Schizophrenia patients with a history of community violence constitute a sub-group of schizophrenia patients (SCZ) that receive much public attention. While brain structural abnormalities are established in SCZ, there are few studies of brain morphology in violent SCZ.

To conduct a pilot study of brain morphology in a SCZ cohort with a history of severe community violence from a high security forensic psychiatric unit.

Investigate differences in hippocampal, ventricular, thalamic, and amygdala volumes in violent SCZ, SCZ, and healthy controls (HC).

Structural 3T MRI scans were acquired of 47 subjects (violent SCZ n=11, mean age 33.2 years (SD 9.0), 91% male; SCZ n= 17, 34.3 years (7.4), 94% male; HC n=19, 33.2 years (9.1), 90% male). Violent offence included murder, attempted murder, or severe assault (with or without weapon) towards other people. The FreeSurfer 5.3.0 software was used to obtain subcortical brain volumes. Effects of age, sex, and intracranial volume were controlled for, and Bonferroni correction was applied.

Violent SCZ had smaller right hippocampal volumes (F(2,42)=4.11, p= .024) compared to HC (padj= .028) and SCZ (pnom= .046). On a trend level, violent SCZ had larger right lateral ventricles than HC (pnom =.032) and SCZ (pnom=.049), and smaller left hippocampus than HC (pnom =.027). No differences in thalamus and amygdala volumes were found.

Violent SCZ may be associated with more pronounced brain abnormalities than non-violent SCZ. Future studies are needed to verify the observed abnormalities and determine the pathophysiological mechanisms and functional consequences.

The insulin receptor substrate-4 (IRS-4) protein is highly expressed in the hypothalamus that plays a main role in the regulation of body weight. at the same time, overweight and obesity are more common in patients with schizophrenia compared to the general population. Therefore, this study was undertaken to investigate potential associations between body mass index (BMI) or height and polymorphisms in the IRS-4 gene in schizophrenia patients and healthy control subjects.

The whole IRS-4 gene of 93 patients and 59 control subjects was screened for DNA sequence variations, and then 10 detected single nucleotide polymorphisms (SNPs) were investigated in relation to BMI and height of patients and control subjects.

Mean BMI was higher in patients than in control subjects, whereas there was no difference regarding height. Significant associations were found between patients' BMI and genotypes of six IRS-4 SNPs or a haplotype including these six SNPs. in contrast, no associations were found between BMI or height of control subjects, or height of patients, and the genotypes or haplotypes.

This study clearly demonstrates associations between BMI and IRS-4 gene variants in schizophrenia patients, but not in healthy control subjects, pointing to a possible involvement of IRS-4 in the control of body weight in schizophrenia.

The authors have not supplied their declaration of competing interest.

To evaluate the initial (3 months) all-cause discontinuation and safety of aripiprazole once-monthly 400mg (AOM-400mg), an extended release injectable suspension of aripiprazole, stratified by previous treatment.

These two studies (NCT00705783 & NCT00706654) were double-blind, placebo- or active-controlled assessing the efficacy and safety of AOM-400mg. Detailed study designs have been reported previously (1, 2). This analysis was conducted on the pooled population in the first 3 months after initiating AOM-400mg treatment, on patients who received at least one dose of AOM-400mg. Outcome measures are reported for groups stratified by prior treatment.

During the first 3 months of treatment, discontinuation due to all-causes (except for those who discontinued due to the sponsor stopping the NCT00705783 study early after pre-specified efficacy parameters were met) as well as due to adverse events are presented in Table 1. The rates of insomnia and akathisia are shown in Table 1

Aripiprazole once-monthly 400mg appeared equally safe and effective (as measured by all cause discontinuation) in the first 3 months after initiation, regardless of treatment prior to entering trials.

Are we making the most of Clozapine?

Clozapine treatment remains the gold standard for treatment-resistant schizophrenia. Currently, clozapine use varies worldwide, from as high as 60% of psychotic patients in China to as low as 2 – 3% of psychotic patients in certain areas of the United States and Canada. Many physicians are reluctant, for a variety of reasons, to prescribe clozapine.

1. 1. To highlight to concerns physicians may have about initiating and maintaining Clozapine therapy in patients with treatment – resistant schizophrenia.

2. 2. To understand the adverse effects that are most pertinent to both physicians and their patients

To understand the barriers to prescribing Clozapine.

The authors obtained contact information for all psychiatrists registered with the College of Physicians and surgeons in Ontario, Canada. Physicians were mailed and invitation to complete a questionnaire online, or receive a paper copy, asking about potential barriers to prescribing Clozapine.

