Chapter 12. Psychopathology: The Biology of Behavioral Disorders

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Max Kozlov Doctors measure blood pressure to track heart disease, and scrutinize insulin levels in people with diabetes. But when it comes to depression, clinicians must rely on people’s self-reported symptoms, making it difficult to objectively measure a treatment’s effects. Now, researchers have used artificial intelligence (AI) to identify a brain signal linked to recovery from depression in people treated with deep-brain stimulation (DBS), a technique that uses electrodes implanted into the brain to deliver electric pulses that alter neural activity. The team reported1 its results on ten people with severe depression, in Nature on 20 September. If replicated in a larger sample, these findings could represent a “game-changer in how we would be able to treat depression”, says Paul Holtzheimer, a neuroscientist at the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, who was not involved in the research. Efforts to treat depression with DBS have so far had limited success: two randomized-controlled trials2,3 failed to demonstrate a benefit compared with a placebo. One problem, says Helen Mayberg, a neurologist at Icahn School of Medicine at Mount Sinai in New York City, and a co-author of the Nature paper, is that doctors only have access to self-reported data to assess whether a person’s stimulation voltage needs adjustment. With self-reported data, clinicians have a difficult time distinguishing between normal, day-to-day mood fluctuations and pathological depression, says Todd Herrington, director of the DBS programme at Massachusetts General Hospital in Boston, who was not involved in the research. To find a more objective measure of depression recovery, Mayberg and her colleagues developed a DBS device that includes sensors to measure brain activity, as well as the standard electrodes for brain stimulation. They implanted this device into the subcallosal cingulate cortex — an area of the brain that has a role in regulating emotional behaviour — in ten people with depression that resisted all forms of treatment. © 2023 Springer Nature Limited

Keyword: Depression; Brain imaging
Link ID: 28932 - Posted: 09.27.2023

Perspective by Dan O'Brien I was 12 years old when I developed obsessive-compulsive disorder. My older brother had recently tried to kill himself by jumping from our attic window. I was the one who saw him first, as he limped around the side of the house, his back and hair matted with snow. Inside I found his suicide note and showed it to our mother. She collapsed in my arms, crying, and whispered, “This is a secret we must take to our graves.” Live well every day with tips and guidance on food, fitness and mental health, delivered to your inbox every Thursday. Before long, I found myself obsessing about any number of vague yet existential threats, and compulsively taking defensive action against them. I cycled through most of the classic OCD manifestations: avoiding cracks in the sidewalk, flipping light switches three, six, nine times (depending on my mood), checking and rechecking — and rechecking again — that our front and back doors were indeed locked. I had no idea what was happening to me. I simply knew with certainty that if I did not execute these actions correctly, my loved ones and I would suffer. And hypochondria, too: A book titled “Symptoms” lived in the tall bookcase behind the potted plant in the living room; one searched for one’s symptoms in an index up front, then proceeded to the indicated page where one would be provided with the most dire diagnosis imaginable. “Symptoms,” with its heft, its red-linen hardcover and tissue-thin paper, became my Bible. I touched things and people with trepidation and regret. I probed my body for swollen glands. My frequent handwashing desiccated my skin like a riverbed in drought, blood breaking through the cracks. I was forever certain that I was coming down with something catastrophic, like tuberculosis, AIDS, cancer. I was morally scrupulous, in the clinical sense, and prayed three times a day. (I wasn’t particularly religious; I was trying to cover all my bases.) Morning and evening prayer was easy, at home, but lunchtime at school could be tricky; I’d have to abscond to the boy’s room, or a shadowy, chain-link corner of the playground. I grew adept at praying without moving my lips in rote run-on sentences in which I begged God’s forgiveness for everything and anything I had done wrong in the past and would do wrong in the future.

