Researchers identify genetic blueprint of mania in bipolar disorder

King's College London

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Researchers at King’s College London and the University of Florence have, for the first time, identified the specific genetic blueprint of mania, the defining feature of bipolar disorder.

Bipolar disorder is one of the most severe and complex psychiatric conditions, affecting around 2% of people worldwide. While episodes of depression, psychosis and other symptoms are common, mania is what distinguishes bipolar disorder from other mental illnesses. Mania is a state of persistently elevated or irritable mood marked by increased energy, reduced need for sleep, rapid thoughts and speech, and, in some cases, impaired judgement, impulsive behaviour or psychotic symptoms. Until now, however, the biology of mania has been difficult to study because many people with a diagnosis of bipolar disorder also have episodes of depression and psychosis, making it hard to determine what is specific to bipolar disorder itself.

To uncover the genetic basis of mania, the researchers used data from very large international genetic studies, including more than 27,000 people with severe bipolar disorder and over 576,000 individuals studied for depression. They applied an advanced statistical approach that allowed them to separate the genetic signals for mania from those for depression. In simple terms, this method works by subtracting the genetic effects associated with depression from those seen in bipolar disorder, leaving behind the genetic component that is specific to mania. This made it possible to study mania as its own biological process for the first time.

The study found that mania accounts for more than 80% of the genetic variation in bipolar disorder, underlining its central role in the condition. The researchers identified 71 genetic variants linked specifically to mania, including 18 regions of genes that had never previously been associated with bipolar disorder. Many of these genes are involved in voltage-gated calcium channels, which are essential for communication between brain cells and for regulating mood. When compared genetically with other traits, mania showed a distinct profile, sharing less genetic overlap with substance use and more with measures related to wellbeing and educational attainment than bipolar disorder as a whole.

Understanding the genetics of mania is critically important because it offers a direct window into the core biology of bipolar disorder. Many people with bipolar disorder first seek help during depressive or other types of episodes, when the condition can look very similar to severe depression or schizophrenia. As a result, individuals can spend up to a decade moving between different diagnoses before bipolar disorder is correctly identified. By defining the genetic features that are unique to mania, this research moves the field closer to identifying early biological indicators of bipolar disorder, with the potential to shorten this diagnostic journey  and ensure people receive the right treatment sooner.

Important implications for diagnosis and treatment

These findings have important implications for diagnosis and treatment. Psychiatrists currently distinguish between several forms of bipolar disorder, such as Bipolar type  I, Bipolar type II and cyclothymia, largely based on patterns of mood episodes over time.  A clearer understanding of the biology of mania may help refine these distinctions, identify additional subtypes, and support more personalised approaches to care. The results also highlight potential treatment pathways, including calcium-channel mechanisms, and suggest that established medications such as lithium may exert their effects through these biological systems.

Dr Giuseppe Pierpaolo Merola, MRC Clinical Research Training Fellow, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, lead author of the study, said: “By isolating the genetic architecture of mania, we have taken a crucial step towards understanding the core biology of bipolar disorder. This allows us to see what makes mania distinct, rather than viewing bipolar disorder simply as a mixture of mania, depression and psychosis, and opens new possibilities for more precise and personalised treatments.”

Professor Gerome Breen, Professor of Psychiatric Genetics at King’s College London and Mental Health BioResource Lead at the NIHR Maudsley Biomedical Research Centre, said: “Mania is what defines bipolar disorder, yet it has remained surprisingly difficult to study in its own right. Our research on the genetics of mania gives us a clearer picture of its biology and how it differs from other psychiatric conditions. In the longer term, this could help clinicians recognise bipolar disorder earlier, reduce the long delays many patients face before receiving a diagnosis, and improve outcomes through more targeted treatment.”

The research was conducted at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London in collaboration with the University of Florence. It was funded by the National Institute for Health and Care Research Maudsley Biomedical Research Centre. The study was published on 28 January 2026 in Biological Psychiatry.

 

Notes to editors 

 

Under Embargo until 00.01 GMT Wednesday 28 January 2026

For more information and a copy of the paper under strict embargo, please contact : 

Alex Booth Senior Communications and Engagement Manager, NIHR Maudsley BRC, alex.booth@kcl.ac.uk 

 

About King’s College London and the Institute of Psychiatry, Psychology & Neuroscience  

King’s College London is amongst the top 35 universities in the world and top 10 in Europe (THE World University Rankings 2023), and one of England’s oldest and most prestigious universities.  

