Brain Disorder: Bipolar Disorder

Symposium highlights scale of mental health crisis and novel methods of diagnosis and treatment

by Lauren Rebecca Thacker | MIT Open Learning |

Digital technologies, such as smartphones and machine learning, have revolutionized education. At the McGovern Institute for Brain Research’s 2024 Spring Symposium, “Transformational Strategies in Mental Health,” experts from across the sciences — including psychiatry, psychology, neuroscience, computer science, and others — agreed that these technologies could also play a significant role in advancing the diagnosis and treatment of mental health disorders and neurological conditions.

Co-hosted by the McGovern Institute, MIT Open Learning, McClean Hospital, the Poitras Center for Psychiatric Disorders Research at MIT, and the Wellcome Trust, the symposium raised the alarm about the rise in mental health challenges and showcased the potential for novel diagnostic and treatment methods.

“We have to do something together as a community of scientists and partners of all kinds to make a difference.” – John Gabrieli

John Gabrieli, the Grover Hermann Professor of Health Sciences and Technology at MIT, kicked off the symposium with a call for an effort on par with the Manhattan Project, which in the 1940s saw leading scientists collaborate to do what seemed impossible. While the challenge of mental health is quite different, Gabrieli stressed, the complexity and urgency of the issue are similar. In his later talk, “How can science serve psychiatry to enhance mental health?,” he noted a 35 percent rise in teen suicide deaths between 1999 and 2000 and, between 2007 and 2015, a 100 percent increase in emergency room visits for youths ages 5 to 18 who experienced a suicide attempt or suicidal ideation.

“We have no moral ambiguity, but all of us speaking today are having this meeting in part because we feel this urgency,” said Gabrieli, who is also a professor of brain and cognitive sciences, the director of the Integrated Learning Initiative (MITili) at MIT Open Learning, and a member of the McGovern Institute. “We have to do something together as a community of scientists and partners of all kinds to make a difference.”

An urgent problem

In 2021, U.S. Surgeon General Vivek Murthy issued an advisory on the increase in mental health challenges in youth; in 2023, he issued another, warning of the effects of social media on youth mental health. At the symposium, Susan Whitfield-Gabrieli, a research affiliate at the McGovern Institute and a professor of psychology and director of the Biomedical Imaging Center at Northeastern University, cited these recent advisories, saying they underscore the need to “innovate new methods of intervention.”

Other symposium speakers also highlighted evidence of growing mental health challenges for youth and adolescents. Christian Webb, associate professor of psychology at Harvard Medical School, stated that by the end of adolescence, 15-20 percent of teens will have experienced at least one episode of clinical depression, with girls facing the highest risk. Most teens who experience depression receive no treatment, he added.

Adults who experience mental health challenges need new interventions, too. John Krystal, the Robert L. McNeil Jr. Professor of Translational Research and chair of the Department of Psychiatry at Yale University School of Medicine, pointed to the limited efficacy of antidepressants, which typically take about two months to have an effect on the patient. Patients with treatment-resistant depression face a 75 percent likelihood of relapse within a year of starting antidepressants. Treatments for other mental health disorders, including bipolar and psychotic disorders, have serious side effects that can deter patients from adherence, said Virginie-Anne Chouinard, director of research at McLean OnTrackTM, a program for first episode psychosis at McLean Hospital.

New treatments, new technologies

Emerging technologies, including smartphone technology and artificial intelligence, are key to the interventions that symposium speakers shared.

In a talk on AI and the brain, Dina Katabi, the Thuan and Nicole Pham Professor of Electrical Engineering and Computer Science at MIT, discussed novel ways to detect Parkinson’s and Alzheimer’s, among other diseases. Early-stage research involved developing devices that can analyze how movement within a space impacts the surrounding electromagnetic field, as well as how wireless signals can detect breathing and sleep stages.

“I realize this may sound like la-la land,” Katabi said. “But it’s not! This device is used today by real patients, enabled by a revolution in neural networks and AI.”

Parkinson’s disease often cannot be diagnosed until significant impairment has already occurred. In a set of studies, Katabi’s team collected data on nocturnal breathing and trained a custom neural network to detect occurrences of Parkinson’s. They found the network was over 90 percent accurate in its detection. Next, the team used AI to analyze two sets of breathing data collected from patients at a six-year interval. Could their custom neural network identify patients who did not have a Parkinson’s diagnosis on the first visit, but subsequently received one? The answer was largely yes: Machine learning identified 75 percent of patients who would go on to receive a diagnosis.

