Collaborative care treatment for major depressive disorder

IntroductionMajor Depressive Disorder (MDD) is a burdensome behavioral health condition that is costly and difficult to treat, particularly for patients with severe cases. The Collaborative Care Model (CoCM) has been shown to be effective for moderate depression treatment but less is known about its effectiveness for severe depression. This study analyzes the impact of CoCM treatment on outcomes for depression patients across all ranges of MDD severity at Concert Health.Materials and methodsAnalysis was completed utilizing all closed patient treatment episodes (N = 30,162) at Concert Health between 2018 and 2025. Of these patients, 5,693 began treatment with severe depression. We compare effect sizes for change between baseline and final screener scores across severity levels. Additionally, we utilize logistic regression to complete analyses to understand treatment factors and patient characteristics that are associated with treatment response and remission, as measured by changes in PHQ-9 scores.ResultsThe primary analysis showed that patients with severe depression (PHQ-9 > 20) had slightly lower odds of achieving response compared to patients with moderate depression (OR: 0.93). The treatment factors of insurance type, suicide risk, anxiety presence, and touchpoints also had significant effects on the odds of achieving response and remission.DiscussionThe results suggest that CoCM may be effective for patients with severe depression in achieving treatment response. Patients on Medicaid or with more complex conditions such as anxiety presence or elevated risk for suicide may need higher levels of engagement from the care team to achieve response and remission.

Dose–response relationship of exercise interventions on sleep quality in patients with depression: a systematic review and meta-analysis

BackgroundThis meta-analysis aimed to systematically evaluate the effects of exercise interventions on sleep quality in patients with depression and to explore the dose–response relationships of key intervention parameters.MethodsA comprehensive search was conducted in PubMed, Web of Science, Embase, Scopus, and the Cochrane Library to identify randomized controlled trials (RCTs). Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup and sensitivity analyses were performed to examine potential dose–response relationships.ResultsA total of 17 publications, including 19 randomized controlled trial comparisons and 1,457 participants, were included in this systematic review and meta-analysis. Pooled estimates indicated that exercise interventions significantly improved sleep quality [SMD = −0.37, 95% CI: −0.48 to −0.27]. Dose–response modeling suggested that exercise doses around 312.75 MET·min/week may be associated with greater improvements [Hedges’ g = −0.51, 95% CI: −0.71 to −0.31]. Subgroup analyses suggested that mind–body exercise [SMD = −0.49, 95% CI: −0.63 to −0.35], durations of 9–12 weeks [SMD = −0.49, 95% CI: −0.74 to −0.24], fewer than two sessions per week [SMD = −0.47, 95% CI: −0.65 to −0.29], and sessions longer than 90 minutes [SMD = −0.42, 95% CI: −0.66 to −0.18] may be associated with favorable changes.ConclusionsExercise interventions may improve sleep quality in individuals with depression, with potential benefits at low doses. These findings support individualized exercise prescriptions, but larger multicenter RCTs with long-term follow-up are needed to confirm the dose–response pattern and subgroup findings.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251105568, identifier PROSPERO (CRD420251105568).

Post-intracerebral hemorrhage depression comorbid with obstructive sleep apnea and REM sleep behavior disorder: a case report and literature review

We report a 63-year-old male with post-cerebral hemorrhage depressive disorder. Previous adequate-dose, full-course antidepressant treatment yielded no significant improvement in depression, anxiety, or sleep disturbance. Detailed history taking and polysomnography (PSG) confirmed comorbid severe obstructive sleep apnea hypopnea syndrome (OSAHS) and rapid eye movement sleep behavior disorder (RBD). Without adjusting antidepressants, the patient first received continuous positive airway pressure (CPAP) for OSAHS, followed by individualized pharmacotherapy for RBD. With the improvement of sleep architecture and respiratory events, obvious remission of depressive and anxiety symptoms and substantial recovery of daytime function were observed. This case emphasizes the bidirectional relationship between sleep and mood disorders. For post-stroke depression (PSD) poorly responsive to antidepressants, active sleep evaluation, multidisciplinary collaboration, and targeted management of comorbid sleep disorders may be crucial to enhance therapeutic efficacy.

What Are Intrusive Thoughts?

When a child confesses a frightening thought that seemed to come out of nowhere — “What if I hurt someone with this knife?” “What if mom dies in a car accident?” “What if germs get into this paper cut and I die of an infection?”  — you can both find it confusing and disturbing.  But in most cases these intrusive thoughts are not evidence of a problem.

