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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: In recent years, there has been increased interest in the development of remote psychological assessments. These platforms increase accessibility and allow clinicians to monitor important health metrics, thereby informing patient-centered treatment. Objective: In this study, we report the properties and usability of a new web-based neurocognitive assessment battery and present a normative data set for future use. Methods: A total of 781 participants completed a portion of 8 tasks that captured performance in auditory processing, visual-spatial working memory, visual-spatial learning, cognitive flexibility, and emotional processing. A subset of individuals (n=195) completed a 5-question survey measuring the acceptability of the tasks. Results: Between 252 and 426 participants completed each task. Younger individuals outperformed their older counterparts in 6 of the 8 tasks. Therefore, central tendency data metrics were presented using 7 different age bins. The broad majority of participants found the tasks interesting and enjoyable and endorsed some interest in playing them at home. Only 1 of 195 individuals endorsed not at all for the statement, "I understood the instructions." Older individuals were less likely to understand the instructions; however, 72% (49/68) of individuals over the age of 60 years still felt that they mostly or very much understood the instructions. Conclusions: Overall, the tasks were found to be widely acceptable to the participants. The use of web-based neurocognitive tasks such as these may increase the ability to deploy precise data-informed interventions to a wider population.

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: 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.

Background: We previously demonstrated that the high heterogeneity of response to computerized Auditory Training (AT) in psychosis can be ascribed to individual differences in sensory processing efficiency and neural plasticity. In particular, we showed that Auditory Processing Speed (APS) serves as a behavioral measure of target engagement, with faster speed predicting greater transfer effects to untrained cognitive domains. Here, we investigate whether the ability of APS to function as a proxy for target engagement is unique to AT, or if it applies to other training interventions, such as Executive Functioning Training (EFT). Additionally, we examine whether changes in APS are durable after these two forms of training. Methods: One hundred and twenty-five participants with Recent Onset Psychosis (ROP) were randomized to AT (n = 66) and EFT (n = 59), respectively. APS was captured at baseline, after treatment, and at 6-month follow-up. Mixed models repeated measures analysis with restricted maximum likelihood was used to examine whether training condition differentiated APS trajectories. Within-group correlational analyses were used to study the relationship between APS and performance improvements in each of the training exercises. Results: The two groups were matched for age, gender, education, and baseline APS. Participants showed high inter-individual variability in APS at each time point. The mixed model showed a significant effect of time (F = 5.99, p =.003) but not a significant group-by-time effect (F =.73, p =.48). This was driven by significant APS improvements AT patients after treatment (d =.75) that were maintained after 6 months (d =.63). Conversely, in EFT patients, APS improvements did not reach statistical significance after treatment (p =.33) or after 6 months (p =.24). In AT patients, baseline APS (but not APS change) highly predicted peak performance for each training exercise (all r’s >.42). Conclusions: Participant-specific speed in process

Sensory discrimination thresholds (i.e., the briefest stimulus that can be accurately perceived) can be measured using tablet-based auditory and visual sweep paradigms. These basic sensory functions have been found to be diminished in patients with psychosis. However, the extent to which worse sensory discrimination characterizes genetic liability for psychosis, and whether it is related to clinical symptomatology and community functioning remains unknown. In the current study we compared patients with psychosis (PSY; N=76), their first-degree biological relatives (REL; N=44), and groups of healthy controls (CON; N=13 auditory and visual/N=275 auditory/N=267 visual) on measures of auditory and visual sensory discrimination, and examined relationships with a battery of symptom, cognitive, and functioning measures. Sound sweep thresholds differed among the PSY, REL, and CON groups, driven by higher thresholds in the PSY compared to CON group, with the REL group showing intermediate thresholds. Visual thresholds also differed among the three groups, driven by higher thresholds in the REL versus CON group, and no significant differences between the REL and PSY groups. Across groups and among patients, higher thresholds (poorer discrimination) for both sound and visual sweeps strongly correlated with lower global cognitive scores. We conclude that low-level auditory and visual sensory discrimination deficits in psychosis may reflect genetic liability for psychotic illness. Critically, these deficits relate to global cognitive disruptions that are a hallmark of psychotic illnesses such as schizophrenia.

