The authors have not supplied their declaration of competing interest.

Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this propensity. This study provides an update regarding the efficacy of agents with some anti-inflammatory actions for schizophrenia symptoms tested in randomized controlled trials (RCTs).

PubMed, Embase, the National Institutes of Health website (http://www.clinicaltrials.gov), and the Cochrane Database of Systematic Reviews were systematically searched for RCTs that investigated clinical outcomes.

Our search yielded 56 studies that provided information on the efficacy of the following components on symptom severity: aspirin, bexarotene, celecoxib, davunetide, dextromethorphan, estrogens, fatty acids, melatonin, minocycline, N-acetylcysteine (NAC), pioglitazone, piracetam, pregnenolone, statins, varenicline, and withania somnifera extract. The results of aspirin [mean weighted effect size (ES): 0.30; n = 270; 95% CI (CI) 0.06–0.54], estrogens (ES: 0.78; n = 723; CI 0.36–1.19), minocycline (ES: 0.40; n = 946; CI 0.11–0.68), and NAC (ES: 1.00; n = 442; CI 0.60–1.41) were significant in meta-analysis of at least two studies. Subgroup analysis yielded larger positive effects for first-episode psychosis (FEP) or early-phase schizophrenia studies. Bexarotene, celecoxib, davunetide, dextromethorphan, fatty acids, pregnenolone, statins, and varenicline showed no significant effect.

Some, but not all agents with anti-inflammatory properties showed efficacy. Effective agents were aspirin, estrogens, minocycline, and NAC. We observed greater beneficial results on symptom severity in FEP or early-phase schizophrenia.

The smr and qacA/B genes in Staphylococcus aureus confer tolerance to antiseptics and are associated with nosocomial acquisition of infection and underlying medical conditions. Such antiseptic tolerance (AT) genes have also been reported in coagulase-negative staphylococci (CoNS) and enterococci, however, few data are available regarding their prevalence. We sought to describe the frequency of AT genes among bloodstream isolates of S. aureus, CoNS and enterococci at Texas Children’s Hospital (TCH).

Banked CoNS, S. aureus and enterococci isolated from blood cultures collected bewteen October 1, 2016, and October 1, 2017, were obtained from the TCH clinical microbiology laboratory. All isolates underwent polymerase chain reaction (PCR) assay for the qacA/B and smr genes. Medical records were reviewed for all cases.

In total, 103 CoNS, 19 Enterococcus spp, and 119 S. aureus isolates were included in the study, and 80.6% of the CoNS possessed at least 1 AT gene compared to 37% of S. aureus and 43.8% of E. faecalis isolates (P < .001). Among CoNS bloodstream isolates, the presence of either AT gene was strongly associated with nosocomial infection (P < .001). The AT genes in S. aureus were associated with nosocomial infection (P = .025) as well as the diagnosis of central-line–associated bloodstream infection (CLABSI; P = .04) and recent hospitalizations (P < .001). We found no correlation with genotypic AT in E. faecalis and any clinical variable we examined.

Antiseptic tolerance is common among bloodstream staphylococci and E. faecalis isolates at TCH. Among CoNS, the presence of AT genes is strongly correlated with nosocomial acquisition of infection, consistent with previous studies in S. aureus. These data suggest that the healthcare environment contributes to AT among staphylococci.

Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinations (AH) have more misperceptions in auditory language perception than those who have never hallucinated.

We used an online survey to determine the presence of hallucinations. Participants filled out the Questionnaire for Psychotic Experiences and participated in an auditory verbal recognition task to assess both correct perceptions (hits) and misperceptions (false alarms). A hearing test was performed to screen for hearing problems.

A total of 5115 individuals from the general Dutch population participated in this study. Participants who reported AH in the week preceding the test had a higher false alarm rate in their auditory perception compared with those without such (recent) experiences. The more recent the AH were experienced, the more mistakes participants made. While the presence of verbal AH (AVH) was predictive for false alarm rate in auditory language perception, the presence of non-verbal or visual hallucinations were not.

The presence of AVH predicted false alarm rate in auditory language perception, whereas the presence of non-verbal auditory or visual hallucinations was not, suggesting that enhanced top-down processing does not transfer across modalities. More false alarms were observed in participants who reported more recent AVHs. This is in line with models of enhanced influence of top-down expectations in persons who hallucinate.

Similar to visual hallucinations in visually impaired patients, auditory hallucinations are often suggested to occur in adults with hearing impairment. However, research on this association is limited. This observational, cross-sectional study tested whether auditory hallucinations are associated with hearing impairment, by assessing their prevalence in an adult population with various degrees of objectified hearing impairment.

Hallucination presence was determined in 1007 subjects aged 18–92, who were referred for audiometric testing to the Department of ENT-Audiology, University Medical Center Utrecht, the Netherlands. The presence and severity of hearing impairment were calculated using mean air conduction thresholds from the most recent pure tone audiometry.

Out of 829 participants with hearing impairment, 16.2% (n = 134) had experienced auditory hallucinations in the past 4 weeks; significantly more than the non-impaired group [5.8%; n = 10/173; p < 0.001, odds ratio 3.2 (95% confidence interval 1.6–6.2)]. Prevalence of auditory hallucinations significantly increased with categorized severity of impairment, with rates up to 24% in the most profoundly impaired group (p < 0.001). The corrected odds of hallucination presence increased 1.02 times for each dB of impairment in the best ear. Auditory hallucinations mostly consisted of voices (51%), music (36%), and doorbells or telephones (24%).