Intrusive thoughts are unwanted ideas, images, or urges that pop into the mind seemingly out of nowhere. They might feel embarrassing, violent, sexual, or just plain strange — and they feel completely out of character, which is exactly why they’re so upsetting. “An intrusive thought is a lot like your brain sending junk mail,” says Theresa Welles, PhD, a clinical psychologist and director of the Bubrick Center for Pediatric OCD at the Child Mind Institute. “Just because it shows up doesn’t mean it’s important or true or something you even want.”

It also doesn’t necessarily mean that a child has OCD or another mental health disorder. Though intrusive thoughts are associated with OCD — in which unwanted thoughts (called obsessions) drive children to perform rituals (called compulsions) to alleviate them — for many children they are just fleeting thoughts. It’s only when kids become unable to let them go that they are concerning. Another way to think about it, says Dr. Welles, is that “the brain’s job is to generate thoughts, the same way an apple tree’s job is to produce apples. Not every apple is perfect — some are misshapen or wormy. And not every thought is meaningful or worth paying attention to. Having a thought is not the same as wanting it or intending to act on it.”

Who has intrusive thoughts

“Everyone who has a brain has them,” says Caitlyn Downie, LCSW, director of trauma and resilience at the Child Mind Institute. “It’s part of the human existence.” A child might suddenly imagine something terrible happening to a parent, or a teenager might have a violent or sexual thought that feels shocking or shameful. Most of the time, these pass quickly — unpleasant, but easy enough to brush aside.

That’s the key distinction: not the thought itself, but what happens after it. The concern isn’t that the thought appeared — it’s how the child responds, how often it returns, and whether it starts getting in the way of daily life.

For some children — particularly those who are anxious, perfectionistic, or who have OCD — intrusive thoughts become “sticky.” Instead of passing through, the thought snags. The child starts paying attention to it, trying to figure it out or make it go away, which only makes it feel more powerful. “Young people lack the experience to recognize that thoughts aren’t the same as intentions, desires, or actions,” Dr. Welles says. “The thoughts feel alarming. So the child pays more attention, and the more attention they give it, the more often it returns.” That loop of fear and self-doubt is what parents and clinicians need to be alert to.

When should parents be concerned?

Many children are too ashamed or frightened to describe what’s actually going on, so parents may never hear about the thought itself. Instead, changes in behavior are often the first clue. Look for signs like:

  • Increased distress, irritability, or moodiness
  • Avoidance of something that wasn’t previously a problem
  • Trouble concentrating or sleeping
  • Excessive guilt or repeated reassurance seeking
  • Rituals like checking, counting, washing hands, or going through routines in a specific way

It’s worth seeking professional support when intrusive thoughts are frequent and intense, hard to shake, causing real distress, or getting in the way of school, friendships, or daily routines.

Why intrusive thoughts feel so frightening

When an intrusive thought appears, it can set off the body’s alarm system — the same ancient survival mechanism that helped people run from danger or fight it off. In anxiety and OCD, that alarm bell rings when there’s no real emergency. The child has a thought, the body reacts with panic, and the child assumes the thought must be important because it feels big and important.

Children may also fall into what clinicians call thought-action fusion. “That’s the mistaken belief that having a thought makes it more likely to happen,” explains Dr. Welles, “or that it reveals something terrible about who they are.” A child who thinks, “What if I hurt my baby brother?” may become convinced the thought means they secretly want to — but intrusive thoughts are often the precise opposite of what a child would ever want. Paradoxically, Dr. Welles says, “for most people with anxiety disorders and OCD, these thoughts are the actual opposite of what they would ever do.”

How parents can help

The first thing to do is stay calm — harder than it sounds if the thought is violent, sexual, or taboo. Children look to their parents to gauge whether something is truly dangerous, so if you look horrified, your child takes that as confirmation the thought is something to fear.

When a child shares an intrusive thought, Downie suggests responding with warmth and curiosity: “Say something like, ‘I appreciate you telling me — it sounds like that was really scary.’ It also helps to normalize it: ‘A lot of people have thoughts they don’t particularly like.’” Some other responses that can help:

  • “That sounds really upsetting — I’m glad you told me.”
  • “Having a thought doesn’t mean you want it or that it’ll ever happen.”
  • “You don’t have to figure this out right now.”