Keyword: OCD - Obsessive Compulsive Disorder
Link ID: 28926 - Posted: 09.27.2023

By Laura Sanders On a hot, sunny Sunday afternoon in Manhattan, time froze for Jon Nelson. He stood on the sidewalk and said good-bye to his three kids, whose grandfather had come into the city from Long Island to pick them up. Like any parent, Jon is deeply attuned to his children’s quirks. His oldest? Sometimes quiet but bitingly funny. His middle kid? Rates dad a 10 out of 10 on the embarrassment scale and doesn’t need a hug. His 10-year-old son, the baby of the family, is the emotional one. “My youngest son would climb back up into my wife’s womb if he could,” Jon says. “He’s that kid.” An unexpected parade had snarled traffic, so Jon parked illegally along a yellow curb on 36th Street, near where his father-in-law was waiting. It was time to go. His youngest gave the last hug. “He looked up, scared and sad,” Jon says, and asked, “Dad, am I going to see you again?” That question stopped the clock. “I was like, ‘Oh man,’” Jon says. “It was one of those moments where I was living it through his eyes. And I got scared for the first time.” Until that good-bye, Jon hadn’t wanted to live. For years, he had a constant yearning to die — he talks about it like it was an addiction — as he fought deep, debilitating depression. But his son’s question pierced through that heaviness and reached something inside him. “That was the first time I really thought about it. I was like, ‘I kind of hope I don’t die.’ I hadn’t had that feeling in so long.” That hug happened around 5 p.m. on August 21, 2022. Twelve hours later, Jon was wheeled into a surgical suite. There, at Mount Sinai’s hospital just southwest of Central Park, surgery team members screwed Jon’s head into a frame to hold it still. Then they numbed him and drilled two small holes through the top of his skull, one on each side. Through each hole, a surgeon plunged a long, thin wire dotted at the end with electrodes deep into his brain. The wiring, threaded under his skin, snaked around the outside of Jon’s skull and sank down behind his ear. From there, a wire wrapped around to the front, meeting a battery-powered control box that surgeons implanted in his chest, just below his collarbone. © Society for Science & the Public 2000–2023.

Keyword: Depression
Link ID: 28924 - Posted: 09.23.2023

Sara Reardon The psychedelic drug MDMA, also known as ecstasy or molly, has passed another key hurdle on its way to regulatory approval as a treatment for mental illness. A second large clinical trial has found that the drug — in combination with psychotherapy — is effective at treating post-traumatic stress disorder (PTSD). The results allow the trial’s sponsor to now seek approval from the US Food and Drug Administration (FDA) for MDMA’s use as a PTSD treatment for the general public, which might come as soon as next year. “It’s an important study,” says Matthias Liechti, a psychopharmacologist who studies MDMA at the University of Basel in Switzerland, but who was not involved with the trial or its sponsor. “It confirms MDMA works.” In June, Australia became the first country to allow physicians to prescribe MDMA for treating psychiatric conditions. MDMA is illegal in the United States and other countries because of the potential for its misuse. But the Multidisciplinary Association for Psychedelic Studies (MAPS), a non-profit organization in San Jose, California, has long been developing a proprietary protocol for using MDMA as a treatment for PTSD and other disorders. MAPS has been campaigning for its legalization — a move that could encourage other countries to follow suit. In 2021, researchers sponsored by MAPS reported the results of a study1 in which 90 people received a form of psychotherapy developed by the organization alongside either MDMA or a placebo. After three treatment sessions, 67% of those who received MDMA with therapy no longer qualified for a PTSD diagnosis, compared with 32% of those who received therapy and a placebo. The results were widely hailed as promising, but the FDA typically requires two placebo-controlled trials before a drug can be approved. The results of a second trial, involving 104 further individuals with PTSD and published on 14 September in Nature Medicine2, were similar to those of the original: 71% of people who received MDMA alongside therapy lost their PTSD diagnosis, compared with 48% of those who received a placebo and therapy. © 2023 Springer Nature Limited

