Rachel A. Batty

Executive dysfunction in psychosis following traumatic brain injury (PFTBI)

Introduction: Executive dysfunction is well established in patients with traumatic brain injury and in schizophrenia (SCZ). However, assessments of executive function in psychosis following traumatic brain injury (PFTBI) are limited and inconsistent, and often do not reflect the deficits demonstrated in patients with traumatic brain injury (TBI) or SCZ. We sought to determine the extent of executive dysfunction in PFTBI relative to three comparison cohorts. Method: Measures of executive function were administered to dually diagnosed patients with PFTBI (n = 10) including tests of mental inhibition and switching, processing speed, and attention: the Stroop Task, Trail Making Test (TMT), and the Attention subtest of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Demographically comparable patients with TBI (n = 10), SCZ (n = 23), and healthy controls (n = 23) underwent an identical battery. Results: Significant executive dysfunction was evident in patients with PFTBI on all measures. Relative to all three comparison cohorts patients with PFTBI performed most poorly. Conclusions: These data present novel evidence of substantially impaired executive function across four task types in PFTBI and suggest that TBI and psychosis have an additive influence on executive function deficits. Treatment programs requiring substantial executive engagement are not suitable for patients dually diagnosed with PFTBI.

Verbal fluency, clustering, and switching in patients with psychosis following traumatic brain injury (PFTBI)

Verbal fluency in patients with psychosis following traumatic brain injury (PFTBI) has been reported as comparable to healthy participants. This finding is counterintuitive given the prominent fluency impairments demonstrated post-traumatic brain injury (TBI) and in psychotic disorders, e.g. schizophrenia. We investigated phonemic (executive) fluency (3 letters: F A and S), and semantic fluency (1 category: fruits and/or vegetables) in four matched groups; PFTBI (N=10), TBI (N=10), schizophrenia (N=23), and healthy controls (N=23). Words produced (minus perseverations and errors), and clustering and switching scores were compared for the two fluency types across the groups. The results confirmed that PFTBI patients do show impaired fluency, aligned with existing evidence in TBI and schizophrenia. PFTBI patients produced the least amount of words on the phonemic fluency (A) trial and total score, and demonstrated reduced switching on both phonemic and semantic tasks. No significant differences in clustering performance were found. Importantly, the pattern of results suggested that PFTBI patients share deficits with their brain-injured (primarily executive), and psychotic (executive and semantic), counterparts, and that these are exacerbated by their dual-diagnosis. These findings add to a very limited literature by providing novel evidence of the nature of fluency impairments in dually-diagnosed PFTBI.

Neurophysiological correlates of configural face processing in schizotypy

Background: Face processing impairment in schizophrenia appears to be underpinned by poor configural (as opposed to feature-based) processing; however, few studies have sought to characterize this impairment electrophysiologically. Given the sensitivity of event-related potentials to antipsychotic medications, and the potential for neurophysiological abnormalities to serve as vulnerability markers for schizophrenia, a handful of studies have investigated early visual P100 and face-selective N170 in “at risk” populations. However, this is the first known neurophysiological investigation of configural face processing in a non-clinical schizotypal sample. Methods: Using stimuli designed to engage configural processing in face perception (upright and inverted Mooney and photographic faces), P100 and N170 components were recorded in healthy individuals characterized by high (Nu2009=u200914) and low (Nu2009=u200914) schizotypal traits according to the Oxford–Liverpool Inventory of Feelings and Experiences. Results: High schizotypes showed significantly reduced N170 amplitudes to inverted photographic faces. Typical N170 latency and amplitude inversion effects (delayed and enhanced N170 to inverted relative to upright photographic faces, and enhanced amplitude to upright versus inverted Mooney faces), were demonstrated by low, but not high, schizotypes. No group differences were shown for P100 analyses. Conclusions: The findings suggest that neurophysiological deficits in processing facial configurations (N170) are apparent in schizotypy, while the early sensory processing (P100) of faces appears intact. This work adds to the mounting evidence for analogous neural processing anomalies at the healthy end of the psychosis continuum.

A brief neurocognitive assessment of patients with psychosis following traumatic brain injury (PFTBI): Use of the Repeatable battery for the Assessment of Neuropsychological Status (RBANS).