The goal is to help your child feel less alone and less ashamed, without treating the thought like a five-alarm emergency. And do your best to avoid reassurance. Reassuring the child about the contents of a specific thought (for example, responding to a child who asks, “Are you sure I’m a good person?” with “Yes, you’re a good person”) can actually make things worse, especially in kids with OCD. They feel very temporary relief but then the thought creeps back and they need more reassurance. It becomes a cycle. Instead try: “I know this feels awful. And I know you can handle it.”

It also helps to redirect the child to something concrete: getting dressed, eating breakfast, watching a show, texting a friend. With younger kids, you might guide them in doing slow breaths or suggest they move to another room so they distract themselves from the thought. With teens, you might mean teach them to resist the urge to Google their fears or thoughts, confess, or ask the same question over and over again. “The idea,” Downie says, “is to validate the feeling without validating the fear. You’re saying: ‘I hear you, this is hard, and you can get through it.’”

What can cause intrusive thoughts?

Intrusive thoughts aren’t a diagnosis on their own — they’re a symptom that can show up across a range of conditions, or in children who have no diagnosis at all. Disorders they may be associated with include:

  • OCD: The most closely associated condition. Common themes include harm, contamination, sexual thoughts, and religious or moral fears.
  • Generalized anxiety: Tends to involve repetitive “what if” worries about everyday concerns — school, safety, family, the future.
  • Social anxiety: Brings intrusive thoughts about embarrassment, rejection, or being judged by peers.
  • PTSD: Can involve intrusive memories, images, or sensations tied to a traumatic event. “A child who has experienced trauma may worry about being harmed again or even about harming someone else,” Downie notes, “but that doesn’t mean every child with trauma will have intrusive thoughts.”
  • Depression: Often involves intrusive thoughts that fit a negative self-image: I’m worthless. I’m a burden. I’m a bad person.
  • Autism spectrum disorder: Repetitive thoughts often center on a special interest and aren’t typically unwanted or distressing the way OCD thoughts are — though they can look similar from the outside.
  • Psychotic disorders: Young people with psychosis tend to experience intrusive thoughts as fixed and real, without the self-awareness that typically accompanies anxiety-driven ones. Psychotic disorders such as schizophrenia are rare in children, though early signs can appear in the teenage years.

How intrusive thoughts are treated

Treatment depends on what’s driving the thoughts and how much they’re disrupting the child’s life:

  • For OCD, the gold-standard treatment is exposure and response prevention (ERP), a specialized form of cognitive behavioral therapy (CBT) where children practice sitting with intrusive thoughts without doing compulsions. Over time, they learn to tolerate uncertainty and discover that the thought, however uncomfortable, isn’t actually dangerous.
  • For anxiety, the same treatments are helpful. CBT helps children understand the connection between thoughts, feelings, and behaviors, and ERP helps kids learn to tolerate the anxiety these thoughts generate, and it gradually diminishes.
  • For trauma, treatment may include trauma-focused CBT. Mindfulness, DBT skills, and breathing exercises can also help regulate the nervous system.
  • Family involvement matters a great deal. “Parents often need help learning how to respond without accidentally feeding the anxiety cycle,” Dr. Welles says. SPACE (Supportive Parenting for Anxious Childhood Emotions) is an evidence-based approach that helps parents reduce accommodation and support their child’s brave behavior instead.
  • For moderate-to-severe OCD or anxiety, medication — typically an SSRI — may also be worth discussing with a psychiatrist or pediatrician.

Helping your child trust their own mind

One of the hardest things about intrusive thoughts is that they can make children afraid of their own minds — convinced that every thought needs to be examined or explained away before they can relax. But no one gets to have only pleasant, well-behaved thoughts.  

What children can learn is that a thought can be upsetting without being meaningful, loud without being true, and it can pass through without becoming a verdict on who they are. As parents, the most powerful thing you can offer is a calm, steady presence — taking it seriously without treating it as a catastrophe. When your child sees you aren’t panicked, they get to borrow some of that calm for themselves.

Frequently Asked Questions

What are intrusive thoughts?

Intrusive thoughts are unwanted ideas, images, or urges that pop into your mind unexpectedly. They often feel upsetting or out of character, but they’re essentially “junk mail” from the brain — not meaningful or important.

Are intrusive thoughts normal?

