Numerous studies shown that structural hippocampal alterations are present in subjects at high risk of developing psychosis or schizophrenia. These findings indicate that in a subset of patients undergoing first-psychosis episode (FPE), hippocampal volume alterations are accompanied by associated cognitive and neuropsychological deficits. The combination of psychological deficits and neuroanatomical alterations, in turn, appears to increase treatment complexity and worsen clinical outcomes.

We aim to determine whether cognitive and neuropsychological functioning deficits precede or follow hippocampal alterations during early onset psychosis.

This cross-sectional study describes 3 case-studies of adolescent subjects, ages 16–17, admitted at the child and adolescent inpatient psychiatric unit in lieu of first psychotic episode. We conducted detailed structured clinical psychiatric interviews, anatomical-structural magnetic resonance imaging (MRI), sleep-deprived electroencephalogram (EEG) recordings, laboratory testing, and a comprehensive battery of psychological testing to better understand their clinical pictures.

Psychological testing in each patient demonstrated the presence of low to borderline intellectual functioning coupled with neuropsychological deficits in different psychiatric domains. Interestingly, these changes coincided with structural MRI alterations in the hippocampal area.

Our case report adds to the armamentarium of literature signifying that radiologically detectable alterations of the hippocampus may occur either concomitantly or closely following the development of early cognitive deficits in patients with FPE.

The value of early functional improvement at week 2 for predicting subsequent functional outcomes at week 8 was assessed in a pooled analysis of patients with major depressive disorder (MDD) treated with desvenlafaxine (50 or 100 mg/d) or placebo.

Data were pooled from eight double-blind, placebo-controlled studies of desvenlafaxine 50 mg/d or 100 mg/d for the treatment of MDD. Optimal week-2 improvement thresholds in Sheehan Disability Scale (SDS) score, which best predicted week-8 treatment success, were determined using receiver operating characteristic (ROC) analysis. Four definitions of treatment success were established: (1) functional response, (2) functional/depression response, (3) functional remission, and (4) functional/depression remission. Odds ratios (ORs) of early improvement for prediction (based on thresholds determined in the ROC analysis) of week-8 treatment success were computed using logistic regression models.

Functional early improvement thresholds of 17%–32% were predictive of week-8 treatment success across treatment groups and definitions of treatment success. Optimal thresholds were higher for more stringent definitions. Negative predictive value exceeded positive predictive value, indicating that failure to achieve early functional improvement was more informative about later treatment success than was the achievement of early functional improvement. Early change in SDS was a highly significant predictor of functional response/remission (ORs, 4.981–8.737; all p < 0.0001); the interaction between treatment and early functional improvement was not significant.

Early improvement in SDS total score was predictive of functional outcomes for patients treated with desvenlafaxine 50 mg, desvenlafaxine 100 mg, or placebo.

To understand that tinnitus may be an aura for sleep paralysis.

Sleep paralysis is a transient-paralysis which occurs during awakening or falling asleep (Wilson, 1928). Those affected experience symptoms including visual, auditory, and haptic hallucinations, voluntary motor paralysis with intact ocular and respiratory motor movements, and diffuse or localized paresthesias. Sleep paralysis associated with tinnitus as an aura, has not heretofore been described.

A 34 year-old, right-handed female presented with a 13 year history of sleep paralysis. One month prior, she began to notice tinnitus prior to the onset of sleep paralysis. The tinnitus was bilateral, high-pitched, with a volume intensity of 5/10, lasting seven seconds prior to sleep initiation. She denied hearing loss, vertigo, dizziness, cataplexy, deja vu and jamais vu. After termination of tinnitus, she experienced paresthesia, “like at a dentist’s office” radiating from her posterior neck, to her tongue and down to her toes. She described seeing a white-shadowy male figure moving around her room, lasting seven seconds. Accompanied by a masculine “ahh” sound, lasting for three seconds. The sleep paralysis occurred after these events, lasting up to eight hours, or until her husband wakes her.

Abnormalities in Physical Examination: General Examination: right arm hemangioma 4 by 5cm. Reflexes: absent bilateral brachioradialis, 1+ bilateral quadriceps femoris and bilateral Achilles tendon. Neuropsychiatric Examination: Calibrated Finger Rub Auditory Screening Test: faint 70 AU (normal).

Tinnitus has been described as an aura for migraines (Schankin, 2014), temporal lobe epilepsy (TLE) (Florindo, 2006), and narcolepsy-cataplexy (Marco, 1978). These epochs may represent amigranous migraines, which initially present with tinnitus that occurs both during the day and night, forcing the patient to be partially awoken at night with induction of the sleep paralysis sequence. It would be worthwhile to query those with narcolepsy or sleep paralysis if tinnitus precedes the event.

