Posts tagged schizophrenia
Articles and news from the latest research reports.
Difficult-to-study diseases such as Alzheimer’s, schizophrenia, and autism now can be probed more safely and effectively thanks to an innovative new method for obtaining mature brain cells called neurons from reprogrammed skin cells. According to Gong Chen, the Verne M. Willaman Chair in Life Sciences and professor of biology at Penn State University and the leader of the research team, “the most exciting part of this research is that it offers the promise of direct disease modeling, allowing for the creation, in a Petri dish, of mature human neurons that behave a lot like neurons that grow naturally in the human brain.” Chen added that the method could lead to customized treatments for individual patients based on their own genetic and cellular information. The research will be published in the journal Stem Cell Research.
"Obviously, we don’t want to remove someone’s brain cells to experiment on, so recreating the patient’s brain cells in a Petri dish is the next best thing for research purposes and drug screening," Chen said. Chen explained that, in earlier work, scientists had found a way to reprogram skin cells from patients to become unspecialized or undifferentiated pluripotent stem cells (iPSCs). "A pluripotent stem cell is a kind of blank slate," Chen explained. "During development, such stem cells differentiate into many diverse, specialized cell types, such as a muscle cell, a brain cell, or a blood cell. So, after generating iPSCs from skin cells, researchers then can culture them to become brain cells, or neurons, which can be studied safely in a Petri dish."
Now, in their new research, Chen and his team have found a way to differentiate iPSCs into mature human neurons much more effectively, generating cells that behave similarly to neurons in the brain. Chen explained that, in their natural environment, neurons are always found in close proximity to star-shaped cells called astrocytes, which are abundant in the brain and help neurons to function properly. “Because neurons are adjacent to astrocytes in the brain, we predicted that this direct physical contact might be an integral part of neuronal growth and health,” Chen explained.
To test this hypothesis, Chen and his colleagues began by culturing iPSC-derived neural stem cells, which are stem cells that have the potential to become neurons. These cells were cultured on top of a one-cell-thick layer of astrocytes so that the two cell types were physically touching each other.
"We found that these neural stem cells cultured on astrocytes differentiated into mature neurons much more effectively," Chen said, contrasting them with other neural stem cells that were cultured alone in a Petri dish. "It was almost as if the astrocytes were cheering the stem cells on, telling them what to do, and helping them fulfill their destiny to become neurons."
To demonstrate the superiority of the neurons grown next to astrocytes, Chen and his co-authors used an electrophysiology recording technique to show that the cells grown on astrocytes had many more synaptic events — signals sent out from one nerve cell to the others. In another experiment, after growing the neural stem cells next to astrocytes for just one week, the researchers showed that the newly differentiated neurons start to fire action potentials — the rapid electrical excitation signal that occurs in all neurons in the brain. In a final test, the team members added human neural stem cells to a mixture with mouse neurons. “We found that, after just one week, there was a lot of ‘cross-talk’ between the mouse neurons and the human neurons,” Chen said. He explained that “cross-talk” occurs when one neuron contacts its neighbors and releases a chemical called a neurotransmitter to modulate its neighbor’s activity.
"Previous researchers could only obtain brain cells from deceased patients who had suffered from diseases such as Alzheimer’s, schizophrenia, and autism," Chen said. "Now, researchers can take skin cells from living patients — a safe and minimally invasive procedure — and convert them into brain cells that mimic the activity of the patient’s own brain cells." Chen added that, by using this method, researchers also can figure out how a particular drug will affect a particular patient’s own brain cells, without needing the patient to try the drug — eliminating the risk of serious side effects. "The patient can be his or her own guinea pig for the design of his or her own treatment, without having to be experimented on directly," Chen said.
Neurochemical Traffic Signals May Open New Avenues for the Treatment of Schizophrenia
Researchers at Boston University School of Medicine (BUSM) have uncovered important clues about a biochemical pathway in the brain that may one day expand treatment options for schizophrenia. The study, published online in the journal Molecular Pharmacology, was led by faculty within the department of pharmacology and experimental therapeutics at BUSM.
