Background: Bipolar disorder (BD) is a complex and heterogeneous psychiatric condition, characterized by fluctuating clinical courses that affect approximately 1%‐2% of the global population in their lifetime. Despite pharmacological advances, treatment response varies significantly among patients, making the identification of individualized treatment strategies a major challenge. Artificial Intelligence (AI), through its classical approaches, has emerged as a powerful tool in precision psychiatry to identify subtle patterns in complex data and inform personalized clinical decisions. Objective: The present systematic review aimed to examine the current evidence on classical AI-supported treatment optimization in the BD spectrum. Methods: The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Four databases (PubMed, Web of Science, Scopus, and Embase) were searched for original studies published after 2015 on the application of classical AI in the treatment of BD in adult patients. Publication bias was evaluated by visual inspection of a funnel plot. The methodological quality, risk of bias, and clinical applicability of the predictive models were assessed using the Prediction Model Risk Of Bias Assessment Tool for prediction models using regression or AI methods (PROBAST+AI; PROBAST+AI Working Group) tool. Results: A total of 35 studies were included and classified into 5 outcome-based categories, including acute symptomatic response, long-term maintenance response, relapse and readmission risk, safety and dose optimization, and brain aging and phenotyping. Acute symptomatic response models performed modestly (pooled area under the curve [AUC] 0.68), while imaging improved accuracy (74%‐77%). Long-term maintenance response models showed moderate-to-high performance (pooled AUC 0.80), with biomarker- and cellular-based models reaching 96%‐99% accuracy. Relapse and readmission prediction achieved a pooled AUC of 0.71, with digital phenotyping and rule-based methods performing best (AUC 0.85‐0.88). Safety and dose optimization models achieved 85%‐97% accuracy. Brain aging and phenotyping studies highlighted accelerated brain aging in BD, partially mitigated by lithium, and revealed novel data-driven subgroups. However, 3 studies were considered at high risk of bias due to small sample sizes associated with disproportionately high-performance estimates. An additional study was identified as potentially biased because it lay markedly distant from the funnel plot’s confidence line. Finally, the PROBAST+AI assessment revealed a high risk of bias in most studies, primarily due to data analysis limitations, small sample sizes, and lack of external validation. Conclusions: The adoption of classical AI tools in BD serves as a driver for therapeutic optimization, although current AI tools in BD should still be considered exploratory rather than ready for clinical use. Effective implementation in real-world clinical scenarios requires more robust, transparent, and externally validated models to ensure reliability and generalizability.
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Digital Reassurance Seeking in OCD
– by Jordan Karr, PhD
We all need reassurance once in a while. Receiving reassurance from a friend, loved one, or expert can reduce short-term distress, foster a sense of connection, and help us move forward in a productive way. On the other hand, excessive reassurance seeking can lead to a painful cycle of stress and doubt. For individuals with obsessive-compulsive disorder (OCD), reassurance is fleeting and is quickly followed by a resurgence of perceived threat and a compelling drive to seek additional reassurance.
As an OCD and anxiety specialist, I am no stranger to reassurance traps. I see them in the patient who repeatedly consults doctors but never fully trusts their answers; the partner who keeps asking, “Do you still love me?” while scrutinizing every response; and the teenager who needs her homework checked repeatedly but does not learn to tolerate uncertainty. While the content of excessive reassurance seeking may vary, its function remains the same, relieving anxiety momentarily while allowing obsessions to rebound more strongly in the long run. In each example, we see an individual desperately trying to protect something they hold dear while being misled by one of OCD’s most convincing lines: “What if this time the reassurance sticks?”