The final results of our project are still under analysis but based on the sampling done so far Clozapine therapy is limited in Ontario, Canada due to concerns of potential adverse side effects associated with clozapine therapy. There is also a limitation of access to resources to initiate and maintain patients on clozapine.

Clozapine use is still limited in many countries including Canada. Providing more education about managing the potential adverse effects and easier access to initiating and maintaining clozapine treatment will be helpful in promoting its use.

Schizophrenia is a chronic disorder with an early onset and high disease burden in terms of life disability. Its early recognition may delay the resulting brain structural/functional alterations and improve treatment outcomes. Unlike conventional group-statistics, machine-learning techniques made it possible to classify patients and controls based on the disease patterns on an individual level. Diagnostic classification in first-episode schizophrenia to date was mostly performed on sMRI or fMRI data. DTI modalities have not gained comparable attention.

We performed the classification of 77 FES patients and 77 healthy controls matched by age and sex from fractional anisotropy data from using linear support-vector machine (SVM). We further analyzed the effect of medication and symptoms on the classification performance using standard statistical measures (t-test, linear regression) and machine learning (Kernel–Ridge regression).

The SVM distinguished between patients and controls with significant accuracy of 62.34% (P = 0.005). There was no association between the classification performance and medication nor symptoms. Group level statistical analysis yielded brain-wide significant differences in FA.

The SVM in combination with brain white-matter fractional anisotropy might help differentiate FES from HC. The performance of our classification model was not associated with symptoms or medications and therefore reflects trait markers in the early course of the disease.

The authors have not supplied their declaration of competing interest.

In the first months of 2020 the COVID-19 epidemic spread in Italy, and the Italian government implemented a general lockdown. These events are at high risk for psychiatric symptoms in the general population, including anxiety/depression and post-traumatic stress symptoms (PTSS).

To characterize the psychopathological correlates of the spread of COVID-19 and lockdown in a sample of subjects from the Italian population, with a before-after follow-up.

Six weeks after the lockdown, 671 subjects aged 18-60 years completed the Brief Symptom Inventory and Impact of Event Scale-Revised, for the evaluation of psychopathology and PTSS respectively. Environmental factors and subjectively-perceived deteriorations related to COVID-19 were also investigated. Pre-COVID-19 data on psychopathology, collected in December 2019/January 2020, were available for 130 subjects and were used for longitudinal analyses.

With respect to males, female subjects more frequently reported deteriorations of relations (21.5% vs 10.9%), household arguments (26.0% vs 12.6%), sleep quality (47.6% vs 26.6%), episodes of overeating (22.5% vs 12.5%), worries for oneself (19% vs 8.9%) and for loved ones (55.7% vs 36.5%). These changes were associated with increased psychopathology, PTSS, and numerous environmental conditions, including significant economic damage from COVID-19/lockdown. Longitudinal analyses showed an increase in phobic anxiety in the whole sample, and in depression for female subjects only, following the spread of COVID-19. Pre-existing psychopathology was a significant predictor of PTSS.

COVID-19 epidemic and lockdown have a high impact on psychopathology and PTSS. Female subjects and those with pre-existing psychopathology were found to be more vulnerable and may need additional support.

No significant relationships.

The term depressive pseudodementia has proved to be a popular clinical concept. Little is known about the long-term outcome of this syndrome.

To compare depressed elderly patients with reversible cognitive impairment and cognitively intact depressed elderly patients.

All patients suffering from moderate or severe depression admitted to St Margaret's Hospital, UK as inpatients or day hospital outpatients between January 1, 1997 and December 31, 1999 (n=182) were screened for entry into the study. Eligible patients were divided into those presenting with pseudodementia and those who were cognitively intact and followed up for 5 to 7 years.

Seventy one percent point four percent of those suffering from pseudodementia had converted into dementia at follow up compared to only 18.2% in the cognitively intact group. The relative risk was 3.929 (95% CI: 1.985 to 7.775) and the ‘number needed to harm’ 1.88.

Reversible cognitive impairment in late-life moderate to severe depression appears to be a strong predictor of dementia. Patients with pseudodementia should probably have a full dementia screening, comprehensive cognitive testing and ongoing monitoring of their cognitive function.

Recent studies have suggested an association between elevated levels of bilirubin and psychotic spectrum disorders. The aim of our study was to compare the levels of bilirubin in the different psychotic disorders among themselves and with other mental disorders.