Patient preferences in schizophrenia (SCZ), including identification of key goals and outcomes for treatment and relative importance of certain treatment goals to patients, have been assessed by several studies. However, there continues to be a lack of sufficient evidence on US patient attitudes and perceptions towards treatment goals and pharmacotherapy options in SCZ, especially taking into context long-acting injectable antipsychotics (LAIs) in this disease area. This lack of evidence is further pronounced in caregivers of individuals with SCZ. The objective of this analysis was to characterize patients with SCZ on LAIs vs patients on oral antipsychotics (OAPs) and evaluate the treatment goals of patients in each group.

This was a real-world, cross-sectional survey of US psychiatrists, patients =18 years old with a diagnosis of SCZ, and caregivers. Data was collected using the Disease Specific Programme (DSP) methodology, which has been previously published. Psychiatrists (n=120) completed detailed record forms for next 8 consecutive outpatients and 2 inpatients matching inclusion criteria, including non-interventional clinical and subjective assessments. The same patients and their caregivers, if present, were invited by their psychiatrist to voluntarily complete a separate survey.

Of 1135 patients on treatment where the physician provided survey data; 251 were on an LAI, and 884 were on an OAP. Mean (SD) time to SCZ diagnosis for those on an LAI was 10.3 (12.0) years vs 7.8 (10.5) years for those on OAPs. More patients in the LAI vs OAP group were being treated as an inpatient (27.1% vs 15.7%, respectively; p<0.0001). Patients on an LAI reported being on their current medication regimen for less time (mean 1.7 years) vs those on OAPs (mean 2.5 years) (p=0.0093). More patients on LAIs were unemployed due to disability vs those on OAPs (56.1% vs 39.5%, respectively), and less patients on LAIs were able to work part-time or full-time (21.1% or 4.1%) vs those on OAPs (23.2% or 11.4%). More patients on an LAI had a caregiver vs those on OAPs (37.3% vs 26.1%, respectively; p=0.0011). Regarding the most important treatment goals reported by patients, both groups reported similar preferences for decrease in disease symptoms (62% on LAI vs 65% on OAPs) and thinking more clearly (53% on LAI vs 46% on OAPs); however, a numerically higher proportion of LAI patients reported that the current medication helped decrease hospitalizations due to relapse vs those on OAPs (38% vs 32%, respectively).

Given the characteristics of patients participating in this real-world survey, those on LAIs exhibited qualities which indicate a higher severity of illness vs those on OAPs. Results suggest that treatment with LAIs is still mainly being provided to patients later in the disease course and/or who have adherence problems, despite a growing body of evidence of utility in younger patients earlier in the course of illness.

Otsuka Pharmaceutical Development & Commercialization, Inc. and Lundbeck LLC

Glycolimia is observed in a plethora of medical conditions including burning mouth syndrome, opioid withdrawal, as well as from a variety of medications including vortioxetine, l-methylfolate, lisdexamfetamine, and gabapentin. While vilazodone, an antidepressant with agonist like effects on 5-HT1A receptors, has been found to induce hyperglycemia, it has not heretofore been reported to induce glycolimia. Such a case is described.

Case study: A 60-year-old, left-handed (pathological) male presented with a past history of depression, minimally responsive to a variety of antidepressant medications, was begun on vilazodone, initially 20 mg and gradually increased to 60 mg a day. On 60 mg a day he noticed severe cravings for sweets, which he had never experienced prior to starting vilazodone. He found he had increased consumption, craving sweet foods including cookies and candy. For instance, in a typical day, he would eat eight Oreos, chocolate-covered graham crackers, one pint of ice cream a day, and he would crave sweets even after feeling satiated after consuming a meal. Along with this increased eating, he gained 20 pounds over the 3 months while on the vilazodone. Upon discontinuing the vilazodone, although the weight didn’t change, the sweet cravings resolved.

Abnormalities on: Neurological examination: Mental status examination: Immediate recall: able to remember 6 digits forwards and 3 digits backwards. Motor examination: Drift testing: right inward drift. Gait examination: unstable tandem gait. Neuropsychiatric examination: Go-No-Go test: 6/6 (normal). Animal Fluency Test: 22 (normal).