Psychologists have long argued that excessive reassurance seeking helps maintain OCD, anxiety, and depression (Abramowitz et al., 2002; Burns et al., 2006). What is new is the landscape. Today, reassurance is available instantly and endlessly through search engines, medical websites, social media, and artificial intelligence tools. Emerging research suggests that online reassurance seeking may be as prevalent as interpersonal reassurance seeking (Parsons & Alden, 2022). These digital reassurance traps present in a variety of forms, including:
- Excessive symptom-checking on WebMD
- Checking a loved one’s location on Find My Friends to make sure they are still alive or where they promised they would be
- Asking Google Gemini whether an intrusive thought makes you a monster, a pedophile, or a bad Christian, Muslim, or Jew
- Analyzing the contents of a partner’s Instagram to see whether their feelings have changed
- Endlessly searching Reddit for answers to existential questions
- Obsessively checking likes and read receipts to monitor the durability of a relationship
- Finding creative ways to ask ChatGPT whether you might be responsible for spreading a virus or causing someone harm
- Compulsively checking the news to confirm whether a feared event has taken place
Why do some individuals seek reassurance primarily from others in face-to-face contexts while others turn to the internet? Findings from one study suggest that individuals may be more likely to seek interpersonal reassurance when they desire emotional support, whereas online reassurance seeking is more likely when individuals feel ashamed or fear judgment from others (Parsons et al., 2025). In the same study, shame was reported more frequently among individuals with OCD. The perceived anonymity of the internet creates a compelling environment for seeking reassurance about our most distressing fears and the fears we feel ashamed to have.
Wait, hold on… shouldn’t having access to all the information on the internet be empowering? After all, there’s that famous saying, “Knowledge is Power.” Well I’m not sure what Francis Bacon would say if he could scroll on TikTok, but in the age of the internet, more information does not always mean more power or knowledge. In fact, information overload seems to trigger excessive reassurance seeking online (Yang & Luo, 2024). Once digital algorithms detect health-related concerns, users may be exposed to increasingly frequent and targeted content, further amplifying health anxiety and driving additional reassurance seeking online (Zhang et al., 2024).
Despite these challenges, evidence-based treatments offer hope. Exposure and response prevention (ERP), the gold-standard treatment for OCD, helps individuals tolerate uncertainty and break free from compulsive behaviors. ERP therapists are prepared to respond to clients who compulsively seek reassurance while taking care to avoid reinforcing a client’s anxiety and setting boundaries when appropriate. On the other hand, AI chatbots are available 24/7 and will continue to reassure users when it would be clear to a skilled therapist that more reassurance is harmful. Some helpful activities I have encouraged clients to try include:
- Going for a walk and leaving your phone behind
- When you have the urge to seek reassurance, use a timer to delay. Start with 5 minutes and gradually increase the time as you go.
- Imaginal exposure: Writing out OCD’s worst case scenario while refraining from seeking reassurance.
- Embracing the uncertainty: When you have the urge to seek reassurance, lean into the uncertainty by responding “maybe that will happen, maybe not.”
- Watch a movie that triggers obsessions but leave your phone in the other room
- Try a fast from social media. Start with a short fast and increase the length of each fast as you gain confidence.
- Agreeing with the obsessions: Whatever your OCD throws at you, respond by saying “Sure, that is true!”
Clinicians working with youth should also attend to parental accommodations that inadvertently facilitate online reassurance seeking. Supportive Parenting for Anxious Childhood Emotions (SPACE) is an evidence-based, parent-focused intervention that emphasizes increasing supportive statements while reducing unhelpful accommodations. Setting reasonable limits on smartphone use while responding with empathy and confidence can help youth build resilience and independence (i.e. “I know it’s tough to be away from your phone and I know you got this!”).
Finally, because shame plays a central role in digital reassurance traps, incorporating self-compassion practices may be beneficial. Compassion-focused exercises help individuals respond to their struggles with kindness rather than self-criticism, complementing ERP by fostering emotional resilience. I sometimes ask clients to imagine that a close friend or loved one is feeling ashamed because they are experiencing obsessions and are stuck in an OCD loop. Then, I invite them to write down how they would support this friend while paying special attention to how compassion feels in their body. By practicing compassion for others, we strengthen the same muscles in our brains that help us turn compassion inward.
If you are getting stuck in digital reassurance traps, you are not alone! Many of these technologies are brand new and we are learning how to integrate them into our lives in a healthy way. If you need help managing compulsive online habits, finding a therapist trained in ERP could be a useful step!
