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Background: The SARS-CoV-2 pandemic compromised the mental health of COVID-19 patients and their family members. Due to social distancing and lockdown measures, a remote, tele-psychotherapy program for former or current COVID-19 patients and their relatives was implemented. Objective: The primary goal of this project was to evaluate intervention feasibility. The secondary aim was to assess the impact of the intervention by means of pre-post psychological changes. Methods: After a phone-based eligibility screening and remote neuropsychological testing, participants completed online self-reports assessing baseline COVID-related psychopathology. Next, participants attended eight tele-psychotherapy sessions. After treatment, the online self-reports were completed again. Results: Of 104 enrolled participants, 88 completed the intervention (84.6 % completion rate). Significant pre-post improvements were observed for generalized anxiety (d = 0.38), depression (d = 0.37), insomnia (d = 0.43), post-traumatic psychopathology (d = 0.54), and general malaise (d = 0.31). Baseline cluster analysis revealed a subgroup of 41 subjects (47.6 %) with no psychopathology, and a second subgroup of 45 subject (52.3 %) with moderate severity. Thirty-three percent of the second group reached full symptom remission, while 66 % remained symptomatic after treatment. Conclusions: Remote brief tele-psychotherapy for COVID-19 patients and their first-degree relatives is feasible and preliminary efficacious at reducing COVID-related psychopathology in a subgroup of patients. Further research is needed to investigate distinct profiles of treatment response.

Background: Across a range of age, educational and clinical characteristics, adults experiencing depression and anxiety already use digital technology to manage their symptoms. Although several reviews and meta-analyses indicated feasibility and efficacy for adults with depression and anxiety, digital treatments are poorly accessed and disseminated. This review illustrates potentials and limitations of interventions that specifically leveraged unique features of digital technology and were grounded in the principles of Cognitive Behavioral Therapy (CBT). Methods: This systematic review followed the PRISMA guidelines. An electronic database search was conducted in October 2021. Peer-reviewed, English-language studies were included if i) they reported data from RCTs for adults aged 18+ who engaged with CBT-informed digital interventions targeting primarily depression and anxiety; ii) they used at least PHQ-9 or GAD-7 as standardized and validated assessment self-report measures for depression and anxiety. Results: Findings from 35 RCTs examining 33 interventions (25 internet-based, 6 mobile-based, a2 mobile/web) are discussed. The quality of the evidence differed widely as many small-scale RCTs reported only short-term feasibility and preliminary efficacy. Effects of CBT-informed digital interventions were substantially larger when compared to waitlist than active control conditions. Greater therapeutic benefits were observed for interventions that offered clinical assistance or were used in combination with other treatments. Conclusions: CBT-informed digital interventions have accumulated enough scientific evidence to be positioned today as: i) a low-intensity tool for those with subclinical levels of symptoms; ii) a first step in a stepped-care approach to service delivery iii) a low-cost, easily accessible option for targeted preventive programs.

Background: Sensory processing abnormalities are common in schizophrenia (SZ) and impact everyday functions, such as speech perception in noisy environments. Auditory-based targeted cognitive training (TCT) is a “bottom up” cognitive remediation intervention designed to enhance the speed and accuracy of low-level auditory information processing. However, the effects of TCT on behavioral measures of central auditory processing (CAP) and the role of CAP function on verbal learning outcomes in SZ are unknown. Methods: SZ (n = 42) and healthy subjects (CTL; n = 18) underwent comprehensive clinical, neurocognitive, and auditory assessments, including tests of hearing sensitivity and speech recognition (Words-in-Noise (WIN), Quick Speech-in-Noise (SIN)). SZ patients were randomized to receive either treatment-as-usual (TAU); or 30-h of TCT + TAU using a stratified, parallel design. SZ patients repeated assessments ~10–12 weeks later. Results: Patients exhibited deficits in both WIN (p < 0.05, d = 0.50) and SIN (p < 0.01, d = 0.63). A treatment × time interaction on WIN (p < 0.05, d = 0.74), but not SIN discriminability, was seen in the TCT group relative to TAU. Specific enhancements in the 4-dB over background range drove gains in WIN performance. Moreover, SZ patients with greater CAP deficits experienced robust gains in verbal learning after 30-h of TCT relative to SZ patients without CAP impairment (p < 0.01, d = 1.28). Conclusion: Findings demonstrate that intensive auditory training enhances the fidelity of auditory processing and perception, such that specific CAP deficits were ‘normalized’ and were predictive of gains in verbal learning after TCT. It is conceivable that patients with deficiencies in CAP measures may benefit most from TCT and other interventions targeting auditory dysfunction in SZ.