With an outstanding reputation for world-class teaching and cutting-edge research, King’s maintained its sixth position for ‘research power’ in the UK (2021 Research Excellence Framework).  

King's has more than 33,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and some 8,500 staff. The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain. 

www.kcl.ac.uk/ioppn | Follow @KingsIoPPN on Twitter, Instagram, Facebook and LinkedIn 

 

The National Institute for Health and Care Research (NIHR) 

The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by: 

• Funding high quality, timely research that benefits the NHS, public health and social care; 

• Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services; 

• Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research; 

• Attracting, training and supporting the best researchers to tackle complex health and social care challenges; 

• Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system; 

• Funding applied global health research and training to meet the needs of the poorest people in low- and middle-income countries. 

NIHR is funded by the Department of Health and Social Care. Its work in low- and middle-income countries is principally funded through UK Aid from the UK government. 

 

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Journal

Biological Psychiatry

DOI

10.1016/j.biopsych.2025.11.008 

Method of Research

Observational study

Subject of Research

Human tissue samples

Article Title

Isolating the genetic component of mania in bipolar disorder

XXI CENTURY MESMERISM

Delivery of magnetic energy to the brain is a cost-effective treatment option for patients with depression, finds a new study

University of Nottingham

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A major new study has found that transcranial magnetic stimulation (TMS), which applies magnetic energy to the brain, can be a cost-effective treatment option for the NHS in treating moderate and severe forms of depression that have not responded to other treatments.

The economic analysis, which is published in BMJ Mental Health, compared TMS to usual care in specialist mental health services, and found that TMS reduces depressive symptoms, eases pressures on informal carers and on NHS resources, and helps people get back to work.

TMS represents an investment in care that recovers its costs over time, primarily from savings to the wider health service and from fewer workdays being lost because of long-term depression.

The study was led by senior health economist Edward Cox from the Nottingham Clinical Trials Unit at the University of Nottingham and Professor Richard Morriss from the Institute of Mental Health, National Institute for Health and Care Research (NIHR) Nottingham Biomedical Research Centre, and the NIHR HealthTech Research Centre in Mental Health (MindTech).

Major depression is the leading cause of disability lost years worldwide (WHO, 2017), and suicide from depression is one of the biggest killers of people aged between 15-49. Antidepressants and therapy delivered as first or second-line treatments help two thirds of people with depression, but the remaining third have treatment resistant depression (TRD). This is defined as a lack of response to two courses of antidepressants.

TMS is an outpatient treatment where people have powerful magnetic pulses delivered to the left side of their head just in front of the temporal area of the scalp. The person is conscious and has at least 20 sessions over a four-to-six-week period.

Although TMS is safe and effective as a treatment for TRD and was approved in 2015 by the National Institute for Health and Care Excellence (NICE) for use in the NHS, it remains inaccessible for the majority of patients. Although TMS was invented in the UK, the equipment produced by UK industry, and has been proven effective and implementable within mental health care services, it is only available in one in seven NHS Trusts. One of the main reasons for this is the lack of evidence showing its value for money.

In this new study, experts set out to assess the cost-effectiveness of two forms of TMS, repetitive transcranial magnetic stimulation therapy (rTMS) and intermittent theta-burst stimulation (iTBS), compared to usual care for TRD. The study also seeks to establish the operational circumstances in which TMS could be deemed to represent value-for-money to the NHS and wider society.

Susan Varley, a patient who has received a course of TMS therapy, said: “As a previously high functioning nurse, I suffered severe depression and had to be admitted to hospital because of the severity of my depression. I tried all sorts of different treatments for my depression. Nothing worked. I then travelled to receive a course of TMS and it has transformed my life. I am back working as a nurse, lost four stone in weight and I am enjoying life again with family and friends. I strongly believe that others suffering like me should be given the option of TMS under the NHS.”

Mr Cox said: “Our economic analysis was informed via feedback from TMS experts across six mental health care services, and from the experiences of 442 participants suffering with difficult-to-treat forms of depression enrolled within two clinical trials. The study found that a proportion of patients receiving TMS therapies can expect to achieve faster and more sustained improvements in depressive symptoms compared to usual care, and that these gains represent a cost-effective allocation of scarce NHS resources.