Background: Greater impairments in early sensory processing predict response to auditory computerized cognitive training (CCT) in patients with recent-onset psychosis (ROP). Little is known about neuroimaging predictors of response to social CCT, an experimental treatment that was recently shown to induce cognitive improvements in patients with psychosis. Here, we investigated whether ROP patients show interindividual differences in sensory processing change and whether different patterns of SPC are (1) related to the differential response to treatment, as indexed by gains in social cognitive neuropsychological tests and (2) associated with unique resting-state functional connectivity (rsFC). Methods: Twenty-six ROP patients completed 10 h of CCT over the period of 4–6 weeks. Subject-specific improvement in one CCT exercise targeting early sensory processing—a speeded facial Emotion Matching Task (EMT)—was studied as potential proxy for target engagement. Based on the median split of SPC from the EMT, two patient groups were created. Resting-state activity was collected at baseline, and bold time series were extracted from two major default mode network (DMN) hubs: left medial prefrontal cortex (mPFC) and left posterior cingulate cortex (PCC). Seed rsFC analysis was performed using standardized Pearson correlation matrices, generated between the average time course for each seed and each voxel in the brain. Results: Based on SPC, we distinguished improvers—i.e., participants who showed impaired performance at baseline and reached the EMT psychophysical threshold during CCT—from maintainers—i.e., those who showed intact EMT performance at baseline and sustained the EMT psychophysical threshold throughout CCT. Compared to maintainers, improvers showed an increase of rsFC at rest between PCC and left superior and medial frontal regions and the cerebellum. Compared to improvers, maintainers showed increased rsFC at baseline between PCC and superior temporal and insular

Recent advances in digital technology and mobile platforms have widely shown the potential to enrich evidence-based psychological treatments by supporting the remote delivery of therapeutic tools to individuals with mental illness. Compared to in-person approaches, mobile apps offer several benefits that are particularly attractive to youths struggling with mental illness. First, mental health apps enable scheduling flexibility and decrease scheduling burden, thus facilitating accessibility and compliance with intervention requirements and ultimately increasing cost-effectiveness. Second, mental health apps can enhance the quality of treatment by incorporating computerized treatments and innovative methods of communication, and by making treatment adaptive and responsive to dynamic, ecologically valid data. Third, mental health apps can be accessed with greater frequency than in-person treatment approaches for brief therapeutic interactions that help consolidate support and maintain inter-session continuity. Fourth, delivering treatment in real-world settings may support the retention, reinforcement and successful generalization of cognitive and behavioral skills. Finally, mental health apps can include opportunities for remote social engagement, like social networking or direct peer-to-peer messaging. The successful development of a mobile intervention for youth experiencing mental illness requires the coordinated activity of clinical researchers with patients, clinicians and the technology sector. The intervention should emerge in response to a symptom dimension or unmet clinical need, which resonates with the patient group it is intended to serve. Finally, building strategic and appropriately formalized academic-industry partnerships can result in long-lasting digital tools that are more easily adopted and disseminated.

Background: The COVID-19 pandemic is negatively impacting the mental health of both patients with COVID-19 and the general population. As current guidelines are limiting in-person contacts to reduce the spread of the virus, the development of a digital approach to implement in psychiatric and psychological consultations is needed. In this paper, we present the DigiCOVID protocol, a digital approach to offer remote, personalized psychological and psychiatric support to former or current patients with COVID-19 and their relatives. Objective: The main goal of this project is to evaluate the feasibility, acceptability, and usability of the DigiCOVID protocol. Furthermore, we also aim to assess the impact of the abovementioned protocol by means of pre-post changes in psychological clinical variables. Methods: Participants undergo an initial telephonic screening to ensure inclusion criteria are met. Secondly, participants complete a video-assisted neuropsychological IQ test as well as web-based self-reports of health and general well-being. Participants are then assigned to a psychotherapist who offers 8 teletherapy sessions. At the end of the therapy cycle, the web-based questionnaires are administered for a posttreatment evaluation. Results: As of April 2022, we enrolled a total of 122 participants, of which 94 have completed neuropsychological tests and web-based questionnaires. Conclusions: Our study aims at testing the feasibility and preliminary efficacy of DigiCOVID, a remote telemedicine protocol for the improvement of psychological and psychiatric health in patients with COVID-19 and their relatives. To date, the approach used seems to be feasible and highly customizable to patients' needs, and therefore, the DigiCOVID protocol might pave the way for future telepsychiatry-based interventions.