Patients with schizophrenia suffer from a life-long condition that can produce delusions, disordered thinking, and breaks with reality. A number of treatments are available for schizophrenia, but many patients do not respond to these therapies or experience side effects that limit their use.
This research focused on key components of the brain known as NMDA receptors. These receptors are located on nerve cells in the brain and serve as biochemical gates that allow calcium ions (electrical charges) to enter the cell when a neurotransmitter, such as glutamate, binds to the receptor. Proper activation of these receptors is critical for sensory perception, memory and learning, including the transfer of short-term memory into long-term storage. Patients with schizophrenia have poorly functioning or “hypoactive” NMDA receptors, suggesting the possibility of treatment with drugs that positively affect these receptors. Currently the only way to enhance NMDA receptor function is through the use of agents called agonists that directly bind to the receptor on the outer surface of the cell, opening the gates to calcium ions outside the cell.
In this study, the researchers discovered a novel “non-canonical” pathway in which NMDA receptors residing inside the cell are stimulated by a neuroactive steroid to migrate to the cell surface (a process known as trafficking), thus increasing the number of receptors available for glutamate activation. The researchers treated neural cells from the cerebral cortex with the novel steroid pregnenolone sulfate (PregS) and found that the number of working NMDA receptors on the cell surface increased by 60 to 100 percent within 10 minutes. The exact mechanism by which this occurs is not completely clear, but it appears that PregS increases calcium ions within the cell, which in turn produces a green light signal for more frequent trafficking of NMDA receptors to the cell surface.
Although still in the early stages, further research in this area may be instrumental in the development of treatments not only for schizophrenia, but also for other conditions associated with malfunctioning NMDA receptors, such as age-related decreases in memory and learning ability.
Avatar therapy helps silence voices in schizophrenia
An avatar system that enables people with schizophrenia to control the voice of their hallucinations is being developed by researchers at UCL with support from the Wellcome Trust.
The computer-based system could provide quick and effective therapy that is far more successful than current pharmaceutical treatments, helping to reduce the frequency and severity of episodes of schizophrenia.
In an early pilot of this approach involving 16 patients and up to seven, 30 minute sessions of therapy, almost all of the patients reported an improvement in the frequency and severity of the voices that they hear. Three of the patients stopped hearing voices completely after experiencing 16, 13 and 3.5 years of auditory hallucinations, respectively. The avatar does not address the patients’ delusions directly, but the study found that they do improve as an overall effect of the therapy.
The team has now received a £1.3 million Translation Award from the Wellcome Trust to refine the system and conduct a larger scale, randomised study to evaluate this novel approach to schizophrenia therapy which will be conducted at King’s College London Institute of Psychiatry.
The first stage in the therapy is for the patient to create a computer-based avatar, by choosing the face and voice of the entity they believe is talking to them. The system then synchronises the avatar’s lips with its speech, enabling a therapist to speak to the patient through the avatar in real time. The therapist encourages the patient to oppose the voice and gradually teaches them to take control of their hallucinations.
Julian Leff, Emeritus Professor in UCL Mental Health Sciences, developed the therapy and is leading the project. He said: “Even though patients interact with the avatar as though it was a real person, because they have created it, they know that it cannot harm them, as opposed to the voices, which often threaten to kill or harm them and their family. As a result the therapy helps patients gain the confidence and courage to confront the avatar, and their persecutor.
“We record every therapy session on MP3 so that the patient essentially has a therapist in their pocket which they can listen to at any time when harassed by the voices. We’ve found that this helps them to recognise that the voices originate within their own mind and reinforces their control over the hallucinations.
The larger-scale study will begin enrolling the first patients in early July. The team are currently training the therapists and research staff to deliver the avatar therapy and finalising the study set-up. The first results of this larger study are expected towards the end of 2015.
Professor Thomas Craig of King’s College London Institute of Psychiatry, who will lead the larger trial, said: “Auditory hallucinations are a very distressing experience that can be extremely difficult to treat successfully, blighting patients’ lives for many years. I am delighted to be leading the group that will carry out a rigorous randomised study of this intriguing new therapy with 142 people who have experienced distressing voices for many years.
