Autobiographical memory is known to be disturbed in schizophrenia. In addition, a leading theory of auditory hallucinations (AVH) is that they are intrusive – typically negative – autobiographical memories that are misinterpreted as perceptions.

The aim of this study was to examine the brain functional correlates of recall of negatively emotionally valanced autobiographical memories in patients with schizophrenia, with a longer term aim of comparing patients with and without AVH.

11 patients meeting DSM-5 criteria for schizophrenia or schizoaffective disorder and 10 age, sex and estimated premorbid IQ-matched healthy controls have so far taken part.

Participants underwent functional MRI in a 3T scanner while performing a task requiring them to recall autobiographical memories in response to individually tailored pairs of cue words. The cue words were based on autobiographical memories previously elicited in an interview with each patient and were designed to evoke the same memory. The cue words were presented in 10 20-second blocks interspersed with blocks where the subjects viewed cue words that did not evoke autobiographical memories. Brain activations were examined in three contrasts of interest: memory evoking words vs baseline, neutral words vs baseline and memory evoking vs neutral words.

Pre-processing and analysis were carried out with the FEAT module included in the FSL software. Statistical analysis was performed by means of a General Linear Model (GLM) approach.

In the memory evoking vs baseline contrast the patients showed hypoactivation in the medial frontal cortex compared to the healthy controls (Figure 1). There were no differences in activation between the patients and the controls comparing the memory evoking and neutral cues.

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The finding of hypoactivation in the medial frontal cortex compared to low level baseline in patients with schizophrenia suggests dysfunction in the default mode network, which is known to activate during recall of autobiographical memories.

These preliminary results suggest that recall of negative autobiographical memories in patients with schizophrenia is associated with reduced activity in the default mode network. A planned larger sample of patients and controls will be used to examine activations in patients with and without AVH.

None Declared

Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.

Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.

Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer’s disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment.

Systematic review, Meta-Analysis

We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023.

RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included.

Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423).

The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer’s Disease Assessment Scale–Cognitive Subscale (SMD = −0.96 [−1.32, −0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity.

The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.

Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers less radiation to healthy brain tissue. PRT has been associated with improved long term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory outcomes.

Survivors of pediatric brain tumor treated with either XRT (n = 29) or PRT (n = 51) completed neuropsychological testing > 1 year following radiotherapy. XRT and PRT groups were similar with respect to sex, handedness, race, age at diagnosis, age at evaluation, tumor characteristics, and treatment history (i.e., craniospinal irradiation, craniotomy, shunting, chemotherapy, radiation dose). Verbal learning and memory were assessed using the age-appropriate version of the California Verbal Learning Test (CVLT-II/CVLT-C). Measures of intellectual functioning, executive functioning, attention and adaptive behavior were also collected. Performance on neuropsychological measures was compared between treatment groups (XRT vs. PRT) using analysis of covariance (ANCOVA). On the CVLT, each participant was classified as having an encoding deficit profile (i.e., impaired learning, recall, and recognition), retrieval deficit profile (i.e., impaired recall but intact recognition), intact profile, or other profile. Chi-squared tests of independence were used to compare the probability of each memory profile between treatment groups. Pearson correlation was used to examine associations between memory performance and strategy use, intellectual functioning, adaptive behavior, attention, and executive functioning.

Overall, patients receiving PRT demonstrated superior verbal learning (CVLT Trials 1-5; t(76) = 2.61, p = .011), recall (CVLT Long Delay Free; t(76) = 3.57, p = .001) and strategy use (CVLT Semantic Clustering; t(76) = 2.29, p = .025) compared to those treated with XRT. Intact performance was more likely in the PRT group than the XRT group (71% PRT, 38% XRT; X2 = 8.14, p = .004). Encoding and retrieval deficits were both more common in the XRT group, with encoding problems being most prevalent (Encoding Deficits: 31% XRT, 12% PRT, X2 = 4.51, p = .034; Retrieval Deficits: 17% XRT, 4% PRT, X2 = 4.11, p = .043). Across all participants, semantic clustering predicted better encoding (r = .28, p = .011) and retrieval (r = .26, p = .022). Better encoding predicted higher intellectual (r = .56, p < .001) and adaptive functioning (r = .30, p = .011), and fewer parent-reported concerns about day-today attention (r = -.36, p = .002), and cognitive regulation (r = -.35, p = .002).

