Tag Archives: #mentalillness

Machine Learning Could Aid Mental Health diagnoses (Psychiatry)

A way of using machine learning to more accurately identify patients with a mix of psychotic and depressive symptoms has been developed by researchers at the University of Birmingham.

Patients with depression or psychosis rarely experience symptoms of purely one or the other illness. Historically, this has meant that mental health clinicians give a diagnosis of a ‘primary’ illness, but with secondary symptoms. Making an accurate diagnosis is a big challenge for clinicians and diagnoses often do not accurately reflect the complexity of individual experience or indeed neurobiology.

Clinicians diagnosing psychosis, for example, would frequently regard depression as a secondary illness, with implications for treatment decisions which focus more on psychosis symptoms (e.g. hallucinations or delusions).

A team at the University of Birmingham’s Institute for Mental Health and Centre for Human Brain Health, working with researchers from the PRONIA consortium wanted to explore the possibility of using machine learning to create highly accurate models of ‘pure’ forms of both illnesses and to use these to investigate the diagnostic accuracy of a cohort of patients with mixed symptoms. Their results are published in Schizophrenia Bulletin.

“The majority of patients have co-morbidities, so people with psychosis also have depressive symptoms and vice versa”, explains lead author Paris Alexandros Lalousis. “That presents a big challenge for clinicians in terms of diagnosing and then delivering treatments that are designed for patients without co-morbidity. It’s not that patients are misdiagnosed, but the current diagnostic categories we have do not accurately reflect the clinical and neurobiological reality”.

The researchers examined questionnaire responses, detailed clinical interviews and data from structural magnetic resonance imaging from a cohort of 300 patients taking part in the PRONIA study, a European Union-funded cohort study taking place across seven European research centres (www.pronia.eu).

Within this cohort, the researchers identified small subgroups of patients who could be classified as suffering either from psychosis without any symptoms of depression, or from depression without any psychotic symptoms.

Using this data, the team identified machine learning models of ‘pure’ depression, and ‘pure’ psychosis. They were then able to use machine learning methods to apply these models to patients with symptoms of both illnesses. The aim was to build a highly accurate disease profile for each patient and test that against their diagnosis to see how accurate it was.

The team found that, while patients with depression as a primary illness were more likely to be diagnosed accurately, patients with psychosis with depression had symptoms which most frequently tended towards the depression dimension. This may indicate that depression plays a greater part in the illness than had previously been thought.

Mr Lalousis added: “There is a pressing need for better treatments for psychosis and depression, conditions which constitute a major mental health challenge worldwide. Our study highlights the need for clinicians to understand better the complex neurobiology of these conditions, and the role of ‘co-morbid’ symptoms; in particular considering carefully the role that depression is playing in the illness”.

“In this study we have shown how using sophisticated machine learning algorithms which take into account clinical, neurocognitive, and neurobiological factors can aid our understanding of the complexity of mental illness. In the future, we think machine learning could become a critical tool for accurate diagnosis. We have a real opportunity to develop data-driven diagnostic methods – this is an area in which mental health is keeping pace with physical health and it’s really important that we keep up that momentum.”


Reference: Paris Alexandros Lalousis, Stephen J Wood, Lianne Schmaal, Katharine Chisholm, Sian Lowri Griffiths, Renate L E P Reniers, Alessandro Bertolino, Stefan Borgwardt, Paolo Brambilla, Joseph Kambeitz, Rebekka Lencer, Christos Pantelis, Stephan Ruhrmann, Raimo K R Salokangas, Frauke Schultze-Lutter, Carolina Bonivento, Dominic Dwyer, Adele Ferro, Theresa Haidl, Marlene Rosen, Andre Schmidt, Eva Meisenzahl, Nikolaos Koutsouleris, Rachel Upthegrove, PRONIA Consortium, Heterogeneity and Classification of Recent Onset Psychosis and Depression: A Multimodal Machine Learning Approach, Schizophrenia Bulletin, 2021;, sbaa185, https://doi.org/10.1093/schbul/sbaa185


Provided by University of Birmingham

Hallucinations Induced in Lab Could be Key to Better Understanding And Treatment (Neuroscience)

Cognitive neuroscientists from UNSW Sydney say if we really want to understand and treat the pathological hallucinations that affect people with physical and mental illnesses, the best place to start is in the laboratory.

