Posts Tagged ‘psychosis’

Longer duration of untreated psychosis was associated with accelerated hippocampal atrophy during initial antipsychotic treatment of first-episode schizophrenia, suggesting that psychosis may have persistent, negative effects on brain structure, according to finding published in JAMA Psychiatry.

“Several factors … have been linked to early psychosis and could mediate an association between [duration of untreated psychosis] and hippocampal volume loss, but evidence from longitudinal studies is lacking,” Donald C. Goff, MD, department of psychiatry, New York University Langone Medical Center, and colleagues wrote. “Whereas the negative association of [duration of untreated psychosis] with clinical course is attenuated by the initiation of antipsychotic treatment, the evidence is mixed as to whether antipsychotics contribute to loss of brain volume or protect against it.”

The extent to which loss of brain volume early in psychosis treatment reflects an illness effect, a drug effect or both remains unknown, according to the researchers. Therefore, Goff and colleagues examined loss of hippocampal volume during the first 8 weeks of treatment for schizophrenia, its link to duration of untreated psychosis and molecular biomarkers related to hippocampal volume loss and duration of untreated psychosis.

At Shanghai Mental Health Center in China, researchers conducted a longitudinal study with age- and sex-matched healthy controls between Mar. 5, 2013, and Oct. 8, 2014. They assessed 71 patients with nonaffective first-episode psychosis treated with second-generation antipsychotics and 73 controls. They reassessed 31 participants with psychosis and 32 controls 8 weeks later, measuring hippocampal volumetric integrity (HVI), duration of untreated psychosis, 13 molecular biomarkers and 14 single-nucleotide polymorphisms from 12 candidate genes.

Participants in the first-episode psychosis group had lower baseline median left HVI (n = 57) compared with those in the control group (n = 54; P = .001). Left HVI decreased in 24 participants with psychosis at a median annualized rate of –.03791 throughout the 8 weeks of treatment, whereas left HVI increased in 31 controls at a rate of 0.00115 (P = .001). Furthermore, researchers observed an inverse association between the change in left hippocampal volume and duration of untreated psychosis (P = .002).

Although they observed similar results in the right HVI, the relationship between change in right HVI and duration of psychosis was not significant. According to the results of analyses that looked at left-side hippocampal volume only, left HVI was associated with molecular biomarkers of inflammation, oxidative stress, brain-derived neurotrophic factor, glial injury and those reflecting dopaminergic and glutamatergic transmission.

“We found significantly lower HVI at baseline in participants with [first episode psychosis] compared with healthy controls and additional HVI reduction during antipsychotic treatment that correlated with [duration of untreated psychosis], consistent with a persistent, possibly deleterious, effect of untreated psychosis on brain structure,” Goff and colleagues wrote. “Larger longitudinal studies of longer duration are needed to examine the association between [duration of untreated psychosis], hippocampal volume and clinical outcomes.” – by Savannah Demko

https://www.healio.com/psychiatry/schizophrenia/news/online/%7Bf6c3c940-fe57-41d1-9eb7-7c835e3c48ea%7D/longer-duration-of-untreated-psychosis-linked-to-loss-of-brain-volume?utm_source=selligent&utm_medium=email&utm_campaign=psychiatry%20news&m_bt=1162769038120

Advertisements

Supplementation with taurine, the additive found in many energy drinks, may improve the symptoms in young people suffering a first episode of psychosis (FEP), according to a new study presented at the International Early Psychosis Association (IEPA) meeting.

Taurine, an amino acid naturally occurring in the body, exhibits an inhibitory neuro-modulatory effect in the nervous system and also functions as a neuroprotective agent. The authors devised a study to analyze the efficacy of taurine supplementation in improving symptoms and cognition in patients with FEP.

The study included 86 individuals with FEP between the ages of 18 and 25 years. It was conducted by Dr. Colin O’Donnell, Donegal Mental Health Service, Co. Donegal, Ireland, and Professor Patrick McGorry and Dr. Kelly Allott, Orygen, The National Centre of Excellence in Youth Mental Health, Australia, and colleagues. Each participant was taking a low dose antipsychotic medication and was attending Orygen.

Forty-seven participants received 4g of taurine daily, while 39 received placebo. Symptoms were assessed Using the scoring system called BPRS (Brief Psychiatric Rating Scale) and cognition was assessed with the MCCB tool (MATRICS consensus cognitive battery).

