Reward Learning as a Potential Mechanism for Improvement in Schizophrenia Spectrum Disorders Following Cognitive Remediation: Protocol for a Clinical, Nonrandomized, Pre-Post Pilot Study.

BACKGROUND: Cognitive impairment is common with schizophrenia spectrum disorders. Cognitive remediation (CR) is effective in improving global cognition, but not all individuals benefit from this type of intervention. A better understanding of the potential mechanism of action of CR is needed. One proposed mechanism is reward learning (RL), the cognitive processes responsible for adapting behavior following positive or negative feedback. It is proposed that the structure of CR enhances RL and motivation to engage in increasingly challenging tasks, and this is a potential mechanism by which CR improves cognitive functioning in schizophrenia. OBJECTIVE: Our primary objective is to examine reward processing in individuals with schizophrenia before and after completing CR and to compare this with a group of matched clinical controls. We will assess whether RL mediates the relationship between CR and improved cognitive function and reduced negative symptoms. Potential differences in social RL and nonsocial RL in individuals with schizophrenia will also be investigated and compared with a healthy matched control group. METHODS: We propose a clinical, nonrandomized, pre-post pilot study comparing the impact of CR on RL and neurocognitive outcomes. The study will use a combination of objective and subjective measures to assess neurocognitive, psychiatric symptoms, and neurophysiological domains. A total of 40 individuals with schizophrenia spectrum disorders (aged 18-35 years) will receive 12 weeks of CR therapy (n=20) or treatment as usual (n=20). Reward processing will be evaluated using a reinforcement learning task with 2 conditions (social reward vs nonsocial reward) at baseline and the 12-week follow-up. Functional magnetic resonance imaging responses will be measured during this task. To validate the reinforcement learning task, RL will also be assessed in 20 healthy controls, matched for age, sex, and premorbid functioning. Mixed-factorial ANOVAs will be conducted to evaluate treatment group differences. For the functional magnetic resonance imaging analysis, computational modeling will allow the estimation of learning parameters at each point in time, during each task condition, for each participant. We will use a variational Bayesian framework to measure how learning occurred during the experimental task and the subprocesses that underlie this learning. Second-level group analyses will examine how learning in patients differs from that observed in control participants and how CR alters learning efficiency and the underlying neural activity. RESULTS: As of September 2023, this study has enrolled 15 participants in the CR group, 1 participant in the treatment-as-usual group, and 11 participants in the healthy control group. Recruitment is expected to be completed by September 2024. Data analysis is expected to be completed and published in early 2025. CONCLUSIONS: The results of this study will contribute to the knowledge of CR and RL processes in severe mental illness and the understanding of the systems that impact negative symptoms and cognitive impairments within this population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52505.

Measuring recovery-oriented rehabilitation language in clinical documentation to enhance recovery-oriented practice.

BACKGROUND: Mental health services are encouraged to use language consistent with principles of recovery-oriented practice. This study presents a novel approach for identifying whether clinical documentation contains recovery-oriented rehabilitation language, and evaluates an intervention to improve the language used within a community-based rehabilitation team. AIMS: This is a pilot study of training to enhance recovery-oriented rehabilitation language written in care review summaries, as measured through a text-based analysis of language used in mental health clinical documentation. METHOD: Eleven case managers participated in a programme that included instruction in recovery-oriented rehabilitation principles. Outcomes were measured with automated textual analysis of clinical documentation, using a custom-built dictionary of rehabilitation-consistent, person-centred and pejorative terms. Automated analyses were run on Konstanz Information Miner (KNIME), an open-source data analytics platform. Differences in the frequency of term categories in 50 pre-training and 77 post-training documents were analysed with inferential statistics. RESULTS: The average percentage of sentences with recovery-oriented rehabilitation terms increased from 37% before the intervention to 48% afterward, a relative increase of 28% (P < 0.001). There was no significant change in use of person-centred or pejorative terms, possibly because of a relatively high frequency of person-centred language (22% of sentences) and low use of pejorative language (2.3% of sentences) at baseline. CONCLUSIONS: This computer-driven textual analysis method identified improvements in recovery-oriented rehabilitation language following training. Our study suggests that brief interventions can affect the language of clinical documentation, and that automated text-analysis may represent a promising approach for rapidly assessing recovery-oriented rehabilitation language in mental health services.

CBTp for people with treatment refractory schizophrenia on clozapine: a systematic review and meta-analysis.

BACKGROUND: Cognitive behavioural therapy for psychosis (CBTp), an effective treatment for people with schizophrenia, may have a role in clozapine refractory schizophrenia. AIMS: A systematic-review and meta-analysis on the impact of CBTp on psychotic symptoms in people on clozapine. METHODS: We searched PubMed, Embase, PsycInfo, CINAHL and Cochrane for randomised control trials of CBTp as augmentation in people with treatment-refractory schizophrenia on clozapine and conducted pair-wise meta-analyses. RESULTS: Four studies met inclusion criteria. On pairwise meta-analyses, the primary outcome of total psychotic symptoms was not significantly altered by CBTp at either therapy endpoint or six to twelve months follow-up. Secondary outcomes showed that CBT improved positive symptoms at both therapy endpoint (SMD -0.33, 95%CI -0.50 to -0.16, p = 0.002, I2 = 0%) and six to twelve months follow-up (SMD -0.20, 95%CI -0.38 to -0.02, p = 0.03, I2 = 0%) though did not alter negative psychotic symptoms at either timepoint. CONCLUSIONS: CBTp may lead to small benefits for positive symptoms refractory to clozapine. Given the low risks associated with CBTp, and the limited alternative options for clozapine refractory schizophrenia, this approach should be considered in this population.