Detecting high-risk patients at an early stage could make a substantial difference for intervention and treatment. Similarly, research by Jordan Smoller, professor of psychiatry at Harvard Medical School and director of the Center for Precision Psychiatry at Massachusetts General Hospital, demonstrated that AI-aided suicide risk prediction model could detect 45 percent of suicide attempts or deaths with 90 percent specificity, about two to three years in advance.

Other presentations, including a series of lightning talks, shared new and emerging treatments, such as the use of ketamine to treat depression; the use of smartphones, including daily text surveys and mindfulness apps, in treating depression in adolescents; metabolic interventions for psychotic disorders; the use of machine learning to detect impairment from THC intoxication; and family-focused treatment, rather than individual therapy, for youth depression.

Advancing understanding

The frequency and severity of adverse mental health events for children, adolescents, and adults demonstrate the necessity of funding for mental health research — and the open sharing of these findings.

Niall Boyce, head of mental health field building at the Wellcome Trust — a global charitable foundation dedicated to using science to solve urgent health challenges — outlined the foundation’s funding philosophy of supporting research that is “collaborative, coherent, and focused” and centers on “What is most important to those most affected?” Wellcome research managers Anum Farid and Tayla McCloud stressed the importance of projects that involve people with lived experience of mental health challenges and “blue sky thinking” that takes risks and can advance understanding in innovative ways. Wellcome requires that all published research resulting from its funding be open and accessible in order to maximize their benefits.

Whether through therapeutic models, pharmaceutical treatments, or machine learning, symposium speakers agreed that transformative approaches to mental health call for collaboration and innovation.

“Understanding mental health requires us to understand the unbelievable diversity of humans,” Gabrieli said. “We have to use all the tools we have now to develop new treatments that will work for people for whom our conventional treatments don’t.”

Unpacking auditory hallucinations

by Thea Singer |

Tamar Regev, the 2022–2024 Poitras Center Postdoctoral Fellow, has identified a new neural system that may shed light on the auditory hallucinations experienced by patients diagnosed with schizophrenia.

Scientist portrait
Tamar Regev is the 2022–2024 Poitras Center Postdoctoral
Fellow in Ev Fedorenko’s lab at the McGovern Institute. Photo: Steph Stevens

“The system appears integral to prosody processing,”says Regev. “‘Prosody’ can be described as the melody of speech — auditory gestures that we use when we’re speaking to signal linguistic, emotional, and social information.” The prosody processing system Regev has uncovered is distinct from the lower-level auditory speech processing system as well as the higher-level language processing system. Regev aims to understand how the prosody system, along with the speech and language processing systems, may be impaired in neuropsychiatric disorders such as schizophrenia, especially when experienced with auditory hallucinations in the form of speech.

“Knowing which neural systems are affected by schizophrenia can lay the groundwork for future research into interventions that target the mechanisms underlying symptoms such as hallucinations,” says Regev. Passionate about bridging gaps between disciplines, she is collaborating with Ann Shinn, MD, MPH, of McLean Hospital’s Schizophrenia and Bipolar Disorder Research Program.

Regev’s graduate work at the Hebrew University of Jerusalem focused on exploring the auditory system with electroencephalography (EEG), which measures electrical activity in the brain using small electrodes attached to the scalp. She came to MIT to study under Evelina Fedorenko, a world leader in researching the cognitive and neural mechanisms underlying language processing. With Fedorenko she has learned to use functional magnetic resonance imaging (fMRI), which reveals the brain’s functional anatomy by measuring small changes in blood flow that occur with brain activity.

“I hope my research will lead to a better understanding of the neural architectures that underlie these disorders—and eventually help us as a society to better understand and accept special populations.”- Tamar Regev

“EEG has very good temporal resolution but poor spatial resolution, while fMRI provides a map of the brain showing where neural signals are coming from,” says Regev. “With fMRI I can connect my work on the auditory system with that on the language system.”

