Category Archives: Neuroscience

Pain Relief Without Side Effects and Addiction – Neuroscience News

Summary: Researchers have developed a new substance that activates adrenalin receptors rather than opioid receptors to help relieve chronic pain. The new compounds have similar pain-relieving qualities as opioids but do not appear to induce respiratory depression or addiction.

Source: Friedrich-Alexander-Universitt Erlangen-Nrnberg

New substances that activate adrenalin receptors instead of opioid receptors have a similar pain-relieving effect to opiates, but without the negative aspects such as respiratory depression and addiction.

This is the result of research carried out by an international team of researchers led by the Chair of Pharmaceutical Chemistry at Friedrich-Alexander-Universitt Erlangen-Nrnberg (FAU).

Their findings,which have now been published in the renowned scientific journalScience, are a milestone in the development of non-opioid pain relief.

Opiates cause addiction, new substances do not

They are a blessing for patients suffering from severe pain, but they also have serious side effects: Opioids, and above all morphine, can cause nausea, dizziness and constipation and can also often cause slowed breathing that can even result in respiratory failure.

In addition, opiates are addictive a high percentage of the drug problem in the USA is caused by pain medication, for example.

In order to tackle the unwanted medical and social effects of opioids, researchers all over the world are searching for alternative analgesics.

Prof. Dr. Peter Gmeiner, Chair of Pharmaceutical Chemistry is one of these researchers. We are focusing particularly on the molecular structures of the receptors that dock onto the pharmaceutical substances, says Gmeiner.

It is only when we understand these on the atomic level that we can develop effective and safe active substances.

Collaborating with an international team of researchers, Prof. Gmeiner discovered an active substance in 2016 that bonds to known opioid receptors and that offers the same level of pain relief as morphine, even though it has no chemical similarity to opiates.

New approach: Adrenaline receptors instead of opioid receptors

Peter Gmeiner is currently following a lead that seems very promising: Many non-opioid receptors are involved in pain processing, but only a small number of these alternatives have as yet been validated for use in therapies, he explains.

Gmeiner and a team of researchers from Erlangen, China, Canada and the USA have now turned their attention to a new receptor that is responsible for binding adrenaline the alpha 2A adrenergic receptor. There are already some analgesics that target this receptor such as brimonidine, clonidine and dexmedetomidine.

Gmeiner: Dexmedetomidine relieves pain, but has a strong sedative effect, which means its use is restricted to intensive care in hospital settings and is not suitable for broader patient groups.

The aim of the research consortium is to find a chemical compound that activates the receptor in the central nervous system without a sedative effect. In a virtual library of more than 300 million different and easily accessible molecules, the researchers looked for compounds that physically match the receptor but are not chemically related to known medication.

After a series of complex virtual docking simulations, around 50 molecules were selected for synthesis and testing and two of these fulfilled the desired criteria. They had good bonding characteristics, activated only certain protein sub-types and thus a very selective set of cellular signal pathways, whereas dexmedetomidine responds to a significantly wider range of proteins.

Pain relief without sedation in animal models

By further optimizing the identified molecules, for which extremely high-resolution cryo-electron microscopic imaging was used, the researchers were able to synthesize agonists that produced high concentrations in the brain and reduced the sensation of pain effectively in investigations with animal models.

Various tests confirmed that docking on the receptor was responsible for the analgesic effect, explains Gmeiner. We are particularly pleased about the fact that none of the new compounds caused sedation, even at considerably higher doses than those that would be required for pain relief.

The successful separation of analgesic properties and sedation is a milestone in the development of non-opioid pain medication, especially as the newly-identified agonists are comparatively easy to manufacture and administer orally to patients.

However, Prof. Gmeiner has to dampen any hopes of rapid widespread use in human medicine: We are currently still talking about basic research. The development of medication is subject to strict controls and in addition to significant amounts of funding, it takes a long time. However, these results still make us very optimistic.

Author: Katrin PiechaSource: Friedrich-Alexander-Universitt Erlangen-NrnbergContact: Katrin Piecha Friedrich-Alexander-Universitt Erlangen-NrnbergImage: The image is in the public domain

Original Research: Closed access.Structure-based discovery of nonopioid analgesics acting through the 2A-adrenergic receptor by Peter Gmeiner et al. Science

Abstract

Structure-based discovery of nonopioid analgesics acting through the 2A-adrenergic receptor

Because nonopioid analgesics are much sought after, we computationally docked more than 301 million virtual molecules against a validated pain target, the 2A-adrenergic receptor (2AAR), seeking new 2AAR agonists chemotypes that lack the sedation conferred by known 2AAR drugs, such as dexmedetomidine.

We identified 17 ligands with potencies as low as 12 nanomolar, many with partial agonism and preferential Giand Gosignaling. Experimental structures of 2AAR complexed with two of these agonists confirmed the docking predictions and templated further optimization.

Several compounds, including the initial docking hit 9087 [mean effective concentration (EC50) of 52 nanomolar] and two analogs, 7075 and PS75 (EC504.1 and 4.8 nanomolar), exerted on-target analgesic activity in multiple in vivo pain models without sedation.

These newly discovered agonists are interesting as therapeutic leads that lack the liabilities of opioids and the sedation of dexmedetomidine.

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Pain Relief Without Side Effects and Addiction - Neuroscience News

Secret Structure in the Wiring Diagram of the Brain – Neuroscience News

Summary: Study reveals a hidden order in seemingly random connections between neurons.

Source: University Hospital Bonn

In the brain, our perception arises from a complex interplay of neurons that are connected via synapses. But the number and strength of connections between certain types of neurons can vary.

Researchers from the University Hospital Bonn (UKB), the University Medical Center Mainz and the Ludwig-Maximilians-University Munich (LMU), together with a research team from the Max Planck Institute for Brain Research in Frankfurt, as part of the DFG-funded Priority Program Computational Connectomics (SPP2041), have now discovered that the structure of the seemingly irregular neuronal connection strengths contains a hidden order. This is essential for the stability of the neuronal network.

The study has now been published in the journal PNAS.

Ten years ago, connectomics, that is the creation of a map of the connections between the approximately 86 billion neurons in the brain, was declared a future milestone of science. This is because in complex neuronal networks, neurons are connected to each other by thousands of synapses. Here, the strength of the connections between individual neurons is important because it is crucial for learning and cognitive performance.