Patients who develop psychosis following a traumatic brain injury (PFTBI) show impaired neurocognition; however, the degree of impairment has not been empirically investigated using a standardised battery. We administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to patients with PFTBI (n=10), and to three groups of controls: traumatic brain injury (TBI) (n=10), schizophrenia (n=23), and nonclinical controls (n=23). The results confirmed that the cognitive neuropsychological profile of dually-diagnosed patients with PFTBI is significantly and substantially impaired. Seventy per cent of patients with PFTBI received a neuropsychological classification between the extremely low and low average ranges. Group-wise analyses on the RBANS indices indicated that patients with PFTBI had the lowest (Immediate Memory, Attention, Delayed Memory, Total Score), or equal lowest (visuospatial, equivalent with schizophrenia patients) scores, with the exception of the Language Index where no group differences were shown (however, the mean PFTBI score on the Language Index was two standard deviations below the RBANS normative score). These findings provide novel evidence of impaired cognitive neuropsychological processing in patients with PFTBI using a standardised and replicable battery.

Who “jumps to conclusions”? A comprehensive assessment of probabilistic reasoning in psychosis following traumatic brain injury (PFTBI), and comparison with TBI, schizophrenia, and nonclinical controls

ABSTRACT Introduction. The “jumping to conclusions” (JTC) bias has received significant attention in the schizophrenia and delusion literature as an important aspect of cognition characterising psychosis. The JTC bias has not been explored in psychosis following traumatic brain injury (PFTBI). Methods. JTC was investigated in 10 patients with PFTBI using the beads task (ratios 85:15 and 60:40). Probabilistic predictions, draws-to-decision, self-rated decision confidence, and JTC bias were recorded. Responses from 10 patients with traumatic brain injury (TBI), 23 patients with schizophrenia, and 23 nonclinical controls were compared. Relationships were explored between draws-to-decision and current intelligence quotient, affective state, executive function, delusions (severity and type), and illness chronicity (duration). Results. Groups were comparable on JTC measures. Delusion severity and type were not related to draws-to-decision for either trial. In the entire sample, executive function (reduced mental flexibility) was significantly related to more draws-to-decision on the 60:40 ratio trial. Conclusions. We found no evidence for an elevated JTC bias in patients with PFTBI or TBI alone. The influence of executive dysfunction should be considered by future studies using the beads tasks in patient populations. These findings need to be replicated in larger PFTBI and TBI samples.

T63. TOWARDS A COMPREHENSIVE SEMANTIC MEMORY NETWORK IN SCHIZOPHRENIA: PRELIMINARY RESULTS USING MAGNETOENCEPHALOGRAPHY (MEG) IN SCHIZOTYPY

Abstract Background Semantic memory (memory for facts, concepts, and knowledge of the external world) abnormalities are predicted to underlie disturbances in thought and language, deficits in cognitive domains, and the development and maintenance of delusions in patients with schizophrenia. Electroencephalographic (EEG) recordings have successfully identified the neural time course for the processing of semantic information as an electrophysiological response between 300 and 500ms post stimulus (i.e., the N400). The N400 is a remarkably consistent and highly sensitive neural response to semantic relationships, and is thought to index the binding of current stimuli into context by detecting whether meaning is shared with recently processed stimuli or items in memory. To date, the N400 appears to be amodal: an index of semantic processing irrespective of stimulus type (e.g., word/picture stimuli alike), and has shown mixed findings in schizophrenia. However, existing literature has largely relied on EEG or functional magnetic resonance imaging (fMRI) techniques, and these are constrained in spatial and temporal resolution, respectively. Comparatively, MEG provides excellent spatio-temporal resolution, not possible from other stand-alone neuroimaging techniques. We aimed to determine the neuromagnetic correlates of novel semantic triads in both lexical and picture form, and to determine N400m differences in high/low schizotypal samples. Methods MEG was recorded (whole-head 306 channel Elekta Neuromag® TRIUX magnetometer system) in 35 nonclinical controls (18 male) while completing a novel explicit semantic association task. MEG data were continuously sampled at 1KHz (0.1Hz high pass filter). Following MaxFiltering, data was processed using MNE for Python. Data were filtered offline (40Hz lowpass) and epoched at -300ms to 800ms post- target stimulus onset. The largest peak was measured at sensor triplets at temporo-parietal sites in both hemispheres. High/low schizotypal samples were determined by a median split of the Oxford-Liverpool Inventory of Feelings and Experiences (cognitive disorganisation scale; high=17, low=18). Results Preliminary sensor level analyses demonstrated an N400m at temporo-parietal sites in response to both word and picture stimulus sets (with an earlier peak to pictures). Neither amplitude nor latency was significantly different between schizotypal samples, however a significant task x hemisphere x group interaction was found for N400m latency, F(1.00,33.00) = 6.18, p<.02. Discussion An N400m was confirmed in response to the novel lexical task. The earlier peak (~200ms) to picture stimuli suggests that pictorial semantic information may be processed more rapidly than lexical information. The significant schizotypal group latency interaction demonstrated that while individuals low in schizotypal traits process lexical stimuli first in the right hemisphere (followed by the left) and picture stimuli first in the left hemisphere (followed by the right), individuals high in schizotypal traits do not demonstrate hemispheric specificity/laterality according to stimulus type. The data is currently being analysed for (i) source localisation, (ii) deep source contributions (e.g., hippocampus), and (iii) de/synchronisation of neural oscillations (across six frequency bands; 1-8Hz, 8-30Hz, 30-50Hz, 70-120Hz, 120-200Hz, and 200-300Hz).

