N-Methyl-D-Aspartate Receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness.

Our aim was to determine if NMDAR availability was lower in patients with first episode psychosis compared to healthy controls.

To address this, we studied 40 volunteers (21 patients with first episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Striatal glutamatergic indices (glutamate and Glx) were measured simultaneously using magnetic resonance spectroscopy imaging (1H-MRS).

Hippocampal DVR, but not VT, was significantly lower in patients relative to controls (p=0.02, Cohen’s d=0.81; p=0.15, Cohen’s d=0.49), and negatively associated with total (rho=-0.47, p= 0.04), depressive (rho=-0.67, p=0.002), and general symptom severity (rho=-0.74, p<0.001). Exploratory analyses found no significant differences in other brain regions (anterior cingulate cortex, thalamus, striatum and temporal cortex). We found an inverse relationship between hippocampal NMDAR availability and striatal glutamate levels in people with first-episode psychosis (rho = -0.74, p <0.001) but not in healthy controls (rho = -0.22, p = 0.44).

These findings are consistent with the NMDAR hypofunction hypothesis and identify the hippocampus as a key locus for relative NMDAR hypofunction, although further studies should test specificity and causality.

No significant relationships.

Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls.

We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder.

Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23–4.47, p = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03–3.39, p = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring.

Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.

The use of mechanical restraint is a challenging area for psychiatry. Although mechanical restraint remains accepted as standard practice in some regions, there are ethical, legal and medical reasons to minimise or abolish its use. These concerns have intensified following the Convention on the Rights of Persons with Disabilities. Despite national policies to reduce use, the reporting of mechanical restraint has been poor, hampering a reasonable understanding of the epidemiology of restraint. This paper aims to develop a consistent measure of mechanical restraint and compare the measure within and across countries in the Pacific Rim.

We used the publicly available data from four Pacific Rim countries (Australia, New Zealand, Japan and the United States) to compare and contrast the reported rates of mechanical restraint. Summary measures were computed so as to enable international comparisons. Variation within each jurisdiction was also analysed.

International rates of mechanical restraint in 2017 varied from 0.03 (New Zealand) to 98.8 (Japan) restraint events per million population per day, a variation greater than 3000-fold. Restraint in Australia (0.17 events per million) and the United States (0.37 events per million) fell between these two extremes. Variation as measured by restraint events per 1000 bed-days was less extreme but still substantial. Within all four countries there was also significant variation in restraint across districts. Variation across time did not show a steady reduction in restraint in any country during the period for which data were available (starting from 2003 at the earliest).

Policies to reduce or abolish mechanical restraint do not appear to be effecting change. It is improbable that the variation in restraint within the four examined Pacific Rim countries is accountable for by psychopathology. Greater efforts at reporting, monitoring and carrying out interventions to achieve the stated aim of reducing restraint are urgently needed.

Basic Self disturbances (BSD), including changes of the 'pre-reflexive' sense of self and the loss first-person perspective, are characteristic of the schizophrenic spectrum disorders and highly prevalent in subjects at 'ultra high risk' for psychosis (UHR). The current literature indicates that cortical midline structures (CMS) may be implicated in the neurobiological substrates of the 'basic self' in healthy controls.

Neuroanatomical investigation of BSD in a UHR sample

To test the hypotheses :(i) UHR subjects have higher 'Examination of Anomalous Self Experience, EASE' scores as compared to controls, (ii) UHR subjects have neuroanatomical alterations as compared to controls in CMS, (iii) within UHR subjects, EASE scores are directly related to structural CMS alterations.

32 HR subjects (27 antipsychotics-naïve) and 17 healthy controls (HC) were assessed with the 57-items semi-structured EASE interview. Voxel-Based Morphometry (VBM) was conducted in the same subjects, with a-priori Region of Interests (ROIs) defined in the CMS (anterior/posterior cingulate and medial-prefrontal cortex).

Despite high variability in the HR group, the overall EASE score was higher (t-test >0.01, Cohen's d =2.91) in HR (mean=30.15, SD=16.46) as compared to HC group (mean=1.79, SD=2.83). UHR subjects had gray matter reduction in CMS as compared to HC (p>0.05 FWE-corrected). Across the whole sample, lower gray matter volume in the anterior cingulate was correlated with higher EASE scores (p>0.05).

This study provides preliminary evidence that gray matter reductions in the CMS are correlated with BSD in UHR people.

The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.

We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.

This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.

Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).

Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.

Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.

Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.

Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.