Yes, everyone can have them. Most children (and adults) experience intrusive thoughts at times, and in many cases they pass quickly without causing problems.

What causes intrusive thoughts?

They’re a normal byproduct of how the brain works, but they can become more frequent or “sticky” in kids who are anxious, perfectionistic, or dealing with conditions like OCD or trauma. Paying extra attention to the thought can also make it return more often.

Do intrusive thoughts mean I want to act on them?

No. Having an intrusive thought doesn’t mean you want to act on it or that it reflects who you are. In fact, these thoughts are often the opposite of what someone would ever want or do.

The post What Are Intrusive Thoughts? appeared first on Child Mind Institute.

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First Huntington’s Disease Patient Dosed with Neural Stem Cell Therapy

Huntington’s disease therapeutics have reached a historic milestone—the first patient has successfully received an experimental neural stem cell therapy at UCI Health. This groundbreaking dose marks the world’s first human trial of embryonic stem cell-derived neural stem cells for the devastating neurodegenerative disorder.

The treatment, performed in May at University of California Irvine (UCI) Health, represents the culmination of more than 12 years of laboratory research and eight years of clinical planning led by scientists and physicians at the University of California, Irvine. Researchers hope the treatment, known as hNSC-01, could eventually slow disease progression, protect vulnerable brain cells and potentially restore damaged neural circuits.

To date, the first participant has not reported any serious adverse effects, according to the clinical team. A second patient is expected to receive the therapy in July.

Leslies Thompson - Huntington's
Leslie M. Thompson, PhD, Donald Bren Professor of psychiatry and human behavior, as well as neurobiology and behavior, at the University of California, Irvine [UC Irvine]

“This clinical trial highlights the important role that an interdisciplinary academic and clinical team, together with the HD families, plays in advancing medicine,” Leslie M. Thompson, PhD, clinical trial sponsor as well as the Donald Bren Professor of psychiatry and human behavior UC Irvine, told Inside Precision Medicine. “We are grateful to our patients and their incredible families for their bravery to provide hope for others with very few options.”

hNSC-01

Huntington’s disease, caused by a mutation in the huntingtin gene, destroys brain cells, causing involuntary movements, cognitive decline, and psychiatric symptoms that begin between 35 and 50 and worsen over time. Without a cure, the fatal disorder burdens patients and families emotionally, physically, and financially, often requiring daily and long-term care.

Current treatments for Huntington’s disease primarily focus on managing symptoms rather than altering the underlying disease process. Drugs such as tetrabenazine and deutetrabenazine can reduce involuntary movements known as chorea, while antidepressants, antipsychotics and mood stabilizers help address psychiatric symptoms. Physical therapy, speech therapy and occupational therapy can also improve quality of life. However, none of these approaches has been shown to slow or stop the progressive loss of neurons that drives the disease.

Over the past decade, researchers have pursued several experimental disease-modifying strategies. Among the most advanced are gene-targeting therapies designed to reduce production of the mutant huntingtin protein. These include antisense oligonucleotides (ASOs), which are delivered through repeated spinal injections, as well as RNA-targeting and gene-editing approaches intended to suppress or correct the faulty gene. While these strategies directly target the genetic cause of Huntington’s disease, clinical results have been mixed, and questions remain about long-term effectiveness, safety and the need for lifelong treatment.

The hNSC-01 neural stem cell therapy being tested at UCI Health takes a different approach. Rather than targeting the mutant gene itself, the therapy aims to protect vulnerable neurons, replace lost cells, rebuild damaged neural circuits and provide supportive factors that promote brain health. 

The UCI researchers believe stem cell-based therapies may offer a new approach by addressing multiple aspects of the disease simultaneously. The experimental treatment, hNSC-01, consists of pluripotent neural stem cells derived from embryonic stem cells and manufactured through the UC Davis Good Manufacturing Practice facility.

Preclinical studies in animal models suggested the cells could perform several functions relevant to Huntington’s disease, including protecting existing neurons, replacing cells that have been lost, rebuilding damaged neural networks and releasing beneficial proteins such as brain-derived neurotrophic factor (BDNF). The cells were also shown to reduce harmful protein accumulations associated with neurodegeneration and demonstrated long-term safety in mice.

Unlike conventional drug therapies, the stem cells are delivered directly into the brain. During the approximately six-hour procedure, performed under general anesthesia, patients lie face down within an MRI scanner while neurosurgeons use a specialized stereotactic navigation and delivery system to implant the cells into the striatum, a deep brain structure heavily affected by Huntington’s disease.