Regev developed a unique fMRI paradigm to do that. While her human subjects are in the scanner, she is comparing brain responses to speech with expressive prosody versus flat prosody to find the role of the prosody system among the auditory, speech, and language regions. She plans to apply her findings to analyze a rich data set drawn from fMRI studies that Fedorenko and Shinn began a few years ago while investigating the neural basis of auditory hallucinations in patients with schizophrenia and bipolar disorder. Regev is exploring how the neural architecture may differ between control subjects and those with and without auditory hallucinations as well as those with schizophrenia and bipolar disorder.

“This is the first time these questions are being asked using the individual-subject approach developed in the Fedorenko lab,” says Regev. The approach provides superior sensitivity, functional resolution, interpretability, and versatility compared with the group analyses of the past. “I hope my research will lead to a better understanding of the neural architectures that underlie these disorders,” says Regev, “and eventually help us as a society to better understand and accept special populations.”

Machine learning can predict bipolar disorder in children and teens

by Jennifer Michalowski |

Bipolar disorder often begins in childhood or adolescence, triggering dramatic mood shifts and intense emotions that cause problems at home and school. But the condition is often overlooked or misdiagnosed until patients are older. New research suggests that machine learning, a type of artificial intelligence, could help by identifying children who are at risk of bipolar disorder so doctors are better prepared to recognize the condition if it develops.

On October 13, 2022, researchers led by McGovern Institute investigator John Gabrieli and collaborators at Massachusetts General Hospital reported in the Journal of Psychiatric Research that when presented with clinical data on nearly 500 children and teenagers, a machine learning model was able to identify about 75 percent of those who were later diagnosed with bipolar disorder. The approach performs better than any other method of predicting bipolar disorder, and could be used to develop a simple risk calculator for health care providers.

Gabrieli says such a tool would be particularly valuable because bipolar disorder is less common in children than conditions like major depression, with which it shares symptoms, and attention-deficit/ hyperactivity disorder (ADHD), with which it often co-occurs. “Humans are not well tuned to watch out for rare events,” he says. “If you have a decent measure, it’s so much easier for a machine to identify than humans. And in this particular case, [the machine learning prediction] was surprisingly robust.”

Detecting bipolar disorder

Mai Uchida, Director of Massachusetts General Hospital’s Child Depression Program, says that nearly two percent of youth worldwide are estimated to have bipolar disorder, but diagnosing pediatric bipolar disorder can be challenging. A certain amount of emotional turmoil is to be expected in children and teenagers, and even when moods become seriously disruptive, children with bipolar disorder are often initially diagnosed with major depression or ADHD. That’s a problem, because the medications used to treat those conditions often worsen the symptoms of bipolar disorder. Tailoring treatment to a diagnosis of bipolar disorder, in contrast, can lead to significant improvements for patients and their families. “When we can give them a little bit of ease and give them a little bit of control over themselves, it really goes a long way,” Uchida says.

In fact, a poor response to antidepressants or ADHD medications can help point a psychiatrist toward a diagnosis of bipolar disorder. So too can a child’s family history, in addition to their own behavior and psychiatric history. But, Uchida says, “it’s kind of up to the individual clinician to pick up on these things.”

Uchida and Gabrieli wondered whether machine learning, which can find patterns in large, complex datasets, could focus in on the most relevant features to identify individuals with bipolar disorder. To find out, they turned to data from a study that began in the 1990s. The study, headed by Joseph Biederman, Chief of the Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital, had collected extensive psychiatric assessments of hundreds of children with and without ADHD, then followed those individuals for ten years.

To explore whether machine learning could find predictors of bipolar disorder within that data, Gabrieli, Uchida, and colleagues focused on 492 children and teenagers without ADHD, who were recruited to the study as controls. Over the ten years of the study, 45 of those individuals developed bipolar disorder.

Within the data collected at the study’s outset, the machine learning model was able to find patterns that associated with a later diagnosis of bipolar disorder. A few behavioral measures turned out to be particularly relevant to the model’s predictions: children and teens with combined problems with attention, aggression, and anxiety were most likely to later be diagnosed with bipolar disorder. These indicators were all picked up by a standard assessment tool called the Child Behavior Checklist.

Uchida and Gabrieli say the machine learning model could be integrated into the medical record system to help pediatricians and child psychiatrists catch early warning signs of bipolar disorder. “The information that’s collected could alert a clinician to the possibility of a bipolar disorder developing,” Uchida says. “Then at least they’re aware of the risk, and they may be able to maybe pick up on some of the deterioration when it’s happening and think about either referring them or treating it themselves.”