“The beauty of the therapy is its simplicity and brevity. Most other psychological therapies for these conditions are costly and take many months to deliver. If we show that this treatment is effective, we expect it could be widely available in the UK within just a couple of years as the basic technology is well developed and many mental health professionals already have the basic therapy skills that are needed to deliver it.”
Schizophrenia affects around 1 in 100 people worldwide, the most common symptoms being delusions (false beliefs) and auditory hallucinations (hearing voices). The illness often has a devastating effect, making it impossible to work and to sustain social relationships. Even with the most effective anti-psychotic medication, around one in four people with schizophrenia continue to suffer from persecutory auditory hallucinations, severely impairing their ability to concentrate.
Current guidelines from the National Institute for Health and Care Excellence (NICE) recommend that schizophrenia is treated using a combination of medication and talking therapies, such as cognitive behavioural therapy. However, fewer than one in ten patients with schizophrenia in the UK have access to this kind of psychological therapy.
Ted Bianco, Director of Technology Transfer and Acting Director of the Wellcome Trust, said: “At a time when many companies have become wary about investing in drug discovery for mental health, we are delighted to be able to facilitate the evaluation of an alternative approach to treatment based on the fusion of a talking therapy with computer-assisted ‘training’.
“In addition to the attraction that the intervention is not reliant on development of a new medication, the approach has the benefit of being directly testable in patients. Should the results of the trial prove encouraging, we expect there may be further applications of the basic strategy worth exploring in other areas of mental health.”
Lead Acts to Trigger Schizophrenia
Study in Mice Points to a Synergistic Relationship Between Lead Exposure and Schizophrenia Gene
Mice engineered with a human gene for schizophrenia and exposed to lead during early life exhibited behaviors and structural changes in their brains consistent with schizophrenia. Scientists at Columbia University’s Mailman School of Public Health and the Johns Hopkins University School of Medicine say their findings suggest a synergistic effect between lead exposure and a genetic risk factor, and open an avenue to better understanding the complex gene-environment interactions that put people at risk for schizophrenia and other mental disorders.
Results appear online in Schizophrenia Bulletin.
Going back to 2004, work by scientists at the Mailman School suggested a connection between prenatal lead exposure in humans and increased risk for schizophrenia later in life. But a big question remained: How could lead trigger the disease? Based on his own research, Tomás R. Guilarte, PhD, senior author of the new study, believed the answer was in the direct inhibitory effect of lead on the N-methyl-D-aspartate receptor (NMDAR), a synaptic connection point important to brain development, learning, and memory. His research in rodents found that exposure to lead blunted the function of the NMDAR. The glutamate hypothesis of schizophrenia postulates that a deficit in glutamate neurotransmission and specifically hypoactivity of the NMDAR can explain a significant portion of the dysfunction in schizophrenia.
In the new study, Dr. Guilarte, professor and chair of the department of Environmental Health Sciences at the Mailman School, and his co-investigators focused on mice engineered to carry the mutant form of Disrupted-in-Schizophrenia-1 (DISC1), a gene that is a risk factor for the disease in humans. Beginning before birth, half of the mutant DISC1 mice were fed a diet with lead, and half were given a normal diet. A second group of normal mice not expressing the mutant DISC1 gene were also split into the two feeding groups. All mice were put through a battery of behavioral tests and their brains were examined using MRI.
Mutant mice exposed to lead and given a psychostimulant exhibited elevated levels of hyperactivity and were less able to suppress a startle in response to a loud noise after being given an acoustic warning. Their brains also had markedly larger lateral ventricles—empty spaces containing cerebrospinal fluid—compared with other mice. These results mirror what is known about schizophrenia in humans.
While the role of genes in schizophrenia and mental disorders is well established, the effect of toxic chemicals in the environment is only just beginning to emerge. The study’s results focus on schizophrenia, but implications could be broader.
“We’re just scratching the surface,” says Dr. Guilarte. “We used lead in this study, but there are other environmental toxins that disrupt the function of the NMDAR.” One of these is a family of chemicals in air pollution called polycyclic aromatic hydrocarbons or PAHs. “Similarly, any number of genes could be in play,” adds Dr. Guilarte, noting that DISC1 is among many implicated in schizophrenia.