Hallucinations have been difficult to study and can be distressing for the person experiencing them, but hallucinations induced in the lab are much more benign. Credit: Shutterstock

Inducing hallucinations in the general population using visual stimulation procedures works similarly to illusions, and enables more objective and repeatable testing. It’s also much less distressing to the test subject than studying pathological hallucinations experienced by people with conditions like Parkinson’s disease or schizophrenia.

“By nature, [lab-induced hallucinations] can be induced in almost anyone at any time,” the neuroscientists write in an opinion piece published recently in Philosophical Transactions B journal.

“This can help to curb the current overreliance on studying pathological hallucinations, thereby reducing burdens placed on patients and simplifying recruitment and testing logistics.”

Seeing something that isn’t there

Most people naturally think of visual hallucinations as being realistic images or scenes, such as seeing humans or spiders (what we call ‘complex’ hallucinations). However, a hallucination in its broadest sense can be defined as the experience of seeing something that is not there. As such, visual hallucinations can also include seeing basic geometric shapes or colors (referred to as ‘simple’ hallucinations), and scientists can trigger both simple and complex hallucinations in the laboratory.

Professor Joel Pearson, the senior author of the opinion piece, says work the group did in 2016 showed that you could induce hallucinations in people reliably and safely using specific types of flickering lights.

“We showed that you could use flickering lights in an annulus—basically a flickering white ring like a doughnut on a black background—and you could induce hallucinations of little dark blobs which rotate around the ring,” he says.

“And you could use that to try and study the mechanisms behind visual hallucinations. But those flicker hallucinations are just the tip of the iceberg, and there are many other techniques for inducing hallucinations that are similar to pathological hallucinations in terms of the experience and underlying neural processes.”

Prof. Pearson says one of the trickier problems is working out which techniques can tell us something about pathological hallucinations.

“A lot of this work shows that it’s hard to separate hallucinations from illusions and veridical (reality-based) perception. Current hallucination definitions are too black and white, and aren’t up to the task of classifying many of these lab-induced experiences.”

Spectrum of experience

Professor Pearson and fellow authors Dr. Sebastian Rogers and Dr. Rebecca Keogh use a continuous spectrum of experience to distinguish hallucinations from other types of perception, based on the similarity between the physical stimulation of the senses (the light that enters the eye) and the actual conscious experience (the image we ‘see’ or experience).

Veridical perception (involving a strong relationship between what is ‘in reality’ and what one sees) is at one end of this spectrum and hallucinations (a weak relationship between what is present in reality and with what one sees) is at the other, with illusions falling somewhere in between.

According to lead author Dr. Rogers, “the thesis of the idea is that the further a lab-induced experience is toward the hallucination end of the spectrum, the more it can tell us about other types of hallucination.”

“If you really don’t want to call one of these lab-induced experiences a hallucination, that’s fine by us. We don’t really mind what the name is, we care most about whether we can study it to learn about pathological and other hallucinations. It’s a way to investigate hallucinatory processes any time we want in the lab, with anyone.”

Dr. Keogh says, “once we understand the underlying mechanisms, that is, what in the brain leads to seeing things that aren’t there, then we’ll be able to develop treatments. There are very few treatments for hallucinations at the moment, and most are medications that can lead to unwanted side effects.

“Using lab hallucination models can allow us to develop new avenues for more targeted treatments, such as electrical or magnetic brain stimulation.”

