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.

Tiny mutation, big impact on schizophrenia treatment

Image Credit: Scientific Frontline

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers identified a rare genetic mutation, C182F, within the TAAR1 brain receptor that completely negates the efficacy of newer schizophrenia treatments by structurally locking the receptor in an inactive state.
• Methodology: The study employed advanced cell biology assays and 500-nanosecond molecular dynamics simulations to analyze the variant, which was originally isolated from an Indian family with a history of schizophrenia.
• Key Data: In the homozygous state, the mutation caused a complete loss of receptor signaling function and reduced protein surface expression by approximately 40%, while heterozygous cells retained only about 50% activity.
• Significance: This discovery explains the clinical failure of promising TAAR1 agonists like ulotaront in certain patients, revealing that the mutation eliminates the critical disulfide bond "tent pole" needed for the drug to bind effectively.
• Future Application: Standard psychiatric care may evolve to include mandatory genetic screening for TAAR1 variants prior to prescribing specific antipsychotics to ensure alignment with the patient's pharmacogenomic profile.
• Branch of Science: Pharmacogenomics and Molecular Psychiatry.
• Additional Detail: While rare globally, the C182F mutation occurs more frequently in South Asian populations, highlighting a specific demographic necessity for targeted genetic testing in drug development.

Rare Brain Cell May Hold the Key to Preventing Schizophrenia Symptoms

A new study from the University of Copenhagen shows that a targeted intervention in a specific type of brain cell can change behavior in mice with symptoms resembling schizophrenia. The researchers hope that this knowledge may eventually pave the way for more targeted treatments for conditions such as schizophrenia.
Image Credit: Scientific Frontline / AI generated

A specific type of brain cell is abnormally active in mice exhibiting behavior reminiscent of schizophrenia, according to a new study from the University of Copenhagen. By dampening the activity of these cells, researchers were able to restore the animals’ behavior—an insight that may pave the way for a new preventive treatment.

Difficulty completing everyday tasks. Failing memory. Unusually poor concentration.

For many people living with schizophrenia, cognitive challenges are part of daily life. Alongside well-known symptoms such as hallucinations and delusions, these difficulties can make it hard to live the life they want. That is why researchers at the University of Copenhagen are working to find ways to prevent such symptoms - and they may now be one step closer.

In a new study, researchers discovered that a specific type of brain cell is abnormally active in mice displaying schizophrenia-like behavior. When the researchers reduced the activity of these cells, the mice’s behavior changed.

“Current treatments for cognitive symptoms in patients with diagnoses such as schizophrenia are inadequate. We need to understand more about what causes these cognitive symptoms that are derived from impairments during brain development. Our study may be the first step toward a new, targeted treatment that can prevent cognitive symptoms,” says Professor Konstantin Khodosevich from the Biotech Research and Innovation Center at the University of Copenhagen, and one of the researchers behind the study.

Schizophrenia and bipolar disorder found in recently evolved region of the ‘dark genome’

They say these new proteins can be used as biological indicators to distinguish between the two conditions, and to identify patients more prone to psychosis or suicide.

Schizophrenia and bipolar disorder are debilitating mental disorders that are hard to diagnose and treat. Despite being amongst the most heritable mental health disorders, very few clues to their cause have been found in the sections of our DNA known as genes.

The scientists think that hotspots in the ‘dark genome’ associated with the disorders may have evolved because they have beneficial functions in human development, but their disruption by environmental factors leads to susceptibility to, or development of, schizophrenia or bipolar disorder.

The results are published in the journal Molecular Psychiatry.

“By scanning through the entire genome we’ve found regions, not classed as genes in the traditional sense, which create proteins that appear to be associated with schizophrenia and bipolar disorder,” said Dr Sudhakaran Prabakaran, who was based in the University of Cambridge’s Department of Genetics when he conducted the research, and is senior author of the report.

He added: “This opens up huge potential for new druggable targets. It’s really exciting because nobody has ever looked beyond the genes for clues to understanding and treating these conditions before.”

