Background and objectives Referentiality is a common symptom in psychotic and also some non-psychotic disorders, but there are few existing measures for assessing it. A recently developed detailed measure for this purpose is the Ideas of Reference Interview Scale (IRIS), which however has only been validated in a Chinese population of first episode psychosis patients. Methods We examined the reliability and validity of a Spanish version of the IRIS (IRIS-S) in 185 patients aged between 18 and 65 with schizophrenia or schizoaffective disorder. Results The IRIS-S showed internal consistency, with this being good or acceptable for the presence scale and its three subsidiary measures. Inter-rater reliability was good and test-retest reliability was also good, except for one subsidiary measure. Convergent reliability was demonstrated but was lower than expected. Conclusion The IRIS-S has acceptable psychometric properties when employed in patients with schizophrenia/schizoaffective disorder. Caution is necessary for its use outside psychotic disorders as it has not been examined in such populations.

Background According to the aberrant salience proposal, reward processing abnormality, specifically erroneous reward prediction error (RPE) signaling due to stimulus-independent release of dopamine, underlies delusions in schizophrenia. However, no studies to date have examined RPE-associated brain activations in relation to this symptom. Methods Seventy-eight patients with a DSM-5 diagnosis of schizophrenia/schizoaffective disorder and 43 healthy individuals underwent fMRI while they performed a probabilistic monetary reward task designed to generate a measure of RPE. Ratings of delusions and referentiality were made in the patients. Results Using whole-brain, voxel-based analysis, schizophrenia patients showed only minor differences in RPE-associated activation compared to healthy controls. Within the patient group, however, severity of delusions was inversely associated with RPE-associated activation in areas including the caudate nucleus, the thalamus and the left pallidum, as well as the lateral frontal cortex bilaterally, the pre- and postcentral gyrus and supplementary motor area, the middle cingulate gyrus, and parts of the temporal and parietal cortex. A broadly similar pattern of association was seen for referentiality. Conclusions According to this study, while patients with schizophrenia as a group do not show marked alterations in RPE signaling, delusions and referentiality are associated with reduced activation in parts of the prefrontal cortex and the basal ganglia, though not specifically the ventral striatum. The direction of the changes is on the face of it contrary to that predicted by aberrant salience theory.

Background and objectives An influential theory of negative symptoms in schizophrenia is that they are due to frontal lobe dysfunction, although this has not been consistently supported by functional imaging studies to date. Recently, our group found evidence of an association between negative symptoms and prefrontal hypoactivation during a novel executive task sensitive to goal neglect. The present study sought to extend this finding using a different functional imaging paradigm, the n-back working memory task. Methods Ninety-six medicated patients with schizophrenia were divided according to the Positive and Negative Symptoms Scale (PANSS) scores into groups with high negative symptom scores (HNS, N=70, negative symptom score range 15-34), and with low negative symptom scores (LNS, N=26, negative symptom score range 6-14). Along with 50 matched healthy controls, they underwent fMRI while performing the 2-back and 1-back versions of the n-back task. Results In the 2-back vs 1-back comparison, working memory-related activation was observed in lateral prefrontal and inferior parietal areas in all groups. The HNS patients, but not the LNS patients showed reduced activation in these task-related regions compared to the healthy controls. The HNS patients also showed hypoactivation in the right dorsolateral prefrontal cortex relative to the LNS patients, although this finding was no longer statistically significant when disorganization scores were added as a covariate. Conclusion Our results provide further evidence supporting the prefrontal hypothesis of negative symptoms, but also highlight the potential role of disorganization in modulating prefrontal activity.

A disturbed sense of identity is one of the major features of borderline personality disorder (BPD), which manifests early in the course of the disorder, and is potentially examinable using functional imaging during tasks involving self-reflection. Twenty-seven medication-naïve adolescent female patients with BPD, who had no psychiatric comorbidities, and 28 matched healthy female controls underwent fMRI while answering questions either about themselves or acquaintances. Control conditions consisted of answering questions involving factual knowledge and a low-level baseline (cross fixation). When self-reflection was compared to fact processing, BPD patients exhibited reduced activation in the right dorsolateral prefrontal cortex (DLPFC), as well as in the left parietal and calcarine cortex and the right precuneus. In contrast, other-reflection was associated with relatively lower activation in the medial frontal cortex in BPD patients, with further analysis revealing that this change reflected a failure of de-activation during the fact processing condition. There were no differences between the BPD patients and controls when self- and other-processing was examined against low-level baseline. This study provides evidence of reduced DLPFC activation during self-reflection in adolescent females with BPD, which may reflect diminished top-down cognitive control of this process, but not other-reflection in the disorder.

