What Is: Schizophrenia

 

Image Credit: Scientific Frontline

Beyond the Misconceptions

Schizophrenia is one of the most misunderstood mental health conditions. It is not, as commonly portrayed, a "split personality" (that is a separate, rare condition called dissociative identity disorder). Rather, schizophrenia is a chronic and severe mental disorder that affects how a person thinks, feels, and behaves. At its core, it is a disorder of cognition and reality testing, characterized by a "fracturing" of the mind's essential functions, leading to a disconnect from reality for the individual experiencing it.

Globally, schizophrenia affects approximately 24 million people, or 1 in 300 worldwide. It is a universal human illness that does not discriminate based on race, culture, or socioeconomic status.

Early changes during brain development may hold the key to autism and schizophrenia

Photo Credit: Michal Jarmoluk

Researchers at the University of Exeter have created a detailed temporal map of chemical changes to DNA through development and aging of the human brain, offering new insights into how conditions such as autism and schizophrenia may arise.

The team studied epigenetic changes – chemical tags on our DNA that control how genes are switched on or off. These changes are crucial in regulating the expression of genes, guiding brain cells to develop and specialize correctly.

One important mechanism, called DNA methylation, was examined in nearly 1,000 donated human brains, spanning life from just six weeks after conception through to 108 years of age. The researchers focused on the cortex, a region of the brain involved in high-level functions such as thought, memory, perception, and behavior. Correct development of the cortex during early life is important to support healthy brain function after birth.

How Does the Brain Differentiate New Stimuli from Old Ones?

The illustration represents how sounds are encoded in the cerebral cortex, with neurons (at right) using "echoing" activity to track auditory stimuli to change and improve its predictions of the future.
Illustration Credit: Yuriy Shymkiv

The cerebral cortex is the largest part of a mammal’s brain, and by some measures the most important. In humans in particular, it’s where most things happen—like perception, thinking, memory storage, and decision-making. One current hypothesis suggests that the cortex’s primary role is to predict what’s going to happen in the future by identifying and encoding new information it receives from the outside world and comparing it with what was expected to occur.

A new study published today in the journal Neuron takes a big step toward proving that hypothesis. The paper’s lead author is Yuriy Shymkiv, a postdoctoral fellow in the lab of Professor Rafael Yuste.

“We found that the cortex acts like a memory machine, encoding new experiences, and predicting the very near future,” Shymkiv said.

Researchers detect that people with schizophrenia have an altered ability to visually perceive contrast

UB researchers Cristina de la Malla and Daniel Linares.
Photo Credit: Courtesy of University of Barcelona

According to a review of more than 600 studies, these patients would have difficulty in detecting differences in light intensity between adjacent areas, without which they cannot adequately see their surroundings and objects.

The article, published in the journal Schizophrenia Bulletin, is signed by researchers Daniel Linares and Cristina de la Malla, together with master’s student Aster Joostens, from the Vision and Control of Action Group of the Faculty of Psychology and the UB Institute of Neurosciences (UBneuro).

A key indicator of visual function

The symptoms of schizophrenia are characterized by alterations in thinking and behavior, such as loss of contact with reality, delusions or hallucinations, but there are also abnormalities in the perception of visual stimuli, such as deficits in the perception of color or contrast. Understanding these abnormalities may provide clues as to how information processing disturbances contribute to the characteristic symptoms of schizophrenia. “Contrast perception is one of the most fundamental abilities of vision, as without it, we cannot adequately perceive the environment and the objects in it, which can compromise everyday tasks such as moving through space, recognizing faces or reading”, explains the research team, part of the Department of Cognition, ​​​​​​​Development and Educational Psychology.

Eight Psychiatric Disorders Share the Same Genetic Causes

Image Credit: Won Lab

Building off previous groundbreaking research, a new study identifies specific genetic variants that have significant impacts on brain development and are shared across eight different psychiatric disorders. Targeting these variants could pave the way for treatments that address multiple conditions at once.

Psychiatric disorders often overlap and can make diagnosis difficult. Depression and anxiety, for example, can coexist and share symptoms. Schizophrenia and anorexia nervosa. Autism and attention deficit/hyperactivity disorder, too. But, why?

Life experiences, environment, and genetics can all influence psychiatric disorders, but much of it comes down to variations in our genetics. Over the past few years, scientists in the field of psychiatric genetics have found that there are common genetic threads that may be linking and causing coexisting psychiatric disorders.

