To explore relationships among post-traumatic stress disorder (PTSD), depressive spectrum symptoms, and intrusiveness in subjects who survived the crash of a train derailed carrying liquefied petroleum gas and exploded causing a fire.

A sample of 111 subjects was enrolled in Viareggio, Italy. AMOS version 21 (IBM Corp, 2012) was utilized for a structural equation model-path analysis to model the direct and indirect links between the exposure to the traumatic event, the occurrence of depressive symptoms, and intrusiveness. Subjects were administered with the SCID-IV (Structured Clinical Interview for DSM-IV), the Questionnaire for Mood Spectrum (MOODS-SR)-Last Month version, the Trauma and Loss Spectrum Questionnaire (TALS-SR), and the Impact of Event Scale-Revised version (IES-R).

Sixty-six (66/111; 59.4%) subjects met SCID-IV criteria for PTSD. Indices of goodness of fit were as followed: χ2/df = 0.2 P = .6; comparative fit index = 1 and root mean square error of approximation = 0.0001. A significant path coefficient for direct effect of potential traumatic events on depressive symptoms (β = 0.25; P < .04) and from depressive symptoms to intrusiveness (β = 0.34; P < .003) was found. An indirect effect was also observed: standardized value of potential traumatic events on intrusiveness was 0.86. The mediating factor of this indirect effect path was represented by depressive symptoms. Potential traumatic events explained 6.2% of the variance of depressive symptoms; 11.8% of the variance of intrusiveness was accounted for traumatic event and depressive symptoms.

Path analysis led us to speculate that depression symptoms might have mediated the relationship between the exposure to potential traumatic events and intrusiveness for the onset of PTSD.

Objective: NeuroStar® Advanced Therapy System is a transcranial magnetic stimulation (TMS) device with FDA-clearance for the treatment of Major Depressive Disorder (MDD) in adult patients who have failed to receive satisfactory improvement from prior antidepressant medication in the current episode. With TMS, magnetic pulses are transmitted into the brain. Though the exact mechanism of action is unknown, it is postulated that resulting neuronal depolarization and changes in brain functional activity may be associated with various physiologic changes that lead to relief of depression in the indicated population. The type of magnetic field generated with TMS is not intended to induce a seizure during therapeutic use, but unintentional seizures have been reported during TMS treatment.

No seizures were reported with the use of the NeuroStar® system in clinical trials conducted prior to FDA clearance. The estimated risk of seizure in the NeuroStar® label is approximately 1 in 30,000 treatments or 1 in 1,000 patients. Since introduction of the NeuroStar® system into clinical practice, the rate at which seizures have been reported is even lower.

We conducted a review of literature that named the NeuroStar® Advanced Therapy System as the device used for TMS treatment and reviewed all seizure events reported to Neuronetics, Inc., directly or through FDA MedWatch through June 30, 2019. Articles reporting seizures in subjects with epilepsy during TMS treatment were excluded.

Previous comprehensive reviews of seizures induced by treatment with any TMS device by Wasserman et al. (1998) and Rossi et al. (2009) revealed that the rate of seizures is low. Many subjects that developed seizures during TMS had either received stimulation at parameters beyond current recommendations or had been predisposed to develop seizures in some way. Some of the events reported as seizures may, in fact, have been non-epileptic events.

Our literature review and analysis of seizures reported to Neuronetics, Inc. revealed that the rate of seizures during TMS treatment with the NeuroStar® appears to be lower than the rate that is published in the NeuroStar® Advanced Therapy prescribing information.

Seizures that take place during TMS treatment with the NeuroStar® system are rare. The rate of seizures reported directly to Neuronetics, Inc. is lower than that included in the NeuroStar® prescribing information. Our literature review validated seizures during TMS treatment with the NeuroStar® system reported in published literature have described either non-epileptic events (syncope) or occurred with risk factors for seizure induction, such as other predisposing clinical factors or treatment parameters outside the guideline recommend “safe” ranges.

Neuronetics, Inc.

