Preclinical evidence has identified the trace amine-associated receptor 1 (TAAR1) as a novel regulator of metabolic control. Ulotaront is a TAAR1 and 5-HT1A agonist currently in Phase 3 clinical trials for the treatment of schizophrenia. Here we summarize preclinical results assessing the effects of ulotaront on weight and metabolic parameters.

Effects of ulotaront administration were evaluated on oral glucose tolerance (oGTT), gastric emptying, and in rodent models of weight gain (high-fat diet [HFD]-, corticosterone-, and olanzapine-induced).

Following 15-day oral administration of ulotaront, rats on HFD showed dose-dependent reduction in body weight, food intake, and liver triglyceride content compared to controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in rats switched to ulotaront (vs. vehicle). Consistent with weight-lowering effects in rats, chronic ulotaront treatment normalized corticosterone-induced weight gain in mice. Assessment of oGTT showed a dose-dependent reduction of glucose excursion in response to acute ulotaront administration in naive and diabetic db/db mice. Ulotaront administration also delayed gastric emptying in mice—a likely mechanism driving reductions in glucose excursions during the oGTT. Whole-brain c-fos imaging of ulotaront-treated mice revealed increased neuronal activity in several brain regions associated with regulation of food intake and metabolic signals.

The data indicate that ulotaront not only lacks metabolic liabilities typically associated with antipsychotics but can reduce body weight and improve glucose tolerance in rodent models. The underlying mechanisms may include TAAR1-mediated peripheral effects on glucose homeostasis and/or direct modulation of homeostatic and hedonic neurocircuits regulating energy balance. The beneficial metabolic effects of ulotaront may suggest a substantially improved risk-benefit profile compared to established antipsychotics.

Sunovion Pharmaceuticals Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

A significant number of people with autism require in-patient psychiatric care. Although the requirement to adequately meet the needs of people with autism in these settings is enshrined in UK law and supported by national guidelines, little information is available on current practice.

To describe characteristics of UK in-patient psychiatric settings admitting people with autism. Also to examine psychiatric units for their suitability, and the resultant impact on admission length and restrictive interventions.

Multiple-choice questions about in-patient settings and their ability to meet the needs of people with autism and the impact on their outcomes were developed as a cross-sectional study co-designed with a national autism charity. The survey was distributed nationally, using an exponential and non-discriminatory snowballing technique, to in-patient unit clinicians to provide a current practice snapshot.

Eighty responses were analysed after excluding duplications, from across the UK. Significant variation between units across all enquired parameters exist. Lack of autism-related training and skills across staff groups was identified, this becoming disproportionate when comparing intellectual disability units with general mental health units particularly regarding psychiatrists working in these units (psychiatrists: 94% specialist skills in intellectual disability units versus 6% specialist skills in general mental health units). In total, 28% of survey respondents felt people with autism are more likely to be subject to seclusion and 40% believed in-patients with autism are likely to end in segregation.

There is no systematic approach to supporting people with autism who are admitted to in-patient psychiatric units. Significant concerns are highlighted of lack of professional training and skill sets resulting in variable clinical practice and care delivery underpinned by policy deficiency. This could account for the reported in-patient outcomes of longer stay and segregation experienced by people with autism.

Emerging data suggest that recovery from mild traumatic brain injury (mTBI) takes longer than previously thought. This paper examines trajectories for cognitive recovery up to 48 months post-mTBI, presenting these visually using a Sankey diagram and growth curve analysis.

This sample (n = 301) represents adults (≥16 years) from a population-based Brain Injury Outcomes in the New Zealand Community study over a 4-year follow-up on the CNS-Vital Signs neuropsychological test. Data were collected within 2 weeks of injury, and then at 1, 6, 12 and 48 months post-injury.

Significant improvement in cognitive functioning was seen up to 6 months post-injury. Using growth curve modelling, we found significant improvements in overall neurocognition from baseline to 6 months, on average participants improved one point per month (0.9; 95% CI 0.42–1.39) p < 0.001. No change in neurocognition was found within the time periods 6–12 months or 12–48 months. The Sankey highlighted that at each time point, a small proportion of participants remained unchanged or declined. Proportionally, few show any improvement after the first 6 months.

Most individuals remained stable or improved over time to 6 months post-injury. Summary statistics are informative regarding overall trends, but can mask differing trajectories for recovery. The Sankey diagram indicates that not all improve, as well as the potential impact of individuals moving in and out of the study. The Sankey diagram also indicated the level of functioning of those most likely to withdraw, allowing targeting of retention strategies.

Rapid diagnosis of dementia is essential to ensure optimum patient care. This study used real-world data to quantify the dementia diagnostic pathway in Australia.

A real-world, cross-sectional survey of physicians and patients.

Clinical practice.

Primary care or specialist physicians managing patients with cognitive impairment (CI).

Descriptive analyses focused on key events in the diagnostic pathway. Regression modeling compared the duration between first consultation and formal diagnosis with various factors.

Data for 600 patients were provided by 60 physicians. Mean time from initial symptoms to first consultation was 6.1 ± 4.4 months; 20% of patients had moderate or severe CI at first consultation. Mean time from first consultation to formal diagnosis was 4.0 ± 7.4 months (1.2 ± 3.6 months if not referred to a secondary physician, and 5.3 ± 8.3 months if referred). Time from first consultation to diagnosis was significantly associated with CI severity at first consultation; time was shorter with more severe CI. There was no association of disease severity and referral to a secondary physician; 69.5% of patients were referred, the majority (57.1%) to a geriatrician. The highest proportion of patients were diagnosed by geriatricians (47.4%). Some form of test or scale was used to aid diagnosis in 98.8% of patients.

A substantial number of Australians experience cognitive decline and behavioral changes some time before consulting a physician or being diagnosed with dementia. Increasing public awareness of the importance of early diagnosis is essential to improve the proportion of patients receiving comprehensive support prior to disease progression.

The impact of traumatic brain injury (TBI) extends beyond the person who was injured. Family caregivers of adults with moderate to severe TBI frequently report increased burden, stress and depression. Few studies have examined the well-being of family members in the mild TBI population despite the latter representing up to 95% of all TBIs.

Five areas of well-being were examined in 99 family members (including parents, partners, siblings, other relatives, adult children, friends or neighbours) of adults (aged ≥16 years) with mild TBI. At 6- and 12-month post-injury, family members completed the Bakas Caregiver Outcomes Scale, Short Form-36 Health Survey, EQ-5D-3L, Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. Outcomes and change over time and associated factors were examined.

At 6 months, group mean scores for health-related quality of life for mental and physical components and overall health status were similar to the New Zealand (NZ) population. Mean scores for sleep, anxiety and depression were below clinically significant thresholds. From 6 to 12 months, there were significant improvements in Bakas Caregiver Outcomes Scale scores by 2.61 (95% confidence interval: 0.72–4.49), health-related quality of life (mental component) and EQ-5D-3L overall health (P = 0.01). Minimally clinically important differences were observed in overall health, anxiety, health-related quality of life and depression at 12 months. Female family members reported significant improvements in physical health over time, and more positive life changes were reported by those caring for males with TBI.

The findings suggest diminished burden over time for family members of adults with mild TBI.