In 2019, researchers at the Psychiatric Genomics Consortium, Harvard University, and the UNC School of Medicine identified 136 “hot spots” within the genome that are associated with eight psychiatric disorders. Among them, 109 hot spots were shared among multiple disorders, or “pleiotropic”. However, it was not clear at the time how genetic variations within these hot spots differed from those that only have roles in only one disorder.

Pilot study shows ketogenic diet improves severe mental illness

A study led by researchers at Stanford Medicine showed that diet can help those with serious mental illness.

Video Credit: Stanford Medicine

For people living with serious mental illness like schizophrenia or bipolar disorder, standard treatment with antipsychotic medications can be a double-edged sword. While these drugs help regulate brain chemistry, they often cause metabolic side effects such as insulin resistance and obesity, which are distressing enough that many patients stop taking the medications.

Now, a pilot study led by Stanford Medicine researchers has found that a ketogenic diet not only restores metabolic health in these patients as they continue their medications, but it further improves their psychiatric conditions. The results published in Psychiatry Research, suggest that a dietary intervention can be a powerful aid in treating mental illness.

“It’s very promising and very encouraging that you can take back control of your illness in some way, aside from the usual standard of care,” said Shebani Sethi, MD, associate professor of psychiatry and behavioral sciences and the first author of the new paper.

Risk factors for faster aging in the brain revealed in new study

Governments have been urged to act decisively before 2035 to ensure global warming can be kept below 2°C by 2100.
Photo Credit: Nöel Puebla

Researchers from the Nuffield Department of Clinical Neurosciences at the University of Oxford have used data from UK Biobank participants to reveal that diabetes, traffic-related air pollution and alcohol intake are the most harmful out of 15 modifiable risk factors for dementia.

The researchers had previously identified a ‘weak spot’ in the brain, which is a specific network of higher-order regions that not only develop later during adolescence, but also show earlier degeneration in old age. They showed that this brain network is also particularly vulnerable to schizophrenia and Alzheimer’s disease.

In this new study, published in Nature Communications, they investigated the genetic and modifiable influences on these fragile brain regions by looking at the brain scans of 40,000 UK Biobank participants aged over 45.

The researchers examined 161 risk factors for dementia, and ranked their impact on this vulnerable brain network, over and above the natural effects of age. They classified these so-called ‘modifiable’ risk factors − as they can potentially be changed throughout life to reduce the risk of dementia − into 15 broad categories: blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking, depressive mood, inflammation, pollution, hearing, sleep, socialization, diet, physical activity, and education.

How bats distinguish different sounds

Seba's short-tailed bat (Carollia perspicillata) filters out important signals from ambient sound and distinguishes between echolocation and communication calls.
Photo Credit: Julio Hechavarría, Goethe University Frankfurt

Bats live in a world of sounds. They use vocalizations both to communicate with their conspecifics and for navigation. For the latter, they emit sounds in the ultrasonic range, which echo and enable them to create an “image" of their surroundings. Neuroscientists at Goethe University Frankfurt have now discovered how Seba's short-tailed bat, a species native to South America, manages to filter out important signals from ambient sound and especially to distinguish between echolocation and communication calls. 

Seba's short-tailed bat (Carollia perspicillata) lives in the subtropical and tropical forests of Central and South America, where it mostly feeds on pepper fruit. The animals spend their days in groups of 10 to 100 individuals in hollow trunks and rocky caverns, and at night they go foraging together. They communicate using sounds that create distinct ambient noise in the colony – like the babble of voices at a lively party. At the same time, the bats also use vocalizations to navigate their surroundings: a phenomenon known as echolocation, for which they emit ultrasonic sounds that reflect off solid surfaces. The animals then assemble these echoes into an “image" of their surroundings. 

An unexpected link between 2 schizophrenia risk proteins

The study findings suggest that when the proteins don’t bind properly, signaling among neurons, illustrated above, becomes imbalanced, which can lead to related negative behavioral symptoms.
 Image Credit: T. Ahmed, A. Buonanno, National institute of Child Health and Human Development

The discovery of a physical interaction between two proteins in brain cells that can be traced in mice to control of movement, anxiety and memory could one day open the door to development of new schizophrenia treatment strategies.

