{"id":74191,"date":"2025-10-12T17:33:08","date_gmt":"2025-10-12T17:33:08","guid":{"rendered":"https:\/\/www.newsbeep.com\/nz\/74191\/"},"modified":"2025-10-12T17:33:08","modified_gmt":"2025-10-12T17:33:08","slug":"elusive-cures-why-its-time-for-new-thinking-on-brain-diseases","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/nz\/74191\/","title":{"rendered":"Elusive cures: Why it\u2019s time for new thinking on brain diseases"},"content":{"rendered":"

\n Why are brain disorders so mind-boggling? When we know so much about what a healthy brain looks like, why do we still not have cures for neurodegenerative diseases such as Parkinson\u2019s and Alzheimer\u2019s? Why do current drugs for anxiety, depression and psychosis not work for a third of people? Why
\n can\u2019t we fix some brains to make them work like healthy ones, in the same way other drugs and treatments can cure physical disease?\n <\/p>\n

Neuroscientist Nicole Rust, a professor of psychology at the University of Pennsylvania, is hooked on understanding how a healthy brain works to guide clinicians in seeking cures and treatments for brain disorders. She uses the analogy of a car: you can only understand how to fix a car if you know how a car works.<\/p>\n

That sounds good in theory. But on a video call with the Listener, Rust talks about how she became frustrated that decades of brain research have not translated into new treatments and cures, while neurodegenerative conditions such as Alzheimer\u2019s and Parkinson\u2019s disease continue to baffle neuroscientists. <\/p>\n

In her new book Elusive Cures, Rust considers the mysteries that continue to elude scientists concerning brain diseases. The book is a personal journey to understand the community she is working within, and why we\u2019re little closer to understanding or solving Alzheimer\u2019s disease, for example, than we were several decades ago.<\/p>\n

Dominoes discredited<\/p>\n

Her theory for this puzzling lack of progress in brain drugs and treatments is that neuroscientists and brain researchers have focused too much on a chain reaction of cause and effect: for instance, that lack of activity in the prefrontal cortex is linked to depression and mood disorders, or amyloid build-up in the brain causes Alzheimer\u2019s disease. <\/p>\n

\"NicoleNicole Rust, a professor of psychology at the University of Pennsylvania. Photo \/ Supplied<\/p>\n

With this approach, the idea is that you \u201cfind the broken domino and fix it\u2019\u2019, or \u201cfind a brain area with aberrant brain activity and stimulate it\u2019\u2019.<\/p>\n

Rust argues the brain is like a complex, chaotic weather system, with many influences. Treating a brain disorder should therefore be like \u201credirecting a hurricane rather than fixing a domino chain of cause and effect\u2019\u2019.<\/p>\n

This kind of thinking isn\u2019t entirely new in scientific circles, but Rust sees it as the central lens through which to view brain disorders and dysfunction. <\/p>\n

\u201cThe most significant thing holding back new treatments is that, for the most part, we have not yet learnt the right things about the brain, and so we still don\u2019t know what causes brain dysfunction.\u2019\u2019<\/p>\n

She notes new drugs introduced to treat brain disorders are not as novel as drug companies would like us to imagine, and are often reworked old ones. \u201cI also assumed that new drugs followed from novel discoveries about the brain more than they do,\u2019\u2019 she writes.<\/p>\n

Environmental impact<\/p>\n

Rust\u2019s book explains that until the 1990s, molecular neuroscience guided brain research and treatments: everything going wrong in the brain could be pinpointed to genes, proteins, neurons and other molecules. <\/p>\n

But the molecular neuroscience approach was too simplistic, she says. To understand what is happening in the brain, we also need to know what is going on in the mind, especially with mental health disorders, and how a person lives: their social, environmental and economic conditions.<\/p>\n

She points to brain disorders that continue to puzzle doctors and neuroscientists: Alzheimer\u2019s, Huntington\u2019s, Parkinson\u2019s, multiple sclerosis, epilepsy, depression, schizophrenia and many more. The first three are diseases \u201cwhere we know the brain has degenerated but we\u2019re not sure what has caused that. Though we have ways of mitigating the effects of these disorders, we cannot cure any of them.\u2019\u2019<\/p>\n

Then there are mental health conditions and neurodevelopmental disorders such as intellectual disabilities and some forms of autism. \u201cThese are the classes of disorders we\u2019ve really had a hard time understanding, and for some of them really developing effective treatments.\u201d<\/p>\n

\"AmyloidAmyloid hypothesis: Amyloid plaques would form around neurons resulting in degeneration. This is thought to be a crucial role in the development of Alzheimer’s. Image \/ Getty Images<\/p>\n