References
Abramowitz, J. S., Schwartz, S. A., & Whiteside, S. P. (2002). A contemporary conceptual model of hypochondriasis. Mayo Clinic Proceedings, 77(12), 1323–1330. https://doi.org/10.4065/77.12.1323
Burns, A. B., Brown, J. S., Plant, E. A., Sachs-Ericsson, N., & Joiner, T. E., Jr. (2006). On the specific depressotypic nature of excessive reassurance-seeking. Personality and Individual Differences, 40(1), 135–145. https://doi.org/10.1016/j.paid.2005.05.019
Parsons, C. A., & Alden, L. E. (2022). Online reassurance-seeking and relationships with obsessive-compulsive symptoms, shame, and fear of self. Journal of Obsessive-Compulsive and Related Disorders, 33, 100714. https://doi.org/10.1016/j.jocrd.2022.100714
Parsons, C. A., Kim, H. J., Singh, S., Lkhagva, T., Wang, J., & Alden, L. E. (2025). Covert or connected: Motivations for online and interpersonal reassurance-seeking in OCD. Journal of Anxiety Disorders, 115, 103057. https://doi.org/10.1016/j.janxdis.2025.103057
Yang, X., & Luo, X. (2024). Unpacking cyberchondria: The roles of online health information seeking, health information overload, and health misperceptions. Telematics and Informatics, 97, 102225.
Zhang, X., Zheng, H., Zeng, Y., Zou, J., & Zhao, L. (2024). Exploring how health-related advertising interference contributes to the development of cyberchondria: A stressor–strain–outcome approach. BMC Public Health, 24, 534.
Jordan Karr, PhD, is the owner of River Falls Therapy in Portland, OR. He is a licensed psychologist in Oregon and Virginia, and specializes in evidence-based therapies for OCD and anxiety disorders. Dr. Karr has experience working in outpatient, community-based, and school-based settings.
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Curcumin attenuates α-synuclein pathology in Parkinson’s disease model mice through modulation of UBC9-associated SUMOylation signaling
BackgroundPost-translational modifications, particularly SUMOylation, plays a crucial role in α-synuclein (α-syn) aggregation, a key pathological feature of Parkinson’s disease (PD). Curcumin, a natural polyphenol, has shown neuroprotective potential, but its effects on SUMOylation-related signaling in PD remain unclear.ObjectiveThis study aimed to investigate whether curcumin modulates α-syn SUMOylation and to elucidate the underlying molecular mechanisms in PD model mice.MethodsA PD model was established in male C57BL/6 mice via unilateral intrastriatal injection of α-syn preformed fibrils (PFFs). Six months after α-syn PFFs injection, mice were treated intravenously with curcumin (25 mg/kg/day) or vehicle for 1 month. Behavioral tests (open field, rotarod) assessed motor function. Neuropathology was evaluated by immunohistochemistry and western blotting for tyrosine hydroxylase (TH), phosphorylated α-syn (p-syn), SUMOylation pathway components (SUMO1, SAE2, UBC9, PIAS1/2), and ubiquitin. Striatal dopamine levels were measured by HPLC.ResultsCurcumin treatment ameliorated motor deficits and anxiety-like behaviors in PD mice. It partially preserved dopaminergic neurons and reduced p-syn aggregation in the substantia nigra, accompanied by increased striatal dopamine levels. Mechanistically, curcumin was associated with reduced SUMO1 and increased ubiquitin levels, suggesting modulation of SUMOylation-related signaling. Among SUMOylation enzymes, UBC9 expression was decreased, whereas E1 (SAE2) and E3 (PIAS1/2) components were not substantially affected.ConclusionOur findings demonstrated that curcumin exerted neuroprotective effects in a PD model by attenuating α-syn pathology. The protective mechanism involves the inhibition of α-syn SUMOylation, primarily through the downregulation of the UBC9 enzyme. This study identifies UBC9-mediated SUMOylation as a potential target for curcumin and highlight a promising strategy for modifying α-syn-associated pathology in PD.