Results suggest that PRT is associated with superior verbal memory outcomes compared to XRT, which may be driven by encoding skills and use of learning strategies. Moreover, encoding ability predicted general intellectual ability and day-to-day functioning. Future work may help to clarify underlying neural mechanisms associated with verbal memory decline following radiotherapy, which will better inform treatment approaches for survivors of pediatric brain tumor.

Primary progressive aphasia semantic variant (PPA-SV) is an atypical dementia subtype on the frontotemporal dementia (FTD) spectrum. PPA-SV is clinically defined by naming and semantic deficits, with progressive language decline that generalizes to other domains over time. Typically, it presents as an early-onset dementia with TDP-43 pathology, but 33-46% of PPA-SV cases display initial onset after age 65 with potentially different clinical features. Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE), a more recently discovered neurodegenerative entity, is defined by an older age of onset, hippocampal sclerosis/atrophy, and TDP-43 pathology with a gradually progressive amnestic profile that expands to other cognitive deficits over time. The authors present a case report with overlapping features and suspected TDP-43 neuropathology ante-mortem for two reasons: first, to highlight the need for clinical criteria to formally diagnose LATE, and second, to address a gap in the literature on the possible clinical differences of late-onset PPA-SV.

The authors present a case of a 78-year-old Indian bilingual man (English dominant) with 18 years of education, noncontributory medical history, and gradually progressive cognitive complaints reported over the past few years who was seen for outpatient neuropsychological evaluation. Prior workup was notable for negative amyloid PET scan, negative p-tau 217 blood test, and abnormal brain MRI revealing marked bilateral hippocampal atrophy with ex vacuo ventriculomegaly and minimal cerebrovascular disease. He scored 23/30 on prior MMSE, was diagnosed with amnestic MCI, prescribed Namenda and Exelon, and complained of minor memory and word-finding difficulties with reportedly intact IADLs and no signs of NPH.

Neuropsychological testing revealed a profound dysnomia (RBANS Naming raw score = 1/10), and he provided 0 words on two semantic fluency tasks but 15 words on letter fluency. Receptive vocabulary score was also impaired (PPVT-4, <1st %). Memory performance also demonstrated rapid forgetting of information (RBANS List Recall raw = 0/10, Story Recall raw = 0/12) with no benefit to recognition cues (RBANS List Recognition raw = 12/20), but slightly better visual memory recall, albeit still impaired (RBANS Figure Recall raw = 4/20). Grooved pegboard scores were significantly worse with right-hand than left-hand. Irregular word reading (NAART = 16th %ile) was significantly below expectations and thought to reflect more of a surface dyslexia rather than a cultural confounder given that he has lived in the US for over 50 years and his occupational and educational history was completed in English.

Results support the clinical utility of neuropsychological evaluation in the differential diagnosis to support a predominant clinical syndrome of PPA-SV despite overlapping features with LATE and suspected TDP-43 pathology. This case report highlights the diagnostic issue with the lack of literature describing the typical clinical progression or suggested diagnostic criteria of LATE. These findings also indicate that late-onset PPA-SV may include greater memory deficits earlier in the course, but this may also be a clinical masquerade that is more reflective of the extent of language deficits. Further research on late-onset manifestations of PPA-SV and LATE consensus clinical guidelines is advised.

We explored the utility of the standardized infection ratio (SIR) for surgical site infection (SSI) reporting in an Australian jurisdiction.

Retrospective chart review.

Statewide SSI surveillance data from 2013 to 2019.

Individuals who had cardiac bypass surgery (CABG), colorectal surgery (COLO), cesarean section (CSEC), hip prosthesis (HPRO), or knee prosthesis (KPRO) procedures.

The SIR was calculated by dividing the number of observed infections by the number of predicted infections as determined using the National Healthcare Safety Network procedure-specific risk models. In line with a minimum precision criterion, an SIR was not calculated if the number of predicted infections was <1.

A SIR >0 (≥1 observed SSI, predicted number of SSI ≥1, no missing covariates) could be calculated for a median of 89.3% of reporting quarters for CABG, 75.0% for COLO, 69.0% for CSEC, 0% for HPRO, and 7.1% for KPRO. In total, 80.6% of the reporting quarters, when the SIR was not calculated, were due to no observed infections or predicted infections <1, and 19.4% were due to missing covariates alone. Within hospitals, the median percentage of quarters during which zero infections were observed was 8.9% for CABG, 20.0% for COLO, 25.4% for CSEC, 67.3% for HPRO, and 71.4% for KPRO.