BACKGROUND:Schizophrenic symptoms are known to segregate into reality distortion, negative and disorganization syndromes, but the correlates of these syndromes with regional brain structural change are not well established. Cognitive impairment is a further clinical feature of schizophrenia, whose brain structural correlates are the subject of conflicting findings.METHODS:165 patients with schizophrenia were rated for symptoms using the PANSS, and cognitive impairment was indexed by estimated premorbid-current IQ discrepancy. Cortical volume was measured using surface-based morphometry in the patients and in 50 healthy controls. Correlations between clinical and cognitive measures and cortical volume were examined using whole-brain FreeSurfer tools.RESULTS:No clusters of volume reduction were seen associated with reality distortion or disorganization. Negative symptom scores showed a significant inverse correlation with volume in a small cluster in the left medial orbitofrontal gyrus. Larger estimated premorbid-current IQ discrepancies were associated with clusters of reduced cortical volume in the left precentral gyrus and the left temporal lobe. The cluster of association with negative symptoms disappeared when estimated premorbid-current IQ discrepancy was controlled for.CONCLUSIONS:This study does not provide support for an association between brain structural abnormality and reality distortion or disorganization syndromes in schizophrenia. The cluster of volume reduction found in the left medial orbitofrontal cortex correlated with negative symptoms may have reflected the association between this class of symptoms and cognitive impairment. The study adds to existing findings of an association between cognitive impairment and brain structural changes in the disorder.

Accessible SummaryWhat is known on the subject? Functioning is one of the most affected areas in schizophrenia. Social, occupational and personal domains are affected, and these deficits are responsible for a major part of the disability associated with the disorder. There are several instruments to measure functioning, but the HoNOS provides a wide assessment of impairment in 12 areas of functioning. What does the paper add to existing knowledge? The Spanish version of the HoNOS shows good properties in terms of reliability and validity for use in schizophrenia patients. Although some authors divide the scale according to proposed underlying dimensions, in schizophrenia this division may not be appropriate. What are the implications for practice? A reliable and easy‐to‐use measure of impairment in different areas of functioning is useful for optimizing the treatment and rehabilitation of patients with schizophrenia. AbstractIntroductionThe HoNOS scale was designed for the assessment of psychosocial impairment in various domains. While it is widely used in psychiatric settings, it has not been validated in Spanish for use in patients with schizophrenia.AimTo examine the psychometric properties of the Spanish version of the HoNOS scale in a sample of schizophrenia patients.MethodA total of 194 individuals aged 18 to 65 with schizophrenia spectrum diagnoses were evaluated using the HoNOS. Illness severity and level of functioning were also assessed.ResultsThe HoNOS showed moderate internal consistency, good inter‐observer reliability and good test‐retest reliability. Factor analysis revealed an internal structure consisting of four factors, with item distribution differing from the theoretical dimensions proposed for the original scale.DiscussionThe Spanish version of the HoNOS scale is a reliable and valid instrument for assessing psychosocial impairment in individuals diagnosed with schizophrenia spectrum disorders. However, further research is needed to determine its internal structure more accurately.Implications for PracticeThe HoNOS scale provides researchers and clinicians with a valid measure of impairment in twelve different domains, which can facilitate and guide the treatment of schizophrenia patients.

Different lines of evidence indicate that the structure and physiology of the basal ganglia and the thalamus is disturbed in schizophrenia. However, it is unknown whether the volume and shape of these subcortical structures are affected in schizophrenia with auditory hallucinations (AH), a core positive symptom of the disorder. We took structural MRI from 63 patients with schizophrenia, including 36 patients with AH and 27 patients who had never experienced AH (NAH), and 51 matched healthy controls. We extracted volumes for the left and right thalamus, globus pallidus, putamen, caudate and nucleus accumbens. Shape analysis was also carried out. When comparing to controls, the volume of the right globus pallidus, thalamus, and putamen, was only affected in AH patients. The volume of the left putamen was also increased in individuals with AH, whereas the left globus pallidus was affected in both groups of patients. The shapes of right and left putamen and thalamus were also affected in both groups. The shape of the left globus pallidus was only altered in patients lacking AH, both in comparison to controls and to cases with AH. Lastly, the general PANSS subscale was correlated with the volume of the right thalamus, and the right and left putamen, in patients with AH. We have found volume and shape alterations of many basal ganglia and thalamus in patients with and without AH, suggesting in some cases a possible relationship between this positive symptom and these morphometric alterations.