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: Patients with post-infective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often show both short- and long-term cognitive deficits within the dysexecutive/inattentive spectrum. However, little is known about which cognitive alterations are commonly found in patients recovered from SARS-CoV-2, and which psychometric tools clinicians should consider when assessing cognition in this population. The present work reviewed published studies to provide a critical narrative of neuropsychological (NPs) deficits commonly observed after SARS-CoV-2 infection and the tests most suited for detecting such cognitive sequelae depending on illness severity. Methods: This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and was pre-registered on Prospective Register of Systematic Reviews (PROSPERO) (CRD42021253079). Observational studies quantitatively assessing cognition in patients with post-infective SARS-CoV-2 were considered. From 711 retrieved articles, 19 studies conducted on patients with SARS-CoV-2 without medical comorbidities were included and stratified by disease severity. Results: The majority of studies (N = 13) adopted first-level tests. The most frequently administered screeners were the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE)—with the former more likely to detect mild, and the latter moderate/severe deficits. Among second-level tests, those assessing attention and executive functions (EFs) were highly represented. Remotely-delivered tests yielded lower percentages of cognitive impairment. Overall, cognitive domains often found to be impaired were EFs, attention, and memory. Conclusion: Cognitive sequelae in patients with post-infective SARS-CoV-2 can be detected with NPs testing. Depending on the psychometric test features, the likelihood of observing cognitive deficits can vary. Further studies on larger sample sizes are needed to investigat

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.

Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%, P < 0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up (p < 0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions.

Objective: The COVID-19 pandemic is negatively impacting the mental health of COVID-19 patients and family members. Given the restrictions limiting in person contact to reduce the spread of the virus, a digital approach is needed to tackle the psychological aftermath of the pandemic. We present the development of a brief remote psychotherapy program for COVID-19 patients and/or their relatives. Methods: We first reviewed the literature on psychotherapeutic interventions for COVID-19 related symptoms. Based on this evidence, we leveraged ongoing clinical experiences with COVID-19 survivors and family members to design an intervention model that could be disseminated and integrated into the workflow of the mental health system. Results: This 8-session model –inspired by constructivist and hermeneutic-phenomenological therapies– serves COVID-19 patients during hospitalization, remission and recovery. This model can also be delivered to people dealing with the COVID-19 hospitalization/discharge of a family member, or the loss of a family member due to COVID-19. Conclusion: We described a remote psychotherapeutic approach to tackle the COVID-19 pandemic psychological aftermath. To date, the approach seems feasible and highly customizable to patients’ needs. Studies are underway to test its preliminary efficacy. Once proven efficacious, this treatment model could provide a blueprint for future tele-psychology wide-scale interventions.

Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%, P < 0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up (p < 0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions.

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

Objective: Peer-to-peer interactions and support groups mitigate experiences of social isolation and loneliness often reported by individuals with psychotic disorders. Online peer-to-peer communication can promote broader use of this form of social support. Peer-to-peer interactions occur naturally on social media platforms, but they can negatively affect mental health. Recent digital interventions for persons with psychotic disorders have harnessed the principles of social media to incorporate peer-to-peer communication. This review examined the feasibility, acceptability, and preliminary efficacy of recent digital interventions in order to identify strategies to maximize benefits of online peer-to-peer communication for persons with psychotic disorders. Methods: An electronic database search of PubMed, EMBASE, PsycINFO, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Health Technology Assessment Database was conducted in February 2017 and yielded a total of 1,015 results. Eight publications that reported data from six independent trials and five interventions were reviewed. Results: The technology supporting peer-to-peer communication varied greatly across studies, from online forums to embedded social networking. When peer-to-peer interactions were moderated by facilitators, retention, engagement, acceptability, and efficacy were higher than for interventions with no facilitators. Individuals with psychotic disorders were actively engaged with moderated peer-to-peer communication and showed improvements in perceived social support. Studies involving service users in intervention design showed higher rates of acceptability. Conclusions: Individuals with psychotic disorders value and benefit from digital interventions that include moderated peer-to-peer interactions. Incorporating peer-to-peer communication into digital interventions for this population May increase compliance with other evidence-based therapies by producing more acceptable and en