References: Sebastian Rogers et al. Hallucinations on demand: the utility of experimentally induced phenomena in hallucination research, Philosophical Transactions of the Royal Society B: Biological Sciences (2020). DOI: 10.1098/rstb.2020.0233

Provided by University of New South Wales

Study Sheds Light On Abnormal Neural Function In Rare Genetic Disorder (Neuroscience)

Findings show deficits in the electrical activity of cortical cells; possible targets for treatment for 22q11.2 deletion syndrome.

A genetic study has identified neuronal abnormalities in the electrical activity of cortical cells derived from people with a rare genetic disorder called 22q11.2 deletion syndrome. The overexpression of a specific gene and exposure to several antipsychotic drugs helped restore normal cellular functioning. The study, funded by the National Institutes of Health (NIH) and published in Nature Medicine, sheds light on factors that may contribute to the development of mental illnesses in 22q11.2 deletion syndrome and may help identify possible targets for treatment development.

This stylistic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). The chromosome is X-shaped because it is dividing. Introns are regions often found in eukaryote genes that are removed in the splicing process (after the DNA is transcribed into RNA): Only the exons encode the protein. The diagram labels a region of only 55 or so bases as a gene. In reality, most genes are hundreds of times longer. Credit: Thomas Splettstoesser/Wikipedia/CC BY-SA 4.0

22q11.2 deletion syndrome is a genetic disorder caused by the deletion of a piece of genetic material at location q11.2 on chromosome 22. People with 22q11.2 deletion syndrome can experience heart abnormalities, poor immune functioning, abnormal palate development, skeletal differences, and developmental delays. In addition, this deletion confers a 20-30% risk for autism spectrum disorder (ASD) and an up to 30-fold increase in risk for psychosis. 22q11.2 deletion syndrome is the most common genetic copy number variant found in those with ASD, and up to a quarter of people with this genetic syndrome develop a schizophrenia spectrum disorder.

“This is the largest study of its type in terms of the number of patients who donated cells, and it is significant for its focus on a key genetic risk factor for mental illnesses,” said David Panchision, Ph.D., chief of the Developmental Neurobiology Program at the NIH’s National Institute of Mental Health. “Importantly, this study shows consistent, specific patient-control differences in neuronal function and a potential mechanistic target for developing new therapies for treating this disorder.”

While some effects of this genetic syndrome, such as cardiovascular and immune concerns, can be successfully managed, the associated psychiatric effects have been more challenging to address. This is partly because the underlying cellular deficits in the central nervous system that contribute to mental illnesses in this syndrome are not well understood. While recent studies of 22q11.2 deletion syndrome in rodent models have provided some important insights into possible brain circuit-level abnormalities associated with the syndrome, more needs to be understood about the neuronal pathways in humans.

To investigate the neural pathways associated with mental illnesses in those with 22q11.2 deletion syndrome, Sergiu Pasca, M.D.(link is external), associate professor of psychiatry and behavioral sciences at Stanford University, Stanford, California, along with a team of researchers from several other universities and institutes, created induced pluripotent stems cells — cells derived from adult skin cells reprogramed into an immature stem-cell-like state — from 15 people with 22q11.2 deletion and 15 people without the syndrome. The researchers used these cells to create, in a dish, three-dimensional brain organoids that recapitulate key features of the developing human cerebral cortex.

“What is exciting is that these 3D cellular models of the brain self-organize and, if guided to resemble the cerebral cortex, for instance, contain functional glutamatergic neurons of deep and superficial layers and non-reactive astrocytes and can be maintained for years in culture. So, there is a lot of excitement about the potential of these patient-derived models to study neuropsychiatric disease,” said Dr. Pasca.