There are myriad mechanisms whereby vilazodone may have induced glycolimia. Possibly due to its antidepressant effects, it increased hedonics, generating appetitive behaviors, including enhanced socialization, sexual, and other consumptive behaviors, including eating. Peradventure it may have enhanced motivation and socialization. Along with socialization, there is escalation in social intercourse, with accompanying commensalism. Along with such consumptive behaviors, we could anticipate glycolimia. As a 5-HT1A receptor agonist, possibly vilazodone may have acted on the arcuate pro-opiomelanocortin neurons associated with hyperphagia, with modulation of energy homeostasis in the serotonin pathway. Alternatively, vilazodone may have triggered an enhanced insulin response with secondary reduction in blood sugar, leading to a homeostatic behavioral response of increased glucose intake. In those who are treated with vilazodone, query as to glycolimia is warranted and warning as to potential manifestations of hyperglycemia should be entertained.

No Funding

The association of sleep disorders and post-traumatic stress disorder (PTSD) is almost universal. Nightmares are not only one of the most commonly associated but also featured as a diagnostic criterion for PTSD. PTSD-related nightmares are particularly distressing, may impair functioning and increase risk of suicide. No specific pharmacologic agent has been demonstrated to impair dreaming. Inhibition of PTSD-related nightmares with pramipexole has not heretofore been described. Such a case is presented.

Case study - This 60 year-old male with PTSD and trauma-related nightmares upon introduction of pramipexole 0.5mg PO qHS for Restless Leg Syndrome (RLS) had total elimination of dreams, which recurred upon discontinuation of this agent as a result of insomnia and increased anxiety. A lower dose of 0.375mg qHS provided optimal RLS-symptom control and overall improved tolerance despite nightmare recurrence.

Abnormalities on Neurological examination: Recent recall: 2 of 4 objects without improvement with reinforcement. Able to spell the word “world” forwards but not backwards. Abstract thought impaired. Chemosensory testing: Anosmia and normogeusia. Motor: Drift: mild right pronator drift with right cerebellar spooning and right abductor digiti minimi sign. Reflexes: 3+ brachioradialis and biceps bilaterally, absent ankle jerks. Other: CT scan with and without contrast: normal.

Nightmares related to PTSD may occur during Rapid Eye Movement (REM) sleep and non-REM sleep. Underlying sympathetic activation may lead to disruptive motor behavior similar to that seen in REM sleep behavior disorder. The exact mechanism of action by which inhibition of dreams occurred with use of pramipexole is unclear. Such a response is consistent with prior documented evidence of REM sleep suppression with low-dose pramipexole such as it‘s efficacy in reducing the intensity and frequency of nightmares and dream enactment related to REM sleep behavior disorder. Further research on therapeutic interventions that target nightmares directly may be beneficial for the management of patients with PTSD.

The goal of this study was to determine physician performance in diagnosis and management of postpartum depression (PPD) and to provide needed education in the consequence free environment of a virtual patient simulation (VPS).

∙ A continuing medical education activity was delivered via an online VPS learning platform that offers a lifelike clinical care experience with complete freedom of choice in clinical decision-making and expert personalized feedback to address learner’s practice gaps

∙ Physicians including psychiatrists, primary care physicians (PCPs), and obstetricians/gynecologists (ob/gyns) were presented with two cases of PPD designed to model the experience of actual practice by including use of electronic health records

∙ Following virtual interactions with patients, physicians were asked to make decisions regarding assessments, diagnoses, and pharmacologic therapies. The clinical decisions were analyzed using a sophisticated decision engine, and clinical guidance (CG) based on current evidence-based recommendations was provided in response to learners’ clinical decisions

∙ Impact of the education was measured by comparing participant decisions pre- and post-CG using a 2-tailed, paired t-test; P <.05 was considered statistically significant

∙ The activity launched on Medscape Education on April 26, 2018, and data were collected through to June 17,2018.

∙ From pre- to post-CG in the simulation, physicians were more likely to make evidence-based clinical decisions related to:

∙ Ordering appropriate baseline tests including tools/scales to screen for PPD: in case 1, psychiatrists (n=624) improved from 34% to 42% on average (P<.05); PCPs (n=197) improved from 38% to 48% on average (P<.05); and, ob/gyns (n=216) improved from 30% to 38% on average (P<.05)

∙ Diagnosing moderate-to-severe PPD: in case 2, psychiatrists (n=531) improved from 46% to 62% (P<.05); PCPs (n=154) improved from 43% to 55% (P<.05); and, ob/gyns (n=137) improved from 55% to 73% (P<.05)

∙ Ordering appropriate treatments for moderate-to-severe PPD such as selective serotonin-reuptake inhibitors: in case 2, psychiatrists (n=531) improved from 47% CG to 75% (P<.05); PCPs (n=154) improved from 55% to 74% (P<.05); and, ob/gyns (n=137) improved from 51% to 78% (P<.05)

∙ Interestingly, a small percentage of physicians (average of 5%) chose investigational agents for PPD which were in clinical trials pre-CG, and this increased to an average of 9% post-CG

Physicians who participated in VPS-based education significantly improved their clinical decision-making in PPD, particularly in selection of validated screening tools/scales, diagnosis, and pharmacologic treatments based on severity. Given that VPS immerses physicians in an authentic, practical learning experience matching the scope of clinical practice, this type of intervention can be used to determine clinical practice gaps and translate knowledge into practice.