Background: Patients with Schizophrenia Spectrum Disorders (SSD) demonstrate poor social functioning. While group-based approaches show long-term improvements, access to treatments is limited. Digital platforms hold promise to overcome barriers to treatment delivery and improve outcomes. Objective: In a parallel arm, double-blind RCT, we tested CLIMB, a clinician-assisted, adjunct to treatment that includes computerized social cognition training (SCT), ecological momentary assessments (EMAs), group tele-therapy, and moderated messaging. CLIMB was compared to an active control that includes computerized general cognitive training (GCT), unstructured support groups, and unmoderated messaging. Methods: The primary outcome was social functioning. Secondary outcomes were negative symptoms and quality of life (QoL). Given the sample size, Propensity Score Models were used to ensure balanced baseline covariates. Mixed-effects models examined change over time. Results: 24 participants completed the study (12 per arm). No significant between-group differences emerged in engagement. CLIMB participants engaged in a median of 8 sessions (IQR = 2), 2.8 h of SCT (IQR = 7.5), and 2710 EMAs; control participants engaged in a median of 9 sessions (IQR = 3) and 2.2 h of GCT (IQR = 7.9). As a group, participants showed significant improvements in social functioning (p = .046), with no between-group differences. Intent-to-treat analyses indicated greater improvements in QoL (p = .025) for the active control. Conclusions: Delivering group-based mobile interventions to individuals with SSD is feasible. EMAs allow clinicians to maintain inter-session engagement, build participant self-awareness, and tailor treatment delivery. In this treatment model, whether SCT or GCT is more effective remains unclear. Further research will evaluate group-based mobile interventions to improve outcomes in SSD.

Background: Cognitive Remediation (CR) is designed to halt the pathological neural systems that characterize major psychotic disorders (MPD), and its main objective is to improve cognitive functioning. The magnitude of CR-induced cognitive gains greatly varies across patients with MPD, with up to 40% of patients not showing gains in global cognitive performance. This is likely due to the high degree of heterogeneity in neural activation patterns underlying cognitive endophenotypes, and to inter-individual differences in neuroplastic potential, cortical organization and interaction between brain systems in response to learning. Here, we review studies that used neuroimaging to investigate which biomarkers could potentially serve as predictors of treatment response to CR in MPD. Methods: This systematic review followed the PRISMA guidelines. An electronic database search (Embase, Elsevier; Scopus, PsycINFO, APA; PubMed, APA) was conducted in March 2021. peer-reviewed, English-language studies were included if they reported data for adults aged 18+ with MPD, reported findings from randomized controlled trials or single-arm trials of CR; and presented neuroimaging data. Results: Sixteen studies were included and eight neuroimaging-based biomarkers were identified. Auditory mismatch negativity (3 studies), auditory steady-state response (1), gray matter morphology (3), white matter microstructure (1), and task-based fMRI (7) can predict response to CR. Efference copy corollary/discharge, resting state, and thalamo-cortical connectivity (1) require further research prior to being implemented. Conclusions: Translational research on neuroimaging-based biomarkers can help elucidate the mechanisms by which CR influences the brain's functional architecture, better characterize psychotic subpopulations, and ultimately deliver CR that is optimized and personalized.

Background: One out of 4 patients who sustains a mild traumatic brain injury (mTBI) experiences persistent complaints, despite the absence of structural brain damage on conventional neuroimaging. Susceptibility to develop post concussive symptoms (PCS) is thought to originate from occult brain dysfunction. However, the influence of such neural changes on the development of persistent PCS is poorly characterized. Methods: In this article, we aim to integrate findings from longitudinal studies that investigated across the spectrum of neuroimaging modalities the changes within the first twelve months following a mTBI, with the goal of identifying possible predictors or biomarkers of persistent PCS. Results: Nine studies met inclusion criteria: 5 that used resting state functional MRI, 2 that used Diffusion Weighted Imaging, and 2 that used 1H-MR Spectroscopy. All studies indicate significant structural, functional and/or metabolic aberrations that occur in the acute and early subacute phases following a mTBI. However, in patients with persistent PCS, these mTBI-induced damages linger and relate to the severity of PCS. These biomarkers include: decreased diffusion along white matter fiber tracts, alteration of perfusion, disrupted metabolism, and reduced connectivity within several resting state networks. Additionally, in PCS patients, disruptions of brain function can manifest exclusively in the chronic phase. Conclusion: This review support the ongoing use of neuroimaging modalities to understand the brain changes that occur throughout the time course of mTBI. Based on the complexity of mTBI, however, more work is required to characterize injury and recovery mechanisms that could impact the emergence and persistence of PCS.