Future research may reveal to what extent schizophrenia is determined by environmental versus genetic factors or their interactions, and what other mental problems might be in the mix. One ongoing study by Dr. Guilarte is looking at whether lead exposure alone can contribute to deficits of one specialized type of neuron called parvalbumin-positive GABAergic interneuron that is known to be affected in the brain of schizophrenia patients. Scientists are also interested to establish the critical window for exposure—whether in utero or postnatal, or both.
“The animal model provides a way forward to answer important questions about the physiological processes underlying schizophrenia,” says Dr. Guilarte.
(Image: Flickr)
Help at hand for schizophrenics
Researchers from the Bergen fMRI Group at the University of Bergen (UiB) are working on how to help schizophrenics, who hear voices. The way they do this is by studying people who also hear voices, but who do not suffer from a mental illness. For a five-year period, the group is studying the brain processes causing people to hear voices. A recent report published in Frontiers in Human Neuroscience shows some of the group’s startling results.
– We have found that the primary auditory cortex of healthy people who hear voices, responds less to outside stimulus than the corresponding area of the brain in people who don’t hear voices, says Post Doctor Kristiina Kompus.
Kompus, who works at UiB’s Department of Biological and Medical Psychology, is lead author of the just published study.
Variations in cognitive control
The primary auditory cortex is the region of the brain that processes sound. Kompus’ study shows that healthy people who hear voices share some attributes with schizophrenics, as the cortical region in both groups reacts less to outside stimulus.
However, there is an important difference between people who hear voices. Whilst those with schizophrenia have a reduced ability to regulate the primary auditory cortex using cognitive control, those who hear voices but are healthy are able to do so.
– Because of this cognitive control, healthy people who hear voices are able to direct their attention outwards. This sets them apart from schizophrenics, who have a tendency to direct their attention inwards due to their decreased ability to regulate their primary auditory cortex, says Kompus before adding.
– These discoveries have brought us one step close to understanding the hallucinations of schizophrenics and why the voices become a problem for some people but not for others.
Many healthy people hear voices
So what is the next step for Kompus and her fellow researchers?
– We will do further research on the brain structure of people with auditory hallucinations. In particular, we wish to look at the brain’s networks that process outside voices. This is to establish whether these voice hallucinations and the outside voices occur in the same parts of the brain. We also wish to establish if hearing voices is a genetical trait, she says.
According to the researchers, approximately five per cent of us hear voices in the head, even if otherwise healthy. This number is based on research from several countries and surveys. For their own research, Kompus and her team used local media in Bergen to call for people who hear voices. The results were overwhelming, with around 30 people getting in touch with the researchers to register for the study.
Pay attention: How we focus and concentrate
Scientists at Newcastle University have shed new light on how the brain tunes in to relevant information.
Publishing in Neuron, the team reveal the interplay of brain chemicals which help us pay attention in work funded by the Wellcome Trust and BBSRC.
By changing the way neurons respond to external stimuli we improve our perceptual abilities. While these changes can affect the strength of a neuronal response, they can also affect the fidelity of that response.
Lead author Alex Thiele, Professor of Visual Neuroscience explains: “When you communicate with others, you can make yourself better heard by speaking louder or by speaking more clearly. Neurons appear to do similar things when we’re paying attention. They send their message more intensely to their partners, which compares to speaking louder. But more importantly, they also increase the fidelity of their message, which compares to speaking more clearly.
“Our earlier work has shown that attention is able to affect the intensity of responses – in effect the loudness - by means of the brain chemical acetylcholine. Now we have shown that the fidelity of the response is altered by a different brain chemical system.”
In the paper, the team reveal that the quality of the response is altered by means of glutamate coupling to NMDA receptors (a molecular device that mediates communication between neurons). Carried out in a primate model, these studies for the first time isolate different attention mechanisms at the receptor level.
The research builds on the team’s previous studies and has potentially significant implications not only for our understanding of how our brains work but also give an insight into conditions such as schizophrenia, Alzheimer’s disease and attention deficit disorder, and may aid in the development of treatments for them.
