iCARE Self-Guided Digital Intervention for Postpartum Depression in Danish Mothers: Formative Research Using User-Centered Design

<strong>Background:</strong> Postpartum depression (PPD) is a major public health concern. Despite advancements in treatment, many barriers to accessing care remain. There has been a growing interest in digital interventions for the prevention and treatment of PPD. However, for mothers with mild and moderate symptoms of depression, there is a limited offer of self-guided internet-based interventions developed with user input and with considerations on how to integrate the intervention into stepped care models for PPD. <strong>Objective:</strong> The aim of this study was (1) to describe the process of the design and development of iCARE, a self-guided digital psychological intervention for mothers with mild and moderate symptoms of PPD in Denmark, (2) present the program’s theory illustrated by a logic model, and (3) explore its initial usability and prospective acceptability. <strong>Methods:</strong> Applying user-centered design methods, the intervention development followed six steps: (1) a literature review to identify evidence‑based therapeutic components of self‑guided interventions for PPD, (2) interviews with women with lived experience of PPD and group discussions with mental health experts and home‑visiting providers to identify user needs, (3) iterative design and content development with stakeholder feedback in collaboration with the Department of Digital Psychiatry, (4) prototype testing using think‑aloud usability sessions and interviews with 5 mothers, (5) a group cognitive walkthrough with mental health experts, and (6) final refinement and implementation of the iCARE program with developers and designers. <strong>Results:</strong> Initial interviews with mothers and maternal health care providers emphasized the importance of a digital intervention offering timely psychoeducation, coping strategies, and pathways to in-person care while addressing the diversity of expressions of PPD symptoms. Stakeholders recommended a flexible program, multimodal content, and integration into maternal care systems with community health nurses supporting engagement and participation. The prototype was designed to be user-centered, engaging, and with multiple interactive features. It included components on psychoeducation, cognitive exercises grounded in cognitive behavioral therapy, acceptance and commitment principles, and mood-monitoring. The prototype was designed to be user-centered and engaging, with interactive features and components on psychoeducation, cognitive exercises grounded in cognitive behavioral and acceptance and commitment principles, and mood-monitoring. Prototype testing indicated high prospective acceptability and led to refinements across 6 themes: appropriateness of content; motivation and engagement; inclusivity and gender representation; clarity of instructions and data use; understanding of therapeutic method; and usability, layout, and navigation. <strong>Conclusions:</strong> iCARE is a self-guided internet-based psychological intervention for mothers with mild and moderate symptoms of PPD in Denmark. It was developed with user input by using qualitative methods, user-centered design, and psychological theory. Further research is needed to evaluate the feasibility and effectiveness of the program in a randomized controlled trial and its integration into maternal health care models such as universal PPD screening and home-visiting.

Roles of NRXN1 in neuropsychiatric disorders: from genetic lesion to molecular mechanism

Numerous neuropsychiatric disorders frequently exhibit overlapping genetic risk factors, implying the molecular basis for their comorbidity. Nevertheless, the pathogenesis of these disorders remains elusive, particularly regarding how genetic variations impair the physiological function of risk genes and contribute to disease phenotypes. Neurexin 1 protein, encoded by NRXN1 gene, belongs to the neurexin family of presynaptic adhesion molecules. And neurexin 1 is involved in synaptogenesis and the maintenance of synaptic action. Genetic variations of NRXN1 have been demonstrated to be associated with a spectrum of neuropsychiatric disorders. Herein, this review focuses on the most recent and relevant literature concerning the genetic and molecular mechanisms through which NRXN1 variants contribute to the pathogenesis of neuropsychiatric disorders, particularly schizophrenia and autism spectrum disorder. Among them, we propose the isoform-dependent excitation-inhibition imbalance hypothesis of NRXN1 in autism spectrum disorder. And this hypothesis may account for both the elevated and decreased excitation-inhibition ratios observed in diverse individuals with autism spectrum disorder. Moreover, both schizophrenia and autism spectrum disorder involve deletions and alternative splicing of NRXN1, offering molecular evidence for their comorbidity. Then, we analyzed and summarized the current research status of NRXN1 in other neuropsychiatric disorders, including attention-deficit hyperactivity disorder, insomnia, epilepsy, suicide, and depression. Additionally, available limited researches on NRXN1-targeted therapeutic strategies and associated pharmacological studies are also incorporated. Finally, we discussed existing challenges in NRXN1 research within the context of neuropsychiatric disorders and proposed potential avenues to overcome these obstacles.