Introduction:: Autism spectrum disorder (ASD), a heterogeneous neurodevelopmental disorder, impacts social experience and functioning throughout the lifespan. Although the postnatal phase of neuroplasticity has been a focus for early interventions in ASD, a second critical period in adolescence has emerged as a promising target for experience-dependent remediation. Interventions addressing the multidimensional construct of social cognition have also shown potential as a therapeutic approach. Yet, to date, evidence-based social cognitive interventions (SCIs) designed for adolescents with ASD are still lacking. In this review, we aim to survey and synthesize the extant literature on SCIs for adolescents with ASD in order to inform next steps for treatment research. Methods:: Using the PRISMA guidelines, we limited our queries to peer-reviewed, English-language journal articles describing SCI trials for adolescents with ASD using a randomized controlled design. Results:: Eighteen articles in total met our inclusion/exclusion criteria. We present and discuss these trials using the non-exclusive categories of group-based social skills interventions, experiential-based interventions, and computer-assisted interventions. Limitations:: To ensure a focus on adolescence, we excluded trials with teen-age participants if mean subject age was not between 12-18 years. Also, given the variability across studies in outcome measures, study designs, samples, and effect sizes, findings were incommensurable. Conclusions:: Several reviewed SCIs reported post-treatment improvements in varied domains but findings were inconsistent. Further investigations of existing and novel interventions are warranted; attention to assessing and improving long-term skill transfer is essential. Technology-assisted augmentations may improve treatment efficacy and ecological validity of therapeutic gains.

Background: Deficits in cognition, social cognition, and motivation are significant predictors of poor functional outcomes in schizophrenia. Evidence of durable benefit following social cognitive training is limited. We previously reported the effects of 70 h of targeted cognitive training supplemented with social cognitive exercises (TCT + SCT) verses targeted cognitive training alone (TCT). Here, we report the effects six months after training. Methods: 111 participants with schizophrenia spectrum disorders were randomly assigned to TCT + SCT or TCT-only. Six months after training, thirty-four subjects (18 TCT + SCT, 16 TCT-only) were assessed on cognition, social cognition, reward processing, symptoms, and functioning. Intent to treat analyses was used to test the durability of gains, and the association of gains with improvements in functioning and reward processing were tested. Results: Both groups showed durable improvements in multiple cognitive domains, symptoms, and functional capacity. Gains in global cognition were significantly associated with gains in functional capacity. In the TCT + SCT group, participants showed durable improvements in prosody identification and reward processing, relative to the TCT-only group. Gains in reward processing in the TCT + SCT group were significantly associated with improvements in social functioning. Conclusions: Both TCT + SCT and TCT-only result in durable improvements in cognition, symptoms, and functional capacity six months post-intervention. Supplementing TCT with social cognitive training offers greater and enduring benefits in prosody identification and reward processing. These results suggest that novel cognitive training approaches that integrate social cognitive exercises may lead to greater improvements in reward processing and functioning in individuals with schizophrenia.

Cognitive impairment in schizophrenia is often severe, enduring, and contributes significantly to chronic disability. A standardized platform for identifying cognitive impairments and measuring treatment effects in cognition is a critical aspect of comprehensive evaluation and treatment for individuals with schizophrenia. In this project, we developed and tested a suite of ten web-based, neuroscience-informed cognitive assessments that are designed to enable the interpretation of specific deficits that could signal that an individual is experiencing cognitive difficulties. The assessment suite assays speed of processing, sustained attention, executive functioning, learning and socio-affective processing in the auditory and visual modalities. We have obtained data from 283 healthy individuals who were recruited online and 104 individuals with schizophrenia who also completed formal neuropsychological testing. Our data show that the assessments 1) are acceptable and tolerable to users, with successful completion in an average of under 40 min; 2) reliably measure the distinct theoretical cognitive constructs they were designed to assess; 3) can discriminate schizophrenia patients from healthy controls with a fair degree of accuracy (AUROC > 0.70); and 4) have promising construct, convergent, and external validity. Further optimization and validation work is in progress to finalize the evaluation process prior to promoting the dissemination of these assessments in real-world settings.

