special consideration. ConclusionAcute agitation is an important presentation that requires prompt recognition and treatment. A focused and thorough examination coupled with appropriate management strategies can assist emergency clinicians to safely and effectively manage these patients.

Between Shell Shock and PTSD? 'Accident Neurosis' and Its Sequelae in Post-War Britain.

SummaryThis article focuses on the concept of ‘accident neurosis’, popularised by neurologist Henry Miller in studies published in 1961. It aims to realise two goals. First, it introduces Miller’s concept of accident neurosis to the broader history of trauma—to a field, that is, more preoccupied with military traumata and clear-cut psychiatric aetiologies. Secondly, I use Miller’s studies, and the considerable legacy they created, to reflect on how historians of trauma construct historical narratives, asking whether there is sufficient appreciation of the ways in which events seem to leak into or retroactively animate one another.