To describe the presence of psychotic symptomatology in a patient with hyperthyroidism

Psychiatric-spectrum symptoms associated with thyrotoxicosis has been well reported in the past. However, psychosis in a patient with a thyroid nodule is a rare find. Here, the case of twenty four-year-old, single, unemployed, Albanian American male with self-reported history of Attention Deficit Disorder (ADD) and Cannabis use disorder was brought in to the Comprehensive Psychiatric Emergency Program (CPEP) due to new onset psychosis. Patient was paranoid, disorganized with labile mood. He had poor insight, judgement and impulse control. The event coincided with a period of unemployment in his life and new onset of hallucinations from past few days. He was brought in to the hospital after he was found pacing and having lack of sleep. Patient was treated with antipsychotic for acute psychosis. He was started on Risperidone initially to which he did not respond to. Blood work showed low TSH and elevated T4. Physical exam was noted for palpable thyroid nodule. Further labs resulted in high thyroid peroxidase antibody. Ultrasound of thyroid with color flow showed single nodule in the left lobe and iodine uptake activity localized to the left lobe. Patient was started on Methimazole 5 mg along with Haldol 5mg orally twice a day which improved his symptoms tremendously. Patient was stabilized and after 1 week was discharged on Haldol 5 mg by mouth two times a day for Psychosis, Cogentin 1 mg by mouth two times a day for extrapyramidal system (EPS), and Methimazole 5 mg by mouth daily for overactive thyroid nodule.

Psychosis associated with thyroid nodule is rare but possible. The onset of psychotic syndrome is an important clinical element whose underlying medical cause must be promptly clarified. Psychosis can present in a number of ways and can have different causes. Apart from psychiatric causes, underlying medical causes should always be considered. In this case it was important to get a full clinical history of the patient as well as complete physical examination. The differential diagnosis of a psychotic disorder in light of a medical disease should always be considered in order to promptly diagnose and treat the underlying cause to reduce the morbidity and possibly the mortality associated with it.

To determine whether amphetamine extended-release oralsuspension (AMPH EROS) has an onset of effect at 30minutes postdose inchildren with ADHD.

This randomized, double-blind, 2-treatment, 2-sequence, placebo-controlled crossover pilot study enrolled subjects aged 6 to 12 years withattention-deficit/hyperactivity disorder (ADHD) and ADHD-Rating Scale-5 scores of ≥90th percentile for sex and age. A dose of 5 to 20mg/day of AMPH EROS was determined during a 1-week open-label phase based on medication history, symptom control, and tolerability. Subjects completed a practice laboratory classroom then received one day of double-blind active drug or placebo each in random sequence during 2 double-blind laboratory classroom days. Subjects completed the first double-blind laboratory classroom session, returned to open label drug for 5days then crossed over on day 6 during a second double-blind laboratory classroom session. DB dose was fixed at AMPH EROS 15, 17.5, or 20mg . The primary endpoint was change from predose in the Swanson, Kotkin, Agler, M-Flynn, Pelham rating scale-combined score (SKAMP-C) at 30minutes postdose on two DB days. The key secondary endpoint was change from predose in the SKAMP-C score at 3hours postdose for AMPH EROS compared with placebo. Safety assessments included vital signs and adverse events.

Eighteen subjects were enrolled in the study (14 males and 4 females) with a mean age of 9 years. At both 30minutes and 3hours postdose, changes from baseline in SKAMP-C for AMPH EROS vs. placebo were statistically significant (p<0.01 and p=0.0002, respectively) with corresponding effect sizes of 0.96 and 1.57. Adverse events (>10%) during the open-label phase included upper respiratory tract infection, fatigue, upper abdominal pain, headache, decreased appetite, and affect lability.

AMPH EROS was effective in reducing ADHD symptoms at 30minutes postdose. AEs were mild or moderate and consistent with those of other extended-release amphetamines.

Funding Acknowledgements: Support was provided by Tris Pharma, Inc.