Direct modulation of human GABA-A α1β2γ2 receptors by the endocannabinoid 2-arachidonoylglycerol: implications for cannabinoid-related ligands and limitations for anxiolytic drug development

Anxiety disorders are associated with impaired inhibitory neurotransmission mediated by γ-aminobutyric acid type A (GABA-A) receptors. Although benzodiazepines remain effective anxiolytics, their clinical utility is limited by sedation, cognitive impairment, tolerance, and dependence, prompting the search for mechanistically distinct GABAergic modulators. Among cannabinoid-related molecules, the strongest evidence for direct GABA-A receptor modulation concerns the endocannabinoid 2-arachidonoylglycerol (2-AG), which potentiates recombinant human α1β2γ2 receptors through residues located in the M4 helix of the β2 subunit. Here, we review the structural architecture, biophysical properties, and pharmacological profile of the human GABA-A α1β2γ2 isoform as the relevant molecular framework for evaluating this mechanism, while discussing the broader relevance of cannabinoid-related ligands and selected phytocannabinoids without assuming mechanistic equivalence. We further assess the hypothesis that 2-AG reaches the β2-M4 site through a membrane-access route and identify five conceptual barriers that currently limit translation of this mechanism into anxiolytic drug development: supraphysiological effective concentrations, unresolved synaptic-versus-extrasynaptic actions, uncertain subtype selectivity, incomplete validation of lipid-environment effects, and lack of clinical evidence linking this mechanism to anxiolysis in humans. We conclude that direct modulation through β2-M4 defines a mechanistically intriguing allosteric pathway distinct from benzodiazepine action; however, its location on a shared β2 subunit and the micromolar concentrations required for modulation represent substantial obstacles to the rational design of anxioselective agents based on this mechanism.

Romanian male patients with the dual diagnosis of schizophrenia and alcohol use disorder: a prospective study of clinical, social, and treatment-related factors affecting quality of life

BackgroundSchizophrenia frequently co-occurs with alcohol use disorder (AUD), resulting in a complex clinical profile associated with poor functional outcomes and reduced quality of life (QoL). Although both conditions independently impair psychosocial functioning, few studies have examined the combined effects of clinical, social, and treatment-related factors on QoL in patients with this dual diagnosis.MethodsThis prospective observational study included 88 male inpatients diagnosed with schizophrenia and comorbid AUD and who were followed over a 6-month period. Quality of life was assessed using the World Health Organization Quality of Life–BREF (WHOQoL–BREF). The clinical variables included severity of psychotic symptoms (Positive and Negative Syndrome Scale), alcohol use severity (Michigan Alcohol Screening Test), and treatment characteristics. Social and personal factors, such as self-care capacity, social support, education, and legal problems, were also evaluated. Multivariable regression analyses were conducted to identify predictors of QoL at baseline and follow-up.ResultsAt baseline, higher QoL was significantly associated with greater self-care capacity, social support, and higher positive symptom scores, while the need for antipsychotic treatment was associated with lower QoL. At the 6-month follow-up, better QoL was predicted by greater self-care capacity, higher educational level, and receipt of anti-craving medication. By contrast, negative and general psychopathology, medico-legal problems, and the need for antidepressant treatment were associated with poorer QoL. Alcohol use severity, as measured by the MAST, was not independently associated with QoL at either timepoint.ConclusionsIn patients with schizophrenia and comorbid AUD, QoL is shaped by a complex interaction of clinical severity, functional capacity, and treatment-related factors. Beyond symptom control, interventions targeting self-care, social functioning, and integrated addiction treatment appear essential to improve long-term outcomes. These findings support the implementation of a multidimensional, recovery-oriented approach for the management of patients with the dual diagnosis.