The research group is the first to determine that the two proteins, both among the dozens of proteins related to risk for the development of schizophrenia, bind to each other under normal conditions in multiple regions of the brain, and that their connection was found in mice to be key to maintaining normal movement, memory function and anxiety regulation.

When that connection doesn’t happen as it should, they found, behavior can be negatively affected – in mice, disruption to the proteins’ ability to interact increased hyperactivity, reduced risk avoidance and impaired memory. Though delusions and hallucinations are hallmark symptoms of schizophrenia, the condition also encompasses additional symptoms, including movement and memory problems. 

“These two proteins are seemingly unrelated, and our study has provided a link between them that wasn’t recognized before,” said lead author Chen Gu, associate professor of biological chemistry and pharmacology in The Ohio State University College of Medicine.  

People with severe mental illness at 50 per cent higher risk of death following COVID-19 infection

Photo Credit: Darina Belonogova

New research from King’s College London has found that people in the UK with severe mental illness were at increased risk of death from all causes following COVID-19 infection compared to those without severe mental illness.

Published in the British Journal of Psychiatry, the study investigated the extent to which having severe mental illness, which includes schizophrenia and psychosis, increased the risk of death during the first two waves of the COVID-19 pandemic.

Researchers at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) and ESRC Centre for Society and Mental Health analyzed data from over 660,000 UK patients between February 2020 and April 2021.

Among the 7146 people with severe mental illness, there was a 50 per cent greater risk of death from all causes following COVID-19 infection compared with those without severe mental illness.

Black Caribbean/Black African people were at 22 per cent higher risk of death following COVID-19 infection than White people, and this was similar for people with and without severe mental illness. However, in around 30 per cent of patient data, ethnicity was not recorded.

How Huntington’s Disease Begins Before Symptoms Appear

A microglia cell (shown in green) and corticostriatal synapses (purple) from a patient with Huntington’s disease.
Image Credit: Dan Wilton

A new study led by researchers at Boston Children’s Hospital and Harvard Medical School reveals how the process of Huntington’s disease begins well before symptoms appear — and shows that in mice, the process can be blocked to prevent cognitive problems related to Huntington’s.

If the findings hold true in humans, they raise the possibility of intervening early in the disease in people who carry the Huntington’s gene mutation.

The work, published in Nature Medicine, also could shed light on other neurodegenerative disorders.

The team found in patient tissue samples and mouse models that two players in the immune system — complement proteins and microglia — are activated very early in Huntington’s, leading to loss of synapses in the brain before cognitive and motor symptoms emerge. The researchers revealed how and where the synapses are lost.

The findings corroborate a potential treatment that’s currently in clinical trials for the disease.

The study was led by senior author Beth Stevens, HMS associate professor of neurology at Boston Children’s, and first author Dan Wilton, HMS research fellow in neurology in the Stevens lab.

Marker for brain inflammation finally decoded

TSPO protein (in green) was quantified in microglia (in red) in proximity to lesion characteristic of Alzheimer’s disease, the amyloid plaques (in blue) and pTau lesions (in white), in post mortem human brain samples.
Image Credit: Stergios Tsartsalis

An international team co-led by UNIGE and HUG has decoded the only protein that can be used to "see" neuroinflammation. This discovery will improve the understanding of neurological and psychiatric disease mechanisms.

 Inflammation is the sign that our body is defending itself against aggression. But when this response escalates, for example in the brain, it can lead to serious neurological or psychiatric diseases. A team from the University of Geneva (UNIGE), the University Hospitals of Geneva (HUG), Imperial College London and Amsterdam UMC, investigated a marker protein targeted by medical imaging to visualize cerebral inflammation, but whose interpretation was still uncertain. The team reveals that a large quantity of this protein goes hand in hand with a large quantity of inflammatory cells, but its presence is not a sign of their overactivation. These results, published in Nature Communications, pave the way for optimal observation of neuroinflammatory processes and a re-reading of previous studies on the subject.

Brain receptor patterns separate sensory and cognitive networks

Receptor patterns define key organizational principles in the brain, scientists have discovered.
Photo Credit: Pete Linforth

An international team of researchers, studying macaque brains, have mapped out neurotransmitter receptors, revealing a potential role in distinguishing internal thoughts and emotions from those generated by external influences.

The comprehensive dataset has been made publicly available, serving as a bridge linking different scales of neuroscience - from the microscopic to the whole brain.