Taming suspect gene reverses schizophrenia-like abnormalities in mice
Scientists have reversed behavioral and brain abnormalities in adult mice that resemble some features of schizophrenia by restoring normal expression to a suspect gene that is over-expressed in humans with the illness. Targeting expression of the gene Neuregulin1, which makes a protein important for brain development, may hold promise for treating at least some patients with the brain disorder, say researchers funded by the National Institutes of Health.
Like patients with schizophrenia, adult mice biogenetically-engineered to have higher Neuregulin 1 levels showed reduced activity of the brain messenger chemicals glutamate and GABA. The mice also showed behaviors related to aspects of the human illness. For example, they interacted less with other animals and faltered on thinking tasks.
“The deficits reversed when we normalized Neuregulin 1 expression in animals that had been symptomatic, suggesting that damage which occurred during development is recoverable in adulthood,” explained Lin Mei, M.D., Ph.D.External Web Site Policy , of the Medical College of Georgia at Georgia Regents University, a grantee of NIH’s National Institute of Mental Health (NIMH).
Mei, Dong-Min Yin, Ph.D., Yong-Jun Chen, Ph.D., and colleagues report on their findings May 22, 2013 in the journal Neuron.
“While mouse models can’t really do full justice to a complex brain disorder that impairs our most uniquely human characteristics, this study demonstrates the potential of dissecting the workings of intermediate components of disorders in animals to discover underlying mechanisms and new treatment targets,” said NIMH Director Thomas R. Insel, M.D. “Hopeful news about how an illness process that originates early in development might be reversible in adulthood illustrates the promise of such translational research.”
Schizophrenia is thought to stem from early damage to the developing fetal brain, traceable to a complex mix of genetic and environmental causes. Although genes identified to date account for only a small fraction of cases, evidence has implicated variation in the Neuregulin 1 gene. For example, postmortem studies have found that it is overexpressed in the brain’s thinking hub, or prefrontal cortex, of some people who had schizophrenia. It codes for a chemical messenger that plays a pivotal role in communication between brain cells, as well as in brain development.
Prior to the new study, it was unclear whether damage caused by abnormal prenatal Neuregulin 1 expression might be reversible in adulthood. Nor was it known whether any resulting behavioral and brain deficits must be sustained by continued errant Neuregulin 1 expression in adulthood.
To find out, the researchers engineered laboratory mice to mimic some components of the human illness by over-expressing the Neuregulin 1 gene in the forebrain, comparable to the prefrontal cortex in humans. Increasing Neuregulin 1 expression in adult animals was sufficient to produce behavioral features, such as hyperactivity, social and cognitive impairments, and to hobble neural communications via the messenger chemicals glutamate and GABA.
Unexpectedly, the abnormalities disappeared when the researchers experimentally switched off Neuregulin 1 overexpression in the adult animals. Treatment with clozapine, an antipsychotic medication, also reversed the behavioral abnormalities. The researchers traced the glutamate impairment to an errant enzyme called LIMK1, triggered by the overexpressed Neuregulin 1 — a previously unknown potential pathological mechanism in schizophrenia.
The study results suggest that even if their illness stems from disruptions early in brain development, adult patients whose schizophrenia is rooted in faulty Neuregulin 1 activity might experience a reduction in some of the symptoms following treatments that target overexpression of the protein, say the researchers.
Children’s brain processing speed indicates risk of psychosis
New research from Bristol and Cardiff universities shows that children whose brains process information more slowly than their peers are at greater risk of psychotic experiences.
These can include hearing voices, seeing things that are not present or holding unrealistic beliefs that other people don’t share. These experiences can often be distressing and frightening and interfere with their everyday life.
Children with psychotic experiences are more likely to develop psychotic illnesses like schizophrenia later in life.
Using data gathered from 6,784 participants in Children of the 90s, researchers from the MRC Centre for Neuropsychiatric Genetics and Genomics in Cardiff University and the School of Social and Community Medicine in the University of Bristol examined whether performance in a number of cognitive tests conducted at ages 8, 10 and 11 was related to the risk of having psychotic experiences at age 12.