To assess differences in cognitive impairment in a group of patients with schizophrenia receiving first-generation long-acting antipsychotics (FG-LAI) versus Aripiprazole long-actinginjectable (ALAI).

A descriptive, cross-sectional, multi-centerstudy.

Study sample: 28 outpatients with stable schizophrenia (18 men and 10 women) with ages ranging from 22 to 64years.

Inclusion criteria were: Clinically stable patients with a diagnosis of schizophrenia (according to DSM-5 criteria) and without any changes to their antipsychotic or antidepressant therapy in the last six months.

Simple stratified sampling was performed to collect data from patients with schizophrenia receiving FG-LAI (n=14) versus patients with schizophrenia receiving Aripiprazole long-acting injectable (ALAI) (n=14)

Groups were matched by age, gender, years of evolution of the disease, and years on formal education.

Functionality in the different cognitive domains was evaluated based on the Brief Assessment of cognition in Schizophrenia (BACS.), a hetero-applied instrument, which Spanish version has been validated. BACS evaluates the following cognitive domains:

Verbal memory (V.M): Word list test

Working memory (W.M): Digit sequencing task

Motor speed (M.S): Token motor task

Verbal fluency (V.F): Semantic or category fluency

Attention (A): Symbol coding

Executive function (E.F): Tower of London

The data obtained were analyzed using the SPSS 22.0 statistical package Differences between the means of quantitative variables were assessed using the independent-sample Student-t test. Individual test scores were converted into standardized (T and Z) scores and composite scores that were corrected for age and gender.

Informed consent was obtained from all patients according to the Declaration of Helsinki (World Medical Association).

In the group receiving ALAI, the most severely impaired cognitive domain was attention, whereas motor speed was barely affected. In contrast, verbal memory was most impaired, whereas motor speed was the least impaired cognitive domain in the group receiving FG-LAI.

Patients with schizophrenia taking ALAI showed a better cognitive function in all domains (except for motor speed and attention) than patients receiving FG-LAI.

Summarized results in Table1.

In our study, patients with schizophrenia receiving Aripiprazole long-acting injectable have better cognitive function than patients receiving first-generation long-acting antipsychotics.

To discuss the psychiatric symptoms that are associated with CADASIL syndrome Abstract Cerebral:

Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare type of hereditary disease involving the small cerebral vessels. The clinical symptoms are various and include recurrent ischemic strokes, migraine with aura, seizures with epilepsy, psychiatric problems such as mood disturbances, and progressive cognitive decline leading to dementia. This disease needs awareness amongst the psychiatrists even though it is discussed much more in neurology literature. Psychiatric symptoms are seen in 20–41% of patients with CADASIL syndrome (1, 2). Psychiatric symptoms are actually the initial presentation in 15% of the cases. (3) The psychiatric disturbance most reported are mood disturbances (9–41%) especially depression. Here a 42-year-old African American female was brought to the hospital emergency room after she was found wandering in the streets. Psychiatry was consulted for altered mental status. Upon evaluation by the psychiatric consult service she was only oriented to person, depressed, anxious and complaining of headaches. Initial CT scan showed marked small vessel disease and old lacunar infarcts in the basal ganglia and right corona radiata. Magnetic Resonance Imaging (MRI) of the brain showed acute infarcts in the right posterior frontal and right parietal lobes along with old infarcts. Her symptoms and findings on imaging were consistent with CADASIL syndrome. Once the diagnosis was confirmed and prior records were obtained patient was resumed on an antidepressant and anxiolytic.

The purpose of this case report was to discuss psychiatric symptoms associated with CADASIL syndrome. Although there has been research showing a relationship between vascular disease and depression, a review of the literature suggests that there needs to be more research done to explore other psychiatric disturbances that may be seen with this syndrome. Psychiatric symptoms that are untreated can have the potential to further impact the quality of life therefore psychiatrists need to be aware of this syndrome in order to treat these patients promptly.