However, each synapse is unique and its strength can vary over time. Even experiments that measured the same type of synapse in the same brain region yielded different values for synaptic strength. However, this experimentally observed variability makes it difficult to find general principles underlying the robust function of neuronal networks, says Prof. Tatjana Tchumatchenko, research group leader at the Institute of Experimental Epileptology and Cognitive Research of the UKB and at the Institute of Physiological Chemistry of the University Medical Center Mainz, explaining the motivation to conduct the study.

Mathematics and laboratory combined purposefully

In the primary visual cortex (V1), the visual stimuli transmitted by the eye via the thalamus, a switching point for sensory impressions in the diencephalon, are first recorded.

The researchers took a closer look at the connections between the neurons that are active during this process.

To do this, the researchers measured experimentally the joint response of two classes of neurons to different visual stimuli in the mouse model. At the same time, they used mathematical models to predict the strength of synaptic connections.

To explain their lab-recorded activities of such network connections in the primary visual cortex, they used the so-called stabilized supralinear network (SSN).

It is one of the few nonlinear mathematical models that offers the unique possibility to compare theoretically simulated activity with actually observed activity, says Prof. Laura Busse, research group leader at LMU Neurobiology.

We were able to show that combining SSN with experimental recordings of visual responses in the mouse thalamus and cortex allows us to determine different sets of connection strengths that lead to the recorded visual responses in the visual cortex.

Sequence between the connection strengths is the key

The researchers found that there was an order behind the observed variability in synapse strength.

For example, the connections from excitatory to inhibitory neurons were always the strongest, while the reverse connections in the visual cortex were weaker. This is because the absolute values of synaptic strengths varied in the modeling as they had in the earlier experimental studies but nevertheless always maintained a certain order.

Thus, the relative ratios are crucial for the course and strength of the measured activity, rather than the absolute values.

It is remarkable that analysis of earlier direct measurements of synaptic connections revealed the same order of synaptic strengths as our model prediction based on measured neuronal responses alone, says Simon Renner, Ph.D., of LMU Neurobiology, whose experimental recordings of cortical and thalamic activity allowed characterization of the connections between cortical neurons.

Our results show that neuronal activity contains much information about the underlying structure of neuronal networks that is not immediately apparent from direct measurements of synapse strengths.

Thus, our method opens a promising perspective for the study of network structures that are difficult to access experimentally, explains Nataliya Kraynyukova, Ph.D., from the Institute of Experimental Epileptology and Cognitive Research of the UKB and Max Planck Institute for Brain Research in Frankfurt.

This study is the result of an interdisciplinary collaboration between the lab of Prof. Busse and Prof. Tchumatchenko, who worked closely together, building on the computational and experimental expertise of their labs.

Author: Inka VthSource: University Hospital BonnContact: Inka Vth University Hospital BonnImage: The image is in the public domain

Original Research: Open access.In vivo extracellular recordings of thalamic and cortical visual responses reveal V1 connectivity rules by Simon Renner et al. PNAS

Abstract

In vivo extracellular recordings of thalamic and cortical visual responses reveal V1 connectivity rules

The brains connectome provides the scaffold for canonical neural computations. However, a comparison of connectivity studies in the mouse primary visual cortex (V1) reveals that the average number and strength of connections between specific neuron types can vary. Can variability in V1 connectivity measurements coexist with canonical neural computations?

We developed a theory-driven approach to deduce V1 network connectivity from visual responses in mouse V1 and visual thalamus (dLGN). Our method revealed that the same recorded visual responses were captured by multiple connectivity configurations.

Remarkably, the magnitude and selectivity of connectivity weights followed a specific order across most of the inferred connectivity configurations. We argue that this order stems from the specific shapes of the recorded contrast response functions and contrast invariance of orientation tuning.

Remarkably, despite variability across connectivity studies, connectivity weights computed from individual published connectivity reports followed the order we identified with our method, suggesting that the relations between the weights, rather than their magnitudes, represent a connectivity motif supporting canonical V1 computations.

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Secret Structure in the Wiring Diagram of the Brain - Neuroscience News

Yale Study Revises Understanding of How the Brain Processes and Responds to Rewards – Yale School of Medicine

A new Yale study of neuron activity in the brain has revised scientists understanding of how the brain processes and responds to rewards.

Researchers have located a set of GABA neurons in the brains ventral tegmental area (VTA) that consistently respond to a primary reward. This response differs from the response of dopamine neurons, which previously have been thought to be the principal cells responsible for mediating reward-related behaviors.

Unlike the activity of dopamine neurons, the response in the GABA pathway does not change as animals learn that a cue predicts reward availability, scientists found. Instead, the GABA cells continue to provide a highly stable signal of the size of the primary reward. In reward learning tasks, stimulating this pathway improved the behavior and motivation of animals as they worked to receive rewards across multiple days.

These findings are exciting because they identify a brain pathway that stably signals the size and intensity of a reward and does not shift during learning, revising our understanding of how reward is encoded in the brain, said Marina Picciotto, PhD, Charles B. G. Murphy Professor of Psychiatry and professor in the Child Study Center, of neuroscience, and of pharmacology, and the studys senior author. This finding also provides a new way to think about how cells in the VTA calculate rewarded outcomes in learning tasks.

The findings were published in the journal Science Advances. They appear to clarify the role of dopamine and GAPA neurons in the VTA, located in the midbrain.

Dopamine neurons were thought to be principally responsible for mediating reward-related behaviors, however researchers now believe the neurons fire in response to cues that predict reward, and not to the presentation of the reward itself.

In contrast, GABA neurons in the VTA have been thought to primarily be local cells that inhibit dopamine neurons, but the study shows these neurons project out of the VTA to the ventral pallidum, the major output nucleus of the mesolimbic reward system. Importantly, the researchers found that these neurons respond consistently to a primary reward, and that the response of these neurons scales with the size of the reward.

Other Yale researchers involved in the study are Wenliang Zhou, PhD, associate research scientist; Kristen Kim, neuroscience graduate student; and Yann S. Mineur, PhD, research scientist.

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Yale Study Revises Understanding of How the Brain Processes and Responds to Rewards - Yale School of Medicine

Cerevel Therapeutics to Report Third Quarter 2022 Financial Results and Pipeline Update on Tuesday, November 8, 2022 – Yahoo Finance

Cerevel Therapeutics

CAMBRIDGE, Mass., Oct. 19, 2022 (GLOBE NEWSWIRE) -- Cerevel Therapeutics (Nasdaq: CERE), a company dedicated to unraveling the mysteries of the brain totreatneurosciencediseases, today announced it will report third quarter 2022 financial results on Tuesday, November 8, 2022, before the U.S. financial markets open.