Subcortical gray matter atrophy and iron deposition in patients with vascular dementia: a multimodal MRI study
PurposeVascular dementia (VAD) is the second most common type of dementia worldwide. Therefore, early detection and diagnosis, along with a clear understanding of its pathogenesis are critical for mitigating disease progression. In the present study, we aimed to elucidate the associations of brain volume and iron deposition with VAD based on structural brain and iron content analyses.MethodsFifty-three patients with VAD and 43 control participants were recruited for this study. All participants underwent the Mini-Mental State Examination (MMSE) and brain MRI scans. This study primarily focused on the volume of specific brain regions (assessed using FreeSurfer) and iron deposition (evaluated using quantitative susceptibility mapping [QSM]). Linear regression analysis was also performed.ResultsPatients with VAD exhibited significant reductions in brain volume in the left putamen (β = −0.342, 95% CI: −0.581 to −0.104), left pallidum (β = −0.099, 95% CI: −0.187 to −0.001), left hippocampus (β = −0.138, 95% CI: −0.271 to −0.004), and right hippocampus (β = −0.235, 95% CI: −0.420 to −0.051). Additionally, significant increases in iron levels were identified in the left (β = 0.006, 95% CI: 0.002 to 0.010) and right (β = 0.005, 95% CI: 0.001 to 0.009) hippocampus.ConclusionsThese findings indicate that brain volume reduction and increased iron levels in specific regions may be associated with cognitive deficits in patients with VAD.
Illness perception, family resilience, and emotional distress among hospitalized older adults with multimorbidity in Xinjiang, China: a latent profile and mediation analysis
BackgroundOlder adults with multimorbidity frequently encounter significant psychological challenges, with negative illness perception being a prevalent issue. Such perceptions can intensify emotional distress. Family resilience—the ability of a family system to adapt positively to adversity—plays a crucial role in alleviating negative emotions, including anxiety and depression. This study aimed to investigate the heterogeneity of illness perception among older patients with multimorbidity and to assess the mediating effect of family resilience on the relationship between illness perception and emotional distress.Materials and MethodsBetween October 2025 and January 2026, 420 multimorbid older patients were recruited in three tertiary hospitals of Xinjiang Province. The evaluation was done based on the Brief Illness Perception Questionnaire, the Chinese version of the Family Resilience Assessment Scale, and the Hospital Anxiety and Depression Scale. The two methods of analysis were the latent profile analysis used to determine the unique patterns of illness perception and the bootstrap-based mediation analysis to determine whether family resilience mediates.ResultsThree distinct illness perception profiles were identified: low (32.6%), moderate (47.6%), and high (19.8%) illness perceptions. Using the low illness perception group as the reference, family resilience showed a significant partial mediating effect between moderate illness perception and anxiety (indirect effect = 0.510, 95% CI: 0.325–0.724), moderate illness perception and depression (indirect effect = 0.450, 95% CI: 0.283–0.631), high illness perception and anxiety (indirect effect = 1.263, 95% CI: 0.819–1.739), and high illness perception and depression (indirect effect = 1.114, 95% CI: 0.707–1.555).DiscussionThe results demonstrated heterogeneity in the perception of illness among older multimorbid patients, as a substantial percentage of the sample had moderate-to-high levels. Family resilience played a major partial mediating role between illness perception and emotional distress. The findings suggest the significance of shifting the clinical emphasis to the family system and integrating family resilience improvement as one of the psychological support measures for chronic patients.
Remimazolam versus propofol on seizure adequacy in electroconvulsive therapy: a retrospective cohort study
ObjectiveElectroconvulsive therapy (ECT) is a core treatment modality for severe mental disorders, and the choice of anesthetic induction agent directly impacts seizure quality and therapeutic outcomes. This study aimed to compare the effects of remimazolam versus propofol on seizure adequacy during ECT.MethodsThis retrospective secondary analysis was conducted using data from a prospective observational cohort. A total of 859 ECT sessions from 114 patients were included. The primary outcome was the rate of adequate seizure, defined as an electroencephalographic (EEG) ictal duration of ≥15 seconds. Secondary outcomes included EEG seizure duration, post-ictal suppression index (PSI), maximum sustained power (MSP), and average seizure energy index (ASEI). Stabilized inverse probability of treatment weighting was employed to balance baseline covariates between groups, with balance assessed by standardized mean differences. Generalized linear mixed models were used to compare intergroup differences, accounting for random effects at the patient level. Subgroup analysis, E-value calculation, and propensity score matching (PSM) at 1:1 and 1:2 ratios were performed as sensitivity analyses to assess the robustness of the results. ResultsA total of 859 ECT sessions were included, with 179 in the remimazolam group and 680 in the propofol group. Baseline characteristics were well-balanced between groups after weighting. The remimazolam group exhibited a significantly higher rate of adequate seizures compared with the propofol group (adjusted odds ratio: 12.054, 95% confidence interval: 5.758–25.233, P < 0.001), along with prolonged EEG seizure duration and elevated MSP. No significant between-group differences were observed in PSI or ASEI. The results of all sensitivity analyses were consistent with those of the primary analysis.ConclusionRemimazolam was associated with a higher rate of EEG seizure adequacy and longer EEG seizure duration; however, whether this electrophysiological advantage translates into better clinical outcomes remains to be investigated in prospective studies.
