Scientists produce strongest evidence yet of schizophrenia's causes

June 3, 2015
Functional magnetic resonance imaging (fMRI) and other brain imaging technologies allow for the study of differences in brain activity in people diagnosed with schizophrenia. The image shows two levels of the brain, with areas that were more active in healthy controls than in schizophrenia patients shown in orange, during an fMRI study of working memory. Credit: Kim J, Matthews NL, Park S./PLoS One.

An international team of scientists led by Cardiff University researchers has provided the strongest evidence yet of what causes schizophrenia - a condition that affects around 1% of the global population.

Published today in the journal Neuron, their work presents strong evidence that disruption of a delicate chemical balance in the brain is heavily implicated in the disorder.

In the largest ever study of its kind, the team found that disease-linked mutations disrupt specific sets of genes contributing to excitatory and inhibitory signalling, the balance of which plays a crucial role in healthy brain development and function.

The breakthrough builds on two landmark studies led by members of the Cardiff University team, published last year in the journal Nature.

"We're finally starting to understand what goes wrong in ," says lead author Dr Andrew Pocklington from Cardiff University's MRC Centre for Neuropsychiatric Genetics and Genomics.

"Our study marks a significant step towards understanding the biology underpinning schizophrenia, which is an incredibly complex condition and has up until very recently kept scientists largely mystified as to its origins.

"We now have what we hope is a pretty sizeable piece of the jigsaw puzzle that will help us develop a coherent model of the disease, while helping us to rule out some of the alternatives.

"A reliable model of disease is urgently needed to direct future efforts in developing new treatments, which haven't really improved a great deal since the 1970s."

Professor Hugh Perry, who chairs the Medical Research Council Neuroscience and Mental Health Board said: "This work builds on our understanding of the genetic causes of schizophrenia - unravelling how a combination of genetic faults can disrupt the chemical balance of the brain.

"Scientists in the UK, as part of an international consortium, are uncovering the genetic causes of a range of mental health issues, such as schizophrenia.

"In the future, this work could lead to new ways of predicting an individual's risk of developing schizophrenia and form the basis of new targeted treatments that are based on an individual's genetic makeup."

A healthy brain is able to function properly thanks to a precise balance between chemical signals that excite and inhibit nerve cell activity. Researchers studying psychiatric disorders have previously suspected that disruption of this balance contributes to schizophrenia.

The first evidence that schizophrenia mutations interfere with excitatory signalling was uncovered in 2011 by the same team, based at Cardiff University's MRC Centre for Neuropsychiatric Genetics and Genomics.

This paper not only confirms their previous findings, but also provides the first strong genetic evidence that disruption of inhibitory signalling contributes to the disorder.

To reach their conclusions scientists compared the genetic data of 11,355 patients with schizophrenia against a control group of 16,416 people without the condition.

They looked for types of mutation known as copy number variants (CNVs), mutations in which large stretches of DNA are either deleted or duplicated.

Comparing the CNVs found in people with schizophrenia to those found in unaffected people, the team was able to show that the mutations in individuals with the disorder tended to disrupt genes involved in specific aspects of brain function.

The disease-causing effects of CNVs are also suspected to be involved in other neurodevelopmental disorders such as intellectual disability, Autism Spectrum Disorder and ADHD.

Around 635,000 people in the UK will at some stage in their lives be affected by schizophrenia.

The estimated cost of schizophrenia and psychosis to society is around £11.8 billion a year.

The symptoms of schizophrenia can be extremely disruptive, and have a large impact on a person's ability to carry out everyday tasks, such as going to work, maintaining relationships and caring for themselves or others.

Explore further: How a risk gene for schizophrenia affects the brain

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9 comments

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oliverlu70
1 / 5 (2) Jun 03, 2015
However the article says nothing about which genes may be involved in the process of disrupting the putative chemical imbalance in other words much ado about nothing (yet once again).

(Saying a disease causes the mutations which causes the disease is a circular argument.)

It's also untrue that treatments haven't improved, there have been psychosocial treatments proven to help but their funding was cut for political reasons.
TheGhostofOtto1923
1 / 5 (1) Jun 03, 2015
However the article says nothing about which genes may be involved in the process of disrupting the putative chemical imbalance in other words much ado about nothing (yet once again).

(Saying a disease causes the mutations which causes the disease is a circular argument.)

It's also untrue that treatments haven't improved, there have been psychosocial treatments proven to help but their funding was cut for political reasons.
I think they are saying that other diseases cause these mutations which lead to schizophrenia. Doesnt that make more sense?

Why would scientists make the obvious mistake you are accusing them of?
LaPortaMA
not rated yet Jun 03, 2015
Are you a clock?
Is the finding a cause, an effect, or an epiphenomenon?
stevmg
not rated yet Jun 03, 2015
We always knew a familial clustering of insanity from years ago. Other than avoidance of marrying someone from a nutty family the study of genetics in the cause of nuttiness has been fruitless. So what about treatments? Nothing in this "study" contributes to any practical approach to schizophrenia treatment.
TogetherinParis
1 / 5 (3) Jun 04, 2015
Schizophrenia results from pheromone insult and pheromone deficiency. It's remedy should be sub gram quantities of healthy adult male facial skin surface lipid p.o. and time to heal.
oliverlu70
not rated yet Jun 04, 2015
I think they are saying that other diseases cause these mutations which lead to schizophrenia. Doesnt that make more sense?

Why would scientists make the obvious mistake you are accusing them of?

It's not clear that the first disease is schizophrenia itself, however, the fact they don't cite which disease(s) they're referring to raises the question of the value of their "finding(s)".

"Scientists" are capable of circular reasoning just look at how psychiatric disorders are defined in terms of symptoms which are caused by...the disorder itself.
darrer
1 / 5 (1) Jun 04, 2015
Like most of science today, it has regressed to spontaneous generations of 'disease'. What has caused the Big Bang? I want withheld the fact that every new invention was caused by someone with a kind of psychosis, nor the tenth percent of left-hand people that psychiatrists don't have the balls to call ill. At least, schizophrenics hear different voices. Most people only hear one and they do what it says! Don't believe in cheap explanations like the one you've just read!
plaasjaapie
not rated yet Jun 07, 2015
A little more detail in he press release would have been helpful... :-/
Noodle_Naut
not rated yet Jun 07, 2015
I think any condition that affects reproductive success is triggered if not outright caused by a pathogen of some kind. At least, anything above the incidence attributable to random mutation. If it was genetically caused, it would have been selected away a long time ago or reduced to a very low incidence.

Every few years we discover a pathogen is responsible for a disease we thought was due to lifestyle, personality, or diet, and the favorite..."how we respond to stress".

Ulcers, lower back pain, quite possible type 2 diabetes (there is recent evidence linking diabetes to superantigens from staph bacteria), about 30% cancers thus far, and well, many things we chalk up to bad genes, stress, diet...

We have attempted to protect people from all the pathogens that kill people right away...just statistically there must be many that do their work over much more time, or just set things in motion. The very antibodies we make for something may be detrimental to us later.

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