Management will host a conference call to discuss third quarter 2022 financial results and recent business updates on Tuesday, November 8, 2022, at 8:00 a.m. ET. To access the call, please register at this link. Once registered, you will receive the dial-in information and a unique PIN number.

A live webcast of the call, along with supporting slides, will be available on the investors section of Cerevels website at investors.cerevel.com. Following the live webcast, an archived version of the call will be available on the website.

About Cerevel TherapeuticsCerevel Therapeutics is dedicated to unraveling the mysteries of the brain to treat neuroscience diseases. The company is tackling diseases with a targeted approach to neuroscience that combines expertise in neurocircuitry with a focus on receptor selectivity. Cerevel Therapeutics has a diversified pipeline comprising five clinical-stage investigational therapies and several preclinical compounds with the potential to treat a range of neuroscience diseases, including Parkinsons, epilepsy, schizophrenia, and dementia-related apathy. Headquartered in Cambridge, Mass., Cerevel Therapeutics is advancing its current research and development programs while exploring new modalities through internal research efforts, external collaborations, or potential acquisitions. For more information, visit http://www.cerevel.com.

Special Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements that are based on managements beliefs and assumptions and on information currently available to management. In some cases, you can identify forward-looking statements by the following words: may, will, could, would, should, expect, intend, plan, anticipate, believe, estimate, predict, project, potential, continue, ongoing or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. These statements involve risks, uncertainties and other factors that may cause actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. Although we believe that we have a reasonable basis for each forward-looking statement contained in this press release, we caution you that these statements are based on a combination of facts and factors currently known by us and our projections of the future, about which we cannot be certain. Forward-looking statements in this press release include, but are not limited to, statements about our upcoming financial results and pipeline update announcement and the potential attributes and benefits of our product candidates. We cannot assure you that the forward-looking statements in this press release will prove to be accurate. Furthermore, if the forward-looking statements prove to be inaccurate, the inaccuracy may be material. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties, including, among others: clinical trial results may not be favorable; uncertainties inherent in the product development process (including with respect to the timing of results and whether such results will be predictive of future results); the impact of COVID-19 on the timing, progress and results of ongoing or planned clinical trials; other impacts of COVID-19, including operational disruptions or delays or to our ability to raise additional capital; whether and when, if at all, our product candidates will receive approval from the FDA or other regulatory authorities, and for which, if any, indications; competition from other biotechnology companies; uncertainties regarding intellectual property protection; and other risks identified in our SEC filings, including those under the heading Risk Factors in our Quarterly Report on Form 10-Q filed with the SEC on August 1, 2022 and our subsequent SEC filings. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. The forward-looking statements in this press release represent our views as of the date of this press release. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release.

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Media Contact:Anna RobinsonCerevel Therapeutics anna.robinson@cerevel.com

Investor Contact:Matthew CalistriCerevel Therapeuticsmatthew.calistri@cerevel.com

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Cerevel Therapeutics to Report Third Quarter 2022 Financial Results and Pipeline Update on Tuesday, November 8, 2022 - Yahoo Finance

One in Two Thousand: Grace Reynolds ‘22.5 The Williams Record – The Williams record

(Luke Chinman/The Williams Record)

Each week, the Record (using a script in R) randomly selects a student at the College for our One in Two Thousand feature, excluding current Record board members. This week, Grace Reynolds 22.5 discussed her neuroscience thesis, her plans after graduation, and how she likes to spend her time outside in Williamstown. This interview has been edited for length and clarity.

Luke Chinman (LC): Youre in the Class of 2022.5, which means that this is your last semester. How does it feel to be so close to the end of your college experience?

Grace Reynolds (GR): Its definitely really exciting. I feel like Im very close and also very far, because I am finishing up my thesis right now, so theres a lot going on with that.

LC: What is your thesis on?

GR: Im doing a neuroscience thesis with [Assistant] Professor [of Psychology Shivon] Robinson. Were studying the developmental effects of early-life exposure to opioids and neonatal opioid withdrawal syndrome.

LC: What is your major?

GR: I am a biology and psychology double major with a neuroscience concentration.

LC: Did you always know that would be your track?

GR: Ive always been interested in neuroscience. I was also [considering] public health for a little bit, but then I did a public health internship, which I didnt really like. So I kind of moved back to neuroscience.

LC: Because this is your last semester, do you have any advice that youd give to your first-year self?

GR: Although I love both my majors, I kind of wish I had taken some other classes outside of the classes Im comfortable with. Right now, for example, Im taking a history class which I really like, but its one of the few classes Ive taken thats very much outside of my comfort zone.

LC: Do you have a favorite class that youve taken?

GR: I think one of my highlights is a neuroethics class. It was such an interesting class and we talked about a lot of different things. I also took a class with my thesis advisor Professor Robinson about the opioid crisis, which is a psychology, public health, [and] neuroscience kind of class, and that was really interesting, too.

LC: How do you feel being a super senior on campus?

GR: I actually dont mind it. I was on campus this summer, so I feel like I kind of never left. So I dont feel like I had to come back for only one more semester. I really have liked doing an off-cycle thesis and having a summer in between. And also, it worked out well for my plans post-grad.

LC: What are your plans post-grad?

GR: I got a job at the Dana-Farber Cancer Institute in Boston, so Ill be working in a pediatric brain cancer lab.

LC: Is that the kind of career that you want to pursue?

GR: I think eventually I want to go to medical school. But I came into Williams very hardcore pre-med. I was interested in research more as something that would help me get into medical school but not really something I actually wanted to do. But working in labs has made me more interested in eventually doing more research, so I think itll be cool working in a lab outside of Williams.

LC: Okay, switching away from academics. Are you involved in any student organizations on campus?

GR: Ive been a part of WRAPS, which is Williams Recovery of All Perishable Surplus. We package leftover dining hall food and deliver it to local communities. Its a really fun way to get involved in the community! I also like teaching, so I worked in the elementary school with second graders.

LC: Id love to hear more about your work at the elementary school!

GR: I was a math tutor at Williamstown Elementary School and worked with second graders. A few times a week, Id go and help them with their math and sometimes teach a lesson. It was fun, because the way that they approached math was just so interesting to see.

LC: Do you have any aspirations for teaching?

GR: Ive always liked teaching, but I never really thought Id be a teacher especially an elementary school teacher. But I hope that in whatever I do, medicine or research, I get to teach in some capacity. But Im not sure I have the patience to teach all day.

LC: You previously mentioned to me that you like to spend time outside. What are some of your favorite outdoor activities?