The researchers think that these genomic components of schizophrenia and bipolar disorder are specific to humans - the newly discovered regions are not found in the genomes of other vertebrates. It is likely that the regions evolved quickly in humans as our cognitive abilities developed, but they are easily disrupted - resulting in the two conditions.

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.

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.  

Schizophrenia: The cerebellum’s unexpected role

Illustrative image of the connectivity between the cerebellum and the VTA.
Image Credit: © Thomas Bolton

Scientific Frontline: "At a Glance" Summary

• Main Discovery: The cerebellum acts as a critical regulator of the brain's reward system, directly influencing the severity of "negative" schizophrenia symptoms such as apathy, loss of motivation, and social withdrawal.
• Specific Detail/Mechanism: Functional analysis reveals that the cerebellum modulates the dopamine-producing ventral tegmental area (VTA); stronger cerebellar regulation correlates with reduced negative symptoms, while weaker regulation is linked to increased symptom severity.
• Key Statistic or Data: The study established these findings by monitoring 146 patients over a period of 3 to 9 months, utilizing an independent validation cohort to confirm the functional connectivity between the cerebellum and the VTA.
• Context or Comparison: Unlike the VTA, which is located deep within the brain and is difficult to target, the cerebellum is situated superficially at the back of the skull, making it accessible for non-invasive interventions.
• Significance/Future Application: This mechanism identifies the cerebellum as a viable target for Transcranial Magnetic Stimulation (TMS); a randomized controlled trial is currently underway to test this therapeutic approach, with results expected in 2028.
• Additional Critical Detail: This research challenges the traditional view of the cerebellum as solely a motor control center, highlighting its pivotal role in emotional and cognitive processing relevant to psychiatric disorders.

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.

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.

Researchers create cells that help the brain keep its cool

Parvalbumin cells play a central role in keeping brain activity in equilibrium. They control nervcell signalling, reduce overactivity and make sure that the brain is working to a rhythm
Image Credit: Scientific Frontline

Researchers at Lund University in Sweden have created a method that makes it possible to transform the brain’s support cells into parvalbumin-positive cells. These cells act as the brain’s rapid-braking system and are significantly involved in schizophrenia, epilepsy, and other neurological conditions. 

Parvalbumin cells play a central role in keeping brain activity in equilibrium. They control nerve cell signaling, reduce overactivity and make sure that the brain is working to a rhythm. Researchers sometimes describe them as the cells that “make the brain sound right”. 

When these cells malfunction or decrease in number, the balance of the brain is disrupted. Previous studies suggest that damaged parvalbumin cells may contribute to disorders such as schizophrenia and epilepsy.  

Coffee linked to slower biological ageing among those with severe mental illness – up to a limit

Photo Credit: Julia Florczak

New research from King’s College London finds that coffee consumption within the NHS recommended limit is linked to longer telomere lengths – a marker of biological ageing – among people with bipolar disorder and schizophrenia. The effect is comparable to roughly five years younger biological age. 

Telomeres are structures that protect DNA. As people get older, their telomeres shorten as part of the natural human ageing process. This process has been shown to be accelerated among people with severe mental illness, such as bipolar disorder and schizophrenia, who have an average life expectancy 15 years shorter than the general population. 

Previous research shows that coffee has health benefits. It may reduce oxidative stress in the general population, helping slow biological ageing processes like telomere shortening. The new study, published in BMJ Mental Health, explores whether coffee consumption could slow this ageing process among those with severe mental illness. 

New research finds the risk of psychotic-like experiences can start in childhood

 

It has long been understood that environmental and socio-economic factors – including income disparity, family poverty, and air pollution – increase a person’s risk of developing psychotic-like experiences, such as subtle hallucinations and delusions that can become precursors to a schizophrenia diagnosis later in life. Research has long focused on young adults but now, thanks to data from the Adolescent Brain Cognitive Development (ABCD) Study, researchers at the University of Rochester have found these risk factors can be observed in pre-adolescent children.