Her book traces the history of Alzheimer\u2019s, which for decades was thought to be caused by viruses or environmental toxins. British woman Carol Jennings changed the course of study in the mid-1980s when she asked Alzheimer\u2019s researchers why her father and his siblings had been diagnosed in their 40s and 50s. The scientists switched to thinking a gene mutation causes amyloid clumps to form in the brain and lead to neurodegeneration.<\/p>\n

\u201cThe amyloid hypothesis fits within this framework, with its emphasis on a domino-chain cascade of events that begins with a mutated gene that produces a protein (amyloid) and ends in cognitive impairment,\u201d says Rust.<\/p>\n

Dementia affects about 1 in 20 New Zealanders aged over-65 and one in five over the age of 80. But after 30 years of looking at genes \u2013 the APOE4 gene variant is one that\u2019s implicated in Alzheimer\u2019s \u2013 neuroscientists and drug companies are no closer to finding a drug that can cure the disease or slow it down. <\/p>\n

Rust says amyloid-clearing drugs \u2013 aducanumab and lecanemab, introduced in the US in 2021 and 2023 \u2013 aren\u2019t the answer, as they clear amyloid from the brain but delay the disease only by an average eight or nine months.<\/p>\n

\u201cIt\u2019s not stopping the disease in its tracks, which is what we really want for Alzheimer\u2019s. So now, everyone is asking the question: why not? What\u2019s gone on? What kind of thing might Alzheimer\u2019s be? And I don\u2019t think this has a simple answer, but one possibility is that in families like Carol Jennings\u2019, amyloid triggers something to happen. Then, once that starts to happen, you can\u2019t just stop it by clearing amyloid from the brain.\u2019\u2019<\/p>\n

Brain disorders cost a staggering $1.5 trillion, or 9% of GDP, in the US, according to a 2016 study.<\/p>\n

Rust writes many treatments were developed when we didn\u2019t understand the brain the way we do now. Some drugs were discovered by accident: the first anti-anxiety drug, iproniazid, was stumbled upon in 1951 during trials for a tuberculosis drug. Methylphenidate (Ritalin) to treat ADHD was created in 1944 as a \u201ctry it and see\u201d drug. <\/p>\n

\u201c[Many] of the drugs we have today are actually not new drugs, but rather refinements of old drugs created before 1960. And, while we now better understand how the old (and new) drugs work, many of the newer drugs operate in the same ways as the original ones,\u201d she writes.<\/p>\n

Worldwide, 970 million people are living with a mental disorder such as depression, anxiety or psychosis, but medications don\u2019t work for many of them. In New Zealand, antidepressants are still the standard treatment for mood disorders \u2013 nearly 12% of New Zealanders, 632,346 patients, were prescribed antidepressants last year, according to Pharmac.<\/p>\n

\"Reduce,Reduce, reuse & recycle: Drugs are not as novel as companies would like us to imagine. Photo \/ Getty Images<\/p>\n

Rust writes: \u201cLike many brain drugs, we know antidepressants work but not how. The most obvious route toward understanding them better begins with understanding how the disorders that these therapies are used to treat \u2013 depression and psychosis \u2013 manifest in the brain.\u2019\u2019<\/p>\n

She tells the Listener, \u201cWe are with depression where we were with understanding weather in the 17th century.\u201d But better understanding of the weather brought an acceptance that it was all but uncontrollable.<\/p>\n

Mood swings<\/p>\n

Rust has recently switched her university research from studying memories and how these are formed in the brain to mood \u2013 what\u2019s happening in the brain which puts us in a good or bad mood. It\u2019s an example of her challenging process: refusing to provide falsely optimistic hope in the form of unrealistic claims, while at the same time insisting that clarity around what is really going on in the brain will be the first step on the path to solving the big problems. <\/p>\n

She doesn\u2019t have all the answers, but she thinks she might finally have figured out the right questions. She describes psychiatric disorders as the most complex and mysterious in medicine \u2013 there is no biological test for them. <\/p>\n

She\u2019s not a fan of medicalising all mental illness and mood disorders and thinks cognitive behavioural therapy and mindfulness can be as effective as drugs or an important counterpart to drug treatment.<\/p>\n

We are with depression where we were with understanding weather in the 17th century.<\/p>\n

Nicole Ruth<\/p>\n

She says our moods are \u201ca running average of recent events. And those events can be real or imagined. If you just keep ruminating on something bad that happens, that can affect your mood. I\u2019m saying things that probably everyone knows, but this leads to a whole suite of behavioural strategies.\u201d<\/p>\n

On that note, another puzzle she wants to understand is this: \u201cWhat are the protective mechanisms which switch on when someone has a chain of events that puts them in a bad mood? Our moods depend on the average of things that have happened to us, but our perception of the things that have happened to us depends on our moods. One of the big questions we\u2019re trying to understand is how is this system possibly set up so it doesn\u2019t spiral out of control? It\u2019s one of the big loops.\u2019\u2019<\/p>\n