Impairments in the attribution of salience are thought to be fundamental to the development of psychotic symptoms and the onset of psychotic disorders. The aim of the present study was to explore longitudinal alterations in salience processing in ultra-high-risk subjects for psychosis.

A total of 23 ultra-high-risk subjects and 13 healthy controls underwent functional magnetic resonance imaging at two time points (mean interval of 17 months) while performing the Salience Attribution Test to assess neural responses to task-relevant (adaptive salience) and task-irrelevant (aberrant salience) stimulus features.

At presentation, high-risk subjects were less likely than controls to attribute salience to relevant features, and more likely to attribute salience to irrelevant stimulus features. These behavioural differences were no longer evident at follow-up. When attributing salience to relevant cue features, ultra-high-risk subjects showed less activation than controls in the ventral striatum at both baseline and follow-up. Within the high-risk sample, amelioration of abnormal beliefs over the follow-up period was correlated with an increase in right ventral striatum activation during the attribution of salience to relevant cue features.

These findings confirm that salience processing is perturbed in ultra-high-risk subjects for psychosis, that this is linked to alterations in ventral striatum function, and that clinical outcomes are related to longitudinal changes in ventral striatum function during salience processing.

Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.

This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.

Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).

For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.

Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear. The objective of this study was to assess prospectively the influence of cannabis use on transition to psychosis in people at ultra-high risk (UHR) for the disorder.

Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people (104 male, 78 female) at UHR for psychosis. Individuals were then followed clinically for 2 years to determine their clinical outcomes.

Lifetime cannabis use was reported by 134 individuals (73.6%). However, most of these individuals had stopped using cannabis before clinical presentation (n = 98, 73.1%), usually because of adverse effects. Among lifetime users, frequent use, early-onset use and continued use after presentation were all associated with an increase in transition to psychosis. Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently (frequent early-onset use: 25%; infrequent or late-onset use: 5%; χ21 = 10.971, p = 0.001). However, within the whole sample, cannabis users were no more likely to develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no use: 18.8%; χ21 = 1.061, p = 0.303).

In people at UHR for psychosis, lifetime cannabis use was common but not related to outcome. Among cannabis users, frequent use, early-onset use and continued use after clinical presentation were associated with transition to psychosis.

Variant anatomy of the hypoglossal nerve is very rare. We report an unusual intra-operative finding of an aberrant branch of the hypoglossal nerve, encountered during a facial reanimation procedure.

A 50-year-old man was referred to the head and neck surgery department by the neurosurgeons for hypoglossal-facial nerve anastomosis to treat his facial paralysis, which had occurred following the removal of an intracranial neoplasm. During surgery, we identified an aberrant branch of the hypoglossal nerve, which took a more ventral and superior course in the carotid triangle, prior to entering the base of the tongue. Following further dissection, we found the main trunk of the ‘true’ hypoglossal nerve. Several interconnecting strands were seen in the proximal aspect of both the aberrant branch and the main trunk of the hypoglossal nerve. These interconnecting fibres appeared to have tethered the main trunk into an abnormal anatomical position.

As far as we can ascertain, this is the first report of an aberrant branch of the hypoglossal nerve. Although this variant would appear to be extremely rare, surgeons must consider all variations of this nerve during head and neck procedures, in order to minimise iatrogenic complications.

Interpersonal sensitivity is a personality trait described as excessive awareness of both the behaviour and feelings of others. Although interpersonal sensitivity has been found to be one of the vulnerability factors to depression, there has been little interest in its relationship with the prodromal phase of psychosis. The aims of this study were to examine the level of interpersonal sensitivity in a sample of individuals with an at-risk mental state (ARMS) for psychosis and its relationship with other psychopathological features.

Method. Sixty-two individuals with an ARMS for psychosis and 39 control participants completed a series of self-report questionnaires, including the Interpersonal Sensitivity Measure (IPSM), the Prodromal Questionnaire (PQ), the Ways of Coping Questionnaire (WCQ) and the Depression and Anxiety Stress Scale (DASS).

Individuals with an ARMS reported higher interpersonal sensitivity compared to controls. Associations between interpersonal sensitivity, positive psychotic symptoms (i.e. paranoid ideation), avoidant coping and symptoms of depression, anxiety and stress were also found.

This study suggests that being ‘hypersensitive’ to interpersonal interactions is a psychological feature of the putatively prodromal phase of psychosis. The relationship between interpersonal sensitivity, attenuated positive psychotic symptoms, avoidant coping and negative emotional states may contribute to long-term deficits in social functioning. We illustrate the importance, when assessing a young client with a possible ARMS, of examining more subtle and subjective symptoms in addition to attenuated positive symptoms.