Results showed that taurine significantly improved symptoms on the BPRS scale, in overall score and in psychosis specific analysis, however, there was no difference between the treatment and placebo group regarding cognition. Depression symptoms (rated by the Calgary Depression Scale for Schizophrenia) and general overall functioning also improved in the taurine group.

“The use of taurine warrants further investigation in larger randomised studies, particularly early in the course of psychosis,” concluded the authors, who themselves, are planning to conduct further studies into the potential benefits of taurine in the treatment of psychosis.

http://www.empr.com/news/energy-drink-additive-could-potentially-improve-psychosis-symptoms/article/567497/?DCMP=EMC-MPR_Charts_rd&cpn=&hmSubId=&NID=&c_id=&dl=0&spMailingID=16159114&spUserID=MzI5NTMwMzQ0NDIyS0&spJobID=921765029&spReportId=OTIxNzY1MDI5S0


St. Jude Children’s Research Hospital scientists have linked disruption of a brain circuit associated with schizophrenia to an age-related decline in levels of a single microRNA in one brain region

St. Jude Children’s Research Hospital scientists have identified a small RNA (microRNA) that may be essential to restoring normal function in a brain circuit associated with the “voices” and other hallucinations of schizophrenia. The microRNA provides a possible focus for antipsychotic drug development. The findings appear today in the journal Nature Medicine.

The work was done in a mouse model of a human disorder that is one of the genetic causes of schizophrenia. Building on previous St. Jude research, the results offer important new details about the molecular mechanism that disrupts the flow of information along a neural circuit connecting two brain regions involved in processing auditory information. The findings also provide clues about why psychotic symptoms of schizophrenia are often delayed until late adolescence or early adulthood.

“In 2014, we identified the specific circuit in the brain that is targeted by antipsychotic drugs. However, the existing antipsychotics also cause devastating side effects,” said corresponding author Stanislav Zakharenko, M.D., Ph.D., a member of the St. Jude Department of Developmental Neurobiology. “In this study, we identified the microRNA that is a key player in disruption of that circuit and showed that depletion of the microRNA was necessary and sufficient to inhibit normal functioning of the circuit in the mouse models.

“We also found evidence suggesting that the microRNA, named miR-338-3p, could be targeted for development of a new class of antipsychotic drugs with fewer side effects.”

There are more than 2,000 microRNAs whose function is to silence expression of particular genes and regulate the supply of the corresponding proteins. Working in a mouse model of 22q11 deletion syndrome, researchers identified miR-338-3p as the microRNA that regulates production of the protein D2 dopamine receptor (Drd2), which is the prime target of antipsychotics.

Individuals with the deletion syndrome are at risk for behavior problems as children. Between 23 and 43 percent develop schizophrenia, a severe chronic disorder that affects thinking, memory and behavior. Researchers at St. Jude are studying schizophrenia and other brain disorders to improve understanding of how normal brains develop, which provides insights into the origins of diseases like cancer.

The scientists reported that Drd2 increased in the brain’s auditory thalamus when levels of the microRNA declined. Previous research from Zakharenko’s laboratory linked elevated levels of Drd2 in the auditory thalamus to brain-circuit disruptions in the mutant mice. Investigators also reported that the protein was elevated in the same brain region of individuals with schizophrenia, but not healthy adults.

Individuals with the deletion syndrome are missing part of chromosome 22, which leaves them with one rather than the normal two copies of more than 25 genes. The missing genes included Dgcr8, which facilitates production of microRNAs.

Working in mice, researchers have now linked the 22q11 deletion syndrome and deletion of a single Dgcr8 gene to age-related declines in miR-338-3p in the auditory thalamus. The decline was associated with an increase in Drd2 and reduced signaling in the circuit that links the thalamus and auditory cortex, a brain region implicated in auditory hallucination. Levels of miR-338-3p were lower in the thalamus of individuals with schizophrenia compared to individuals of the same age and sex without the diagnosis.

The miR-338-3p depletion did not disrupt other brain circuits in the mutant mice, and the findings offer a possible explanation. Researchers found that miR-338-3p levels were higher in the thalamus than in other brain regions. In addition, miR-338-3p was one of the most abundant microRNAs present in the thalamus.

Replenishing levels of the microRNA in the auditory thalamus of mutant mice reduced Drd2 protein and restored the circuit to normal functioning. That suggests that the microRNA could be the basis for a new class of antipsychotic drugs that act in a more targeted manner with fewer side effects. Antipsychotic drugs, which target Drd2, also restored circuit function.