Our findings reveal that auditory hallucinations are common among patients with hearing impairment, and increase with impairment severity. Although more research on potential confounding factors is necessary, clinicians should be aware of this phenomenon, by inquiring after hallucinations in hearing-impaired patients and, conversely, assessing hearing impairment in patients with auditory hallucinations, since it may be a treatable factor.

Decline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.2 deletion syndrome (22q11DS) is an appealing model in this context, as 25% of patients develop psychosis. Furthermore, we recently showed that cognitive decline also precedes the onset of psychosis in individuals with 22q11DS. Here, we investigate whether the early cognitive decline in patients with 22q11DS is associated with alterations in white matter microstructure.

We compared the fractional anisotropy (FA) of white matter in 22q11DS patients with cognitive decline [n = 16; −18.34 (15.8) VIQ percentile points over 6.80 (2.39) years] to 22q11DS patients without cognitive decline [n = 18; 17.71 (20.17) VIQ percentile points over 5.27 (2.03) years] by applying an atlas-based approach to diffusion-weighted imaging data.

FA was significantly increased (p < 0.05, FDR) in 22q11DS patients with a cognitive decline in the bilateral superior longitudinal fasciculus, the bilateral cingulum bundle, all subcomponents of the left internal capsule and the left superior frontal-occipital fasciculus as compared with 22q11DS patients without cognitive decline.

Within 22q11DS, the early cognitive decline is associated with microstructural differences in white matter. At the mean age of 17.8 years, these changes are reflected in increased FA in several tracts. We hypothesize that similar brain alterations associated with cognitive decline take place early in the trajectory of schizophrenia.

Auditory Hallucinations (AH) are nowadays regarded as symptoms following a continuum; from a (transient) phenomenon in healthy individuals on one end to a symptom of (psychiatric) illnesses at the other. An accumulating number of epidemiological studies focused on the prevalence of AH in the general population, but results vary widely. The current meta-analysis aims to synthesize existing evidence on lifetime prevalence of AH across the lifespan.

We conducted a quantitative review and meta-analysis according to PRISMA guidelines. Studies were combined to calculate a mean lifetime general population AH prevalence rate. Moreover, prevalences were calculated for four age groups: children (5–12 years), adolescents (13–17 years), adults (18–60 years) and elderly (⩾60 years).

We retrieved 25 study samples including 84 711 participants. Mean lifetime prevalence rate of AH was 9.6% (95% CI 6.7–13.6%). The mean lifetime prevalence was similar in children (12.7%) and adolescents (12.4%), but these two groups differed significantly from the adults (5.8%) and the elderly (4.5%). Significant heterogeneity indicated that there is still dispersion in true prevalence rates between studies, even within the different age categories.

Current meta-analysis shows that AH are quite common (up to one in ten individuals) in the general population during lifetime, with children and adolescents reporting these experiences significantly more often compared with adults and elderly. Large follow-up studies on the longitudinal course of AH are needed to reveal associated risk and resilience factors.

Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.

This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).

Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.

Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

In patients with borderline personality disorder (BPD), about 22–50% experience auditory verbal hallucinations (AVH). However, the impact of these hallucinations on suicidal ideation, suicide attempts, crisis-service interventions, and hospital admissions is unknown.

In a cross-sectional design, data were collected with the Psychotic Symptom Rating Scales (PSYRATS) and the MINI International Neuropsychiatric Interview Plus, as well as from the medical records of a convenience sample of outpatients fulfilling the DSM-IV criteria for BPD.

Of the 89 included patients, 27 experienced AVH. In the latter group, the presence of AVH was associated with a significantly higher incidence of suicidal plans and attempts in the month prior to study participation, more hospitalisations, and a shorter interval until hospitalisation. All subscales of the PSYRATS correlated positively with suicide plans, while the phenomenological and emotional subscales also correlated positively with suicide attempts. Moreover, higher scores on the emotional subscale were associated with more hospital admissions.

AVH experienced by patients with BPD might constitute a risk factor for suicide plans and attempts, and hospitalisation. This finding emphasises that this population requires adequate clinical attention, as well as effective treatment for AVH.

Previously, we described 103 adults (mean age 41 years) who experienced frequent, auditory verbal hallucinations (AVH), in the absence of a need for mental healthcare. Importantly, these adults were largely past the peak incidence age for psychosis (15–35 years). It is unclear if these older individuals with AVH are still at increased risk for psychosis or other psychopathology. To address this question, we conducted a 5-year follow-up of previously included individuals (103 with AVH, 60 controls).

Eighty-one adults with AVH (78.6%) and forty-nine controls (81.7%) could be contacted and were willing to participate. Participants were screened for psychosis and a need for mental healthcare at follow-up using the Comprehensive Assessment of Symptoms and History interview (CASH). Need for mental healthcare was defined as a clinical diagnosis as identified using the CASH and/or treatment by a mental healthcare specialist. Phenomenology of AVH was assessed with the PSYRATS Auditory Hallucinations Rating Scale.

Five individuals with AVH (6.2%) had developed psychosis and 32 (39.5%) had developed a need for mental healthcare. Voice-related distress at baseline significantly predicted need for mental healthcare. AVH persisted in most individuals (86.4%), without significant changes in phenomenology. None of the controls had developed psychotic symptoms, and need for mental healthcare (n = 6, 12.2%) was significantly lower in this group.

These findings suggest that frequent AVH in non-psychotic adults past the peak incidence age for psychosis constitute a rather static symptom and that individuals with AVH may be best viewed as situated on a need for care continuum.