Introduction Autobiographical memory is known to be disturbed in schizophrenia. In addition, a leading theory of auditory hallucinations (AVH) is that they are intrusive – typically negative – autobiographical memories that are misinterpreted as perceptions. Objectives The aim of this study was to examine the brain functional correlates of recall of negatively emotionally valanced autobiographical memories in patients with schizophrenia, with a longer term aim of comparing patients with and without AVH. Methods 11 patients meeting DSM-5 criteria for schizophrenia or schizoaffective disorder and 10 age, sex and estimated premorbid IQ-matched healthy controls have so far taken part. Participants underwent functional MRI in a 3T scanner while performing a task requiring them to recall autobiographical memories in response to individually tailored pairs of cue words. The cue words were based on autobiographical memories previously elicited in an interview with each patient and were designed to evoke the same memory. The cue words were presented in 10 20-second blocks interspersed with blocks where the subjects viewed cue words that did not evoke autobiographical memories. Brain activations were examined in three contrasts of interest: memory evoking words vs baseline, neutral words vs baseline and memory evoking vs neutral words. Pre-processing and analysis were carried out with the FEAT module included in the FSL software. Statistical analysis was performed by means of a General Linear Model (GLM) approach. Results In the memory evoking vs baseline contrast the patients showed hypoactivation in the medial frontal cortex compared to the healthy controls (Figure 1). There were no differences in activation between the patients and the controls comparing the memory evoking and neutral cues. Image: Conclusions The finding of hypoactivation in the medial frontal cortex compared to low level baseline in patients with schizophrenia suggests dysfunction in the default mode network, which is known to activate during recall of autobiographical memories. These preliminary results suggest that recall of negative autobiographical memories in patients with schizophrenia is associated with reduced activity in the default mode network. A planned larger sample of patients and controls will be used to examine activations in patients with and without AVH. Disclosure of Interest None Declared

Background: Relapse prevention is an important goal in the clinical management of psychosis. Cognitive deficits/ deterioration can provide useful insights for monitoring relapse in psychosis patients. Methods: This was a prospective, naturalistic 1-year follow-up study involving 110 psychosis patients with full clinical remission. Relapse, defined as the recurrence of psychotic symptoms, was monitored monthly along with digital tracking of verbal and visual working memory using a mobile app developed for this study. Cognitive deterioration was defined as worsening performance over 2 months prior to relapse or study termination, whichever was earlier. Other clinical, cognitive, functioning, and psychosocial variables were also collected.Results: At 1 year, 18 (16.36%) patients relapsed, of which 6 (33.33%) required hospitalization. Relapse was predicted by verbal working memory deterioration 2 months prior to relapse (p = 0.029), worse medication adherence (p = 0.018), and less resilience (p = 0.014). Conclusions: Verbal working memory deterioration is a novel early sign of relapse. It is a clearly defined, objectively measurable, and reproducible marker that can help clinicians and healthcare workers identify pa-tients at risk of relapse and make decisions about maintenance therapy. Moreover, digital monitoring is a viable tool in the management of relapse.

Background The brain functional correlates of delusions have been relatively little studied. However, a virtual reality paradigm simulating travel on the London Underground has been found to evoke referential ideation in both healthy subjects and patients with schizophrenia, making brain activations in response to such experiences potentially identifiable. Method Ninety patients with schizophrenia/schizoaffective disorder and 28 healthy controls underwent functional magnetic resonance imaging while they viewed virtual reality versions of full and empty Barcelona Metro carriages. Results Compared to the empty condition, viewing the full carriage was associated with activations in the visual cortex, the cuneus and precuneus/posterior cingulate cortex, the inferior parietal cortex, the angular gyrus and parts of the middle and superior temporal cortex including the temporoparietal junction bilaterally. There were no significant differences in activation between groups. Nor were there activations associated with referentiality or presence of delusions generally in the patient group. However, patients with persecutory delusions showed a cluster of reduced activation compared to those without delusions in a region in the right temporal/occipital cortex. Conclusions Performance of the metro task is associated with a widespread pattern of activations, which does not distinguish schizophrenic patients and controls, or show an association with referentiality or delusions in general. However, the finding of a cluster of reduced activation close to the right temporoparietal junction in patients with persecutory delusions specifically is of potential interest, as this region is believed to play a role in social cognition.