Keyword: Drug Abuse; Stress
Link ID: 28911 - Posted: 09.16.2023

By Phil Jaekl In the mid-1970s, a British researcher named Anthony Barker wanted to measure the speed at which electrical signals travel down the long, slender nerves that can carry signals from the brain to muscles like those in the hand, triggering movement. To find out, he needed a way to stimulate nerves in people. Researchers had already used electrodes placed on the skin to generate a magnetic field that penetrated human tissue — this produced an electric current that activated the peripheral nerves in the limbs. But the technique was painful, burning the skin. Barker, at the University of Sheffield in England, and his colleagues started to work on a better method. In 1985, with promising results under their belts, they tried positioning the coil-shaped magnetic device they’d developed on participants’ heads. The coil emitted rapidly alternating magnetic pulses over the brain region that controls movement, generating weak electrical currents in the brain tissue and activating neurons that control muscles in the hand. After about 20 milliseconds, the participants’ fingers twitched. The technique, now called transcranial magnetic stimulation (TMS), has proved a vital tool for investigating how the human brain works. When targeted to specific brain regions, TMS can temporarily inhibit or enhance various functions – blocking the ability to speak, for instance, or making it easier to commit a series of numbers to memory. And when brain imaging technologies such as functional magnetic resonance imaging (fMRI) emerged in the 1990s, researchers could now “see” inside people’s brains as they received TMS stimulation. They could also observe how neural pathways respond differently to stimulation in psychiatric illnesses like schizophrenia and depression. In recent decades, this fundamental research has yielded new treatments that alter brain activity, with TMS therapies for depression at the fore. In 2008, the US Food and Drug Administration approved NeuroStar, the nation’s first TMS depression device, and many other countries have since sanctioned the approach. Yet even though TMS is now a widely available depression treatment, many questions remain about the method. It’s not clear how long the benefits of TMS can last, for example, or why it appears to work for some people with depression but not others. Another challenge is disentangling the effects of TMS from the placebo effect — when someone believes that they will benefit from treatment and gets better even though they’re receiving a “sham” form of stimulation. © 2023 Annual Reviews

Keyword: Depression
Link ID: 28903 - Posted: 09.10.2023

By Astrid Landon In June 2015, Jeffrey Thelen’s parents noticed their son was experiencing problems with his memory. In the subsequent years, he would get lost driving to his childhood home, forget his cat had died, and fail to recognize his brother and sister. His parents wondered: Was electroconvulsive therapy to blame? Thelen had been regularly receiving the treatment to help with symptoms of severe depression, which he’d struggled with since high school. At 34 years old, he had tried medications, but hadn’t had a therapy plan. His primary care physician referred him to get an evaluation for ECT, which was then prescribed by a psychiatrist. Electroconvulsive therapy has been used to treat various mental illnesses since the late 1930s. The technique, which involves passing electrical currents through the brain to trigger a short seizure, has always had a somewhat torturous reputation. Yet it’s still in use, in a modified form of its original version. According to one commonly cited statistic, 100,000 Americans receive ECT annually — most often to ease symptoms of severe depression or bipolar disorder — although exact demographic data is scarce. For Thelen, the treatment appeared to relieve his depression symptoms somewhat, but he reported new headaches and concentration issues, in addition to the memory loss. Those claims are central to a lawsuit Thelen filed in 2020 against Somatics, LLC and Elektrika, Inc., manufacturers and suppliers of ECT devices, alleging that the companies failed to disclose — and even intentionally hid — risks associated with ECT, including “brain damage and permanent neurocognitive injuries.” Thelen’s legal team told Undark that they have since reached a resolution with Elektrika on confidential terms. With regard to Somatics, in June a jury found that the company failed to warn about risks associated with ECT, but could not conclude that there was a legal causation between that and Thelen’s memory loss. The following month, his lawyers filed a motion for a new trial. (In response to a request for comment, Conrad Swartz, one of Somatics’ co-founders, directed Undark to the company’s attorney, Sue Cole. Cole did not respond to multiple emails. Lawyers for Elektrika declined to comment.)

Keyword: Depression; Learning & Memory
Link ID: 28899 - Posted: 09.07.2023

By Amanda Holpuch Doctors in Australia had screened, scanned and tested a woman to find out why she was sick after being hospitalized with abdominal pains and diarrhea. They were not prepared for what they found. A three-inch red worm was living in the woman’s brain. The worm was removed last year after doctors spent more than a year trying to find the cause of the woman’s distress. The hunt for the answer, and the alarming discovery, was described this month in Emerging Infectious Diseases, a monthly journal published by the Centers for Disease Control and Prevention. The woman, whom the article identifies as a 64-year-old resident of southeastern New South Wales, Australia, was admitted to a hospital in January 2021 after complaining of diarrhea and abdominal pain for three weeks. She had a dry cough and night sweats. Scientists and doctors from Canberra, Sydney and Melbourne said in the journal article that the woman was initially told she had a rare lung infection, but the cause was unknown. Her symptoms improved with treatment, but weeks later, she was hospitalized again, this time with a fever and cough. Doctors then treated her for a group of blood disorders known as hypereosinophilic syndrome, and the medicine they used suppressed her immune system. Over a three-month period in 2022, she experienced forgetfulness and worsening depression. An MRI showed that she had a brain lesion and, in June 2022, doctors performed a biopsy. Inside the lesion, doctors found a “stringlike structure” and removed it. The structure was a red, live parasitic worm, about 3.15 inches long and .04 inches in diameter. © 2023 The New York Times Company