“These findings could have a major impact on public health initiatives to reduce the risk of psychotic-like experiences,” said Abhishek Saxena, a graduate student in the department of Psychology at the University of Rochester and first author of the study recently published in Frontiers in Psychiatry. “Past research has largely focused on the biological factors that lead to development of schizophrenia spectrum disorders, but we now know that social and environmental factors can also play a large role in the risk and development of schizophrenia. And this research shows these factors impact people starting at a very young age.”

Researchers looked at data collected from 8,000 kids enrolled in the ABCD study. They found that the more urban of an environment a child lived in – proximity to roads, houses with lead paint risks, families in poverty, and income disparity – the greater number of psychotic-like experiences they had over a year’s time. These findings are in line with past research conducted in young adults, but have not been found like this in pre-adolescences.

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.

One way brain ‘conductors’ find precise connection to target cells

Visualizations of cells in mouse brains show that under normal conditions (left), the connection between chandelier cells and the axon initial segment (AIS) in pyramidal cells results in the placement of synapses, dyed pink, on the AIS. At right, when genes carrying instructions for the protein gliomedin are deleted, fewer synapses are formed on the AIS — an indication that gliomedin is necessary for the “handshake” between the two cell types.
Image Credit: Hiroki Taniguchi and Yasufumi Hayano

Scientific Frontline: "At a Glance" Summary

• Discovery of Synaptic "Handshake" Mechanism: Researchers identified the specific molecular interaction that allows chandelier cells (inhibitory interneurons) to precisely locate and connect to the axon initial segment (AIS) of excitatory pyramidal neurons.
• Identification of Key Proteins: The process is governed by the binding of gliomedin, a cell surface molecule enriched in chandelier cells, to neurofascin-186, a receptor localized specifically at the AIS of target neurons.
• Methodological Validation: Using RNA sequencing and genetic manipulation in mouse models, the team demonstrated that deleting the genes for these proteins significantly reduced synapse formation, while overexpressing them increased synaptic density.
• Strategic Precision of Innervation: The connection occurs at the AIS, the "faucet" of the neuron where action potentials are generated; this allows a single chandelier cell to exert powerful inhibitory control over hundreds of excitatory cells simultaneously.
• Clinical Relevance: Disruption of this precise "handshake" and the resulting circuit imbalance are linked to the pathophysiology of neurodevelopmental and psychiatric disorders, including epilepsy, schizophrenia, and autism.
• Future Research Directions: The study establishes a systematic framework for investigating the molecular markers that guide other specialized inhibitory interneurons in organizing complex brain circuitry.

New report finds smoking is a cause of depression and schizophrenia

Credit: Uki Eiri from Pixabay

Smoking increases the risk of developing schizophrenia by between 53% and 127% and of developing depression by 54% to 132%, a report by academics from the University of Bristol published today has shown. More research is needed to identify why this is the case, and more evidence is needed for other mental health conditions such as anxiety or bipolar disorder.

The evidence presented today at the Royal College of Psychiatrists International Congress has been shared with the Government which is currently developing a new Tobacco Control Plan for publication later this year.

The Congress will also be given new data on the numbers of smokers with mental health conditions. Rates of smoking are much higher among people with mental health conditions than those without, and among England’s 6 million smokers there are an estimated:

• 230k smokers with severe mental illness (e.g., schizophrenia and bi-polar disorder)
• 1.6 million with depression and anxiety

These analyses are timely as the Government is currently considering recommendations by the Khan Review for the forthcoming Tobacco Control Plan to deliver its Smokefree 2030 ambition. The independent review by Javed Khan was commissioned by the Secretary of State to help the Government to identify the most impactful interventions to reduce the uptake of smoking, and support people to stop smoking, for good. One of Khan’s 15 recommendations was that action is needed to tackle the issue of smoking and mental health.

Cannabis users at 'much higher' risk of developing poor mental health

 

Those with a recorded history of cannabis use in general practice records are at a much higher risk of developing mental ill health problems such as anxiety or depression as well as severe mental illnesses, new research shows.

The findings point to the need for a public health approach to the management of people misusing cannabis, including the need to emphasize the importance of general practitioners to continue enquiring about recreational drug use.

While the links between cannabis use and severe mental illnesses such as schizophrenia and psychosis are well researched, the associations are less clear between cannabis use as described in patient’s GP records and other, more common types of mental ill health such as depression and anxiety.