Observational, retrospective, in a sample of patients admitted to the Acute Psychiatric Unit between January 2007 and December 2009. We included all patients with plasma concentrations of bilirubin in the blood analysis. We excluded patients with toxic abuse and alterations in the liver reflected in increased transaminases.

The final sample of 523 patients. Patients with psychotic disorder had bilirubin levels significantly higher than patients with other diagnosis (p < 001).

Psychotic disorders were subdivided into 5 groups: schizophrenia (N = 76), schizoaffective disorder (N = 53), delusional disorder (N = 21), brief psychotic disorder (N = 29) and other unspecified psychotic disorders (N = 34). The brief psychotic disorder patients had bilirubin levels significantly higher than other categories of the same spectrum (p < 0.001).

The psychotic spectrum patients have higher bilirubin levels at admission than other diagnostic entities, and this increase is mainly explained by Brief Psychotic Disorder. Bilirubin figures correlate negatively with psychotic symptoms days, so the brief psychotic disorder, is proclaimed as an ideal model for the llaboratory studies about psychotic spectrum disorders.

Presentation of a clinical case and use of a bibliography from the following search engines: PubMed, Science direct, Medscape.

This case is about a 62-year-old woman, hypertensive and obese, who had a gastric by-pass complicated by deficiency neuropathy and Gayet Wernicke’s encephalopathy. While neurological symptoms were improved by treatment with B1 and B12 vitamins, carbamazepine and clomipramine, a state of psychomotor excitation persisted and prompted a psychiatric consultation. The diagnosis of a maniac episode was retained and the patient was put under mood stabilizer treatment.

Etiological research discussed three cases:

A mania induced by Vitamin B12 deficiency, associated to neurological symptoms with impaired memory, paresthesia, and ataxia.

A mania induced by treatment with clomipramine.

A primary mania in an obese woman. This possibility is not uncommon. Indeed, several studies have confirmed the frequency of comorbidity of mood disorders and obesity.

Foreign accent syndrome (FAS) is a rare condition involving speech output that usually occurs subsequent to cerebrovascular injury. Articulatory distortions of the native language are perceived as foreign/dialectical by others of the region.

This report considers a case of FAS during two distinct periods of mania without evidence of cerebrovascular injury. The case provides a detailed explanation of the patient's history, course, speech and neuropsychological testing patterns.

To describe in the literature the first case of mania-induced FAS.

This case study was detailed retrospectively, providing a thorough psychiatric and medical history, formal neuropsychological testing, and speech analysis of baseline and exacerbation periods via voice recordings.

The patient displayed two distinct episodes of FAS only present during mania. Due to signs of limited effort, as well as potential effects of anxiety on performance, neuropsychological testing reflected inconsistent findings irreconcilable with any particular diagnostic pattern. Speech samples from both exacerbation and recovery periods parsed for comparison showed excess-equal stress, and consonant-vowel distortions when symptomatic. Elevated fundamental frequency, higher intensity, decreased speech intelligibility, and faster rate of speech were produced during exacerbation. No significant medical abnormalities were revealed by laboratory, CT scan or physical exam results.

As the patient had no history of cardiovascular or cerebrovascular disease, negative medical workup, negative brain imaging, and neuropsychological testing failing to demonstrate an etiology for the FAS exacerbation, we conclude the patient's FAS was a result of mania. Speech analysis also supported this theory.

Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo.

This is a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. 210 treatment-seekers with DSM-IV diagnosis of cocaine dependence consented and enrolled. 72 participants were randomized to placebo, 69 to modafinil 200mg, and 69 to modafinil 400mg, taken once daily on awakening. Participants attended the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy once per week. The primary outcome was the increase in weekly percentage of non-use days. Secondary outcomes included: decrease in the weekly median log of urine benzoylecgonine, subgroup analyses of balancing factors and co-morbid conditions, self-report of alcohol use, addiction severity, craving, and risk behaviors for HIV.

125 participants completed 12 weeks of treatment (60%). The GEE regression analysis showed that for the total sample, the difference between modafinil groups and placebo in the weekly percentage of cocaine non-use days over the 12-week treatment period was not statistically significant (p=0.95). A post-hoc analysis showed a significant effect for modafinil, only in the subgroup of cocaine patients without alcohol dependence. Modafinil 200mg also showed significant effects of an increase in the total number of consecutive non-use days for cocaine (p=0.02), and a reduction in craving (p=0.04).

These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing craving.