Individual neurons responsible for complex social reasoning in humans identified

by MGH News and Public Affairs |

This story is adapted from a January 27, 2021 press release from Massachusetts General Hospital.

The ability to understand others’ hidden thoughts and beliefs is an essential component of human social behavior. Now, neuroscientists have for the first time identified specific neurons critical for social reasoning, a cognitive process that requires individuals to acknowledge and predict others’ hidden beliefs and thoughts.

The findings, published in Nature, open new avenues of study into disorders that affect social behavior, according to the authors.

In the study, a team of Harvard Medical School investigators based at Massachusetts General Hospital and colleagues from MIT took a rare look at how individual neurons represent the beliefs of others. They did so by recording neuron activity in patients undergoing neurosurgery to alleviate symptoms of motor disorders such as Parkinson’s disease.

Theory of mind

The researcher team, which included McGovern scientists Ev Fedorenko and Rebecca Saxe, focused on a complex social cognitive process called “theory of mind.” To illustrate this, let’s say a friend appears to be sad on her birthday. One may infer she is sad because she didn’t get a present or she is upset at growing older.

“When we interact, we must be able to form predictions about another person’s unstated intentions and thoughts,” said senior author Ziv Williams, HMS associate professor of neurosurgery at Mass General. “This ability requires us to paint a mental picture of someone’s beliefs, which involves acknowledging that those beliefs may be different from our own and assessing whether they are true or false.”

This social reasoning process develops during early childhood and is fundamental to successful social behavior. Individuals with autism, schizophrenia, bipolar affective disorder, and traumatic brain injuries are believed to have a deficit of theory-of-mind ability.

For the study, 15 patients agreed to perform brief behavioral tasks before undergoing neurosurgery for placement of deep-brain stimulation for motor disorders. Microelectrodes inserted into the dorsomedial prefrontal cortex recorded the behavior of individual neurons as patients listened to short narratives and answered questions about them.

For example, participants were presented with the following scenario to evaluate how they considered another’s belief of reality: “You and Tom see a jar on the table. After Tom leaves, you move the jar to a cabinet. Where does Tom believe the jar to be?”

Social computation

The participants had to make inferences about another’s beliefs after hearing each story. The experiment did not change the planned surgical approach or alter clinical care.

“Our study provides evidence to support theory of mind by individual neurons,” said study first author Mohsen Jamali, HMS instructor in neurosurgery at Mass General. “Until now, it wasn’t clear whether or how neurons were able to perform these social cognitive computations.”

The investigators found that some neurons are specialized and respond only when assessing another’s belief as false, for example. Other neurons encode information to distinguish one person’s beliefs from another’s. Still other neurons create a representation of a specific item, such as a cup or food item, mentioned in the story. Some neurons may multitask and aren’t dedicated solely to social reasoning.

“Each neuron is encoding different bits of information,” Jamali said. “By combining the computations of all the neurons, you get a very detailed representation of the contents of another’s beliefs and an accurate prediction of whether they are true or false.”

Now that scientists understand the basic cellular mechanism that underlies human theory of mind, they have an operational framework to begin investigating disorders in which social behavior is affected, according to Williams.

“Understanding social reasoning is also important to many different fields, such as child development, economics, and sociology, and could help in the development of more effective treatments for conditions such as autism spectrum disorder,” Williams said.

Previous research on the cognitive processes that underlie theory of mind has involved functional MRI studies, where scientists watch which parts of the brain are active as volunteers perform cognitive tasks.

But the imaging studies capture the activity of many thousands of neurons all at once. In contrast, Williams and colleagues recorded the computations of individual neurons. This provided a detailed picture of how neurons encode social information.

“Individual neurons, even within a small area of the brain, are doing very different things, not all of which are involved in social reasoning,” Williams said. “Without delving into the computations of single cells, it’s very hard to build an understanding of the complex cognitive processes underlying human social behavior and how they go awry in mental disorders.”

Adapted from a Mass General news release.

A new way to deliver drugs with pinpoint targeting

by David L. Chandler |

Most pharmaceuticals must either be ingested or injected into the body to do their work. Either way, it takes some time for them to reach their intended targets, and they also tend to spread out to other areas of the body. Now, researchers at the McGovern Institute at MIT and elsewhere have developed a system to deliver medical treatments that can be released at precise times, minimally-invasively, and that ultimately could also deliver those drugs to specifically targeted areas such as a specific group of neurons in the brain.

