Pupillary responses as a biomarker of cognitive effort and the impact of task difficulty on reward processing in schizophrenia.

Negative symptoms of schizophrenia robustly predict functional outcomes but remain relatively resistant to available treatments. Better measures of negative symptoms, especially motivational deficits, are needed to better understand these symptoms and improve treatment development. Recent research shows promise in linking behavioral effort tasks to motivational negative symptoms, reward processing deficits, and defeatist attitudes, but few studies account for individual or group (patient v.

The effect of obstructive sleep apnea severity on PTSD symptoms during the course of esketamine treatment: a retrospective clinical study.

Study Objectives: Intranasal administration of esketamine is Food and Drug Administration-approved for treatment-resistant depression. In a recent retrospective case series, we show that it has promise in reducing symptoms of posttraumatic stress disorder (PTSD) as well. Untreated obstructive sleep apnea (OSA) is prevalent among veterans with PTSD and has been shown to interfere with other PTSD treatments.

Effects of intranasal ()-ketamine on Veterans with co-morbid treatment-resistant depression and PTSD: A retrospective case series.

Background: ()-ketamine is a glutamatergic drug with potent and rapid acting effects for the treatment of depression. Little is known about the effectiveness of intranasal ()-ketamine for treating patients with comorbid depression and post-traumatic stress disorder (PTSD).

Methods: We performed a retrospective case series analysis of clinical outcomes in 35 Veterans with co-morbid depression and PTSD who were treated with intranasal ()-ketamine treatments at the VA San Diego Neuromodulation Clinic between Jan 2020 and March 2021.

Response to intravenous racemic ketamine after switch from intranasal (S)-ketamine on symptoms of treatment-resistant depression and post-traumatic stress disorder in Veterans: A retrospective case series.

Background: Racemic (R,S)-ketamine is a glutamatergic drug with potent and rapid acting antidepressant effects. An intranasal formulation of (S)-ketamine was recently approved by the US Food and Drug Administration (FDA) to be used in individuals with treatment-resistant depression (TRD). There are no data directly comparing outcomes on depression or other comorbidities between these two formulations of ketamine.

Electrophysiological biomarkers of behavioral dimensions from cross-species paradigms.

There has been a fundamental failure to translate preclinically supported research into clinically efficacious treatments for psychiatric disorders. One of the greatest impediments toward improving this species gap has been the difficulty of identifying translatable neurophysiological signals that are related to specific behavioral constructs. Here, we present evidence from three paradigms that were completed by humans and mice using analogous procedures, with each task eliciting candidate a priori defined electrophysiological signals underlying effortful motivation, reinforcement learning, and cognitive control.

The viability of the frequency following response characteristics for use as biomarkers of cognitive therapeutics in schizophrenia.

Deficits in early auditory information processing contribute to cognitive and psychosocial disability; this has prompted development of interventions that target low-level auditory processing, which may alleviate these disabilities. The frequency following response (FFR) is a constellation of event-related potential and frequency characteristics that reflect the processing of acoustic stimuli at the level of the brainstem and ascending portions of the auditory pathway. While FFR is a promising candidate biomarker of response to auditory-based cognitive training interventions, the psychometric properties of FFR in schizophrenia patients have not been studied.

Verbal learning deficits associated with increased anticholinergic burden are attenuated with targeted cognitive training in treatment refractory schizophrenia patients.

Targeted cognitive training (TCT) has been reported to improve verbal learning deficits in patients with schizophrenia (SZ). Despite positive findings, it is not clear whether demographic factors and clinical characteristics contribute to the success of TCT on an individual basis. Medication-associated anticholinergic burden has been shown to impact TCT-associated verbal learning gains in SZ outpatients, but the role of anticholinergic medication burden on TCT gains in treatment refractory SZ patients has not been described.

Divergence of subjective and performance-based cognitive gains following cognitive training in schizophrenia.