“It’s important to recognise that the cost-effectiveness of TMS is dependent specifically on how it is going to be delivered in wider practice. Our study findings demonstrate that services that can achieve a streamlined high throughput model of care can expect to deliver a highly cost-effective treatment. Our findings should provide much needed evidence for policymakers to rationalise and establish cost-effective models for implementing TMS within the NHS.”

The team developed a decision-analytic model (DAM) to integrate evidence from three sources – (i) the BRIGhTMIND trial  – a large randomised controlled trial (RTC), funded by the Efficacy and Mechanism Evaluation (EME) Programme - a partnership between the NIHR and the Medical Research Council (MRC) -  that showed TMS was effective for at least six months; (ii) The Specialist Mood Disorder (SMD) trial – the first UK multicentre outpatient RTC in patients with moderate of severe unipolar depression in the UK funded by the NIHR Applied Research Collaboration East Midlands; and (iii) a study-specific structured expert elicitation exercise, where experts highly experienced in the delivery of TMS therapies for depression were interviewed on the longer-term effectiveness and operational realities of providing treatment.

NICE typically considers medical interventions to be cost-effective if the incremental cost-effectiveness ratio (ICER) for a treatment [the expected cost to the health service per unit of benefit] falls within or below a threshold of £20,000–£30,000 per quality-adjusted life-year (QALY) gained. This threshold is set to rise to £25,000–£35,000 per QALY imminently.

From a health-service perspective rTMS and iTBS had ICERs of £12,093 and £12,959 per QALY compared to TAU, respectively. From a broader societal perspective both rTMS and iTBS improved health, reduced informal care hours and were cost-saving compared with TAU.

The study findings were sensitive to service delivery, but provided there is a high throughput of patients receiving TMS and currently recommended protocols for TMS are followed, then this research suggests that TMS is a cost-effective alternative to usual care.  

Professor Richard Morriss, Research Theme Lead for Mental Health and Technology at the NIHR Nottingham Biomedical Research Centre, and the School of Medicine at the University, said: “Our view is that TMS should be considered as a cost-effective alternative for treating moderate to severe depression after the second course of treatment has failed.

“Compared to usual care, our study shows that TMS is cost-effective below the lowest NICE threshold for cost-effectiveness for health costs and cost saving if health, informal care and work productivity are included.

“Two main objections for implementing TMS for TRD in the NHS was that it was only effective for a short period and there was no UK economic study showing that it was cost-effective or cost-saving. The BRIGhtMIND study in 2024 proved that the treatment was effective for at least six months and this new study now shows cost-effectiveness in health costs and in terms of in wider societal costs too. With this in mind, we feel that it is time for the NHS to seriously consider implementing TMS in NHS services across the UK.”

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Journal

BMJ Mental Health

DOI

10.1136/bmjment 

Method of Research

Meta-analysis

Subject of Research

People

Article Title

Is it time for mental health services to invest in neurostimulation? An economic evaluation of transcranial magnetic stimulation therapies for the treatment of moderate to severe treatment-resistant depression in the UK

Article Publication Date

28-Jan-2026

Artificial nighttime lighting is suppressing moth activity

University of Exeter

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Black Arches moth

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Credit: Dr Emmanuelle Briolat

Moths move significantly less when exposed to artificial nighttime light, new research shows.

Moths’ attraction to artificial light, such as streetlights, is common knowledge and has been much studied. But, as many people will have observed, moths may also remain still if they land near a light, apparently “trapped”.

To understand this behaviour, University of Exeter researchers caught more than 800 moths from 23 species and exposed them to LED lights (of various colours and brightness) or to natural night conditions.

Moths were collected with light traps and butterfly nets on the Penryn Campus grounds, then placed outside in individual pots exposed to one of the light conditions, and filmed to record their movements overnight.

Under 10 lux – a level you might experience near residential streetlighting – moths moved 85% less on average than moths in natural nighttime conditions. This is a big impact on how moths behave, with implications for the time they have for essential activities like finding food or mates.

This could be because the artificial light confuses the moths’ sense of time, causing them to remain still as they do in the daytime, or because the light interferes with their vision.