The striatum plays a central role in motor control, decision-making, motivation and learning. Degeneration of this region contributes significantly to the hallmark symptoms of the disorder. The first intervention was delivered by UCI Health neurosurgeon Jefferson W. Chen, MD, and a multidisciplinary surgical team.

Tracking treatment impact

As a Phase Ib/IIa study, the trial’s primary objective is to evaluate safety. However, researchers will also track biomarkers and clinical indicators that may provide early clues about whether the treatment is affecting disease progression.

When asked which biomarkers would help identify how the therapy is working in patients, Thompson emphasized that current measurements are focused more on assessing treatment impact than revealing biological mechanisms. “We will be including HD relevant clinical endpoints and biomarkers, including NfL in plasma and NfL and PENK in CSF; however, these are geared to understanding whether the treatment is having a benefit to these outcome measures versus informing the mechanism of action,” Thompson said.

One of the most important early indicators will be whether disease-related biomarkers remain stable rather than continuing their expected decline. “The earliest sign first and foremost is safety in this initial trial,” Thompson said. “Initial signs that the therapy could be meaningfully altering disease progression would be if the blood-based or CSF-based biomarkers do not show progression.”

Reaching the point of treating the first patient required overcoming a series of scientific, manufacturing and logistical hurdles. According to Thompson, selecting the optimal cell line was among the most significant challenges, testing multiple cell lines in vitro and in vivo.

Researchers also had to establish quality-control standards for the final therapeutic product and create Good Manufacturing Practice cell banks following extensive testing in Huntington’s disease mouse models. The COVID-19 pandemic introduced additional delays. “Disruptions caused by COVID-19, in particular the safety and tumorigenicity studies, delayed the timeline,” Thompson explained.

Another major undertaking involved creating the clinical infrastructure necessary for a first-of-its-kind procedure. Thompson said that it’s not really a challenge, but getting the overall procedural pipeline in place is the first study of this kind at the UCI Health–Irvine hospital in the MRI suite.

Despite the complexity of the project, Thompson said interactions with regulators proceeded smoothly. “We actually had a very good experience in terms of regulatory activities. A very helpful pre-pre-IND, pre-IND and relevant feedback from the FDA on the clinical trial.”

Scalability and competitive landscape

Whether hNSC-01 will ultimately compete with or complement emerging gene-targeting therapies remains unclear. Gene-silencing approaches may be easier to distribute because they do not require brain surgery, but repeated administrations over many years could result in substantial cumulative costs. In contrast, hNSC-01 involves a specialized MRI-guided neurosurgical procedure that may initially be limited to major medical centers, but it is designed as a one-time treatment whose long-term costs could compare favorably with chronic therapies if benefits prove durable.

Thompson believes the infrastructure requirements may be less of a barrier than many assume. “Yes, major medical centers can eventually offer it, and several medical centers are now using this system for other indications,” she said. “The other aspect is this would be a one-time administration so an individual could even travel to a medical center that offers the procedure.”

The REGEN4HD trial plans to enroll 21 adults aged 18 to 65 with early-stage Huntington’s disease. Twelve participants will be included in a Phase Ib dose-escalation cohort, while nine additional participants will be enrolled in a Phase IIa expansion group. The study is funded through a $12 million grant from the California Institute for Regenerative Medicine and coordinated through the UC Irvine Alpha Clinic, one of nine state-supported regenerative medicine clinical research centers.

Even if the therapy proves safe and beneficial, researchers caution that it remains unclear whether stem cell transplantation alone will be sufficient to combat Huntington’s disease over the long term. “At this point we do not know whether this will be sufficient alone or will need to be delivered with other disease-modifying therapies,” said Thompson. “For example, ones that specifically target an HD mechanism such as somatic repeat instability,” Thompson said. “However, these cells also have the potential to exert therapeutic effects directly while serving as vehicles for the delivery of additional interventions.”

For families affected by Huntington’s disease, the first successful treatment in the REGEN4HD trial represents more than a scientific milestone. It marks the beginning of a new chapter in regenerative medicine—one that researchers hope could eventually transform the outlook for a disease that has long remained untreatable.

The post First Huntington’s Disease Patient Dosed with Neural Stem Cell Therapy appeared first on Inside Precision Medicine.