GR: I grew up swimming, and I ran cross country in high school. If I dont get outside, I usually feel antsy. Most days I run outside or go for a bike ride. I just really love the Williamstown mountains.

LC: Whats your favorite outdoor spot?

GR: I really like going up Bee Hill. I love the view up there. I also just love running in Hopkins Forest.

LC: Okay, I have some rapid fire questions. Goodrich or Tunnel City if youre a coffee drinker?

GR: I definitely drink lots of coffee. I think Tunnel.

LC: Schow or Sawyer?

GR: I always worked in Schow my freshman year, but now I never go to Schow anymore. But I also never really go to Sawyer anymore. You can always find me in Wachenheim thats my preferred spot.

LC: Whats your favorite dining hall?

GR: Probably Driscoll.

LC: Whats your milk of choice?

GR: Oat milk, definitely.

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One in Two Thousand: Grace Reynolds '22.5 The Williams Record - The Williams record

Supercharging Brain Stimulation by Repurposing an Antibiotic – Neuroscience News

Summary: D-Cycloserine, an antibiotic used for the treatment of tuberculosis, increases the effectiveness of transcranial magnetic stimulation for those with major depressive disorder.

Source: University of Calgary

University of Calgary researchers have shown that the antibiotic D-Cycloserine (DCS) increases the effectiveness of transcranial magnetic stimulation (TMS) for people with major depressive disorder (MDD).

TMS is a non-invasive, well-recognized therapy for people who have treatment resistant depression. Even so, it doesnt work for everyone. Researchers suspect the problem may be connected to a process in the brain essential for learning and memory.

We think TMS works by driving the brain to adapt to stimulation through a process called synaptic plasticity, explainsDr. AlexanderMcGirr, MD, PhD, principal investigator on the study.

One of the challenges, however, is that major depression is associated with reduced synaptic plasticity, and so TMS may be asking the depressed brain to adapt to stimulation in a way that it can not readily do. Adding D-Cycloserine to the TMS treatment appears to enhance TMSs ability to drive synaptic plasticity and treat depression.

All participants in the study underwent TMS every day for four weeks. Half of those also received DCS while the other half received a placebo. Results, published inJAMA Psychiatry, show that almost 75 percent of participants treated with DCS and TMS benefitted, compared to only 30 percent of those treated with TMS and a placebo. Depressive symptom severity was measured using the gold standardMontgomery Asberg Depression Rating Scale.

The combination treatment seemed to have benefits beyond depressive symptoms. The participants in this study that received DCS and TMS also had greater improvements in their symptoms of anxiety and overall well-being, says study first author Jaeden Cole a member of theMcGirr lab.

The clinical trial involved 50 people. McGirrs team plans to duplicate the research method with a larger group to be sure of the clinical efficacy and safety of this experimental treatment.

It is hard to convey how important this work could be for patients or the level of excitement that has been brewing since Dr. McGirr first presented these results, says Dr. Valerie Taylor, MD, PhD, head of the Department of Psychiatry at the Cumming School of Medicine.

If confirmed, this could change practice and have a very significant impact on patients treatment outcomes.

DCS is still used in the treatment of multidrug resistant tuberculosis and has been researched in other psychiatric applications such as trauma, and anxiety-related disorders. While the drug is not currently available in Canada, McGirr believes additional research proving the benefit of this combined therapy could pave the way for the drugs reintroduction here.

Alexander McGirr has a provisional patent filing for the combination of DCS and TMS in the treatment of depression.

Author: Kelly JohnstonSource: University of CalgaryContact: Kelly Johnston University of CalgaryImage: The image is in the public domain

Original Research: Closed access.Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder A Randomized Clinical Trial by McGirr et al. JAMA Psychiatry

Abstract

Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder A Randomized Clinical Trial

Importance

The antidepressant effects of transcranial magnetic stimulation protocols for major depressive disorder (MDD) are thought to depend on synaptic plasticity. The theta-burst stimulation (TBS) protocol synaptic plasticity is known to beN-methyl-D-aspartate (NMDA)receptor dependent, yet it is unknown whether enhancing NMDA-receptor signaling improves treatment outcomes in MDD.

Objective

To test whether low doses of the NMDA-receptor partial-agonist,D-cycloserine, would enhance intermittent TBS (iTBS) treatment outcomes in MDD.

Design, Setting, and Participants

This was a single-site 4-week, double-blind, placebo-controlled, randomized clinical trial conducted from November 6, 2019, to December 24, 2020, including 50 participants with MDD. Participants were recruited via advertisements and referral. Inclusion criteria were as follows: age 18 to 65 years with a primary diagnosis of MDD, a major depressive episode with score of 18 or more on the 17-item Hamilton Depression Rating Scale, a Young Mania Rating Scale score of 8 or less, and normal blood work (including complete blood cell count, electrolytes, liver function tests, and creatinine level).

Interventions

Participants were randomly assigned 1:1 to either iTBS plus placebo or iTBS plusD-cycloserine (100 mg) for the first 2 weeks followed by iTBS without an adjunct for weeks 3 and 4.

Main Outcomes and Measures

The primary outcome was change in depressive symptoms as measured by the Montgomery-sberg Depression Rating Scale (MADRS) at the conclusion of treatment. Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores.

Results

A total of 50 participants (mean [SD] age, 40.8 [13.4] years; 31 female [62%]) were randomly assigned to treatment groups: iTBS plus placebo (mean [SD] baseline score, 30.3 [4.2]) and iTBS plusD-cycloserine (mean [SD] baseline score, 30.4 [4.5]). The iTBS plusD-cycloserine group had greater improvements in MADRS scores compared with the iTBS plus placebo group (mean difference, 6.15; 95% CI, 2.43 to 9.88; Hedgesg=0.99; 95% CI, 0.34-1.62). Rates of clinical response were higher in the iTBS plusD-cycloserine group than in the iTBS plus placebo group (73.9% vs 29.3%), as were rates of clinical remission (39.1% vs 4.2%). This was reflected in lower CGI-severity ratings and greater CGI-improvement ratings. No serious adverse events occurred.

Conclusions and Relevance

Findings from this clinical trial indicate that adjunctiveD-cycloserine may be a promising strategy for enhancing transcranial magnetic stimulation treatment outcomes in MDD using iTBS requiring further investigation.

Trial Registration

ClinicalTrials.gov Identifier:NCT03937596

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Supercharging Brain Stimulation by Repurposing an Antibiotic - Neuroscience News

Speech as a New Diagnostic Tool in ALS and FTD – Neuroscience News

Summary: With the help of AI, researchers are developing digital biomarkers that use speech data to identify ALS and frontotemporal dementia.