Latest developments in the use of e-cigarettes by people with schizophrenia spectrum disorders who smoke: a scoping review
BackgroundTobacco use is significantly more prevalent among individuals with schizophrenia spectrum disorders (SSD) compared to the general population, contributing to elevated rates of premature mortality from smoking-related diseases. Despite a decline in smoking prevalence in the general population, individuals with SSD continue to smoke at persistently high rates, driven by biological, psychological, and social factors. Standard smoking cessation approaches yield markedly poorer outcomes in this group compared to non-psychiatric populations. This scoping review aimed to map the emerging evidence on the use of e-cigarettes among individuals with SSD or serious mental illness (SMI).MethodsThis scoping review was conducted in accordance with the Population–Concept–Context (PCC) framework and reported following the PRISMA extension for Scoping Reviews (PRISMA-ScR) guidelines. The review focused on studies published between January 2020 and February 2026, searched on PubMed and EMBASE, providing an up-to-date synthesis of emerging evidence on e-cigarette use in this vulnerable population.ResultsThree studies reported across four publications were included (total N = 323); one research group (Pratt et al.) contributed two separate publications reporting distinct outcomes from the same study cohort. Findings suggest that e-cigarette-based interventions are feasible and acceptable in individuals with SSD and SMI, with preliminary evidence of smoking reduction and decreased exposure to tobacco-related carcinogens. However, sustained harm reduction appeared dependent on a combined approach considering that device provision was empowered in its efficacy to sustain harm reduction over time when integrated with behavioral support.ConclusionsThe available evidence, while preliminary and limited by the small number of included studies, should be interpreted with caution regarding generalizability to patients with Schizophrenia Spectrum Disorders exclusively, as three of the four included publications recruited participants with broader SMI diagnoses of which SSD represents only a subset. Further research, including larger adequately powered trials with standardized outcome measures and longer follow-up, is needed to establish the generalizability and long-term impact of these interventions.
A Study to Assess the Efficacy and Safety of Solriamfetol in Adolescents With ADHD
Conditions: ADHD
Interventions: Drug: Solriamfetol Dose A; Drug: Solriamfetol Dose B; Drug: Placebo
Sponsors: Axsome Therapeutics, Inc.
Recruiting
Interventions: Drug: Solriamfetol Dose A; Drug: Solriamfetol Dose B; Drug: Placebo
Sponsors: Axsome Therapeutics, Inc.
Recruiting
A Study to Assess the Efficacy and Safety of Solriamfetol in Children With ADHD
Conditions: ADHD
Interventions: Drug: Solriamfetol Dose A; Drug: Solriamfetol Dose B; Drug: Placebo
Sponsors: Axsome Therapeutics, Inc.
Recruiting
Interventions: Drug: Solriamfetol Dose A; Drug: Solriamfetol Dose B; Drug: Placebo
Sponsors: Axsome Therapeutics, Inc.
Recruiting
Home Play-based Intervention for Parents and Infants
Conditions: Attention-Deficit/Hyperactivity Disorder (ADHD); Autism Spectrum Disorder; Premature Birth; Global Developmental Delay
Interventions: Behavioral: SPRINT Intervention; Other: Waitlist Protocol
Sponsors: Nanyang Technological University; Agency for Science, Technology and Research (A*STAR); KK Women’s and Children’s Hospital; Institute for Human Development and Potential (IHDP), Singapore
Not yet recruiting
Interventions: Behavioral: SPRINT Intervention; Other: Waitlist Protocol
Sponsors: Nanyang Technological University; Agency for Science, Technology and Research (A*STAR); KK Women’s and Children’s Hospital; Institute for Human Development and Potential (IHDP), Singapore
Not yet recruiting