Radically different
Generative Artificial Intelligence (AI) tools are increasingly integrated into daily life, offering cognitive support across domains such as writing, decision-making, and social interpretation. While beneficial, excessive reliance may contribute to diminished confidence in one’s own thinking. This report describes a woman in her mid-20s with Generalized Anxiety Disorder and Major Depressive Disorder who developed a pattern of functional dependence on generative AI tools- specifically ChatGPT. She historically had strong social, academic and occupational functioning. Psychiatric consultation did not suggest the presence of a personality disorder, and although she was a high-achieving individual, clinically significant perfectionistic traits were not evident. Despite this, she increasingly relied on AI for routine cognitive and interpersonal tasks including composing emails, interpreting social interactions, predicting the future and making decisions and felt increasingly uncomfortable completing such tasks independently. This case highlights the potential danger of generative AI tools in reassurance seeking behavior and how it might compound anxiety. These behaviors were observed across both professional and personal contexts, suggesting that AI use was not limited to task-specific assistance but reflected a generalized strategy for managing uncertainty and self-doubt. This behavioral pattern is characterized in this case by cognitive offloading, reduced confidence in independent judgment, and reinforcement of externalized thinking processes. This led to the subjective belief of declining skill and compromised functional autonomy. The Interaction of Person-Affect-Cognition-Execution (I-PACE) model was used to describe this pattern of behavior. While repeatedly turning to a family member or friend for validation and reassurance might lead to interpersonal fatigue, AI tools have no such limits and are infinitely accessible. This might ultimately worsen a patient’s ability to tolerate uncertainty. Given the ubiquity of AI tools and the prevalence of anxiety disorders, clinicians may need to be aware of the role AI tools potentially play in reassurance seeking and thus perpetuation of anxiety.
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Attention-deficit/hyperactivity disorder (ADHD), marked by excessive activity and impulsivity, is linked to changes in the brain’s dopamine system, though the mechanisms remain unclear. Researchers at the University of Fukui have now found that in genetically modified, conditional knockout mice, loss of a protein called N-ethylmaleimide-sensitive factor (NSF)—which is linked to dopamine receptors—in D2 receptor-expressing cells led to lower dopamine levels and ADHD-like behaviors. Their results also pointed to a potential therapeutic strategy.
The team, headed by assistant professor Min-Jue Xie, PhD, at the Division of Development of Mental Functions, Research Centre for Child Mental Development, suggests that the results offer insight into how brain changes may contribute to ADHD and informing future treatments.
“This is basic research and will not immediately lead to a new treatment,” Xie acknowledged. “However, it provides important clues for understanding how dopaminergic dysfunction may contribute to ADHD. In the future, these findings may help develop new therapeutic strategies targeting D2R function and striatal dopamine signaling, especially for treatment-resistant ADHD.”
Xie is first and corresponding author of the researchers’ published paper in Neuropsychopharmacology, titled “Deletion of N-ethylmaleimide-sensitive factor in dopamine D2 receptor-expressing cells impairs striatal development and dopaminergic function and induces ADHD-like behaviors in mice.”
ADHD is a neurodevelopmental disorder that can affect attention, activity levels, and impulse control, with symptoms often beginning in childhood and sometimes continuing into adulthood. Although the exact causes of ADHD are not fully understood, changes in the brain’s dopamine system have long been linked to the condition. Dopamine is a chemical messenger that helps brain cells communicate and plays an important role in movement, motivation, and behavior.
While dopamine-related changes have been associated with ADHD, it remains unclear how the brain cells that respond to dopamine are maintained and how their disruption may contribute to ADHD-related behaviors. This is particularly relevant to dopamine D2 receptor (D2R)-expressing cells, which are found in the striatum, a brain region involved in movement and behavioral control. Understanding what helps these cells develop and function normally could provide new insights into the biological processes involved in ADHD. “Although D2R has been extensively studied, the upstream mechanisms regulating its function and localization remain unclear,” the authors wrote.
Against this backdrop, a research team from Japan, led by Xie, set out to investigate the role of NSF in these dopamine-related brain cells. NSF regulates membrane fusion, helping brain cells release chemical messengers and move proteins within their membranes. “NSF dysfunction is implicated in neuropsychiatric disorders, with reduced expression in autism spectrum disorder (ASD) and schizophrenia and aggregates in Parkinson’s disease,” the investigators noted.
“The motivation for this study came from previous findings suggesting that NSF may be involved in neurodevelopmental and neuropsychiatric disorders,” Xie explained. “NSF was known to interact with D2R; however, the role of this interaction in vivo remained unclear. Because ADHD is thought to involve reduced striatal dopaminergic function and D2R dysfunction, we hypothesized that NSF may be important for maintaining D2R-expressing neurons and dopaminergic function. This led us to initiate the present study.”