Keyword: Depression
Link ID: 28892 - Posted: 08.30.2023

Linda Geddes I’ve made a cup of coffee, written my to-do list and now I’m wiring up my ear to a device that will send an electrical message to my brainstem. If the testimonials are to believed, incorporating this stimulating habit into my daily routine could help to reduce stress and anxiety, curb inflammation and digestive issues, and perhaps improve my sleep and concentration by tapping into the “electrical superhighway” that is the vagus nerve. From plunging your face into icy water, to piercing the small flap of cartilage in front of your ear, the internet is awash with tips for hacking this system that carries signals between the brain and chest and abdominal organs. Manufacturers and retailers are also increasingly cashing in on this trend, with Amazon alone offering hundreds of vagus nerve products, ranging from books and vibrating pendants to electrical stimulators similar to the one I’ve been testing. Meanwhile, scientific interest in vagus nerve stimulation is exploding, with studies investigating it as a potential treatment for everything from obesity to depression, arthritis and Covid-related fatigue. So, what exactly is the vagus nerve, and is all this hype warranted? The vagus nerve is, in fact, a pair of nerves that serve as a two-way communication channel between the brain and the heart, lungs and abdominal organs, plus structures such as the oesophagus and voice box, helping to control involuntary processes, including breathing, heart rate, digestion and immune responses. They are also an important part of the parasympathetic nervous system, which governs the “rest and digest” processes, and relaxes the body after periods of stress or danger that activate our sympathetic “fight or flight” responses. In the late 19th century, scientists observed that compressing the main artery in the neck – alongside which the vagus nerves run – could help to prevent or treat epilepsy. This idea was resurrected in the 1980s, when the first electrical stimulators were implanted into the necks of epilepsy patients, helping to calm down the irregular electrical brain activity that triggers seizures. © 2023 Guardian News & Media Limited

Keyword: Depression; Obesity
Link ID: 28886 - Posted: 08.26.2023

By Jonathan Moens When the war in Ukraine broke out, many countries and agencies around the world lent their support in the form of financial aid, weapons, and food. But Olga Chernoloz, a Ukrainian neuroscientist based in Canada, wanted to provide a different kind of assistance: a combination of therapy and the psychedelic drug MDMA. Such therapy, she said, could help countless people on the ground who are suffering from psychological trauma. “I thought that the most efficacious way I could be of help,” she told Undark, “would be to bring psychedelic-assisted therapy to Ukraine.” Chernoloz’s confidence stems in part from the results of clinical trials on MDMA to treat post-traumatic stress disorder in vulnerable populations, which suggest that such treatments may improve symptoms, or do away with them altogether. But the approach is experimental and has not yet cleared major regulatory hurdles in Canada, Europe, or the United States. Still, Chernoloz, who is a professor at the University of Ottawa, plans on carrying out clinical trials with Ukrainian refugees in a psychedelic center in the Netherlands in early 2024. This month, Chernoloz and her colleagues organized an education session for 20 Ukrainian therapists to learn about MDMA-assisted therapy for PTSD from the Multidisciplinary Association for Psychedelic Studies, or MAPS, one of the most influential organizations dedicated to education and promotion of psychedelic drugs.

Keyword: Stress
Link ID: 28878 - Posted: 08.24.2023

David Cox In June 2021, 32-year-old actor Kate Hyatt travelled to a farmhouse near Great Malvern in Worcerstershire for a plant medicine retreat that she hoped would improve her mental health after a difficult time during the pandemic lockdowns. While there, she is believed to have taken a substance called wachuma, or San Pedro cactus, a powerful hallucinogen used by Indigenous people in the Andes for thousands of years. But Hyatt did not experience relief; instead, her mental health worsened. Three months later, she described being in “some sort of psychotic break” and feeling as if her brain was going to explode. Later that autumn she took her own life. At the subsequent inquest, the coroner’s report linked her worsening symptoms to the hallucinogens she had consumed. Such tragedies represent the darker side of the psychedelics renaissance. These cases are often forgotten amid the feverish anticipation surrounding the therapeutic potential of these drugs, combined with exhaustive media coverage, the rapid rise of a billion-dollar industry – ranging from venture capital-backed startups to wellness retreats – and the hype around last year’s Netflix series How to Change Your Mind (based on Michael Pollan’s bestselling book). Yet without careful monitoring and scrutiny of who receives them, this class of drugs – which includes LSD, MDMA (commonly known as ecstasy or molly) and psilocybin (the active ingredient of magic mushrooms) – can be dangerous. There is evidence that they can destabilise vulnerable individuals who have experienced a previous psychotic episode or have a family history of psychosis. The substances are illegal to distribute and possess in the UK, although they are often obtained on the hidden market. Scientific researchers and biotechnology companies are able to use them in clinical trials only after obtaining a Home Office licence and applying extensive security arrangements. © 2023 Guardian News & Media Limited