Randomised controlled trial of Compensatory Cognitive Training and a Computerised Cognitive Remediation programme.

BACKGROUND: Compensation and adaptation therapies have been developed to improve community functioning via improving neurocognitive abilities in people with schizophrenia. Various modes of delivering compensation and adaptation therapies have been found to be effective. The aim of this trial is to compare two different cognitive interventions, Compensatory Cognitive Training (CCT) and Computerised Interactive Remediation of Cognition-Training for Schizophrenia (CIRCuiTS). The trial also aims to identify if mismatch negativity (MMN) can predict an individual's response to the compensation and adaptation programmes. METHODS: This study will use a randomised, controlled trial of two cognitive interventions to compare the impact of these programmes on measures of neurocognition and function. One hundred clinically stable patients aged between 18 and 65 years with a diagnosis of a schizophrenia spectrum disorder will be recruited. Participants will be randomised to either the CCT or the CIRCuiTS therapy groups. The outcome measures are neurocognition (BACS), subjective sense of cognitive impairment (SSTICS), social functioning (SFS), and MMN (measured by EEG) in people with schizophrenia spectrum disorders. DISCUSSION: This trial will determine whether different approaches to addressing the cognitive deficits found in schizophrenia spectrum disorders are of comparable benefit using the outcome measures chosen. This has implications for services where cost and lack of computer technology limit the implementation and dissemination of interventions to address cognitive impairment in routine practice. The trial will contribute to the emerging evidence of MMN as a predictor of response to cognitive interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000161224 . Registered on 2 February 2018. Protocol version: 4.0, 18 June 2018.

Varenicline for cognitive impairment in people with schizophrenia: systematic review and meta-analysis.

BACKGROUND: People with schizophrenia frequently have cognitive dysfunction, which does not respond to pharmacological interventions. Varenicline has been identified as a potential treatment option for nicotinic receptor dysfunction with a potential to treat cognitive impairment in schizophrenia. METHODS: We conducted a systematic review of Pubmed, Embase, Psycinfo, CINAHL and the Cochrane Schizophrenia Trial Registry for randomised controlled trials of varenicline in people with schizophrenia for cognitive dysfunction. We excluded trials among people with dementia. We then undertook a meta-analysis with the primary outcome of difference in change of cognitive measures between varenicline and placebo as well as secondary outcomes of difference in rates of adverse events. We conducted a sensitivity analysis on smoking status and study duration. RESULTS: We included four papers in the meta-analysis (n = 339). Varenicline was not superior to placebo for overall cognition (SMD = -0.022, 95% CI -0.154-0.110; Z = -0.333; p = 0.739), attention (SMD = -0.047, 95% CI -0.199-0.104; Z = -0.613; p = 0.540), executive function (SMD = -0.060, 95% CI -0.469-0.348; Z =- 0.290; p = 0.772) or processing speed (SMD = 0.038, 95% CI -0.232-0.308; Z = 0.279; p = 0.780). There was no difference in psychotic symptoms, but varenicline was associated with higher rates of nausea. Sensitivity analyses for smoking status and study duration did not alter the results. CONCLUSION: Within the present literature, varenicline does not appear to be a useful target compound for improving cognitive impairment in schizophrenia. Based on these results, a trial would need over 2500 participants to be powered to show statistically significant findings.

Mania associated with self-prescribed acetyl-l-carnitine in a man with bipolar I disorder.

OBJECTIVE: Complementary medicines are readily available and becoming increasingly popular. Acetyl-l-carnitine (ALC) is widely recognised as a safe dietary supplement to aid weight loss. We present the case of a patient who had a relapse of mania in the context of ALC use for weight loss over a two week period, on the background of bipolar I disorder previously in remission. The patient's symptoms resolved a few days after ALC was ceased. CONCLUSIONS: Given the high rates of obesity among people with mental illness, it is possible ALC may be utilised in the hope of aiding weight loss. This case highlights the importance of psychiatrists maintaining open communication with their patients about use of complementary medicines, and the risks and benefits of their use.

Improved sensitivity of the rapid screen of mild traumatic brain injury.