1 https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0778-8 2 http://dx.doi.org/10.32474/OJNBD.2018.01.000101 3 https://pdfs.semanticscholar.org/47f6/5952ee3c5dcf2a61345f704914b17fa8dc0d.pdf

Gambling disorder is common, affects 0.5–2% of the population, and is under-treated. Duration of untreated illness (DUI) has emerged as a clinically important concept in the context of other mental disorders, but DUI in gambling disorder, has received little research scrutiny.

Data were aggregated from previous clinical trials in gambling disorder with people who had never previously received any treatment. DUI was quantified, and clinical characteristics were compared as a function of DUI status.

A total of 298 individuals were included, and the mean DUI (standard deviation) was 8.9 (8.4) years, and the median DUI was 6 years. Longer DUI was significantly associated with male gender, older age, earlier age when the person first started to gamble, and family history of alcohol use disorder. Longer DUI was not significantly associated with racial-ethnic status, gambling symptom severity, current depressive or anxiety severity, comorbidities, or disability/functioning. The two groups did not differ in their propensity to drop out of the clinical trials, nor in overall symptom improvement associated with participation in those trials.

These data suggest that gambling disorder has a relatively long DUI and highlight the need to raise awareness and foster early intervention for affected and at-risk individuals. Because earlier age at first gambling in any form was strongly linked to longer DUI, this highlights the need for more rigorous legislation and education to reduce exposure of younger people to gambling.

To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response.

A post hoc analysis of pooled data from ASPIRE I and ASPIRE II evaluated ESK plus SoC vs PBO plus SoC in adults with MDSI without response (≥50% improvement from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] score) at 24 hours after the first dose or at week 1 after the first two doses (ie, 24-hour and week 1 nonresponders). Response and remission (MADRS score ≤ 12) rates were assessed on day 25.

The analysis included 362 patients (n = 182, ESK plus SoC; n = 180, PBO plus SoC). Among 24-hour nonresponders, more patients receiving ESK plus SoC vs PBO plus SoC achieved response (63.9% vs 48.0%, P = .010) and remission (35.1% vs 24.4%, P = .074) at day 25. Odds of response/remission were higher with ESK plus SoC vs PBO plus SoC (response: 1.89, 95% CI, 1.17-3.05; remission: 1.48, 95% CI, 0.93-2.35). Similar findings were observed among week 1 nonresponders for response (48.4% vs 34.5%, P = .075), remission (25.0% vs 13.1%, P = .060), and odds of response/remission (response: 2.03, 95% CI, 1.22-3.40; remission: 1.63, 95% CI, 1.01-2.62).

Patients with MDSI not responding within the first week of treatment with ESK plus SoC may still benefit from a full 4-week treatment course.

Combination olanzapine and samidorphan (OLZ/SAM) is in development for treatment of schizophrenia and bipolar I disorder and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension study (NCT02873208; ENLIGHTEN-2-EXT) in schizophrenia assessed the safety and tolerability of OLZ/SAM. Methods: Patients completing the 24-week, randomized, double-blind, phase 3 ENLIGHTEN−2 study comparing weight gain with OLZ/SAM vs olanzapine were eligible for ENLIGHTEN-2-EXT enrollment. Initial OLZ/SAM doses were based on olanzapine dose (10 or 20 mg) received at the conclusion of ENLIGHTEN-2; subsequent olanzapine dose adjustments were allowed. The samidorphan dose (10 mg) remained fixed throughout. Assessments included adverse events (AEs), weight, waist circumference, metabolic laboratory parameters, and Positive and Negative Syndrome Scale (PANSS) scores. Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study.

265 patients received OLZ/SAM; 167 (63.0%) completed the extension study. Common AEs (= 5%) were weight decreased (n=23; 8.7%), extra dose administered (n=21; 7.9%), headache (n=18; 6.8%), and weight increased (n=16; 6.0%). At week 52, mean (SD) change from baseline for weight and waist circumference was −0.03 (6.216) kg and −0.35 (6.115) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. PANSS total scores remained stable during the extension.

OLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.

Alkermes, Inc.