Lead author Sean Froudist-Walsh, from the University of Bristol’s Department of Computer Science explained: “Imagine the brain as a city. In recent years, brain research has been focused on studying its roads, but in this research, we've made the most detailed map yet of the traffic lights - the neurotransmitter receptors - that control information flow.

“We've discovered patterns in how these 'traffic lights' are arranged that help us understand their function in perception, memory, and emotion.

“It's like finding the key to a city's traffic flow, and it opens up exciting possibilities for understanding how the normal brain works.

“Potentially in the future, other researchers may use these maps to target particular brain networks and functions with new medicines.

New study reveals strong connection between heart and brain health

A growing amount of evidence points to interactions between heart health and brain health.

Cardiovascular diseases serve as a crucial backdrop for brain diseases like stroke, dementia, cerebral small vessel disease and cognitive impairment. Studies have shown, for example, that atrial fibrillation, even in stroke-free individuals, is associated with an increased incidence of dementia and silent cerebral damage. Heart failure has been linked to cognitive impairment and dementia due to reduced cerebral blood flow caused by a failing heart. Conversely, mental disorders and negative psychological factors may contribute to the onset and progression of cardiovascular diseases. Individuals with conditions such as schizophrenia, bipolar disorder, epilepsy or depression are more prone to cardiovascular diseases.

Despite this growing knowledge, previous studies on heart-brain interactions and associated risk factors have been limited in scope, focusing on specific diseases or utilizing small sample sizes. Consequently, the overall understanding of the structural and functional links between the heart and brain remains incomplete.

A new study conducted by researchers from UNC-Chapel Hill, the University of Pennsylvania and Purdue University leverages large magnetic resonance imaging (MRI) data to shed light on the close relationship between cardiovascular diseases and brain diseases such as stroke, dementia and cognitive impairment, unraveling the underlying genetic signatures and inter-organ connections between the heart and brain.

Researchers Unveil New Collection of Human Brain Atlases that Chart Postnatal Development

Surface-volume atlases from 2 weeks to 24 months.
Image Credit: © 2023, Ahmad et al., CCBY 4.0

Led by Pew-Thian Yap, PhD, researchers at the UNC School of Medicine created monthly infant brain atlases to help researchers analyze the developing brain in detail to investigate neurological disorders and other conditions.

Human brain atlases can be used by medical professionals to track normative trends over time and to pinpoint crucial aspects of early brain development. By using these atlases, they are able to see what typical structural and functional development looks like, making it easier for them to spot the symptoms of abnormal development, such as attention-deficit / hyperactivity disorder (ADHD), dyslexia, and cerebral palsy.

Pew-Thian Yap, PhD, professor in the UNC Department of Radiology, and colleagues in the department and the Biomedical Research Imaging Center (BRIC) have created a new collection of month-by-month infant brain atlas (IBA) that capture fine spatiotemporal details of the early developing brain.

Scientists Have Created New Substance to Treat Neurological Disorders

Scientists used a set of 1,2,3-triazole derivatives and modeled the structure of the putative inhibitor.
 Photo Credit: Andrey Fomin

The international team of scientists, including chemists from the Ural Federal University, has developed a substance that may become the basis for drugs that suppress or alleviate a number of neurological disorders. These include, for example, psychosis, schizophrenia, Parkinson's and Huntington's diseases, etc. The scientists reported the development and first results of the study in the Journal of Biomolecular Structure and Dynamics. The study was supported by a grant from the Ministry of Science and Higher Education of the Russian Federation (Project No. 075-15-2020-777).

"We found that the enzyme Phosphodiesterase 10A, which is produced in the body, is directly linked to neurological disorders. If you inhibit this enzyme, you can significantly slow down or even suppress the disease. For this purpose, we used a set of derivatives of 1,2,3-triazole, a pharmacophore whose fragments are contained in many drugs, and modeled the structure of the putative TP-10 inhibitor. We hypothesize that it would have a positive effect on conditions associated with brain dysfunction by reducing the activity of the Phosphodiesterase 10A enzyme. Other inhibitors developed by foreign companies still have no reliable antipsychotic efficacy so far," notes Dhananjay Bhattacherjee, senior researcher at the Department of Organic and Biomolecular Chemistry at UrFU.