As she said on science podcast The Transmitter: \u201cThere might be some cases where we also just throw up our hands and say this might be uncontrollable in a brain-based therapeutic way. That\u2019s where the mood disorders come in in certain cases. It might be that some classes of depression are just a brain that has become entrenched in a maladaptive state because it\u2019s just learnt its way in there. The only therapy to fix this is a benevolent reprogramming of the brain.\u201d <\/p>\n

\"TheThe best medicine of all? Nourishment. Photo \/ Getty Images<\/p>\n

One possibility: \u201cPsychedelic therapies are starting to gain some traction. The idea behind those is you just want to trigger plasticity in the brain and you want to combine that with talk therapy \u2026 so it can wiggle itself back to health. It really informs how we should be going about it, if true.\u201d <\/p>\n

If that sounds mildly concerning, she added: \u201cWe only want to do something as dramatic as is required.\u201d After all, \u201cTalk therapies, where a patient is reliving their trauma, that can just reinforce the trauma and actually make it worse, not better. It\u2019s really important that we proceed cautiously and ethically.\u201d<\/p>\n

AI, inevitably<\/p>\n

Her book would make depressing reading if it wasn\u2019t for the glimmer of hope at the end. Artificial intelligence and biotechnology should \u2013 if all goes to plan \u2013 allow us to develop models to get a better glimpse of what is happening in the brain \u2013 genes, brain activity and lived experience \u2013 when it becomes diseased or disordered.<\/p>\n

As Rust says, \u201cI could have written a book about neuro AI. It\u2019s just exploding, It\u2019s hard to keep up. You don\u2019t even want to write that book because it\u2019s going to be out of date in two months.\u201d<\/p>\n

But beyond that, she argues we should nourish our brains to make them healthier in the same way we nourish our bodies. She\u2019s an advocate of healthy living to reduce the risk of developing a neurodegenerative condition, and exercise is No 1.<\/p>\n

Sleep allows our brains to repair, although, again, it\u2019s not clear why. \u201cWe don\u2019t really understand well what\u2019s happening in the brain during sleep. What we do know is that brains that sleep a normal number of hours are healthier.\u2019\u2019<\/p>\n

As she has written elsewhere: \u201cThere is a gap between what we\u2019re learning and actual, impactful treatment. The most profound insight, I think, that follows from thinking about the brain in this new way is how hard the end goal of treatments really is.\u201d<\/p>\n

If Rust has one key message about treating brain disorders it could be summed up as \u201clet\u2019s get real\u201d. As with our thinking about the weather, she believes we will \u201ccontrol\u201d the brain when we shift to \u201cthinking about it as a complex dynamical system \u2026 In a complex system, you\u2019re not going to have a single cause.\u201d <\/p>\n

Elusive Cures: Why Neuroscience Hasn\u2019t Solved Brain Disorders \u2013 and How We Can Change That, by Nicole Rust (Princeton University Press, $46.40)<\/p>\n

Save<\/a>Share this article<\/p>\n

Reminder, this is a Premium article and requires a subscription to read.<\/p>\n

Copy LinkEmailFacebookTwitter\/XLinkedInReddit<\/p>\n","protected":false},"excerpt":{"rendered":"Why are brain disorders so mind-boggling? When we know so much about what a healthy brain looks like,…\n","protected":false},"author":2,"featured_media":74192,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[1443,8347,3404,1596,32635,2068,58204,58201,7123,3419,7191,4701,5841,1757,9094,2082,305,134,5110,302,6036,13840,663,5812,58202,5969,58203,117,111,139,69,90,48211,193,24830,384,2849,1581,4514,544,6100,9100,2846,1960,3755,2044,3524,6923,1316,4276,4576],"class_list":["post-74191","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-about","tag-alzheimers","tag-anxiety","tag-brain","tag-brains","tag-cant","tag-cure","tag-cures","tag-current","tag-depression","tag-disease","tag-diseases","tag-disorders","tag-drugs","tag-elusive","tag-for","tag-have","tag-health","tag-healthy","tag-its","tag-know","tag-like","tag-looks","tag-make","tag-mindboggling","tag-much","tag-neurodegenerative","tag-new","tag-new-zealand","tag-newzealand","tag-nz","tag-on","tag-ones","tag-other","tag-parkinsons","tag-people","tag-physical","tag-psychosis","tag-same","tag-some","tag-still","tag-such","tag-them","tag-thinking","tag-third","tag-time","tag-treatments","tag-what","tag-when","tag-why","tag-work"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/74191","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=74191"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/74191\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/74192"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=74191"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=74191"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=74191"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}