The study also found that, at that same 10 lux intensity, amber lighting – commonly thought to be less harmful to insects – reduced moth movement just as much as typical white LEDs.

“Our results suggest that light pollution has widespread effects on nocturnal moth activity, irrespective of lighting type,” said Dr Emmanuelle Briolat, from the Centre for Ecology & Conservation at Exeter’s Penryn Campus in Cornwall.

“This could have important knock-on effects for moth populations and the ‘ecosystem services’ they provide; moths are important pollinators, and a key food source for many other species, from birds to bats.

“Across Europe, moths are in decline, part of a worrying picture of global insect losses, linked to threats like pollution and land-use change – and light pollution could be a significant contributing factor.

“We already know that artificial lighting has many negative impacts on nocturnal insects, and our findings further stress the importance of preserving dark skies.”

Some moth species were even affected by white LED lighting at low levels of 0.1 lux. This is equivalent to indirect ‘skyglow’, where light from towns and cities illuminates the entire sky across many kilometres, meaning the effects could be more far reaching.

The study also looked at how the activity of moths changed through the course of the night.

Dr Jolyon Troscianko said: “While we might think that most moths are simply ‘nocturnal’ and active through the whole night, we found huge variability among species. Some were most active at the start of the night, others at the end, and most were only ever active for short periods.

“Having such short windows of activity has implications for how artificial light could interfere with the moths’ ability to find food or mates before their short adult lives end. While sitting still under artificial lights won’t kill the moths immediately, these sub-lethal effects could easily add up and prevent them from breeding successfully.”

The study was funded by the Natural Environment Research Council.

The paper, published in the journal Proceedings of the Royal Society B, is entitled: “Severe and widespread reductions in nighttime activity of nocturnal moths under modern artificial lighting spectra.”

 

Common Emerald moth

 

The experimental setup

Credit

Dr Emmanuelle Briolat

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Journal

Proceedings of the Royal Society B Biological Sciences

DOI

10.1098/rspb.2025.2704 

Article Title

Severe and widespread reductions in nighttime activity of nocturnal moths under modern artificial lighting spectra

Article Publication Date

27-Jan-2026

 

Altered brain connection found in people with ME/CFS and Long COVID

People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID experience a disruption to their brain connectivity during a mentally demanding task.

Griffith University

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Altered brain connection found in people with ME/CFS and Long COVID

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Credit: Griffith University

People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID experience a disruption to their brain connectivity during a mentally demanding task.

The new Griffith University research, published today, used ultra-high field MRI technology to investigate the significant reduction in brain connectivity in specific parts of the brain.

Professor Sonya Marshall-Gradisnik from Griffith’s National Centre for Neuroimmunology and Emerging Diseases said there were common symptoms experienced by people with ME/CFS or Long COVID with this study focusing on neurological features.

“The symptoms include cognitive difficulties, such as memory problems, difficulties with attention and concentration, and slowed thinking,” Professor Marshall-Gradisnik said.

Lead author and PhD candidate Maira Inderyas said the study saw participants undertake a cognitive test while inside the MRI machine to gauge their brain activity.

“The task, called a Stroop task, was displayed to the participants on a screen during the scan, and required participants to ignore conflicting information and focus on the correct response, which places high demands on the brain’s executive function and inhibitory control,” Ms Inderyas said.

“The set up allowed us to precisely measure which areas of the brain were activated while the patient was performing a mentally demanding task.

“The scans show changes in the brain regions which may contribute to cognitive difficulties such as memory problems, difficulty concentrating, and slower thinking.”

The research supported what many people with ME/CFS and Long COVID experience which was that cognitive effort was not just tiring but could have real neurological impacts, and adequate rest was not optional but essential.

The ultra-high field MRI used in the study was one of only two available in Australia.

The research was funded by ME Research UK and the Stafford Fox Medical Research Foundation.

The paper ‘Distinct functional connectivity patterns in myalgic encephalomyelitis and Long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study’ has been published in the Journal of Translational Medicine.

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Journal

Journal of Translational Medicine

DOI

10.1186/s12967-026-07708-y 

Method of Research

Case study

Subject of Research

People

Article Title

Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study

Article Publication Date

29-Jan-2026