Human evolution wasn’t just the sheet music, but how it was played

The fluorescent glow of mouse brain cells on the right indicates the effectiveness of a human-derived gene enhancer, HAQER0059, versus a 6-million-year-old version of the enhancer at left.
Image Credit: Riley Mangan, Duke University

A team of Duke researchers has identified a group of human DNA sequences driving changes in brain development, digestion and immunity that seem to have evolved rapidly after our family line split from that of the chimpanzees, but before we split with the Neanderthals.

Our brains are bigger, and our guts are shorter than our ape peers.

“A lot of the traits that we think of as uniquely human, and human-specific, probably appear during that time period,” in the 7.5 million years since the split with the common ancestor we share with the chimpanzee, said Craig Lowe, Ph.D., an assistant professor of molecular genetics and microbiology in the Duke School of Medicine.

Specifically, the DNA sequences in question, which the researchers have dubbed Human Ancestor Quickly Evolved Regions (HAQERS), pronounced like hackers, regulate genes. They are the switches that tell nearby genes when to turn on and off. The findings appear Nov.23 in the journal Cell.

The rapid evolution of these regions of the genome seems to have served as a fine-tuning of regulatory control, Lowe said. More switches were added to the human operating system as sequences developed into regulatory regions, and they were more finely tuned to adapt to environmental or developmental cues. By and large, those changes were advantageous to our species.

Awareness of one’s own body is based on uncertainty and guesses

Researchers at Karolinska Institutet have found that the perception of one's own body is very based on the brain making guesses based on probability theory. It shows a study recently published in the journal eLife.

How we perceive our own body is largely based on probability assessments based on past experiences, in combination with sensory information such as vision and feeling, for example.

You could say that the experience of your own body is a statistical estimate of reality based on sensory information, sensorory uncertainty, and past experiences that can be summed up in the mathematical model explain Henrik Ehrsson, professor at the Department of Neuroscience, Karolinska Institutet.

Covid-19 is linked to increased degradation of connections between nerve cells in a new brain model

Postdoctoral fellow Samudyata and doctoral student Susmita Malwade.
Source: Karolinska Institutet

Researchers at Karolinska Institutet have used cellular reprogramming in a new study to create human three-dimensional brain models and infected them with SARS-CoV-2. In infected models, the brain's immune cells showed an excessive elimination of connections between the nerve cells. The gene expression of these cells also mimicked changes observed in neurodegenerative diseases. The results hope to identify new treatments for cognitive symptoms after Covid-19 infection.

Several studies have reported persistent cognitive symptoms following a covid-19 infection, but the underlying mechanisms for this are still unknown. The researchers behind the study, published in the journal Molecular Psychiatry, have created from human induced pluripotent stem cells (iPS) three-dimensional models of the brain in test tubes, so-called brain organoids. The model differs from previous organoid models in that they also contain microglia - the brain's immune cells. In the infected models, microglia regulated genes involved in phagocytosis, "cell-eating," the researchers could also see how microglia contained an increased amount of proteins from brain cell connections, so-called synapses. The developed model and results of the study can help guide future efforts to address cognitive symptoms in the aftermath of COVID-19 and other neuroinvasive viral infections.

Making lab-grown brain organoids ‘brainier

 Slices of mini–brain organoids with neural stem cells (red) and cortical neurons (green).
Credit: Hajime Ozaki, Watanabe lab/UCI

By using stem cells to grow miniature brain-like organs in the lab, scientists have opened a new avenue for studies of neurological development, disease and therapies that can’t be conducted in living people. But not all mini–brain organoids are created equal and getting them to precisely mimic the human brain tissues they’re modeling has been a persistent challenge.

“Right now, it’s like the Wild West because there is no standard method for generating mini–brain organoids,” said Bennett Novitch, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and the senior author of a new paper on the topic. “Every neuroscientist wants to make a brain organoid model of their favorite disease, and yet everyone’s organoids do not always look alike.”

In fact, because there is no common protocol for their production and a lack of quality-control guidelines, organoids can vary from lab to lab — and even from batch to batch — which means that a finding made in one organoid may not hold true in another.

“If my lab and another lab down the hall were to conduct drug screens using mini–brain organoid models of the same disorder, we could still get different results,” said Momoko Watanabe, the new paper’s first author and an assistant professor of anatomy and neurobiology at UC Irvine. “We won’t know whose findings are correct because the differences we’re seeing could be reflections of how our models differ rather than reflections of the disease.”