The tests assessed how quickly the children could process information, as well as their attention, memory, reasoning, and ability to solve problems.
Among those interviewed, 787 (11.6 per cent) had suspected or definite psychotic experiences at age 12. Children that scored less well in the various tests at the ages of 8, 10 and 11 were more likely to have psychotic experiences at age 12.
This was particularly the case for the test that assessed how quickly the children processed information. Furthermore, children whose speed of processing information became slower between ages 8 and 11 had greater risk of having psychotic experiences at age 12.
These findings did not change when other factors, including the parent’s psychiatric history and the children’s own developmental delay, were taken into account. The study’s findings could have important implications for identifying children at risk of psychosis, with the benefit of early treatment.
Speaking about the findings, lead author and PhD student, Miss Maria Niarchou from Cardiff University’s School of Medicine, said:
‘Previous research has shown a link between the slowing down of information processing and schizophrenia and this was found to be at least in part the result of anti-psychotic medication.‘However, this study shows that impaired information processing speed can already be present in childhood and associated with higher risk of psychotic experiences, irrespective of medication.
‘Our findings improve our understanding of the brain processes that are associated with high risk of psychotic experiences in childhood and in turn high risk of psychotic disorder later in life.’
Senior author, Dr Marianne van den Bree of Cardiff University’s School of Medicine, said:
‘Schizophrenia is a complex and relatively rare mental health condition, occurring at a rate of 1 per cent in the general population. Not every child with impaired information processing speed is at risk of psychosis later in life. Further research is needed to determine whether interventions to improve processing speed in at-risk children can lead to decreased transition to psychotic disorders.’
Ruth Coombs, Manager for Influence and Change at Mind Cymru, said:
‘This is a very interesting piece of research, which could help young people at risk of developing mental health problems in later life build resilience and benefit from early intervention. It is important to remember that people can and do recover from mental health problems and we also welcome further research which supports resilience building in young people.’
(Source: bristol.ac.uk)
Sniffing Out Schizophrenia
Neurons in the nose could be the key to early, fast, and accurate diagnosis, says a TAU researcher
A debilitating mental illness, schizophrenia can be difficult to diagnose. Because physiological evidence confirming the disease can only be gathered from the brain during an autopsy, mental health professionals have had to rely on a battery of psychological evaluations to diagnose their patients.
Now, Dr. Noam Shomron and Prof. Ruth Navon of Tel Aviv University’s Sackler Faculty of Medicine, together with PhD student Eyal Mor from Dr. Shomron’s lab and Prof. Akira Sawa of Johns Hopkins Hospital in Baltimore, Maryland, have discovered a method for physical diagnosis — by collecting tissue from the nose through a simple biopsy. Surprisingly, collecting and sequencing neurons from the nose may lead to “more sure-fire” diagnostic capabilities than ever before, Dr. Shomron says.
This finding, which was reported in the journal Neurobiology of Disease, could not only lead to a more accurate diagnosis, it may also permit the crucial, early detection of the disease, giving rise to vastly improved treatment overall.
From the nose to diagnosis
Until now, biomarkers for schizophrenia had only been found in the neuron cells of the brain, which can’t be collected before death. By that point it’s obviously too late to do the patient any good, says Dr. Shomron. Instead, psychiatrists depend on psychological evaluations for diagnosis, including interviews with the patient and reports by family and friends.
For a solution to this diagnostic dilemma, the researchers turned to the olfactory system, which includes neurons located on the upper part of the inner nose. Researchers at Johns Hopkins University collected samples of olfactory neurons from patients diagnosed with schizophrenia and a control group of non-affected individuals, then sent them to Dr. Shomron’s TAU lab.
Dr. Shomron and his fellow researchers applied a high-throughput technology to these samples, studying the microRNA of the olfactory neurons. Within these molecules, which help to regulate our genetic code, they were able to identify a microRNA which is highly elevated in those with schizophrenia, compared to individuals who do not have the disease.