Assessing directional connections between symptoms, cognition, insight, and real-life functioning in schizophrenia: a partial ancestor graphs analysis

IntroductionSchizophrenia is a severe chronic mental disorder causing significant global disability. Understanding the intricate relationships between symptoms, cognitive functions, and real-life outcomes is essential for developing effective interventions. Prior research, while informative, could not often determine the direction of the association between these illness-related factors. This study aimed to investigate the possible causal connections within the interrelationships of these variables. MethodsThis cross-sectional study included 215 clinically stable patients diagnosed with schizophrenia. Comprehensive assessments covered psychopathology, neurocognition, social cognition, metacognition, clinical insight, and real-life functioning. Causal relationships were explored using Partial Ancestral Graphs, a causal discovery framework that accounts for mediators and confounders. The Greedy Fast Causal Inference algorithm was employed with 1,000 bootstrap replications to assign edge orientations.ResultsA central neurocognitive–metacognitive–functional system of directed connection emerged: visual learning was linked to attention/vigilance and working memory. Working memory showed a direct relationship with metacognition, which, in turn, was connected to real-life functioning. Two partly independent contributions to real-life functioning were also identified: conceptual disorganization and experiential negative symptoms, which were directly related to expressive deficits. Positive symptoms, depressive symptoms, and social cognition occupied peripheral positions, showing no significant connection with other variables. Unawareness and misattribution of symptoms showed an indeterminate association disconnected from the main network.DiscussionThe findings show a set of directed associations that start with neurocognitive abilities, pass through working memory and metacognition, and terminate in real-life functioning. Independently, conceptual disorganization and expressive negative symptoms also exert direct influences. These directed systems of connections provide operational guidance for clinical practice, highlighting critical targets for interventions such as cognitive remediation focused on working memory, metacognitive therapies, and strategies addressing disorganization and avolition, all aimed at improving real-life outcomes in schizophrenia.

Internalizing and externalizing pathways to internet gaming disorder: the roles of anger and social anxiety

BackgroundInternet Gaming Disorder (IGD) represents a significant behavioral health concern, yet the roles of internalizing and externalizing psychological vulnerabilities in its development remain underexplored, particularly in Arabic-speaking populations.ObjectiveThis study examined anger and social anxiety as distinct externalizing and internalizing predictors of IGD severity in a Saudi Arabian community sample.MethodsA cross-sectional survey was administered to 303 participants (60.1% female; estimated mean age = 29.79 years, SD = 8.83) across five regions of Saudi Arabia. Participants completed the Internet Gaming Disorder Scale–Short Form (IGDS9-SF), a three-item Anger Screening Scale, and a two-item Social Anxiety screener. Hierarchical linear regression and structural equation modeling (SEM) were conducted to examine unique and incremental contributions of anger and social anxiety to IGD symptoms.ResultsAnger and social anxiety were strongly intercorrelated (r = .86, p <.001) but demonstrated divergent patterns in multivariate models. Hierarchical regression indicated that both predictors contributed unique variance when entered simultaneously, with anger positively and social anxiety negatively predicting IGD after controlling for shared variance. However, SEM clarified that only social anxiety significantly predicted latent IGD severity (β = .32, p = .027), whereas anger did not (β = .07, p = .68). The final model explained approximately 13% of variance in IGD symptoms.ConclusionsSocial anxiety was associated with IGD severity as a distinct internalizing correlate, consistent with avoidance-based coping and online social preference accounts. These preliminary, cross-sectional findings suggest that social anxiety warrants consideration in future IGD screening and research efforts in Arabic-speaking contexts.

From cats to cortex: T. gondii and psychosis, depression, and anxiety

This review examines whether cat ownership, via exposure to the neurotropic parasite T. gondii, contributes to vulnerability for psychotic, depressive, and anxiety symptoms. T. gondii establishes lifelong latent infection in the brain and muscle, where it can modulate dopaminergic signaling, neuroinflammation, and tryptophan–kynurenine metabolism, providing a biologically plausible pathway to altered cognition, mood, and behavior. Epidemiological and meta-analytic data indicate small-to-moderate associations between T. gondii seropositivity and schizophrenia, with more variable but suggestive links to depression and anxiety. Evidence for cat ownership as an independent risk factor is inconsistent: some cohorts and recent meta-analyses report elevated odds of schizophrenia-related outcomes in those exposed to cats, whereas rigorously controlled studies frequently find attenuated or null effects. Methodological limitations, alternative explanations, and cultural implications are discussed, and priorities for mechanism-informed, longitudinal and interventional research are outlined.

The Download: a Nobel winner on AI, and the case for fixing everything

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

Three things in AI to watch, according to a Nobel-winning economist

A few months before he won the Nobel Prize in economics in 2024, Daron Acemoglu published a paper that earned him few fans in Silicon Valley. He argued that AI would give only a small boost to US productivity and would not eliminate the need for human work.

Two years later, Acemoglu’s measured take has not caught on. The technology has advanced quite a bit since his cautious predictions, but the data is still largely on his side. 