Funding Acknowledgements: The educational activity and outcomes measurement were funded through an independent educational grant from Sage Therapeutics, Inc.

Cognitive impairment is a major determinant of poor functional outcome in schizophrenia and there are currently no available pharmacotherapies. Deficits in glutamatergic signaling play a key role in the neuropathology of cognitive symptoms. Iclepertin (BI 425809), an inhibitor of glycine transporter-1, enhances glutamatergic signaling by increasing synaptic levels of the N-methyl-D-aspartate receptor co-agonist, glycine. A 12-week, Phase II trial (NCT02832037) in 509 patients with schizophrenia demonstrated that iclepertin was well tolerated and significantly improved cognition. The Phase III CONNEX program aims to confirm the efficacy, safety, and tolerability of iclepertin in improving cognition and functioning in a larger cohort of patients.

CONNEX consists of three replicate randomized, double-blind, placebo-controlled parallel-group trials in patients with schizophrenia (NCT04846868, NCT04846881, NCT04860830) currently stable on antipsychotic treatment. Each trial aims to recruit ~586 patients, 18–50 years old, treated with 1–2 antipsychotic medications (≥12 weeks on current drug; ≥35 days on current dose prior to treatment), who have functional impairment in day-to-day activities, and interact ≥1 hour per week with a designated study partner. Patients with cognitive impairment due to developmental, neurological, or other disorders, or receiving cognitive remediation therapy within 12 weeks prior to screening, will be excluded. Patients will be recruited from multiple centers across 32 countries in Asia, North and South America, and Europe, and randomized 1:1 to receive either oral iclepertin 10 mg (n=293), or placebo (n=293) once daily over 26 weeks. The primary efficacy endpoint is change from baseline (CfB) in the MATRICS Consensus Cognitive Battery overall composite T-score. Key secondary efficacy endpoints are CfB in Schizophrenia Cognition Rating Scale total score and CfB in the adjusted total time in the Virtual Reality Functional Capacity Assessment Tool. Long-term safety and tolerability data will be collected in an open-label safety extension study (CONNEX-X).

The studies are currently recruiting (first patients enrolled Aug–Sept 2021), with completion expected in Q2 2024. Here we present an overview of the current study status, including any information relating to screening failures, and the experience of collecting these data as part of a large multi-country, multi-center study.

To date, most large, industry-sponsored studies testing various compounds to address cognitive function have failed to show proof-of-clinical concept. Demonstration of efficacy of iclepertin in improving cognition in this Phase III program would provide important insight into the role of glutamate in cognitive symptoms that may also have relevance for other cognitive disorders. Iclepertin may represent the first efficacious medication for cognitive impairment associated with schizophrenia.

Boehringer Ingelheim International GmbH (1346-0011, NCT04846868; 1346-0012, NCT04846881; 1346-0013, NCT04860830)

This study explores the effectiveness of Chaihu Hehuan Jieyu Tang (CHT) combined with career guidance to alleviate employment anxiety among college students. Employment anxiety is a common concern among college students, and targeted interventions are necessary to mitigate its negative impact.

One hundred sixty college students with employment anxiety were selected for this study. They were randomly divided into four groups: the CHT combined with the career guidance group (n=40), the CHT alone group (n=40), the career guidance alone group (n=40), and the control group (n=40). The Stanford Acute Stress Response Questionnaire (SASRQ) and the 3-min Confusion Assessment Scale (3D-CAM) measured the participants’ anxiety levels. The intervention was conducted over twelve weeks, with regular sessions twice weekly.

Statistical analysis using SPSS23.0 revealed a significant reduction in anxiety levels in all intervention groups compared to the control group (P<0.001). However, the group receiving the combined intervention of CHT and career guidance exhibited a more substantial decrease in anxiety symptoms than those receiving single interventions (P<0.05), as measured by the SASRQ and 3D-CAM. These findings suggest that the combined intervention has a more substantial effect on alleviating employment anxiety among college students.

This study indicates that combining Chaihu and Huanjieyu Tang with career guidance effectively reduces employment anxiety among college students. These results highlight the importance of combining traditional Chinese medicine interventions such as CHT with career guidance to achieve more comprehensive and effective results.