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: Access and engagement with psychosocial interventions for people with psychotic disorders (PD) remain limited. This is because these interventions require specially trained therapists, are often not available in clinical settings, and have a high scheduling burden, requiring a commitment of hours of clinic visits per week for several months. Delivering interventions remotely via mobile devices increases scalability and facilitates access, while also improving scheduling flexibility and decreasing burden, thus improving adherence to intervention requirements. To address these needs, we designed CLIMB, a digital intervention that aims to enhance social functioning in people with PD. CLIMB consists of 2 treatment components: a computerized social cognition training (SCT) program and optimized remote group therapy—an innovative treatment that combines remote group therapy with group texting. In this pilot study, we investigated the feasibility of delivering 6 weeks of CLIMB remotely to people with PD and explored effects on outcomes. We recruited, screened and enrolled participants online, and delivered assessments and intervention remotely using provided iPads. Participants were asked to complete 18 hours of SCT and to attend 6 remote group therapy sessions. Methods: To assess feasibility, we evaluated adherence to study procedures, attrition rates, engagement metrics, and reported acceptability of the intervention. We also explored changes on measures of social cognition, quality of life, and symptoms. Results: Twenty-seven participants were enrolled. Remote assessments were completed successfully on 96% of enrolled participants. Retention in the trial was 77.7%. Ninety-five percent of the iPads were returned undamaged after intervention. Participants on average attended 84% of the group tele-therapy sessions, completed a median of 9.5 hours of SCT, and posted a median of 5.2 messages per week on the group text chat. Participants rated CLIMB in the medium

The rapidly expanding field of mobile health (mHealth) seeks to harness increasingly affordable and ubiquitous mobile digital technologies including smartphones, tablets, apps and wearable devices to enhance clinical care. Accumulating evidence suggests that mHealth interventions are increasingly being adopted and valued by people living with serious mental illnesses such as schizophrenia and bipolar disorder, as a means of better understanding and managing their condition. We draw on experiences from three geographically and methodologically distinct mHealth studies to provide a pragmatic overview of the key challenges and considerations relating to the process of developing digital interventions for this population.

Background Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population. Method We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants' facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES). Results While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z =Â-2.33, p = 0.02) and at trend level in healthy controls (Z =Â-1.87, p = 0.06). Conclusions These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.

Background: Mood disorders are dynamic disorders characterized by multimodal symptoms. Clinical assessment of symptoms is currently limited to relatively sparse, routine clinic visits, requiring retrospective recollection of symptoms present in the weeks preceding the visit. Novel advances in mobile tools now support ecological momentary assessment of mood, conducted frequently using mobile devices, outside the clinical setting. Such mood assessment may help circumvent problems associated with infrequent reporting and better characterize the dynamic presentation of mood symptoms, informing the delivery of novel treatment options. Objectives: The aim of our study was to validate the Immediate Mood Scaler (IMS), a newly developed, iPad-deliverable 22-item self-report tool designed to capture current mood states. Methods: A total of 110 individuals completed standardized questionnaires (Patient Health Questionnaire, 9-item [PHQ-9]; generalized anxiety disorder, 7-Item [GAD-7]; and rumination scale) and IMS at baseline. Of the total, 56 completed at least one additional session of IMS, and 17 completed one additional administration of PHQ-9 and GAD-7. We conducted exploratory Principal Axis Factor Analysis to assess dimensionality of IMS, and computed zero-order correlations to investigate associations between IMS and standardized scales. Linear Mixed Model (LMM) was used to assess IMS stability across time and to test predictability of PHQ-9 and GAD-7 score by IMS. Results: Strong correlations were found between standard mood scales and the IMS at baseline (r=.57-.59, P<.001). A factor analysis revealed a 12-item IMS (“IMS-12”) with two factors: a “depression” factor and an “anxiety” factor. IMS-12 depression subscale was more strongly correlated with PHQ-9 than with GAD-7 (z=1.88, P=.03), but the reverse pattern was not found for IMS-12 anxiety subscale. IMS-12 showed less stability over time compared with PHQ-9 and GAD-7 (.65 vs.91), potentially reflecting more se

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