Source: DZNE

With the help of speech tests, an initial diagnosis of severe neurodegenerative diseases should be possible in the future.

Researchers at the DZNE are developing so-called digital biomarkers for this purpose these are criteria that artificial intelligence can use to detect whether a patients speech pattern has changed as a result of a disease. The technology manages to detect even the slightest speech changes that are inaudible to the human ear.

The DZNE project, PROSA (A High-Frequency PROgnostic Digital Speech Biomarker with Low Stress), is now funded with $200,000 from the Alzheimers Drug Discovery Foundation and the Target ALS Initiative, both based in the United States.

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are the focus of interest for the involved DZNE researchers. In FTD, nerve cells die primarily in the frontal and temporal areas of the brain in the frontal and temporal lobes, which are responsible for controlling emotions and social behavior, among other things.

In ALS, nerve cells in the brain and spinal cord die off. Up to now, both diseases have been extremely difficult to diagnose.

Language has long been considered by researchers as a conceivable indicator of neurodegenerative diseases.

There have been earlier approaches in which scientists have evaluated textual factors: How complex grammar did the subjects use, how large is their vocabulary, how do they string words together? explains Prof. Dr. Anja Schneider, working group leader at the DZNE and director of the Department of Neurodegenerative Diseases and Gerontopsychiatry at Bonn University Hospital.

However, it was tedious and slow work based on detailed transcripts of what was said. Modern technology now offers new possibilities: Artificial intelligence can perform such analyses much faster and also take melodic aspects of speech into account. Anja Schneider is leading the study on linguistic changes in FTD patients as part of the now-funded project, while her DZNE colleague Prof. Dr. Andreas Hermann is focusing on ALS patients. Two private companies are also involved in the project.

The procedure of a language test is very simple for the patients: They are asked three open questions about their leisure activities, for example, or about their career. Free descriptions of a picture presented are also conceivable. The decisive factor is that the test subjects speak spontaneously.

The artificial intelligence then analyzes the complexity of the speech and it also takes into account pauses between words, the speed of speech and other melodic aspects of the language.

In ALS patients, whose breathing is typically restricted by the progression of the disease, the artificial intelligence can additionally detect abnormalities here as well at a very early stage.

Dialects and other individual characteristics of speech have no influence on the accuracy of the results, says Anja Schneider.

Her observation: Artificial intelligence detects such subtle nuances of speech changes that a normal listener would not recognize at all without technical aids.

The Bonn researchers are incorporating data from two DZNE studies in the development of the method: In Describe FTD and Describe ALS, patients are followed over a longer course of the disease with complex clinical examinations. For the PROSA project, some subjects also undergo various language tests. Their results are combined with cognitive examinations.

Thanks to these multi-layered insights, the researchers hope, the language indicators can be further developed: If brain recordings and genetic testing show how far the disease has progressed then scientists can use language recordings from the exact same stage of the diseases progression to determine how language is changing.

We also want to find answers to other questions, says Anja Schneider:

For example, is the precision of the speech test related to the patients daily form? Does language deteriorate linearly in the course of the disease, so that we could use a linguistic marker not only to make a diagnosis, but even to draw conclusions about how quickly the disease is progressing in the respective patient?

100 patients from the ALS cohort and 100 patients from the FTD cohort will be included in the study; additional subjects will be added for the control group.

Up to now, the diagnosis of FTD and ALS patients has been extremely complex. It can usually only be made in highly specialized expert centers. The necessary examinations take at least ten hours, and the waiting time for an appointment is up to half a year.

With the help of a language test, potential patients could be examined beforehand, ideally even by telephone, to provide doctors with support for their diagnosis.

Author: Sabine HoffmannSource: DZNEContact: Sabine Hoffmann DZNEImage: The image is in the public domain

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Speech as a New Diagnostic Tool in ALS and FTD - Neuroscience News

Can resilience be learned? Study finds that prior stressful events can help build resilience – EurekAlert

image:A new study published in the journal Nature found that mice who defended themselves against aggressors learned to be more resilient to aggression, and that the neurotransmitter dopamine plays a role in reinforcing resilience. view more

Credit: Danielle Capparella, Princeton University

Faced with climate change, a pandemic, and political unrest around the globe, it can feel all too easy to succumb to a sense of hopelessness. How do some people bounce back from adversity faster than others, and can those who struggle teach themselves to be more resilient over time?

A new study conducted in mice and published Oct. 19 in the journal Nature suggests resilience can be learned, and can even be reinforced. A team of researchers from the Princeton Neuroscience Institute placed small mice in close proximity with larger, aggressive mice and found that a display of defensive behaviors predicted the mices ability to be resilient after the stressful event. Further, the team found that by activating dopamine while the mice fought back, they could further reinforce resilience.

From the researchs inception, Lindsay Willmore, who earned her Ph.D. in 2022 and is lead author on the paper, was intrigued by the relatively rare subset of mice who would defend themselves tenaciously when faced with an aggressor.

Theyd turn back towards the aggressor, theyd throw their paws out, theyd jump on him, and they would just not give up, said Willmore. I thought, wow, theres something going on in these guys brains thats super interesting and could be the key to resilience.

In the study, the researchers gauged resilience by monitoring the mices behaviors in the 10 days during which they sustained attacks by the aggressor.

The mice that tended not to defend themselves ended up displaying depression-like behaviors such as social avoidance following the stressful event. Meanwhile, the mice that fought back displayed greater resilience.

By stimulating dopamine while the mice were fighting back, the researchers found they could make the mice even more likely to become resilient. On the flip side, stimulating dopamine during avoidant behavior did not make the mice more resilient.

Its a complicated environment where a mouse has to decide what to do around a bully mouse, said Ilana Witten, a professor of neuroscience and author on the study. What decision it makes has profound consequences in terms of how it ends up.

While the defensive stances associated with fighting back were key in predicting a mouses resilience in the face of attack, Willmore said, Even more strongly related to resilience was how much dopamine the animals had in their reward system during the time when they were starting to fight back. Thats what was really cool to me that an animal that is not just fighting back but is rewarded for fighting back is the one that becomes resilient.

For the study, the researchers put a smaller mouse in a cage with a larger, more aggressive mouse that typically would attack its smaller cage-mate. Afterward, the two mice would stay in the enclosure but this time separated by a wall so that they could not interact physically.

Im very interested in the question of whether we can teach resilience, said said Annegret Falkner, an assistant professor of neuroscience and author on the paper. The series of experiments the team conducted seemed to suggest the answer was indeed yes, that the mice could be nudged toward performing resilient behaviors.