Keyword: Depression; Drug Abuse
Link ID: 28873 - Posted: 08.19.2023

By Pam Belluck The Food and Drug Administration on Friday approved the first pill for postpartum depression, a milestone considered likely to increase recognition and treatment of a debilitating condition that afflicts about a half-million women in the United States every year. Clinical trial data show the pill works quickly, beginning to ease depression in as little as three days, significantly faster than general antidepressants, which can take two weeks or longer to have an effect. That — along with the fact that it is taken for just two weeks, not for months — may encourage more patients to accept treatment, maternal mental health experts said. The most significant aspect of the approval may not be the features of the drug, but that it is explicitly designated for postpartum depression. Several doctors and other experts said that while there were other antidepressants that are effective in treating the condition, the availability of one specifically shown to address it could help reduce the stigma of postpartum depression by underscoring that it has biological underpinnings and is not something women should blame themselves for. The hope is that it will encourage more women to seek help and prompt more obstetricians and family doctors to screen for symptoms and suggest counseling or treatment. “This is a patient population that just so often falls through the cracks,” said Dr. Ruta Nunacs, a psychiatrist with the Center for Women’s Mental Health at Massachusetts General Hospital. “When women are told, ‘You have postpartum depression,’ it’s embarrassing, it is demeaning, it makes them feel like a bad mom.” She added, “There’s also a lot of stigma about taking antidepressant medication, so that might make this treatment more appealing because it’s really a treatment specific for postpartum depression.” © 2023 The New York Times Company

Keyword: Depression; Sexual Behavior
Link ID: 28867 - Posted: 08.05.2023

by Brendan Borrell The New York State Psychiatric Institute in New York City is undergoing an audit and a change in leadership following a suicide that occurred during one of its clinical trials. Autism researcher Jeremy Veenstra-VanderWeele has abruptly taken the helm as the interim executive director of the institute and chair of the Columbia University psychiatry department, replacing Helen Blair Simpson, Spectrum has learned. The New York State Psychiatric Institute is part of the New York State Office of Mental Health, but it shares buildings and staff with Columbia University and the university’s hospital. The Office of Mental Health is currently conducting an audit of the institute, according to Carla Cantor, the institute’s director of communications. The audit and turnover in leadership comes after the halting of a series of clinical trials conducted by Columbia psychiatrist Bret Rutherford, which tested whether the drug levodopa — typically used to treat Parkinson’s disease — could improve mood and mobility in adults with depression. During a double-blind study that began in 2019, a participant in the placebo group died by suicide. That study was suspended prior to completion, according to an update posted on ClinicalTrials.gov in 2022. Two published reports based on Rutherford’s pilot studies have since been retracted, as Spectrum has previously reported. The National Institute of Mental Health has terminated Rutherford’s trials and did not renew funding of his research grant or K24 Midcareer Award. Former members of Rutherford’s laboratory describe it as a high-pressure environment that often put publications ahead of study participants. “Research is important, but not more so than the lives of those who participate in it,” says Kaleigh O’Boyle, who served as clinical research coordinator there from 2018 to 2020. © 2023 Simons Foundation