F104. A STANDARDISED EMPIRICAL INVESTIGATION OF THE CLINICAL PROFILE OF PSYCHOSIS FOLLOWING TRAUMATIC BRAIN INJURY (PFTBI)

Abstract Background Persons who experience symptoms of psychosis following a brain injury live with a complex dual diagnosis that is often accompanied by substantial distress and disability. However, a comprehensive examination of the clinical presentation of PFTBI using standardised clinical measures has not been reported in the literature. This information is vital for accurate diagnosis and effective treatment. Methods Patients with PFTBI (n =10) and schizophrenia (n =98) participated in a comprehensive clinical assessment that included the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I/P), the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Thought Language and Communication Index (TLC). Results The clinical profiles of the PFTBI group met symptom/course criteria for: schizophrenia (n = 6), schizoaffective (n = 2), schizophreniform (n = 1), and paranoid psychosis (n = 1). PFTBI patients had a significantly reduced PANSS negative score relative to schizophrenia patients. No other significant differences between PFTBI and schizophrenia clinical profiles were found. Discussion The clinical profile of PFTBI appears to be comparable to schizophrenia/ schizoaffective disorder except with respect to negative psychotic symptoms. Reduced negative symptoms in PFTBI have previously been reported in a small number of case studies, and thus warrant further investigation as a diagnostic distinction in this patient group.

Efficacy and Harms of Pharmacological Interventions for Neurobehavioral Symptoms in Post Traumatic Amnesia after Traumatic Brain Injury – A Systematic Review

Many individuals in post-traumatic amnesia (PTA) following traumatic brain injury (TBI) experience neurobehavioral symptoms (NBS) in addition to disorientation and amnesia. These symptoms are associated with low rehabilitation engagement, self-inflicted harm, and risk of violence. The aim of this systematic review was to evaluate the efficacy and harms of pharmacological interventions for NBS in PTA following TBI in adults. Studies in English published before December 2017 were reviewed. Six databases were searched, with additional hand searching of key journals, clinical trials registries, and international drug regulators. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. Thirteen studies were identified: three randomized controlled trials (RCTs), three cohort studies, and seven case series. In the RCTs, neither amantadine nor sertraline reduced NBS. Less rigorous studies reported reduced NBS in patients administered haloperidol, ziprasidone, carbamazepine, amitriptyline, desipramine, and varied neuroleptics. There is a paucity of well-designed, adequately powered and controlled studies of pharmacological interventions for NBS in PTA. More research is needed to provide evidence-based treatment recommendations and improve care.

Efficacy and harms of pharmacological interventions for neurobehavioral symptoms in post traumatic amnesia after traumatic brain injury: a systematic review and meta-analysis protocol.

Review objective/question: The objective of this systematic review is to synthesize the best available evidence on the effectiveness and harms of pharmacotherapy as compared to all types of comparators for the management of neurobehavioral symptoms in post-traumatic amnesia in adults aged 16 years and over who have sustained a traumatic brain injury. This review forms part of a larger project which aims to gather the evidence for the pharmacological treatment of neurobehavioral symptoms post traumatic brain injury as a prelude to the development of a clinical guideline.

Safety and effectiveness of pharmacotherapy for depression in adults who have sustained a traumatic brain injury: a systematic review protocol.

REVIEW OBJECTIVE/QUESTIONnThe objective of this systematic review is to synthesize the current evidence on the effectiveness and harms of pharmacotherapy in the management of depression in adults who have sustained a traumatic brain injury.