While the researchers began the project before the start of the COVID-19 pandemic, Falkner said since the pandemic hit, shes been thinking more than ever about resilience. We need to think about ways to help the people who seem to be more susceptible to cope with the stresses of the world, said Falkner.

As the researchers continue their studies on resilience, they hope that in the future such work could be applied beyond animals to human health. For example, devices such as smart watches could give real-time feedback about good habits to promote healthy mechanisms like resilience. Information about our dynamic interactions with the environment will be useful for tracking our habits that might be helpful or harmful, said Willmore.

The study was funded by the New York Stem Cell Foundation, the Esther A. and Joseph Klingenstein Fund, the Simons Foundation, the Alfred P. Sloan Foundation, the National Science Foundation, and the National Institutes of Health.

The study, Behavioral and dopaminergic signatures of resilience, by Lindsay Willmore, Courtney Cameron, John Yang, Ilana Witten and Annegret Falkner, was published in the journal Nature on Oct. 19, 2022. DOI 10.1038/s41586-022-05328-2.

Experimental study

Animals

Behavioral and dopaminergic signatures of resilience

19-Oct-2022

The authors declare no competing interests.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Can resilience be learned? Study finds that prior stressful events can help build resilience - EurekAlert

The Appeal of Scientific Heroism – The New Yorker

In 2008, the journalist Jonah Lehrer paid a visit to a lab in Lausanne, Switzerland, to profile Henry Markram, a world-renowned neuroscientist. Markram, a South African, had trained at a series of lite institutions in Israel, the United States, and Germany; in the nineties, he published foundational papers on neural connections and synaptic activity. Markrams work in the laboratory, which involved piercing neural membranes with what Lehrer described as an invisibly sharp glass pipette, was known for its painstaking precision. Lehrers visit, however, had been occasioned not by Markrams incremental contributions to the fieldits not easy to sell a colorful profile on the basis of such publications as The neural code between neocortical pyramidal neurons depends on neurotransmitter release probabilitybut by Markrams pivot, in the early two-thousands, to brain simulation.

Neuroscience, Markram declaimed to Lehrer, had reached an impasse. Researchers had generated an enormous wealth of fine-grained data, but the marginal returns had begun to diminish. If there was to be real progress in understanding what exactly was going on in our heads, a more enterprising approach would be required. With the help of supercomputers descended from I.B.M.s Deep Blue, he planned to construct a full-scale model of the brain from the ground up: each individual neuron would have a digital analogue. A by-product of this computational strategy would be a solution to the mystery of consciousness. Of his effort, Lehrer wrote in the sadly long-defunct Seed magazine, Markram hopes that it represents a whole new kind of neuroscience. As Markram put it to Lehrer, You need to look at the history of physics. He continued, From Copernicus to Einstein, the big breakthroughs always came from conceptual models.

Such unapologetic self-mythologizing on the part of a subject is difficult for a journalist to resist, and Lehrer was patently captivated by Markram, who had an aquiline nose and a lustrous mop of dirty blond hair that he likes to run his hands through when contemplating a difficult problem. Though his eyes were bloodshot from lack of sleep, Lehrer comments, Markram could pass for a European playboy. Lehrer was primed to believe Markram, and, when treated to a theatrical visualization of one of the teams preliminary achievements, of a simulated portion of a mouse brains neocortex, he was not disappointed. One of Markrams scientists told Lehrer that their study of neurons in silicothat is, on a chipwas more propitious than the in-vivo and in-vitro processes used by actual experimenters: they enjoyed access to much cleaner data than their error-prone human colleagues did. Lehrer wrote, The model, in other words, has exceeded its own inputs. The virtual neurons are more real than reality.

At the time, Noah Hutton was studying neuroscience as an undergraduate at Wesleyan University. Hutton was an aspiring filmmakerhis first documentary, Crude Independence, which he shot in a North Dakota boomtown between his junior and senior years, premiered at SXSW before he graduated from college. Hutton had encountered Markrams seminal early work in a class on mammalian cortical circuits, but, as with Lehrer, it was the brain-simulation effortthe attempt to construct the legendary brain in a vat, with all of the philosophical issues it entailedthat took hold of his imagination. In 2009, when Hutton was in his final year of college, Markram delivered a viral TED talk in which he claimed that he could simulate a human brain within ten years.

I was fully awe-inspired, Hutton told me recently. Markram was a hero of mine, and I thought, I need to get in on the ground floor of this. Lehrers profile had ended with the usual backside-covering caveatsto be sure, Markram might not succeed, etc.but Hutton wanted the entire glorious arc. He e-mailed Markram a few times but received no response. Hutton had recently shot a music video for a band called the Amygdaloids, a side project of the N.Y.U. neuroscientist Joseph LeDoux, and LeDoux offered to vouch for Hutton. With LeDouxs endorsement, Hutton secured an invitation to Lausanne to make his pitch. There were other documentarians circling the program, which was called the Blue Brain Project, but, if Markram was committed to seeing the whole thing through in ten years, Hutton said, he was prepared to make the same investment. Hutton was twenty-two. There was no one else crazy enough to commit to that timeline, Hutton told me, and Markram was won over by an ambition that seemed commensurate with his own. Hutton was taken to a screening room to experience an updated version of the fly-through that the team had shown Lehrer, and he shared Lehrers fervor. I was just awestruck by the visuals. I was an acolyte, and we immediately had a kind of teacher-student relationship. I had not a shred of critical energy.

For the next decade, Hutton made an annual pilgrimage to Lausanne to check in on the project and interview Markram. The first eight visits were self-fundedHutton was supporting himself as a commercial editor in New Yorkand all of them were solo; Hutton had no one to help schlep his equipment around or set up his shots. His final product, the excellent In Silico, had its streaming dbut in September. Hutton is a talented filmmakerLapsis, a low-budget sci-fi movie that he wrote and directed himself, appeared last year, and portends a career in the conceptual mode of someone like Alex Garlandbut few documentary projects extend for more than a year or two, and in most instances their trajectories are rigged up to fit an arbitrary ending. Had Hutton encountered his subject over the standard documentary interval, he almost inevitably would have come away with a version of the story that Lehrer told: a familiar tale of a bold, charismatic visionary destined to triumph over the forces of cautious bureaucracy, opening up expansive new vistas of inquiry. As it turned out, however, Hutton found himself narrating a much more complicated storyone in which his own personal hopes for the project would be implicated.