Background: Cognitive training is effective for improving cognitive performance among people with schizophrenia. An individual's perception of their own cognition is dissociable from performance on objective cognitive tests. Since subjective cognitive benefit may impact engagement, motivation, and satisfaction with time-intensive cognitive interventions, this study aimed to determine whether subjective cognitive difficulties improve in conjunction with cognitive gains following 30 h of cognitive training.

Neurophysiologic measures of target engagement predict response to auditory-based cognitive training in treatment refractory schizophrenia.

Cognitive impairment is a core feature of schizophrenia and a strong predictor of psychosocial disability. Auditory-based targeted cognitive training (TCT) aims to enhance verbal learning and other domains of cognitive functioning through "bottom-up" tuning of the neural systems underlying early auditory information processing (EAIP). Although TCT has demonstrated efficacy at the group level, individual response to TCT varies considerably, with nearly half of patients showing little-to-no benefit.

Targeted cognitive training improves auditory and verbal outcomes among treatment refractory schizophrenia patients mandated to residential care.

Computerized targeted cognitive training (TCT) of auditory processing has been shown to improve verbal learning in several clinical trials of schizophrenia outpatients. Less is known, however, about the effectiveness of this promising intervention in more chronic, treatment-refractory patients who are treated in non-academic settings. This study aimed to determine whether TCT improves auditory processing, verbal learning, and clinical symptoms in SZ patients mandated to receive care at a locked residential rehabilitation center.

Computerized cognitive training is associated with improved psychosocial treatment engagement in schizophrenia.

Poor treatment engagement is an enduring problem in the care of patients with schizophrenia. Evidence suggests that targeted cognitive training (TCT) improves cognition and functional outcomes, but this time-consuming intervention might reduce patients' engagement in other treatment activities when implemented in real-world settings. This is especially true of residential care programs which encourage patients to engage in group therapies, self-care, and a wide variety of structured social, work, and other rehabilitation activities.

Reverse translated and gold standard continuous performance tests predict global cognitive performance in schizophrenia.

Attentional dysfunction contributes to functional impairments in schizophrenia (SZ). Sustained attention is typically assessed via continuous performance tasks (CPTs), though many CPTs have limited cross-species translational validity and place demands on additional cognitive domains. A reverse-translated 5-Choice Continuous Performance Task (5C-CPT) for human testing-originally developed for use in rodents-was designed to minimize demands on perceptual, visual learning, processing speed, or working memory functions.

Relationship between effortful motivation and neurocognition in schizophrenia.

Effortful motivation and reward valuation learning deficits are associated with negative symptoms and impaired cognition in schizophrenia (SZ) patients. Whereas clinical assessments of motivation and reward value typically rely upon clinician ratings or self-report scales, behavioral measures often confound these constructs. Simple reverse-translated behavioral tasks that independently quantify motivation and reward valuation-which could then be linked to cognition-may facilitate the development of pro-cognitive therapeutics by bridging the "preclinical-to-clinical" gap.

Evidence of systematic attenuation in the measurement of cognitive deficits in schizophrenia.

Cognitive tasks that are too hard or too easy produce imprecise measurements of ability, which, in turn, attenuates group differences and can lead to inaccurate conclusions in clinical research. We aimed to illustrate this problem using a popular experimental measure of working memory-the N-back task-and to suggest corrective strategies for measuring working memory and other cognitive deficits in schizophrenia. Samples of undergraduates (n = 42), community controls (n = 25), outpatients with schizophrenia (n = 33), and inpatients with schizophrenia (n = 17) completed the N-back.

Neurophysiological Characterization of Attentional Performance Dysfunction in Schizophrenia Patients in a Reverse-Translated Task.

Attentional dysfunction in schizophrenia (SZ) contributes to the functional deficits ubiquitous to the disorder. Identifying the neural substrates of translational measures of attentional dysfunction would prove invaluable for developing therapeutics. Attentional performance is typically assessed via continuous performance tasks (CPTs), though many place additional cognitive demands with little cross-species test-relevance.