In a new study, published in Psychological Medicine, researchers in the University of Birmingham’s Institute for Mental Health and the Institute of Applied Health Research found a strong link between general practice recorded cannabis use and mental ill health in one of the largest cohorts ever explored.

Senior author Dr Clara Humpston said: “Cannabis is often considered to be one of the ‘safer’ drugs and has also shown promise in medical therapies, leading to calls for it be legalized globally. Although we are unable to establish a direct causal relationship, our findings suggest we should continue to exercise caution since the notion of cannabis being a safe drug may well be mistaken.”

Dr Joht Singh Chandan said: “The research reaffirms the need to ensure a public health approach to recreational drug use continues to be adopted across the UK. We must continue to progress measures to improve the prevention and detection of drug use as well as implement the appropriate supportive measures in an equitable manner to prevent the secondary negative health consequences.”

Using primary care data drawn from the IQVIA Medical Research Database (IMRD-UK), the researchers found following the first recorded use of cannabis, patients were three times more likely to develop common mental health problems such as depression and anxiety. In addition, they were almost 7 times more likely to develop severe mental illnesses such as psychosis or schizophrenia.

The dataset included records from 787 GP practices around the UK gathered over a 23-year period between 1995 and 2018. The researchers were able to include data from 28,218 patients who had a recorded exposure to cannabis. These were matched to 56,208 patients who had not been using cannabis and controlled for sex, age, ethnicity, smoking status and other relevant characteristics.

The cannabis users also had much higher rates of having a recorded history of using other drugs such as heroin, cocaine and amphetamines.

Future research in this area will investigate the levels of cannabis use or the potency of ingredients.

Source/Credit: University of Birmingham

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Scientists discover genetic variants that speed up and slow down brain aging

Researchers from a USC-led consortium have discovered 15 “hot spots” in the genome that either speed up brain aging or slow it down — a finding that could provide new drug targets to resist developmental delays, Alzheimer’s disease and other degenerative brain disorders.

The research appeared online Tuesday in Nature Neuroscience.

“The big game-changer here is discovering locations on the chromosome that speed up or slow down brain aging in worldwide populations. These can quickly become new drug targets,” said Paul Thompson of USC, a lead author on the study and the co-founder and director of the ENIGMA Consortium. “Through our AI4AD [Artificial Intelligence for Alzheimer’s Disease] initiative we even have a genome-guided drug repurposing program to target these and find new and existing drugs that help us age better.”

ENIGMA is working group based at USC that is exploring a vast trove of brain data and has published some of the largest-ever neuroimaging studies of schizophrenia, major depression, bipolar disorder, epilepsy, Parkinson’s disease, and even HIV infection.

To discover the hot spots, or genomic loci, more than 200 ENIGMA-member scientists from all over the world looked for people whose brains were scanned twice with MRI. The scans provided a measure of how fast their brains were gaining or losing tissue in regions that control memory, emotion and analytical thinking.

How brain waves shape our sense of self

Participants took part in an experiment called the rubber hand illusion in Henrik Ehrsson's lab at Karolinska Institutet.
Photo Credit: Martin Stenmark

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Alpha oscillations in the parietal cortex function as the primary neural mechanism for distinguishing one’s own body from the external environment by regulating the integration of sensory signals.
• Methodology: Researchers combined the "rubber hand illusion" with EEG recordings, computational modeling, and non-invasive electrical brain stimulation across 106 participants to causally link brain wave speeds to perception.
• Mechanism: The specific frequency of alpha waves determines the brain's "temporal binding window"; faster oscillations create a higher temporal resolution, allowing for a precise rejection of asynchronous (non-self) stimuli.
• Key Correlation: Individuals with naturally slower alpha frequencies demonstrated a broader integration window, causing the brain to erroneously merge mismatched visual and tactile inputs into a false sense of body ownership.
• Significance: These findings establish a physiological target for treating self-disorders in conditions like schizophrenia and provide a blueprint for improving the "embodiment" of prosthetic limbs and virtual reality systems.

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.

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.