MIT Technology Review spoke with him to understand if any of the latest developments have changed his thesis. Here are the three things Acemoglu is paying closest attention to in AI right now.

—James O’Donnell

This story is from The Algorithm, our weekly newsletter giving you the inside track on all things AI. Sign up to receive it in your inbox every Monday. 

The case for fixing everything

Stewart Brand, the counterculture icon and tech industry legend, considers maintenance a “civilizational” act. His new book argues that taking responsibility for maintaining something, whether a motorcycle, a monument, or the planet, can be radical.

Brand argues that maintainers haven’t gotten the laurels they deserve—and he’s right. Yet his vision of maintenance often feels solitary: profound, but more about personal fulfillment than tending to a shared world or making it better.

Read the full review of his handsome new book, Maintenance: Of Everything, Part One.

—Lee Vinsel

Lee Vinsel is an associate professor of science, technology, and society at Virginia Tech, a cofounder of The Maintainers, and the host of Peoples & Things, a podcast about human life with technology.

This story is from the latest edition of our print magazine, which is all about nature. Subscribe now to read the full issue and receive future print copies once they land.

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 The first zero-day exploit built by AI has been discovered
Google spotted and stopped the attempted “mass exploitation event.” (CNBC)
+ The hackers used AI to discover an unknown bug. (NYT $)
+ AI-powered hacking has exploded into an industrial-scale threat. (Guardian)
+ New tools are simplifying online crime. (MIT Technology Review)

2 OpenAI just launched its answer to Claude Mythos
Daybreak patches vulnerabilities before attackers find them. (The Verge)
+ Sam Altman said it will “continuously secure software.” (Gizmodo)
+ It will rival Anthropic’s Claude Mythos, which arrived a month ago. (BBC)
+ OpenAI is allowing wider access to its cyber models than Anthropic. (CNBC)

3 Trump is heading to China to spread the gospel of American tech
While taking cues from Beijing’s more stringent approach. (Guardian)
+ But investors want Trump and Xi to stay out of AI’s way. (Reuters $)
+ Elon Musk and Tim Cook are joining him on the trip this week. (BBC)

4 Ilya Sutskever has testified on Sam Altman’s “pattern of lying”
OpenAI co-founder Sutskever took the stand in the Altman v. Musk trial. (BI)
+ He said he spent a year gathering proof of Altman’s dishonesty. (Reuters $)
+ But he also added to OpenAI’s defense. (Wired $)
+ While Satya Nadella called attempts to remove Altman “amateur city.” (FT $)
+ Here’s what happened last week in the trial. (MIT Technology Review)

5 A new hantavirus vaccine is in the works
Moderna and Korea University are developing an mRNA vaccine. (Wired $)
+ Here’s what you need to know about the cruise ship outbreak. (MIT Technology Review)

6 Texas has sued Netflix over alleged data harvesting and “addictive” design
AG Ken Paxton accuses Netflix of secretly collecting and selling user data. (Quartz)
+ And spying on children while deliberately fostering addiction. (Guardian)

7 A data center guzzled 30 million gallons of water—and no one noticed
The curious case serves as a warning for other data center projects. (Ars Technica)

8 Europe is reportedly selling spyware to human rights abusers
EU states allegedly sold the tech to countries violating rights. (Bloomberg $)

9 The US government’s AI vetting announcement has mysteriously vanished
It had detailed a security test agreement with Google, xAI, and Microsoft. (Gizmodo)

10 Amazon staff are using AI for pointless tasks just to inflate usage scores
In a bid to impress managers. (FT $)
+ An AI expert says we should stop using AI so much. (MIT Technology Review)


Quote of the day

“This is like the cheating husband complaining about the cheating wife.” 

—Anupam Chander, a professor of law and technology at Georgetown Law School, tells the New York Times that Elon Musk’s hypocrisy over OpenAI becoming a for-profit company will undermine his courtroom battle with Sam Altman.

One More Thing

""

STUART BRADFORD


How sounds can turn us on to the wonders of the universe

For decades, astronomy has relied on visual information to make sense of the cosmos: images, charts, and graphs. Now, some researchers are trying something different: listening to the universe.

Using sonification, the process of turning information into sound, they’re helping blind and visually impaired researchers explore the cosmos—and even uncover patterns that might otherwise go unnoticed. The approach is spreading beyond astronomy into fields like climate science, navigation, and education.