The findings provide insight into the age-related delay in the onset of schizophrenia symptoms. Researchers noted that microRNA levels declined with age in all mice, but that mutant mice began with lower levels of miR-338-3p. “A minimum level of the microRNA may be necessary to prevent excessive production of the Drd2 that disrupts the circuit,” Zakharenko said. “While miR-338-3p levels decline as normal mice age, levels may remain above the threshold necessary to prevent overexpression of the protein. In contrast, the deletion syndrome may leave mice at risk for dropping below that threshold.”

The study’s first authors are Sungkun Chun, Fei Du and Joby Westmoreland, all formerly of St. Jude. The other authors are Seung Baek Han, Yong-Dong Wang, Donnie Eddins, Ildar Bayazitov, Prakash Devaraju, Jing Yu, Marcia Mellado Lagarde and Kara Anderson, all of St. Jude.

https://www.stjude.org/media-resources/news-releases/2016-medicine-science-news/small-rna-identified-that-offers-clues-for-quieting-the-voices-of-schizophrenia.html


A new study finds an algorithmic word analysis is flawless at determining whether a person will have a psychotic episode.

by ADRIENNE LAFRANCE

Although the language of thinking is deliberate—let me think, I have to do some thinking—the actual experience of having thoughts is often passive. Ideas pop up like dandelions; thoughts occur suddenly and escape without warning. People swim in and out of pools of thought in a way that can feel, paradoxically, mindless.

Most of the time, people don’t actively track the way one thought flows into the next. But in psychiatry, much attention is paid to such intricacies of thinking. For instance, disorganized thought, evidenced by disjointed patterns in speech, is considered a hallmark characteristic of schizophrenia. Several studies of at-risk youths have found that doctors are able to guess with impressive accuracy—the best predictive models hover around 79 percent—whether a person will develop psychosis based on tracking that person’s speech patterns in interviews.

A computer, it seems, can do better.

That’s according to a researchers at Columbia University, the New York State Psychiatric Institute, and the IBM T. J. Watson Research Center. They used an automated speech-analysis program to correctly differentiate—with 100-percent accuracy—between at-risk young people who developed psychosis over a two-and-a-half year period and those who did not. The computer model also outperformed other advanced screening technologies, like biomarkers from neuroimaging and EEG recordings of brain activity.

“In our study, we found that minimal semantic coherence—the flow of meaning from one sentence to the next—was characteristic of those young people at risk who later developed psychosis,” said Guillermo Cecchi, a biometaphorical-computing researcher for IBM Research, in an email. “It was not the average. What this means is that over 45 minutes of interviewing, these young people had at least one occasion of a jarring disruption in meaning from one sentence to the next. As an interviewer, if my mind wandered briefly, I might miss it. But a computer would pick it up.”

Researchers used an algorithm to root out such “jarring disruptions” in otherwise ordinary speech. Their semantic analysis measured coherence and two syntactic markers of speech complexity—including the length of a sentence and how many clauses it entailed. “When people speak, they can speak in short, simple sentences. Or they can speak in longer, more complex sentences, that have clauses added that further elaborate and describe the main idea,” Cecchi said. “The measures of complexity and coherence are separate and are not correlated with one another. However, simple syntax and semantic incoherence do tend to aggregate together in schizophrenia.”

Here’s an example of a sentence, provided by Cecchi and revised for patient confidentiality, from one of the study’s participants who later developed psychosis:

I was always into video games. I mean, I don’t feel the urge to do that with this, but it would be fun. You know, so the one block thing is okay. I kind of lied though and I’m nervous about going back.

While the researchers conclude that language processing appears to reveal “subtle, clinically relevant mental-state changes in emergent psychosis,” their work poses several outstanding questions. For one thing, their sample size of 34 patients was tiny. Researchers are planning to attempt to replicate their findings using transcripts from a larger cohort of at-risk youths.

They’re also working to contextualize what their findings might mean more broadly. “We know that thought disorder is an early core feature of schizophrenia evident before psychosis onset,” said Cheryl Corcoran, an assistant professor of clinical psychiatry at Columbia University. “The main question then is: What are the brain mechanisms underlying this abnormality in language? And how might we intervene to address it and possibly improve prognosis? Could we improve the concurrent language problems and function of children and teenagers at risk, and either prevent psychosis or at least modify its course?”