Keyword: Depression; Parkinsons
Link ID: 28861 - Posted: 08.02.2023

By Stephanie Pappas Have you felt butterflies in your stomach or hunger pangs? Those “gut feelings” happen thanks to the vagus nerve, which is a superhighway that connects the brain and the gut. In recent years the vagus nerve has become an intriguing target for researchers looking to cure disorders of both the brain and the body. Vagus nerve stimulation—usually achieved with an electrode implanted in the neck to deliver electrical pulses directly to the nerve—is an approved treatment for epilepsy and some forms of depression. Scientists are now studying vagus nerve stimulation (VNS) for disorders such as rheumatoid arthritis and the inflammatory bowel disease Crohn’s. What gives this nerve such widespread impact? The vagus nerve is the longest of the cranial nerves, which emerge directly from the brain rather than traveling through the spinal cord. It begins at an opening at the base of the skull and runs down the neck and into the abdomen, where it collects signals from the viscera and helps regulate the automatic processes of the body, from digestion to sleep to inflammation. About 80 percent of its signals are sensory ones that travel from the inner organs up to the brain, while the other 20 percent travel from the brain to the body and regulate things such as intestinal contractions and heart rate. The vagus nerve is the key player in the parasympathetic nervous system, which is the “rest and digest” system that calms the body during times of low stress. “If you are relaxed, if you are sleeping, if you are in a restorative phase, it’s the vagus nerve dominating,” says Gregor Hasler, a psychiatrist at the University of Fribourg in Switzerland, who has written about the gut-brain connection.

Keyword: Depression; Epilepsy
Link ID: 28843 - Posted: 07.06.2023

By Sujata Gupta Teenagers in the United States are in crisis. That news got hammered home earlier this year following the release of a nationally representative survey showing that over half of high school girls reported persistent feelings of “sadness or hopelessness” — common words used to screen for depression. Almost a third of teenage boys reported those same feelings. “No one is doing well,” says psychologist Kathleen Ethier. She heads the U.S. Centers for Disease Control and Prevention’s Division of Adolescent and School Health, which has overseen this biennial Youth Risk Behavior Survey since 1991. During the latest round of data collection, in fall 2021, over 17,000 students from 31 states responded to roughly 100 questions related to mental health, suicidal thoughts and behaviors, sexual behavior, substance use and experiences of violence. One chart in particular garnered considerable media attention. From 2011 to 2021, persistent sadness or hopelessness in boys went up 8 percentage points, from 21 to 29 percent. In girls, it rose a whopping 21 percentage points, from 36 to 57 percent. Some of that disparity may arise from the fact that girls in the United States face unique stressors, researchers say. Compared with boys, girls seem more prone to experiencing mental distress from social media use, are more likely to experience sexual violence and are dealing with a political climate that is often hostile to women’s rights (SN: 7/16/22 & 7/30/22, p. 6). But the gap between boys and girls might not be as wide as the numbers indicate. Depression manifests differently in boys and men than in girls and women, mounting evidence suggests. Girls are more likely to internalize feelings, while boys are more likely to externalize them. Rather than crying when feeling down, for instance, boys may act irritated or lash out. Or they may engage in risky, impulsive or even violent acts. Inward-directed terms like “sadness” and “hopelessness” miss those more typically male tendencies. And masculine norms that equate sadness with weakness may make males who are experiencing those emotions less willing to admit it, even on an anonymous survey. © Society for Science & the Public 2000–2023

Keyword: Depression; Development of the Brain
Link ID: 28841 - Posted: 07.01.2023

By Charlotte Stoddart Charlotte Stoddart: Can a sugar pill make you feel better? What about the rituals surrounding a visit to the doctor? Can the care of a doctor or your trust in them reduce the amount of pain you feel? I’m Charlotte Stoddart and this is Knowable. This episode is all about the placebo effect. We’re going to look in detail at one key paper to learn how the placebo effect has been used in medicine and how it’s been understood and misunderstood. The paper is called “The Powerful Placebo.” It was written by Henry Beecher and published in JAMA, the Journal of the American Medical Association, in 1955. I chose this paper because it’s often referred to as a classic, and it’s still one of the most frequently cited papers on the placebo effect. I’ve enlisted the help of Ted Kaptchuk, who knows the paper well. Ted Kaptchuk: I enjoyed rereading it, actually. It’s a remarkable paper. I’ve read it probably 15 times in my life. Charlotte Stoddart: Ted is director of the Program in Placebo Studies at the Beth Israel Deaconess Medical Center in Boston and a professor of medicine at Harvard Medical School, where Henry Beecher also held a professorship. Beecher also worked at Massachusetts General Hospital. Charlotte Stoddart: During the Second World War, Beecher served in the US Army, and there’s a story about how that experience got him interested in the placebo effect. It goes like this: Beecher was working at a military hospital. One day, a badly injured soldier needed surgery, but the hospital had run out of morphine. So Beecher injected the soldier with saline solution instead. The soldier relaxed and Beecher carried out the operation without any real anesthetic. This, so the story goes, is when Beecher realized the power of the mind over the body. There are several different versions of this story, but Ted says it’s likely some version of it is true. © 2023 Annual Reviews