An early montage sets us up for what seems like the first version of the story: a series of neuroscientists at prestigious institutions explain that we dont know nearly enough about the brains intricacies to permit wholesale simulation, and that it might be a century or more before we have such knowledge. In his TED talk, Markram explains that hell have nothing to do with such prognoses of impossibility, and in his year-one interview with Hutton he goes even further: as he sees it, the epistemic modesty of the neuroscience community is an alibi for timidity and self-preservation. A full-brain simulation, in his view, is the necessary basis we need to solve such problems as Alzheimers and severe autism; his son is autistic, which gives his work a particular personal urgency. As a scientist, you want to sit back and say, O.K., its enough for me to study my microcircuit, and Im happy, he tells Hutton, shuffling papers in front of himself with feigned dismissiveness, as he nods in imitation of scientific paper shufflers. I dont think thats enough. And thats what keeps me going.

If Markram succeeds, Hutton explains, in voice-over, brain researchers will neither need to experiment with animals anymore, nor run up against the limits of invasive procedures on human subjects. Markram goes on, Well have an intelligence. Youll be able to dial down a molecule and see that you dropped the I.Q., dial up a molecule, see that you raised the I.Q. I believe that we will understand the brain before we finish building it. With nave admiration, Hutton asks Markram what keeps him going, and Markram responds to the softball with a gentle head pat of a smile. Well, I want to see this built. In ten years, as I said, its going to be built. Hutton is ushered into a screening room and shown a fly-through of a portion of simulated mouse brain; the Blue Danube waltz plays, and stunning visuals unfurl before his eyes. Hutton says, Though it was just a tiny piece of the whole, this was the first rendering of the most detailed brain simulation ever attempted. He told me, I thought, Holy shit! No one else has ever seen thisIm seeing inside of a brain! I had a few years of that feeling.

When Hutton returns for another visit, in 2011, the team has made what they describe as a significant leap: they have seen, for the first time, glimmers of brain activity that they hadnt themselves programmed, a sign that the simulated brain has begun to exhibit emergent properties. Hutton lingers on a shot of their computer displays, where a wave of color washes over the digital neurons. Their promotional apparatus has also been upgraded, and Hutton notes the introduction of giant touch screens. One of Markrams lieutenants shows him a bottle of champagne theyve locked in a desk drawer for future celebrations of breakthroughs they feel certain are imminent.

That year, Hutton read a new book by the neuroscientist Sebastian Seung, then at M.I.T., that described his skepticism of Markrams brain-simulation project. In an interview, Seung, who is just as good-looking, charismatic, and camera-ready as Markram, seems unable to take Markrams venture seriously: If we dont have detailed knowledge about the connections in neural networks that we can really depend on, I think that the endeavor of simulating them is really bound to fail. Seung explains that the fundamental problem with Blue Brain is that there are no intermediate benchmarks. Absent some connection to the real, experimental world of rats in mazes or humans in MRI machines, Seung explains, theres no way to know whether Markrams team is simulating something like actual brain activity or merely producing cool graphics. Hutton cuts back and forth between his interviews with Seung, who calls brain simulation highly unrealistic and a waste of time, and Markram, who calmly explains that his efforts have been severely distorted by his critics, who are hopelessly limited by the old, plodding ways of doing things. Markram seems to pity them in their attachment to a superannuated model, as if they were still hard at work refining inquiries into the Ptolemaic spheres; as he puts it to Hutton, Were dealing with a cultural change.

Hutton, for the most part, gives Markram the final word; after all, he had hitched his own ten-year project to Markrams. Privately, however, Hutton was less sure. He told me, I thought, Do I need to jump over and follow Sebastian now? Have I picked the right vessel for the film? But I felt I had to stay with it. Hutton felt malleable, tossed in two directions. When he met with Markrams critics, he found their storythat Markram represented the conquest of traditional neuroscience by computational colonistspersuasive, but, when he relayed versions of these opinions to Markram, he was once again convinced that Markram was misunderstood, a maverick visionary. Hutton realized that his own role in the documentary had to change. He told me, Id made two documentaries before, and I wasnt in those films at allthey were vrit-style. Id thought this film would be the same. But then I thought: whos the narrator? It wasnt Henry, because at that point I couldnt place him at the center of the film. I had to step in, which meant I had to figure out my own point of view. Before Hutton returned to Lausanne for the third year, a short portion of his work in progress, including his interview with Seung, was published by the Scientific American. When he arrived for the next shoot, he was steered aside by one of Markrams subordinates; in the future, they told him, they wanted to know who else he was talking to. Hutton put the warning into the film.

On a superficial level, the rest of In Silico is about Markrams rise and fall: through the brute force of his salesmanship, he brings together hundreds of researchers from as many institutions to win a flagship billion-dollar grant from the European Commission, and his efforts at Blue Brain become the centerpiece of whats known as the Human Brain Project. Hutton is swept up in the renewed enthusiasm for a far-reaching effort now described as akin to the Human Genome Project, or to CERN, the European Organization for Nuclear Research; at one point, he appeared on MSNBC to announce that he had updated his own timeline to fifteen years, to track Markrams, and he was partway through what was now a fifteen-year documentary. Markrams imperial stewardship of the Human Brain Project was, however, short-lived: eight hundred neuroscientists signed an open letter of protest, arguing that the neuroscientific community had been sold a bill of goods, and that participants had been enlisted against their better judgment in what was no longer a cordinated effort to study the brain but a monumental boondoggle and an egregious squandering of scientific resources on expensive information technology. Markram was pushed out of the Human Brain Project, and resumed his old position at Blue Brain, which was supported by the Swiss government.

By year seven, Markram has begun to fully turn inward; he tells Hutton that hes tired of fighting for his position in the media, and that hes decided that this is his silent year, that hes going into hibernation. His science, he believes, will speak for itself. He removes his microphone, ending the interview early. In voice-over, Hutton explains the way hes been buffeted back and forth between the outside critics and Blue Brains spellbinding visuals. (Huttons own animated sequences, by the wonderful illustrator Andrew Khosravani, are, by deliberate contrast, decidedly anti-realistic; cartoonishly florid and surreal, they bring to mind the interstitial scenes from Monty Python.) Now, Huttons narration continues, something else was starting to creep in, a sense of multiplying touch screens, curved screens, headsets, but a lack of meaning to anything and anyone outside this glass-and-steel building in Geneva. Markram now suggests, against all evidence, that the ten-year timeline was never supposed to be taken literally, he insists that his team remains on track to complete the construction of a digital mouse brain; he produces as confirmation the fact that their simulations are growing larger and more theatrically vivid with the passage of time. Where Jonah Lehrer, the journalist, had to conclude with boilerplate about how Markram might very well fail, Hutton has put himself in the opposite position: Markram, he grants, might be vindicated in the end. But, even if that never proves to be the case, Hutton goes on, the story of scientific progress is as much a story of mistakes as it is one of successes. He allows that theres a certain grandeur in Markrams ability to make mistakes on such a tremendous scale, and with such tremendous initiative.