Intervention has long been the goal. And so far it has been an elusive one. Clinicians are already quite good at identifying people who are at increased risk of developing schizophrenia, but taking that one step farther and determining which of those people will actually end up having the illness remains a huge challenge.

“Better characterizing a behavioral component of schizophrenia may lead to a clearer understanding of the alterations to neural circuitry underlying the development of these symptoms,” said Gillinder Bedi, an assistant professor of clinical psychology at Columbia University. “If speech analyses could identify those people most likely to develop schizophrenia, this could allow for more targeted preventive treatment before the onset of psychosis, potentially delaying onset or reducing the severity of the symptoms which do develop.”

All this raises another question about the nature of human language. If the way a person speaks can be a window into how that person is thinking, and further, a means of assessing how they’re doing, which mechanisms of language are really most meaningful? It isn’t what you say, the aphorism goes, it’s how you say it. Actually, though, it’s both.

As Cecchi points out, the computer analysis at the center of the study didn’t include any acoustic features like intonation, cadence, volume—all characteristics which could be meaningful in interpreting a person’s pattern of speaking and, by extension, thinking. “There is a deeper limitation, related to our current understanding of language and how to measure the full extent of what is being expressed and communicated when people speak to each other, or write,” Cecchi said. “The discriminative features that we identified are still a very simplified description of language. Finally, while language provides a unique window into the mind, it is still just one aspect of human behavior and cannot fully substitute for a close observation and interaction with the patient.”

http://www.theatlantic.com/technology/archive/2015/08/speech-analysis-schizophrenia-algorithm/402265/


2C-E was one of the hundreds of drugs synthesised by Alexander Shulgin, who was known as the ‘godfather of ecstasy’. Photograph: Scott Houston/Corbis

Police investigating a mass intoxication of a homeopathy conference in Germany with psychedelic drugs have said they still do not know nearly a week later whether it was an accident or an experiment gone wrong.

Emergency services called to the meeting in Handeloh, south of Hamburg, found a group of 29 alternative healers hallucinating, staggering around, groaning and rolling on the grass.

Police spokesman Lars Nicklesen said on Thursday that investigators believe a psychedelic drug was to blame but remain unsure of how or why it was taken. The delegates are now all out out of physical danger, he said, but there may yet be legal consequences for the healers in the course of the ongoing criminal investigation.

“We’re now questioning the delegates and awaiting the results of blood and urine tests,” he said. “We still don’t know if they took the drugs on purpose. The question is whether they want to talk about it; they have the right to remain silent.”

Nicklesen added that police suspect the group took 2C-E, known in Germany as Aquarust, a drug which heightens perceptions of colours and sounds and in higher doses triggers hallucinations, psychosis and severe cramps.

Germany’s health ministry banned the drug last year due to its highly addictive nature and unknown side effects.

The homeopaths’ meeting – billed as a “further education seminar” – was suspended shortly after it started when delegates began experiencing psychotic hallucinations, cramps, racing heartbeats and shortage of breath. One of them alerted the emergency services.

Alarmed by the sight of so many grown men and women rolling around on the floor, the first fire crews on the scene called for backup, triggering a major incident response. A total of 160 police, fire crews, and ambulance staff and a helicopter were involved in the four hour operation to treat the group.

“It was great that none of the people were in mortal danger in the end”, said fire service spokesman Matthias Köhlbrandt. “The leading emergency doctor at the scene believed they would all recover without lasting damage.”

Unsure of what they had taken, medical staff gave the homeopaths oxygen on site before transferring them to seven different nearby hospitals.

The Hamburger Abendblatt newspaper reported that in one clinic, the Asklepios in Harburg, hallucinating patients had to be strapped down to a bed to prevent them causing danger to others. “They were completely off their heads,” a spokesman for the clinic said.

Staff at the conference centre were unable to shed light on the mystery as they had all gone home at the time of the incident. “We’re absolutely shocked, we’ve only had good experiences in the past with the group,” a spokeswoman for the Tanzheimat Inzmühlen conference centre told the Hamburger Abendblatt.

The Association of German Healing Practitioners was quick to distance itself from the incident and emphasised that hallucinogenic drugs had no place in the study of homeopathy. “If I find out that one of our members took part [in what happened in Handeloh] then they will be excluded from the association,” Heinz Kropmanns, the association president, told NDR.