Keyword: Pain & Touch; Attention
Link ID: 28832 - Posted: 06.28.2023

Sara Reardon Psychedelic drugs are promising treatments for many mental-health conditions, but researchers don’t fully understand why they have such powerful therapeutic effects. Now, a study in mice suggests that psychedelics all work in the same way: they reset the brain to a youthful state in which it can easily absorb new information and form crucial connections between neurons1. The findings raise the prospect that psychedelic drugs could allow long-term changes in many types of behavioural, learning and sensory system that are disrupted in mental-health conditions. But scientists caution that more research needs to be done to establish how the drugs remodel brain connections. The study was published on 14 June in Nature. Psychedelics such as MDMA (also known as ecstasy), ketamine and psilocybin — the active ingredient in magic mushrooms — are known for producing mind-altering effects, including hallucinations in some cases. But each compound affects a different biochemical pathway in the brain during the short-term ‘trip’, leaving scientists to wonder why so many of these drugs share the ability to relieve depression2, addiction and other difficult-to-treat conditions in the long term. Gül Dölen, a neuroscientist at Johns Hopkins University in Baltimore, Maryland, and her colleagues sought answers by studying how psychedelics affect social behaviour in mice. Mice can learn to associate socializing with positive feelings, but only during an adolescent ‘critical period’, which closes as they become adults. The scientists trained mice to associate one ‘bedroom’ in their enclosure with mousy friends and another room with solitude. They could then examine how psychedelics affected the rodents’ room choices — a proxy for whether the drug affects the critical period. © 2023 Springer Nature Limited

Keyword: Depression; Drug Abuse
Link ID: 28825 - Posted: 06.17.2023

By Daniel Bergner If severe mental illness, untreated, underlies the feeling of encroaching anarchy and menace around the homeless encampments of San Francisco or in the subways of New York City, then the remedy appears obvious. Let’s rescue those who, as New York’s mayor, Eric Adams, says, “slip through the cracks” of our mental health care systems; let’s give people “the treatment and care they need.” It sounds so straightforward. It sounds like a clear way to lower the odds of tragic incidents occurring, like the chokehold killing of Jordan Neely, a homeless, psychiatrically troubled man, or the death of Michelle Alyssa Go, who was pushed off a Times Square subway platform to her death by a homeless man with schizophrenia. Improving order and safety in public spaces and offering compassionate care seem to be convergent missions. But unless we confront some rarely spoken truths, that convergence will prove illusory. The problems with the common-sense approach, as it’s currently envisioned, run beyond the proposed solutions we usually read about: funding more beds on hospital psychiatric wards, establishing community-based programs to oversee treatment when people are released from the hospital and providing housing for those whose mental health is made increasingly fragile by the constant struggle for shelter. The most difficult problems aren’t budgetary or logistical. They are fundamental. They involve the involuntary nature of the care being called for and the flawed antipsychotic medications that are the mainstay of treatment for people dealing with the symptoms of psychosis, like hallucinatory voices or paranoid delusions, which can come with a range of severe psychiatric conditions. © 2023 The New York Times Company

Keyword: Schizophrenia
Link ID: 28810 - Posted: 06.03.2023

By Christina Caron A new study suggests that, for some patients, the anesthetic ketamine is a promising alternative to electroconvulsive therapy, or ECT, currently one of the quickest and most effective therapies for patients with difficult-to-treat depression. The study is the largest head-to-head comparison of the two treatments. Patients who don’t respond to at least two antidepressants — about one-third of clinically depressed patients — have a condition that clinicians refer to as “treatment-resistant.” Their options for relief are limited. Doctors typically recommend up to 12 sessions of ECT, which has a long-established efficacy, but is tainted by the stigma of historical misuse and frightening Hollywood images of people strapped to tables, writhing in agony. Today’s ECT is much safer and done under general anesthesia, but the procedure remains underutilized. The study, published on Wednesday in The New England Journal of Medicine, found that ketamine, when administered intravenously, was at least as effective as ECT in patients with treatment-resistant depression who do not have psychosis. (For people with psychosis, ketamine, even in very low doses, can worsen psychosis-like symptoms.) “The results were very surprising to us,” said Dr. Amit Anand, lead author of the study and a professor of psychiatry at Harvard Medical School who studies mood disorders at Mass General Brigham. His team had initially hypothesized that ketamine would be nearly as effective as ECT. Instead, Dr. Anand said, they found that ketamine performed even better than that. This is significant in part because some patients are uncomfortable with ECT’s potential side effects, such as temporary memory loss, muscle pain or weakness. (In rare cases it can result in permanent gaps in memory.) © 2023 The New York Times Company