For their study the team created knockout mice in which NSF was removed specifically from D2R-expressing neurons. “… we generated D2R-specific Nsf conditional knockout (Nsf f/f;D2R-Cre) mice to examine NSF function in D2R-expressing cells in vivo,” they explained. They then studied the animals’ brain development, dopamine levels, and behavior. The team also tested whether drugs that affect dopamine signaling could reduce the behavioral changes seen in the modified mice.
The loss of NSF affected the developing brain, resulting in fewer dopamine D2R-expressing cells, increased early developmental cell death, and a smaller striatum. The mice also had markedly lower dopamine levels in this brain region. Together, these findings suggest that NSF helps maintain dopamine-related cells and supports normal development and dopamine function.
The brain changes were accompanied by ADHD-like behaviors. “Nsf f/f;D2R-Cre mice exhibited attention-deficit/hyperactivity disorder (ADHD)-like behaviors, including hyperactivity and impulsivity,” the team reported. The knockout mice were more hyperactive than control mice and showed more impulsive-like behavior in a test that measured how quickly they jumped from an elevated platform. By the end of the seven-minute test, 86% of the experimental group mice had jumped, compared with 31% of the control group mice. “These findings indicate that a reduction in D2R-expressing cells coincides with ADHD-like behaviors, suggesting a link between D2R dysfunction and these abnormalities.”
The researchers then explored whether these behaviors could be reduced by changing dopamine signaling. Methylphenidate, a medicine commonly used to treat ADHD, did not significantly reduce hyperactivity when given alone to the modified mice. However, when it was given together with quinpirole, a drug that activates D2R, the mice became less hyperactive and showed less impulsive-like behavior. During the seven-minute test, the proportion of knockout mice that jumped fell from 78% without treatment to 11% after the two drugs were given together. “Combined administration of methylphenidate and a D2R agonist, quinpirole, alleviated both behaviors, suggesting a potential complementary approach for ADHD treatment,” the investigators wrote.
“This study supports the translational relevance of the Nsf f/f;D2R-Cre model for ADHD and indicates that targeting D2R dysfunction, particularly in treatment-resistant ADHD, may be a promising therapeutic strategy.”
The post Brain Protein in Mice Offers Insights Into Brain Development and ADHD appeared first on GEN – Genetic Engineering and Biotechnology News.
Personal narratives describing lived experiences of the entire spectrum of mental health challenges are now widely available to the public, including through autobiographies from public figures, thematic collections of narratives assembled by mental health organizations, and individual narratives published on video sharing services. Mental health lived experience narratives have been used as an “active ingredient” in interventions intended to create change, such as in campaigns against mental health stigma. In the narrative inquiry research approach, they are used to explore mental health phenomenology. Researchers and organizations working with mental health lived experience narratives have to contend with a wide range of legal and ethical challenges, such as how to handle narratives disclosing sensitive personal information about third parties and the ethical trade-off between preserving narrator autonomy over their presentation of personal identity and protecting narrators from harm due to mental health stigma if a narrator is identifiable in their narrative. In 2022, we formed the Interdisciplinary Consortium on Narratives in Context (ICONIC) of people with knowledge of narrative practices across disciplines. Members are engaged in health research, liberal arts, modern languages, history, and philosophy. In this viewpoint, we present four case studies of narrative practices by ICONIC members: (1) a narrative inquiry into the experiences of Ethiopian citizens with schizophrenia, (2) work to curate and share 2 collections of mental health recovery narratives, (3) an exploration of the use of poetic transcription to condense narrative interviews with mental health content, and (4) the development of safe approaches to working with personal narratives shared through an online mental health peer support service. In presenting these case studies, we focused on documenting decision-making on ethical and legal challenges as the best knowledge on ethical and legal decision-making regarding mental health lived experience narratives may come from integrating knowledge across disciplines. Through reflecting on these case studies, we identified cross-cutting challenges regarding consent processes, narrative analysis, and the interpretation and dissemination of data and findings. These challenges have transdisciplinary and disciplinary-specific features and can be used as a preliminary checklist in research design processes. In presenting what we learned, our intent was to demonstrate that greater knowledge on narrative practices can emerge through interdisciplinary contact and inform future decision-making on narrative practices by researchers working across disciplines. We conclude by contemplating interdisciplinary explorations with the potential to expand knowledge, including examining the use of pathographic narratives in philosophical inquiry.
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