The Early Psychosis Intervention Center (EPICENTER): development and six-month outcomes of an American first-episode psychosis clinical service.

Background: There is growing evidence that specialized clinical services targeted toward individuals early in the course of a psychotic illness may be effective in reducing both the clinical and economic burden associated with these illnesses. Unfortunately, the United States has lagged behind other countries in the delivery of specialized, multi-component care to individuals early in the course of a psychotic illness. A key factor contributing to this lag is the limited available data demonstrating the clinical benefits and cost-effectiveness of early intervention for psychosis among individuals served by the American mental health system.

Meta-cognitive skills training enhances computerized cognitive remediation outcomes among individuals with first-episode psychosis.

Aim: Meta-cognitive skills training (MST) is a frequent component of cognitive remediation programmes for individuals with psychosis. However, no study has investigated whether incorporating such activities produces increased clinical benefits compared with computerized cognitive remediation alone.

Methods: Individuals with first-episode psychosis who completed computerized cognitive remediation with concurrent meta-cognitive skills training (CCR + MST) were compared with a historical control group who received computerized cognitive remediation alone (CCR) and did not differ from the CCR + MST group with regard to pre-intervention cognition, diagnosis, age, duration of psychotic illness or sex.

The role of outcome expectations in the generation of the feedback-related negativity.

The feedback-related negativity (FRN) is thought to index activity within the midbrain dopaminergic reward-learning system, with larger FRN magnitudes observed when outcomes are worse than expected. This view holds that the FRN is an index of neural activity coding for prediction errors, and reflects activity that can be used to adaptively alter future performance. Untested to date, however, is a key prediction of this view: the FRN should not appear in response to negative outcomes when outcome expectations are not allowed to develop.

Larger Error Signals in Major Depression are Associated with Better Avoidance Learning.

The medial prefrontal cortex (mPFC) is particularly reactive to signals of error, punishment, and conflict in the service of behavioral adaptation and it is consistently implicated in the etiology of major depressive disorder (MDD). This association makes conceptual sense, given that MDD has been associated with hyper-reactivity in neural systems associated with punishment processing. Yet in practice, depression-related variance in measures of mPFC functioning often fails to relate to performance.

Diagnosing premenstrual dysphoric disorder: the reliability of a structured clinical interview.

Premenstrual dysphoric disorder (PMDD), a diagnosis included for further study in the DSM-IV-TR (American Psychiatric Association 2000), lacks a structured interview. The reliability of a Structured Clinical Interview for DSM-IV-TR-Defined PMDD (SCID-PMDD) was assessed with 96 participants who spanned the full range of premenstrual problems. All individual SCID-PMDD items had high inter-rater agreement, and the overall reliability of diagnosis was high (kappa = 0.

Resting frontal EEG asymmetry as an endophenotype for depression risk: sex-specific patterns of frontal brain asymmetry.

Resting frontal electroencephalographic (EEG) asymmetry has been hypothesized as a marker of risk for major depressive disorder (MDD), but the extant literature is based predominately on female samples. Resting frontal asymmetry was assessed on 4 occasions within a 2-week period in 306 individuals aged 18-34 (31% male) with (n = 143) and without (n = 163) lifetime MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric Association, 1994). Lifetime MDD was linked to relatively less left frontal activity for both sexes using a current source density (CSD) reference, findings that were not accounted for solely by current MDD status or current depression severity, suggesting that CSD-referenced EEG asymmetry is a possible endophenotype for depression.

Polymorphisms of the HTR1a allele are linked to frontal brain electrical asymmetry.

Polymorphic variations in genes related to serotonin synthesis, transport, recognition, or degradation may convey subtle changes in serotonin system architecture that may place an individual at risk for psychopathology when faced with life stressors. The relationship between three key serotonin alleles and frontal brain electrical asymmetry, a putative endophenotype of depression, was examined. Risk alleles were hypothesized to predict relatively greater right frontal brain activity regardless of current clinical state.