The researchers analyzed gene expression in the organoids across 100 days of development. They found changes in the expression of genes linked to neuronal excitability in the organoids that were created using cells from individuals with 22q11.2 deletion syndrome. These changes prompted the researchers to take a closer look at the properties associated with electrical signaling and communication in these neurons. One way neurons communicate is electrically, through controlled changes in the positive or negative charge of the cell membrane. This electrical charge is created when ions, such as calcium, move into or out of the cell through small channels in the cell’s membrane. The researchers imaged thousands of cells and recorded the electrical activity of hundreds of neurons derived from individuals with 22q11.2 deletion syndrome and found abnormalities in the way calcium was moved into and out of the cells that were related to a defect in the resting electrical potential of the cell membrane.

A gene called DGCR8 is part of the genetic material deleted in 22q11.2 deletion syndrome, and it has been previously associated with neuronal abnormalities in rodent models of this syndrome. The researchers found that heterozygous loss of this gene was sufficient to induce the changes in excitability they had observed in 22q11.2-derived neurons and that overexpression of DGCR8 led to partial restoration of normal cellular functioning. In addition, treating 22q11.2 deletion syndrome neurons with one of three antipsychotic drugs (raclopride, sulpiride, or olanzapine) restored the observed deficits in resting membrane potential of the neurons within minutes.

“We were surprised to see that loss in control neurons and restoration in patient neurons of the DGCR8 gene can induce and, respectively, restore the excitability, membrane potential, and calcium defects,” said Pasca. “Moving forward, this gene or the downstream microRNA(s) or the ion channel/transporter they regulate may represent novel therapeutic avenues in 22q11.2 deletion syndrome.”

References: Khan, T.A., Revah, O., Gordon, A. et al. Neuronal defects in a human cellular model of 22q11.2 deletion syndrome. Nat Med (2020). https://doi.org/10.1038/s41591-020-1043-9 link: http://www.nature.com/articles/s41591-020-1043-9

Provided by NIH

Folie A Duex Is The Psychosis You Share With The One You Love (Psychiatry)

When you live in close proximity to someone, it’s common for illness to spread from one person to another. But mental illness? It’s possible. The phenomenon is technically called shared psychotic disorder, but it’s most famously known as folie à deux.

The first case of the condition was documented in the 19th century and described a 30-something married couple, Margaret and Michael. The couple shared a delusion that people were sneaking into their house at night spreading dust, dropping pieces of fluff, and wearing down the soles of the couple’s shoes.

In another instance, not two, but three sisters experienced what could be called “folie à trois.” Two of the sisters moved into a house near a third sister to help her care for her children, and over time, all three became closer and more religious. At one point, the youngest began believing that there were troubling discrepancies between different versions of the Bible and became determined to make them right. For three days, the sisters prayed nonstop without sleeping until they believed that God wanted them to have a particular house in the town. Even though the house didn’t belong to them, the sisters went to the house and demanded to be let in, even breaking windows and attacking the occupant until police arrived.

According to a review published in the Canadian Journal of Psychiatry, shared psychotic disorder most often affects people in very close relationships, such as married couples, siblings, and parents and children. They’re also usually socially isolated, and often have pre-existing mental illness. The condition takes several forms, the most common and oldest known of which is “folie imposée,” or “imposed madness.” In that form, the more dominating person in the pair spreads his or her delusion to the more submissive, who doesn’t resist the ideas.

There’s also “folie simultanée”, or “simultaneous madness,” where two people with a deep connection both experience the delusion at once; “folie communiquée,” or “communicated madness,” which is like imposed madness except there’s a period of resistance from the second person; and “folie induite” or “induced madness,” which is like communicated madness except that extra delusions are spread from a second person.

Luckily, in most of these forms, the cure is simple: just separate the two people. When that doesn’t work — which, especially in cases of folie communiquée and folie induite, it may not — psychiatrists can resort to medication or electroconvulsive therapy. But, as Esther Inglis-Arkell of io9 points out, the tendency to share mental eccentricities isn’t always bad — and we all do it. “There are few old married [couples] who don’t share eccentricities. There are few families, or even close friendships, that don’t require both people to work with the various mental glitches of the other. We all go a little crazy for the other people in our lives.”