The new approach is based on the use of tiny magnetic particles enclosed within a tiny hollow bubble of lipids (fatty molecules) filled with water, known as a liposome. The drug of choice is encapsulated within these bubbles, and can be released by applying a magnetic field to heat up the particles, allowing the drug to escape from the liposome and into the surrounding tissue.

The findings are reported today in the journal Nature Nanotechnology in a paper by MIT postdoc Siyuan Rao, Associate Professor Polina Anikeeva, and 14 others at MIT, Stanford University, Harvard University, and the Swiss Federal Institute of Technology in Zurich.

“We wanted a system that could deliver a drug with temporal precision, and could eventually target a particular location,” Anikeeva explains. “And if we don’t want it to be invasive, we need to find a non-invasive way to trigger the release.”

Magnetic fields, which can easily penetrate through the body — as demonstrated by detailed internal images produced by magnetic resonance imaging, or MRI — were a natural choice. The hard part was finding materials that could be triggered to heat up by using a very weak magnetic field (about one-hundredth the strength of that used for MRI), in order to prevent damage to the drug or surrounding tissues, Rao says.

Rao came up with the idea of taking magnetic nanoparticles, which had already been shown to be capable of being heated by placing them in a magnetic field, and packing them into these spheres called liposomes. These are like little bubbles of lipids, which naturally form a spherical double layer surrounding a water droplet.

Electron microscope image shows the actual liposome, the white blob at center, with its magnetic particles showing up in black at its center.
Image courtesy of the researchers

When placed inside a high-frequency but low-strength magnetic field, the nanoparticles heat up, warming the lipids and making them undergo a transition from solid to liquid, which makes the layer more porous — just enough to let some of the drug molecules escape into the surrounding areas. When the magnetic field is switched off, the lipids re-solidify, preventing further releases. Over time, this process can be repeated, thus releasing doses of the enclosed drug at precisely controlled intervals.

The drug carriers were engineered to be stable inside the body at the normal body temperature of 37 degrees Celsius, but able to release their payload of drugs at a temperature of 42 degrees. “So we have a magnetic switch for drug delivery,” and that amount of heat is small enough “so that you don’t cause thermal damage to tissues,” says Anikeeva, who also holds appointments in the departments of Materials Science and Engineering and the Brain and Cognitive Sciences.

In principle, this technique could also be used to guide the particles to specific, pinpoint locations in the body, using gradients of magnetic fields to push them along, but that aspect of the work is an ongoing project. For now, the researchers have been injecting the particles directly into the target locations, and using the magnetic fields to control the timing of drug releases. “The technology will allow us to address the spatial aspect,” Anikeeva says, but that has not yet been demonstrated.

This could enable very precise treatments for a wide variety of conditions, she says. “Many brain disorders are characterized by erroneous activity of certain cells. When neurons are too active or not active enough, that manifests as a disorder, such as Parkinson’s, or depression, or epilepsy.” If a medical team wanted to deliver a drug to a specific patch of neurons and at a particular time, such as when an onset of symptoms is detected, without subjecting the rest of the brain to that drug, this system “could give us a very precise way to treat those conditions,” she says.

Rao says that making these nanoparticle-activated liposomes is actually quite a simple process. “We can prepare the liposomes with the particles within minutes in the lab,” she says, and the process should be “very easy to scale up” for manufacturing. And the system is broadly applicable for drug delivery: “we can encapsulate any water-soluble drug,” and with some adaptations, other drugs as well, she says.

One key to developing this system was perfecting and calibrating a way of making liposomes of a highly uniform size and composition. This involves mixing a water base with the fatty acid lipid molecules and magnetic nanoparticles and homogenizing them under precisely controlled conditions. Anikeeva compares it to shaking a bottle of salad dressing to get the oil and vinegar mixed, but controlling the timing, direction and strength of the shaking to ensure a precise mixing.

Anikeeva says that while her team has focused on neurological disorders, as that is their specialty, the drug delivery system is actually quite general and could be applied to almost any part of the body, for example to deliver cancer drugs, or even to deliver painkillers directly to an affected area instead of delivering them systemically and affecting the whole body. “This could deliver it to where it’s needed, and not deliver it continuously,” but only as needed.