Introduction: During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds as reflected in the N1 component of the auditory event-related potential (ERP). N1 suppression during talking is reduced in patients with schizophrenia. We hypothesized that these deficits would recover with auditory training that targets the speech processing system. Methods: Forty-nine individuals early in the course of a schizophrenia-spectrum illness (ESZ) were randomly assigned to 40 h of Targeted Auditory Training (TAT; n = 23) or Computer Games (CG; n = 26). The N1 ERP component was elicited during production (Talk) and playback (Listen) of vocalization. Effects of Treatment on Global Cognition, N1 suppression (Talk-Listen), N1 during Talking and Listening were assessed. Simple effects of the passage of time were also assessed in the HC after 28 weeks. Results: There was a Treatment × Time interaction revealing that N1 suppression was improved with TAT, but not with CG. TAT, but not CG, also improved Global Cognition. However, TAT and CG groups differed in their pre-treatment N1 suppression, and greater N1-suppression abnormalities were strongly associated with greater improvement in N1 suppression. Conclusions: In this sample of ESZ individuals, targeted auditory training appeared to improve the function of the efference copy/corollary discharge mechanism which tended to deteriorate with computer games. It remains to be determined if baseline N1 suppression abnormalities are necessary for TAT treatment to have a positive effect on efference copy/corollary discharge function or if improvements observed in this study represent a regression to the mean N1 suppression in ESZ.

Background: Cognitive impairments are prominent features of individuals diagnosed with major psychotic disorders (MPD), negatively affecting occupational and social functioning. Over the past few years, several cognitive remediation (CR) interventions have been developed, with different foundation principles, targets, and mechanisms of action. The vast majority consists of drill and practice approaches that are grounded in the principle of neuropsychology. More recently, neuroplasticity-based cognitive training (NBCT) has shown promise. While several CR approaches have shown moderate efficacy, improving both cognition and real-world functioning, there is considerable variability in individual treatment response. Studies that have investigated factors that predict CR outcome and can be used to guide treatment have historically grouped all CR approaches together. Here, we aim to explore common and distinct predictors of response to neuroplasticity-based and neuropsychology-based CR. Methods: an electronic database search on MEDLINE/PubMed was conducted in February 2020 to identify articles investigating predictors of response to CR. We limited our queries to peer-reviewed, English-language journal articles describing trials of CR for adults with MPD. Results: a total of 58 articles were examined, and 14 different categories of CR predictors were identified. CR predictors that most stood out were age, shorter illness duration, lower symptoms severity, lower antipsychotic medications, and the delivery of CR in combination with other treatments. Although results are still mixed, demographical variables appear to be far less important for NBCT than they are for other CR programs. Clinical and genetic variables – such as symptoms severity, lower antipsychotic dose, serum BDNF and serum D-serine – seem to influence more significantly NBCT than neuropsychology-based CR. Conclusions:Data on NBCT is relatively scarce, and further research is required to better understand which

Background: Adolescence is a period of brain plasticity that is affected by social and affective stimuli. Adaptive neurodevelopmental changes in the context of complex social situations may precipitate or exacerbate cognitive biases (i.e., attention and/or interpretation biases) and predispose at-risk individuals to symptoms of social anxiety. Methods: This systematic review followed the PRISMA guidelines. Nine adolescent studies were examined including 3 studies using Cognitive Bias Modification Training (CBMT) to target attention biases (CBMT-A), 3 studies using CBMT to target interpretation biases (CBMT-I), and 3 aimed at reducing both attention and interpretation biases. Results: The studies of CBMT-A alone did not find significant effects on cognitive and clinical outcomes. However, studies of CBMT-I alone showed some improvement in interpretation bias. The combination of CBMT-A and CBMT-I appeared promising in reducing both attentionl and interpretation biases. Limitations: The paucity of studies and the heterogeneity across studies (e.g., format of CBMT, assessment measures) limit the calculation of overall effect sizes and the examination of predictors, moderators, and mediators of outcome. Conclusions: Technology-driven interventions such as CBMT have the potential to extend treatments outside the clinic setting and to augment current therapies for social anxiety. Further research is needed to develop CBMT procedures that optimize learning in group and real-world settings and to identify predictors of treatment response. Understanding the neural correlates of response to CBMT may help identify future targets for intervention.