Calculating an SIR for SSIs is challenging for hospitals in our regional network, primarily because of low event numbers and many facilities with predicted infections <1. Our SSI reporting will continue to use risk-indexed rates, in tandem with SIR values when predicted number of SSI ≥1.

Up to 50% of patients with brain tumors experience psychiatric symptoms, and rates up to 80% have been reported in malignant neoplasms such as glioblastoma multiforme (GBM). Still, clinical presentation as mania-like syndromes is a rare phenomenon, mainly occurring when frontal structures are compromised.

We present the case of a 42-year-old woman who was admitted to our hospital due to manic symptoms coinciding with a recurrence of a bifrontal GBM, for which she underwent surgery 5 months prior.

1) To describe the clinical particularities of this case, focusing on the differential diagnosis.

2) To review the association between manic symptoms and frontal dysfunction caused by brain tumors, with special interest on GBM.

A review of the patient’s clinical history and complementary tests performed was carried out. Likewise, we reviewed the available literature in relation to manic symptoms related to brain tumors.

The patient’s GBM recurrence presented with late onset symptoms of mania, including euphoric mood, increased spending, ideas of grandiosity and hyper-religiosity. She had no previous psychiatric history but, interestingly, she had an extensive affective burden in her family, with 4 consummated suicides. However, she also presented other clinical signs, such as disorientation, perseveration, mild memory impairment and stereotyped motor behaviors, that pointed to relevant frontal lobe dysfunction, suggesting Moria as a possible contribution for the symptoms described.

Manic symptoms in the context of brain tumors appear in 7-15% of patients with psychiatric symptoms, usually associated with right frontal dysfunction (75% of cases). Bifrontal affectation, such as this patient, is only described in 6% of cases. Although fast growing, malignant tumors have been associated with higher rates of psychiatric symptoms, no correlation has been described between these and brain tumor histology.

- The presence of atypical manic symptoms, such as those presented in this case, should raise clinical concern for secondary mania.

- Moria shares similarities with mania, including mood elevation, tendency to hilarity or hyper-sexuality, that may hinder diagnosis of patients with frontal dysfunction.

- This case outlines the difficulties in making a differential diagnosis in patient with both manic and neurological signs, and highlights the implication of frontal structures in the development of manic symptoms.

None Declared

The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world’s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19.

The aim of this sudy was to test the potential antiviral and anti-inflammatory activities of fluoxetine against SARS-CoV-2 in a K18-hACE2 mouse model of infection, and against several variants of concern in vitro, and test the hypothesis of the implication of ceramides and/or their derivatives hexosylceramides.

We evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5.

Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres (Figure 1) and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10) (Figure 2). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects (Figure 3).

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Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.

None Declared

Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.

In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.

Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.

Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Our study aimed to (1) identify trajectories on different mental health components during a two-year follow-up of the COVID-19 pandemic and contextualise them according to pandemic periods; (2) investigate the associations between mental health trajectories and several exposures, and determine whether there were differences among the different mental health outcomes regarding these associations.

We included 5535 healthy individuals, aged 40–65 years old, from the Barcelona Brain Health Initiative (BBHI). Growth mixture models (GMM) were fitted to classify individuals into different trajectories for three mental health-related outcomes (psychological distress, personal growth and loneliness). Moreover, we fitted a multinomial regression model for each outcome considering class membership as the independent variable to assess the association with the predictors.

For the outcomes studied we identified three latent trajectories, differentiating two major trends, a large proportion of participants was classified into ‘resilient’ trajectories, and a smaller proportion into ‘chronic-worsening’ trajectories. For the former, we observed a lower susceptibility to the changes, whereas, for the latter, we noticed greater heterogeneity and susceptibility to different periods of the pandemic. From the multinomial regression models, we found global and cognitive health, and coping strategies as common protective factors among the studied mental health components. Nevertheless, some differences were found regarding the risk factors. Living alone was only significant for those classified into ‘chronic’ trajectories of loneliness, but not for the other outcomes. Similarly, secondary or higher education was only a risk factor for the ‘worsening’ trajectory of personal growth. Finally, smoking and sleeping problems were risk factors which were associated with the ‘chronic’ trajectory of psychological distress.

Our results support heterogeneity in reactions to the pandemic and the need to study different mental health-related components over a longer follow-up period, as each one evolves differently depending on the pandemic period. In addition, the understanding of modifiable protective and risk factors associated with these trajectories would allow the characterisation of these segments of the population to create targeted interventions.