Discover how sound could make science more accessible—and even more revealing.

—Corey S. Powell

We can still have nice things

A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)

+ This musical mashup beautifully blends LCD Soundsystem with Twin Peaks.
+ Match your speculative ideas to sci-fi stories with the Extrapolated Futures Archive.
+ A live-action animation Coyote vs. ACME is coming soon—and the first trailer just dropped.
+ Want to surf elsewhere in the galaxy? Here’s what it would be like to catch waves on distant planets.

Revolution’s aftermath: population based cross-sectional study to understand the intergeneration mental health and wellbeing following the 2024 student-led uprising

BackgroundBangladesh was confronted with a nationwide student uprising in July 2024, that exposed both participants and observers to widespread unrest and traumatic events. To better understand the kind of support the population will need, it is important to understand its immediate impact on mental wellbeing.AimAim was to examine the prevalence of trauma symptoms among the Bangladeshi general population, aged 15+, within three-months following revolution.MethodsThis cross-sectional survey using the Post Traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5, five-point Likert scale), was combined with a one-off online workshop to sensitise this population on mental health, trauma, and resilience. Associations between sociodemographic factors and PCL-5 scores were examined with multiple linear regression (ANOVA/ANCOVA). Probable PTSD (PCL-5 ≥ 31) was assessed using log-binomial regression. We estimated Population Attributable Fractions (PAF), Absolute Risk Reduction (ARR) to estimate the proportion of high PTSD attributable to each exposure, and applied min–max normalisation of Likert scales for cross-item comparison.ResultsMore than half of the surveyed participants (n=207; mean age 27.6 ± 9.7 years; 72% Gen Z) had clinically suggestive PTSD. This was more common among women (53.7%), and respondents from Chattogram (57.4%) and Khulna (66.7%). Adjusted analyses suggested modestly higher prevalence among Millennials (PR 1.23, 95% CI 0.87-1.74). PAF estimates indicated small contributions from age groups (Millennials +6.5%, GenX/Boomers -3.6%), and gender (men -3.1%). Under hypothetical elimination of exposure, absolute PTSD reduction was greatest among Millennials. Symptom clusters varied: women, and older adults showed consistently higher scores, while Gen Z reported more negative thoughts/feelings.ConclusionThe study underscores the potential higher prevalence of probable PTSD following large-scale demonstrations and confrontations, and recommends targeted culturally appropriate mental health interventions. Further research involving a representative sample from the population and longitudinal data is recommended to monitor long-term psychological impacts in Bangladesh.

Therapeutic Interventions Targeted at Problematic Use of Digital Technology: Systematic Review and Meta-Analysis of Evidence

Background: Problematic use of digital technology has increased across the world. Despite growing research, evidence on treatment effectiveness across digital behaviors remains fragmented. Objective: This study aimed to systematically evaluate and compare the effectiveness of therapeutic interventions targeted at problematic use of digital technology across various behavioral domains. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines (PROSPERO: CRD420251052442). Electronic searches of PubMed, Scopus, and Embase (up to April 2025) were conducted. It identified 125 eligible studies, including 73 randomized controlled trials (RCTs), 32 non-RCTs, 14 pre-post studies, and 6 pilot studies. The interventions that were assessed in these studies included psychological therapies, digital or web-based programs, exercise-based interventions, pharmacological treatments, neuromodulation, parent-focused programs, virtual reality–based interventions, educational programs, and multicomponent approaches. Random-effects meta-analyses using standardized mean differences (SMDs) were performed. Results: For problematic internet use, psychological treatments showed a strong effect (effect size=−2.68; <.001). Digital interventions also showed significant benefit (effect size=−1.16; <.001). For smartphone addiction, psychological treatments (effect size=−1.49; <.001) and exercise-based programs (effect size=−3.07; =.001) showed significant improvement. For gaming disorder, psychological treatments showed improvement (effect size=−1.01; =.02), but results were mixed. There were limited studies to calculate pooled results for social media addiction, pornography use, gambling, screen time, and over-the-top content watching. No treatment studies were found for problematic over-the-top content watching. High heterogeneity and evidence of small-study effects were observed in several studies. Conclusions: Overall, structured psychological therapies showed the most consistent benefit. These findings support structured interventions that aim for control of use and reduce cues linked to high use. Evidence remains limited for several emerging digital behaviors. More high-quality studies are needed in clinical settings and for less-studied forms of digital addiction.