Because the magnetic particles themselves are similar to those already in widespread use as contrast agents for MRI scans, the regulatory approval process for their use may be simplified, as their biological compatibility has largely been proven.

The team included researchers in MIT’s departments of Materials Science and Engineering and Brain and Cognitive Sciences, as well as the McGovern Institute for Brain Research, the Simons Center for Social Brain, and the Research Laboratory of Electronics; the Harvard University Department of Chemistry and Chemical Biology and the John A. Paulsen School of Engineering and Applied Sciences; Stanford University; and the Swiss Federal Institute of Technology in Zurich. The work was supported by the Simons Postdoctoral Fellowship, the U.S. Defense Advanced Research Projects Agency, the Bose Research Grant, and the National Institutes of Health.

Feng Zhang

Engineering Physiology

The primary focus of Feng Zhang’s work is to improve human health by discovering ways to modify cellular function and activity –  including the restoration of diseased, stressed, or aged cells to a more healthful state. His team is developing new molecular technologies to modify the cell’s genetic information, vehicles to deliver these tools into the correct cells, and larger-scale engineering to restore organ function. Zhang hopes to apply these approaches to neurodegenerative diseases, immune disorders, aging, and other disease states.

Ann Graybiel

Probing the Deep Brain

Ann Graybiel studies the basal ganglia, forebrain structures that are profoundly important for normal brain function. Dysfunction in these regions is implicated in neurologic and neuropsychiatric disorders ranging from Parkinson’s disease and Huntington’s disease to obsessive-compulsive disorder, anxiety and depression, and addiction. Graybiel’s laboratory is uncovering circuits underlying both the neural deficits related to these disorders, as well as the role that the basal ganglia play in guiding normal learning, motivation, and behavior.

John Gabrieli

Images of Mind

John Gabrieli’s goal is to understand the organization of memory, thought, and emotion in the human brain, and to use that understanding to help people live happier, more productive lives. By combining brain imaging with behavioral tests, he studies the neural basis of these abilities in human subjects. One important research theme is to understand the neural basis of learning in children and to identify ways that neuroscience could help to improve learning in the classroom. In collaboration with clinical colleagues, Gabrieli also seeks to use brain imaging to better understand, diagnose, and select treatments for neurological and psychiatric diseases.

What is CRISPR?

by The Brain |

CRISPR (which stands for Clustered Regularly Interspaced Short Palindromic Repeats) is not actually a single entity, but shorthand for a set of bacterial systems that are found with a hallmarked arrangement in the bacterial genome.

When CRISPR is mentioned, most people are likely thinking of CRISPR-Cas9, now widely known for its capacity to be re-deployed to target sequences of interest in eukaryotic cells, including human cells. Cas9 can be programmed to target specific stretches of DNA, but other enzymes have since been discovered that are able to edit DNA, including Cpf1 and Cas12b. Other CRISPR enzymes, Cas13 family members, can be programmed to target RNA and even edit and change its sequence.

The common theme that makes CRISPR enzymes so powerful, is that scientists can supply them with a guide RNA for a chosen sequence. Since the guide RNA can pair very specifically with DNA, or for Cas13 family members, RNA, researchers can basically provide a given CRISPR enzyme with a way of homing in on any sequence of interest. Once a CRISPR protein finds its target, it can be used to edit that sequence, perhaps removing a disease-associated mutation.

In addition, CRISPR proteins have been engineered to modulate gene expression and even signal the presence of particular sequences, as in the case of the Cas13-based diagnostic, SHERLOCK.

Do you have a question for The Brain? Ask it here.

Satrajit Ghosh

Personalized Medicine

A fundamental problem in psychiatry is that there are no biological markers for diagnosing mental illness or for indicating how best to treat it. Treatment decisions are based entirely on symptoms, and doctors and their patients will typically try one treatment, then if it does not work, try another, and perhaps another. Satrajit Ghosh hopes to change this picture, and his research suggests that individual brain scans and speaking patterns can hold valuable information for guiding psychiatrists and patients. His research group develops novel analytic platforms that use such information to create robust, predictive models around human health. Current areas include depression, suicide, anxiety disorders, autism, Parkinson’s disease, and brain tumors.