Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70–84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsychological investigations can offer important insights into the nature, origin and pathophysiology of treatment-resistant schizophrenia (TRS), but methodological limitations in a still emergent field of research have obscured the neuropsychological discriminability of TRS. We report on the first systematic review and meta-analysis to investigate neuropsychological differences between TRS patients and treatment-responsive controls across 17 published studies (1864 participants). Five meta-analyses were performed in relation to (1) executive function, (2) general cognitive function, (3) attention, working memory and processing speed, (4) verbal memory and learning, and (5) visual−spatial memory and learning. Small-to-moderate effect sizes emerged for all domains. Similarly to previous comparisons between unselected, drug-naïve and first-episode schizophrenia samples v. healthy controls in the literature, the largest effect size was observed in verbal memory and learning [dl = −0.53; 95% confidence interval (CI) −0.29 to −0.76; z = 4.42; p < 0.001]. A sub-analysis of language-related functions, extracted from across the primary domains, yielded a comparable effect size (dl = −0.53, 95% CI −0.82 to −0.23; z = 3.45; p < 0.001). Manipulating our sampling strategy to include or exclude samples selected for clozapine response did not affect the pattern of findings. Our findings are discussed in relation to possible aetiological contributions to TRS.

We report on the first open-label, parallel group randomised controlled trial of automated appointment reminders in a psychosis community service in the UK. Ninety-five patients were randomly allocated to receiving/not receiving automated messaging reminders 7 days and 1 day before appointments. All ‘Attended’ and ‘Missed’ appointment outcomes over 6 months were analysed using cluster regression analysis. Reminded appointments were significantly more frequently attended than non-reminded appointments (unadjusted odds ratio (OR) = 3.54, 95% CI 1.36–9.22, P = 0.01; adjusted OR = 2.95, 95% CI 1.05–8.85, P < 0.05). Automated messaging reminders can provide a robust strategy for promoting engagement with psychosis services.

We analysed Stroop (neuropsychological screening test) measures of response inhibition in 18 twin pairs discordant for bipolar I disorder compared with 17 healthy control pairs, as well as 40 singletons with bipolar disorder with psychotic features and a family history of psychosis, 46 of their first-degree relatives without bipolar disorder or psychosis and 48 controls. In both studies, individuals with bipolar disorder showed Stroop deficits and their first-degree relatives showed intact performance. In the twin patients, an interference score was associated with depressive symptoms. Having a first-degree relative with bipolar disorder, even a familial, psychotic form, did not confer risk for enhanced susceptibility to interference in our studies.

We assessed premorbid functioning during childhood and adolescence in 50 people with schizophrenia from multiply affected families, 39 of their unaffected siblings, 69 people with schizophrenia with no family history of psychosis, 67 of their unaffected siblings and 83 controls. People with schizophrenia had poorer premorbid social and academic adjustment and exhibited a decline between childhood and adolescence compared with controls. Unaffected siblings from multiply affected families also had poor academic functioning in adolescence, with a decline between childhood and adolescence. This may represent a familial (presumed genetic) effect.

Background. Electrophysiological endophenotypes are far less explored in bipolar disorder as compared to schizophrenia. No previous twin study of event-related potentials (ERPs) in bipolar illness has been reported. This study uses a twin design and advanced genetic model fitting analyses aiming to (1) assess and quantify the relationship of a range of ERP components with bipolar disorder with psychotic features, and (2) examine the source of the relationship (due to genetic or environmental factors).

Method. P300, P50 suppression and mismatch negativity (MMN) were recorded in 10 discordant monozygotic (MZ) bipolar twin pairs, six concordant MZ bipolar twin pairs and 78 control twin pairs. Statistical analyses were based on structural equation modelling.

Results. Bipolar disorder was significantly associated with smaller P300 amplitude and decreased P50 suppression. Genetic correlations were the main source of the associations, estimated to be −0·33 for P300 amplitude and 0·46 for P50 ratio. Individual-specific environmental influences were not significant. MMN and P300 latency were not associated with the illness.

Conclusions. The results provide supporting evidence that P300 amplitude and P50 suppression ratio are ERP endophenotypes for bipolar disorder.

Intellectual asymmetry with superiority of verbal skills to spatial skills frequently characterises patients with schizophrenia, but it is unclear whether this pattern also reflects genetic susceptibility to the disorder. We examined the association of a continuous measure of genetic liability to schizophrenia with Verbal-Spatial Contrast IQ (an index of intellectual asymmetry) in 108 first-degree relatives without psychosis of probands with schizophrenia. Higher genetic liability was significantly associated with greater intellectual asymmetry in favour of verbal skills. Intellectual asymmetry with a relative superiority of verbal skills to spatial skills represents a putative endophenotype of schizophrenia.

We report cognitive performance of a group of individuals who are likely to have transmitted liability to psychosis to their offspring. Out of 230 relatives of patients with psychosis, 27 met our criteria for a presumed obligate carrier, that is a non-psychotic individual who had a parent or a sibling as well as an offspring with psychosis. The presumed obligate carriers showed impairments in verbal memory and in visuospatial manipulations, suggesting that these individuals transmit vulnerability for psychosis to their offspring in terms of a disability to recall verbal information and an impaired capacity to perceive spatial relations.