"We were able to narrow down the microRNA to a differentially expressed set, and from there down to a specific microRNA which is elevated in individuals with the disease compared to healthy individuals," explains Dr. Shomron. Further research revealed that this particular microRNA controls genes associated with the generation of neurons.
In practice, material for biopsy could be collected through a quick and easy outpatient procedure, using a local anesthetic, says Dr. Shomron. And with microRNA profiling results ready in a matter of hours, this method could evolve into a relatively simple and accurate test to diagnose a very complicated illness.
Early detection, early intervention
Though there is much more to investigate, Dr. Shomron has high hopes for this diagnostic method. It’s important to determine whether this alteration in microRNA expression begins before schizophrenic symptoms begin to exhibit themselves, or only after the disease fully develops, he says. If this change comes near the beginning of the timeline, it could be invaluable for early diagnostics. This would mean early intervention, better treatment, and possibly even the postponement of symptoms.
If, for example, a person has a family history of schizophrenia, this test could reveal whether they too suffer from the disease. And while such advanced warning doesn’t mean a cure is on the horizon, it will help both patient and doctor identify and prepare for the challenges ahead.
(Source: aftau.org)
Scientists unpack testosterone’s role in schizophrenia
Testosterone may trigger a brain chemical process linked to schizophrenia but the same sex hormone can also improve cognitive thinking skills in men with the disorder, two new studies show.
Scientists have long suspected testosterone plays an important role in schizophrenia, which affects more men than women. Men are also more likely to develop psychosis in adolescence, previous research has shown.
A new study on lab rodents by researchers from Neuroscience Research Australia analysed the impact increased testosterone had on levels of dopamine, a brain chemical linked to psychotic symptoms of schizophrenia.
The researchers found that testosterone boosted dopamine sensitivity in adolescent male rodents.
“From these rodent studies, we hypothesise that adolescent increases in circulating testosterone may be a driver of increased dopamine activity in the brains of individuals susceptible to psychosis and schizophrenia,” said senior Neuroscience Research Australia researcher and author of the study, Dr Tertia Purves-Tyson, who is presenting her work at the International Congress on Schizophrenia Research in Florida this week.
Dr Philip Mitchell, Scientia Professor and Head of the School of Psychiatry at the University of NSW, said the research was very interesting.
“The relationship between sex steroids, such as testosterone, and psychiatric disorders has long intrigued researchers. For example, we have known for many years that schizophrenia presents earlier in males than females, but the biological mechanism for this has been poorly understood,” said Dr Mitchell, who was not involved in the study.
“The rodent study by Professor Shannon Weickert from the School of Psychiatry at UNSW and NeuRA is therefore of particular interest. This study suggests an important interplay between circulating testosterone levels and the brain’s sensitivity to dopamine – a neurochemical which has been long implicated in the cause of schizophrenia,” said Dr Mitchell.
“This study suggests that it is the interplay between testosterone and dopamine which is critical. This is an important observation which may very well throw an important light on solving the puzzle of the biological causes of schizophrenia.”
Cognitive thinking
A separate study by Dr Thomas Weickert at Neuroscience Research Australia examined the role testosterone plays in the cognitive thinking skills of men with schizophrenia.
The researchers examined testosterone levels in a group of 29 chronically ill men with schizophrenia or schizoaffective disorder, and a control group of 20 healthy men and asked both groups to take a series of cognition tests.
“Circulating testosterone levels significantly predicted performance on verbal memory, processing speed, and working memory in men with schizophrenia … such that increased normal levels of testosterone were beneficial to thought processing in men with schizophrenia but circulating sex steroid levels did not appear to be related to cognitive function in healthy men,” the researchers reported.
“The results suggest that circulating sex steroids may influence thought processes in men with schizophrenia.”
Dr Melanie McDowall, a researcher at the University of Adelaide’s Robinson Institute, said the study added to a large body of evidence demonstrating a link between testosterone and schizophrenia.
“This is not surprising, given the link between testosterone and dopamine,” she said, adding that symptoms of schizophrenia predominantly began after puberty.
“However, as with most endocrine and mental illnesses, schizophrenia is multifaceted (genetic, environmental etc.), hence this may not be the be all and end.”
(Source: theconversation.com)