Keyword: Depression; Drug Abuse
Link ID: 28806 - Posted: 05.31.2023

By Casey Schwartz Kay Redfield Jamison arrives punctually at a towering marble statue of Jesus Christ in the entrance of the old hospital building on Johns Hopkins Medical Campus. Next to it, two guest books are left open to receive the wishes and prayers of those who pass through these halls. “Dear God please help our daughter feel better. …” “Dear Lord, please heal my grandpa and let him live happily. …” This building, decorated with rows of oil paintings of Hopkins doctors and nurses through the ages, is redolent of the history of healing. The desperate, uncertain, even heroic attempt to heal is at the center of Jamison’s new book, “Fires in the Dark: Healing the Unquiet Mind,” out on May 23 from Knopf. “If I could have subtitled it ‘A Love Song to Psychotherapy,’ I would have,” she said. Jamison, 76, her blond hair cut into a bob, wears a colorful floral dress as she makes her way through hallways filled with people in scrubs to a quiet corridor reserved for psychiatry. She is the co-director of the Center for Mood Disorders and a professor of psychiatry. Her bookcase displays her many publications: her psychobiography of the poet Robert Lowell, which was nominated for the Pulitzer Prize, and her books on suicide, on exuberance and on the connection between mania and artistic genius. And, of course, her best-known work, “An Unquiet Mind,” a memoir she published in 1995 in which she went public with her own manic depression, at considerable personal cost. Jamison had been a thriving, sporty high school senior in the Pacific Palisades neighborhood of Los Angeles until suddenly, falling into a deep depression after a mild mania, “I couldn’t count on my mind being on my side,” she said. She was bewildered by what she was going through. Her high school English teacher handed her a book of poems by Robert Lowell, who had struggled all his life with manic-depression, and with whom she felt an instant connection. That same teacher also gave her “Sherston’s Progress,” by the English poet Siegfried Sassoon. More than fifty years later, Sassoon’s book would become one of the central inspirations of “Fires in the Dark.” © 2023 The New York Times Company

Keyword: Schizophrenia; Depression
Link ID: 28792 - Posted: 05.23.2023

By Claudia Lopez Lloreda Ketamine is a powerful anesthetic and sometimes recreational drug that causes people to feel dissociated from their own bodies. Recent studies suggest the drug may help treat people with depression who have tried more conventional treatments without success. But there are major questions about what makes it work. Is it the weird dissociative experience? Some molecular effect on the brain? Or just the experience of being in a clinical trial? In a new study that is yet to be peer reviewed, researchers attempted to find the answer in a unique way: They gave volunteers ketamine while they were under general anesthesia, theoretically preventing the participants from going on a trip. The approach alleviated the subjects’ depression, but not any better than a placebo did. The authors interpret this as evidence that ketamine’s effects on depression are strongly tied to a patient’s experience of being seen by medical professionals. But other experts say the study’s implications may be more complicated. Ketamine causes “dissociative” effects such as out-of-body experiences. Patients sometimes also report visual and auditory hallucinations—the voices of friends and family members who aren’t there, for example. The dissociative effects of ketamine have been linked to a stronger antidepressant response, possibly by helping patients reframe their experience from an outside perspective. But it’s a problem for researchers running double-blinded clinical trials, as participants can usually tell whether they have received ketamine or a placebo. To disentangle the subjective experience of ketamine from the biochemical effects of the drug, researchers at Stanford University recruited 40 participants who were preparing to undergo general surgery and who also had mild to moderate depression. The scientists gave the volunteers ketamine or saline as placebo right after they were put under anesthesia, but before their surgery, essentially blinding them to any psychedelic or dissociative effects. Then, for the next 3 days, the researchers surveyed the participants on their depression symptoms, scoring them on such factors as sadness, loss of appetite, and lack of sleep.

Keyword: Depression; Drug Abuse
Link ID: 28789 - Posted: 05.21.2023