BACKGROUND:A leading theory of the negative symptoms of schizophrenia is that they reflect reduced responsiveness to rewarding stimuli. This proposal has been linked to abnormal (reduced) dopamine function in the disorder, because phasic release of dopamine is known to code for reward prediction error (RPE). Nevertheless, few functional imaging studies have examined if patients with negative symptoms show reduced RPE-associated activations. METHODS:Matched groups of DSM-5 schizophrenia patients with high negative symptom scores (HNS, N = 27) or absent negative symptoms (ANS, N = 27) and healthy controls (HC, N = 30) underwent fMRI scanning while they performed a probabilistic monetary reward task designed to generate a measure of RPE. RESULTS:In the HC, whole-brain analysis revealed that RPE was positively associated with activation in the ventral striatum, the putamen, and areas of the lateral prefrontal cortex and orbitofrontal cortex, among other regions. Group comparison revealed no activation differences between the healthy controls and the ANS patients. However, compared to the ANS patients, the HNS patients showed regions of significantly reduced activation in the left ventrolateral and dorsolateral prefrontal cortex, and in the right lingual and fusiform gyrus. HNS and ANS patients showed no activation differences in ventral striatal or midbrain regions-of-interest (ROIs), but the HNS patients showed reduced activation in a left orbitofrontal cortex ROI. CONCLUSIONS:The findings do not suggest that a generalized reduction of RPE signalling underlies negative symptoms. Instead, they point to a more circumscribed dysfunction in the lateral frontal and possibly the orbitofrontal cortex.

Background and Hypothesis The existing developmental bond between fingerprint generation and growth of the central nervous system points to a potential use of fingerprints as risk markers in schizophrenia. However, the high complexity of fingerprints geometrical patterns may require flexible algorithms capable of characterizing such complexity. Study Design Based on an initial sample of scanned fingerprints from 612 patients with a diagnosis of non-affective psychosis and 844 healthy subjects, we have built deep learning classification algorithms based on convolutional neural networks. Previously, the general architecture of the network was chosen from exploratory fittings carried out with an independent fingerprint dataset from the National Institute of Standards and Technology. The network architecture was then applied for building classification algorithms (patients vs controls) based on single fingers and multi-input models. Unbiased estimates of classification accuracy were obtained by applying a 5-fold cross-validation scheme. Study Results The highest level of accuracy from networks based on single fingers was achieved by the right thumb network (weighted validation accuracy = 68%), while the highest accuracy from the multi-input models was attained by the model that simultaneously used images from the left thumb, index and middle fingers (weighted validation accuracy = 70%). Conclusion Although fitted models were based on data from patients with a well established diagnosis, since fingerprints remain lifelong stable after birth, our results imply that fingerprints may be applied as early predictors of psychosis. Specially, if they are used in high prevalence subpopulations such as those of individuals at high risk for psychosis.

INTRODUCTION:Few studies have examined the functional brain correlates of the performance of the Stroop task in bipolar disorder (BD). It is also not known whether it is associated with failure of de-activation in the default mode network, as has been found in studies using other tasks.METHODS:Twenty-four BD patients and 48 age, sex and educationally estimated intellectual quotient (IQ) matched healthy subjects (HS) underwent a functional MRI during performance of the counting Stroop task. Task-related activations (incongruent versus congruent condition) and de-activations (incongruent versus fixation) were examined using whole-brain, voxel-based methodology.RESULTS:Both the BD patients and the HS showed activation in a cluster encompassing the left dorsolateral and ventrolateral prefrontal cortex and the rostral anterior cingulate cortex and supplementary motor area, with no differences between them. The BD patients, however, showed significant failure of de-activation in the medial frontal cortex and the posterior cingulate cortex/precuneus.CONCLUSIONS:The failure to find activation differences between BD patients and controls suggests that the 'regulative' component of cognitive control remains intact in the disorder, at least outside episodes of illness. The failure of de-activation found adds to evidence documenting trait-like default mode network dysfunction in the disorder.