Background: Bipolar disorder (BD) is characterized by cognitive impairments that are known to predict psychosocial functioning and quality of life. While cognitive remediation (CR) was originally developed to directly target cognitive symptoms in traumatic brain injury and psychotic illnesses, the efficacy of CR in BD has begun to emerge only in the last decade. Functional Remediation (FR) is an integrated intervention that has been developed to restore psychosocial functioning by means of ecological neurocognitive techniques that involve psychoeducation about cognitive dysfunctions and their impact on the general functioning. Because of the heterogeneity of treatment targets and mechanisms of actions, here we aim to illustrate the effects induced by existing CR/FR approaches in BD. Methods: In this systematic review, we evaluated cognitive and functional outcomes after CR/FR in studies conducted in BD. Results: Eleven studies met inclusion criteria: 3 RCTs that compared CR/FR to one or more control condition (n = 354), 5 secondary analyses that further examined data from these trials, 2 single-arm studies, and 1 naturalistic study. While features such as the use of computerized training tools and a group-based format recurred across studies, CR/FR paradigms targeting different cognitive and functional domains showed specificity of training focus to outcomes. Effect sizes were in the medium-large range, suggesting that patients with BD respond to treatment at or above the level reported in psychotic patients. Integrated approaches that combined cognitive exercises with group-based experiences were associated with both cognitive and functional improvements. Conclusions: In this review, we found support for the use of CR/FR paradigms in patients with BD with evidence of cognitive and functional improvements. The scarcity of currently published RCTs as well as of data examining mechanisms of action and neural correlates limits the generalizability of our findings.

Background: Schizophrenia, schizoaffective disorder, and related illnesses are associated with significant impairment in cognitive functioning which is among the strongest predictors of disability and poor quality of life. Cognitive remediation (CR) was developed as a set of behavioral interventions directly targeting cognitive symptoms. Studies have shown that CR produces cognitive improvements in patients with schizophrenia and bipolar disorder that may be associated with improvements in functioning. However, the relative efficacy of CR across diagnoses has not been established. Indirect evidence suggests that CR is effective in patients with affective illness as well as patients with schizophrenia (SZ); however, the one study to evaluate the effects of diagnosis on outcomes directly in patients with SZ versus schizoaffective disorder (SZA) found no differences by diagnosis. Methods: In this systematic review, we evaluated cognitive and functional outcomes after CR in studies including patients with SZA, and examined specificity of training content to outcomes. Results: Sixteen studies met inclusion criteria: 10 studies that compared CR to a control condition (n = 779) and 6 comparative effectiveness studies. None of the studies explicitly compared patients by diagnosis. Studies included a mixture of patients with SZA or SZ. Of the CR versus control studies, effect sizes for cognitive outcomes were moderate-large (d =.36–.94). Studies comparing CR paradigms targeting different cognitive domains showed specificity of training focus to outcomes. Five of studies reported significant functional improvement after CR as secondary outcomes. Conclusions: In this review, we found support for the use of CR paradigms in patients with affective psychosis, with evidence that reported treatment effects in mixed affective and non-affective samples are at or above the levels previously reported in SZ. However, lack of availability of data directly comparing patients by diagnosis

A priority for improving outcome in individuals at clinical high risk (CHR) is enhancing our understanding of predictors of psychosis as well as psychosocial functioning. Social functioning, in particular, is a unique indicator of risk as well as an important outcome in itself. Negative symptoms are a significant determinant of social functioning in CHR individuals; yet, it is unclear which specific negative symptoms drive functional outcome and how these symptoms function relative to other predictors, such as neurocognition and mood/anxiety symptoms. In a sample of 85 CHR individuals, we examined whether a two-factor negative symptom structure that is found in schizophrenia (experiential vs expressive symptoms) would be replicated in a CHR sample; and tested the degree to which specific negative symptoms predict social functioning, relative to neurocognition and mood/anxiety symptoms, which are known to predict functioning. The two-factor negative symptom solution was replicated in this CHR sample. Negative symptom severity was found to be uniquely predictive of social functioning, above and beyond depression/anxiety and neurocognition. Experiential symptoms were more strongly associated with social functioning, relative to expression symptoms. In addition, experiential symptoms mediated the relationship between expressive negative symptoms and social functioning. These results suggest that experiences of motivational impairment are more important in determining social functioning, relative to affective flattening and alogia, in CHR individuals, thereby informing the development of more precise therapeutic targets. Developing novel interventions that stimulate goal-directed behavior and reinforce rewarding experiences in social contexts are recommended.

Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal-striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal-striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life.