All of this is, of course, true enough, but Huttons more profound point is that there remains an important difference between being wrong and being not even wrong. The danger isnt that Markram has made mistakes, but that the mistakes hes making arent productiveor are only productive on a meta level, insofar as they suggest that science is only on rare occasion the proper realm for Nietzschean heroism, and that layers of bureaucratic oversight tend to exist for good reason. The portrait of Markram that ultimately emerges is of a lordly sovereign stalking the halls of an island mansion, an autumn of the scientific patriarch. Perhaps Lehrer was caught in the usual short-term trapthat, had he had Huttons longitudinal Sitzfleisch, he would have discovered that the whole thing was a castle in the air. (As the blogger Scott Alexander recently put it, just as economists have predicted ten of the last two recessions, so science journalists have predicted ten of the last two paradigm shifts.) But there were clues available to Lehrer even thenones that made their way, unexamined, into his own article. Markram had compared himself to Copernicus, suggesting that his own conceptual breakthrough would be of the same order. But Copernicus did not begin with a new conceptual framework. Copernicus began with the sense that there was something about our astronomical measurements that didn't quite add up. It may have been a conceptual breakthrough that solved the problem, but it was the painstaking incremental workwhat Thomas Kuhn called the practice of normal sciencethat demonstrated that there was in fact a problem to be solved.

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The Appeal of Scientific Heroism - The New Yorker

Timely Interventions for Depression Might Lower the Future Risk of Dementia – Neuroscience News

Summary: Symptomatic depression increases the risk of developing dementia by 51%, but those being treated for depression had a significantly lower risk of being diagnosed with depression later in life.

Source: Elsevier

Depression has long been associated with an increased risk of dementia, and now anew studyprovides evidence that timely treatment of depression could lower the risk of dementia in specific groups of patients.

Over 55 million people worldwide live with dementia, a disabling neurocognitive condition that mainly affects older adults. No effective treatment for dementia exists but identifying ways to help minimize or prevent dementia would help to lessen the burden of the disease.

The study, led by Jin-Tai Yu, MD, PhD, Huashan Hospital, Shanghai Medical College, Fudan University, and Wei Cheng, PhD, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China, appears inBiological Psychiatry.

Professor Yu and Professor Cheng used data collected by the UK Biobank, a population-based cohort of over 500,000 participants. The current study included more than 350,000 participants, including 46,280 participants with depression. During the course of the study, 725 of the depressed patients developed dementia.

Previous studies examining whether depression therapies such as pharmacotherapy and psychotherapy could lower the risk for dementia produced mixed results, leaving the question unresolved.

Older individuals appear to experience different depression patterns over time, said Professor Yu.

Therefore, intra-individual variability in symptoms might confer different risk of dementia as well as heterogeneity in effectiveness of depression treatment in relation to dementia prevention.

To address that heterogeneity, the researchers then categorized participants into one of four courses of depression: increasing course, in which mild initial symptoms steadily increase; decreasing course, starting with moderate- or high-severity symptoms but subsequently decreasing; chronically high course of ongoing severe depressive symptoms; and chronically low course, where mild or moderate depressive symptoms are consistently maintained.

As expected, the study found that depression elevated the risk of dementia by a striking 51% compared to non-depressed participants. However, the degree of risk depended on the course of depression; those with increasing, chronically high, or chronically low course depression were more vulnerable to dementia, whereas those with decreasing course faced no greater risk than participants without depression.

The researchers most wanted to know whether the increased risk for dementia could be lowered by receiving depression treatment. Overall, depressed participants who received treatment had reduced risk of dementia compared to untreated participants by about 30%.

When the researchers separated the participants by depression course, they saw that those with increasing and chronically low courses of depression saw lower risk of dementia with treatment, but those with a chronically high course saw no benefit of treatment in terms of dementia risk.

Once again, the course of ineffectively treated depression carries significant medical risk, saidBiological Psychiatryeditor John Krystal, MD. He notes that, in this case, symptomatic depression increases dementia risk by 51%, whereas treatment was associated with a significant reduction in this risk.

This indicates that timely treatment of depression is needed among those with late-life depression, added Professor Cheng. Providing depression treatment for those with late-life depression might not only remit affective symptoms but also postpone the onset of dementia.

The new findings shed some light on previous work as well, said Professor Cheng. The differences of effectiveness across depression courses might explain the discrepancy between previous studies.

Author: Eileen LeahySource: ElsevierContact: Eileen Leahy ElsevierImage: The image is in the public domain

Original Research: Closed access.Depression, Depression Treatments, and Risk of Incident Dementia: A Prospective Cohort Study of 354,313 Participants by Wei Cheng et al. Biological Psychiatry

Abstract

Depression, Depression Treatments, and Risk of Incident Dementia: A Prospective Cohort Study of 354,313 Participants

To investigate the associations between courses of depression, the application of depression treatment, and the risk of incident dementia.

In this prospective cohort study, 354,313 participants aged 50 to 70 years were recruited from the UK Biobank between 2006 and 2010, and were followed-up until 2020, with a total of 4,212,929 person-years. We initially studied the effect of depression on dementia incidence across four subgroups characterized by courses of depressive symptoms. Then, 46,820 participants with depression diagnose were further categorized into the treated and untreated groups. We compared the risks of dementia among different depression treatments groups in all participants that depressed as well as four courses of depressive symptoms by performing survival analyses.

Depression was associated with a 51% higher risk of dementia, among which the increasing, chronically high and chronically low courses were associated with increased dementia risk while no association was found in the decreasing course. Compare to those who were depressed but untreated, receiving depression treatments corresponded to a hazard ratio of 0.7 (95% confidence interval= 0.62-0.77). Among the three detrimental courses, treatments for increasing and chronically low symptoms of depression were associated with a 42% and 29% lower risk of dementia while the reduction effect for chronically high symptoms was insignificant.

The negative association between depression treatment and incident dementia was significant in the increasing and chronically low course, highlighting the necessity of timely interventional strategies before depression progress to a chronically severe state.

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Timely Interventions for Depression Might Lower the Future Risk of Dementia - Neuroscience News