This study aimed to investigate the acute effects of mild traumatic brain injury (mTBI) in an emergency department sample. A total of 246 (186 male, 60 female) cases of mTBI and 102 (65 male and 37 female) cases of orthopedic injuries were tested within 24 hours of injury. Mild TBI patients performed more poorly on all subtests of the Rapid Screen of Concussion (RSC) and completed fewer symbols on Digit Symbol than did orthopedic controls. RSC scores predicted group membership better than chance, and Digit Symbol scores contributed significantly to predicting group membership over and above the contribution of the RSC, resulting in 70.4% sensitivity and 74% specificity for the extended protocol. The results of this study indicate that learning and memory, orientation, and speed of information processing are impaired immediately following mTBI. Furthermore, a brief battery of tests that include word recall, orientation, and the Digit Symbol Substitution Test could assess the severity of dysfunction following mTBI, and assist in clinical decision making regarding discharge, return to routine activities, and management of the effects of injury.

The effects of post-traumatic amnesia on information processing following mild traumatic brain injury.

PRIMARY OBJECTIVE: The aim of this study was to determine whether a single measurement of level of PTA could distinguish patients more severely injured from those less so, by investigating the effect of PTA on psychometric test performance. METHODS AND PROCEDURES: Ninety patients with mTBI completed a word recall test, a spoken version of the Speed of Comprehension test and the Digit Symbol Substitution Test (Digit Symbol), within 24 hours of injury. These patients were divided into two groups, based on the presence (n=42) or absence (n=48) of PTA at the time of testing. PTA was measured with an eight-item orientation scale. MAIN OUTCOMES AND RESULTS: An independent groups design showed that patients with mTBI in PTA recalled fewer words after two presentations and after a delay and completed fewer symbols in 90 seconds on Digit Symbol than patients with mTBI not in PTA. Discriminant function analysis was applied to explore whether classifying severity of injury in terms of number of orientation questions answered would be useful. CONCLUSIONS: These results indicate that for individuals with mTBI in PTA, speed of information processing and verbal memory are impaired. A single brief administration of orientation questions may be sufficient to provide an index of severity of mTBI within the first 24 hours.

Test-retest reliability and practice effects of a rapid screen of mild traumatic brain injury.

Test-retest reliabilities and practice effects of measures from the Rapid Screen of Concussion (RSC), in addition to the Digit Symbol Substitution Test (Digit Symbol), were examined. Twenty five male participants were tested three times; each testing session scheduled a week apart. The test-retest reliability estimates for most measures were reasonably good, ranging from .79 to .97. An exception was the delayed word recall test, which has had a reliability estimate of .66 for the first retest, and .59 for the second retest. Practice effects were evident from Times 1 to 2 on the sentence comprehension and delayed recall subtests of the RSC, Digit Symbol and a composite score. There was also a practice effect of the same magnitude found from Time 2 to Time 3 on Digit Symbol, delayed recall and the composite score. Statistics on measures for both the first and second retest intervals, with associated practice effects, are presented to enable the calculation of reliable change indices (RCI). The RCI may be used to assess any improvement in cognitive functioning after mild Traumatic Brain Injury.

The acute effects of mild traumatic brain injury on finger tapping with and without word repetition.

This study aimed to investigate the acute effects of mild Traumatic Brain Injury (mTBI) on the performance of a finger tapping and word repetition dual task in order to determine working memory impairment in mTBI. Sixty-four (50 male, 14 female) right-handed cases of mTBI and 26 (18 male and 8 female) right-handed cases of orthopaedic injuries were tested within 24 hours of injury. Patients with mTBI completed fewer correct taps in 10 seconds than patients with orthopaedic injuries, and female mTBI cases repeated fewer words. The size of the dual task decrement did not vary between groups. When added to a test battery including the Rapid Screen of Concussion (RSC; Comerford, Geffen, May, Medland & Geffen, 2002) and the Digit Symbol Substitution Test, finger tapping speed accounted for 1% of between groups variance and did not improve classification rates of male participants. While the addition of tapping rate did not improve the sensitivity and specificity of the RSC and DSST to mTBI in males, univariate analysis of motor performance in females indicated that dual task performance might be diagnostic. An increase in female sample size is warranted. These results confirm the view that there is a generalized slowing of processing ability following mTBI.

Double cross-validation and improved sensitivity of the rapid screen of mild traumatic brain injury.

This study aimed to replicate and cross-validate the Rapid Screen of Concussion (RSC) for diagnosing mild TBI (mTBI). One hundred (81 male, 19 female) cases of mTBI and 35 (23 male and 12 female) cases of orthopaedic injuries were tested within 24 hr of injury. Double cross-validation was used to examine whether total RSC scores obtained in the current sample, generalised to one previously reported. In the new sample, mTBI patients answered fewer orientation questions, recalled fewer words on the learning trial and after a delay, judged fewer sentences in 2 min, and completed fewer symbols in the Digit Symbol Substitution Test than orthopaedic controls. The formulae and cut-offs developed on the original and new samples produced similar sensitivity and overall correct classification rates. Inclusion of the Digit Symbol Substitution Test performance of the new sample improved the sensitivity (80.2%) and specificity (82.6%) in males. It did not improve the correct classification rate in females, which was 89.5% sensitivity and 91.7% specificity before the inclusion of the Digit Symbol Substitution Test. Taken together, these results indicate that a combined score on this 12-min screen yields a measure of level of brain impairment up to 24 hr after mTBI.