The drug 2C-E was one of hundreds synthesised by the American chemist Alexander Shulgin. The scientist, who died in 2014, and had become known as the godfather of ecstasy after he introduced MDMA to psychotherapists on the US west coast in the late 1970s.

http://www.theguardian.com/science/2015/sep/10/homeopathy-conference-in-germany-goes-awry-as-delegates-take-lsd-like-drug

Thanks to Kebmodee for bringing this to the It’s Interesting community.

An automated speech analysis program correctly differentiated between at-risk young people who developed psychosis over a two-and-a-half year period and those who did not. In a proof-of-principle study, researchers at Columbia University Medical Center, New York State Psychiatric Institute, and the IBM T. J. Watson Research Center found that the computerized analysis provided a more accurate classification than clinical ratings. The study, “Automated Analysis of Free Speech Predicts Psychosis Onset in High-Risk Youths,” was recently published in NPJ-Schizophrenia.

About one percent of the population between the age of 14 and 27 is considered to be at clinical high risk (CHR) for psychosis. CHR individuals have symptoms such as unusual or tangential thinking, perceptual changes, and suspiciousness. About 20% will go on to experience a full-blown psychotic episode. Identifying who falls in that 20% category before psychosis occurs has been an elusive goal. Early identification could lead to intervention and support that could delay, mitigate or even prevent the onset of serious mental illness.
Speech provides a unique window into the mind, giving important clues about what people are thinking and feeling. Participants in the study took part in an open-ended, narrative interview in which they described their subjective experiences. These interviews were transcribed and then analyzed by computer for patterns of speech, including semantics (meaning) and syntax (structure).

The analysis established each patient’s semantic coherence (how well he or she stayed on topic), and syntactic structure, such as phrase length and use of determiner words that link the phrases. A clinical psychiatrist may intuitively recognize these signs of disorganized thoughts in a traditional interview, but a machine can augment what is heard by precisely measuring the variables. The participants were then followed for two and a half years.
The speech features that predicted psychosis onset included breaks in the flow of meaning from one sentence to the next, and speech that was characterized by shorter phrases with less elaboration. The speech classifier tool developed in this study to mechanically sort these specific, symptom-related features is striking for achieving 100% accuracy. The computer analysis correctly differentiated between the five individuals who later experienced a psychotic episode and the 29 who did not. These results suggest that this method may be able to identify thought disorder in its earliest, most subtle form, years before the onset of psychosis. Thought disorder is a key component of schizophrenia, but quantifying it has proved difficult.

For the field of schizophrenia research, and for psychiatry more broadly, this opens the possibility that new technology can aid in prognosis and diagnosis of severe mental disorders, and track treatment response. Automated speech analysis is inexpensive, portable, fast, and non-invasive. It has the potential to be a powerful tool that can complement clinical interviews and ratings.

Further research with a second, larger group of at-risk individuals is needed to see if this automated capacity to predict psychosis onset is both robust and reliable. Automated speech analysis used in conjunction with neuroimaging may also be useful in reaching a better understanding of early thought disorder, and the paths to develop treatments for it.

http://medicalxpress.com/news/2015-08-psychosis-automated-speech-analysis.html

Schizophrenia is associated with structural and functional alterations of the visual system, including specific structural changes in the eye. Tracking such changes may provide new measures of risk for, and progression of the disease, according to a literature review published online in the journal Schizophrenia Research: Cognition, authored by researchers at New York Eye and Ear Infirmary of Mount Sinai and Rutgers University.

Individuals with schizophrenia have trouble with social interactions and in recognizing what is real. Past research has suggested that, in schizophrenia, abnormalities in the way the brain processes visual information contribute to these problems by making it harder to track moving objects, perceive depth, draw contrast between light and dark or different colors, organize visual elements into shapes, and recognize facial expressions. Surprisingly though, there has been very little prior work investigating whether differences in the retina or other eye structures contribute to these disturbances.

“Our analysis of many studies suggests that measuring retinal changes may help doctors in the future to adjust schizophrenia treatment for each patient,” said study co-author Richard B. Rosen, MD, Director of Ophthalmology Research, New York Eye and Ear Infirmary of Mount Sinai, and Professor of Ophthalmology, Icahn School of Medicine at Mount Sinai. “More studies are needed to drive the understanding of the contribution of retinal and other ocular pathology to disturbances seen in these patients, and our results will help guide future research.”

The link between vision problems and schizophrenia is well established, with as many as 62 percent of adult patients with schizophrenia experience visual distortions involving form, motion, or color. One past study found that poorer visual acuity at four years of age predicted a diagnosis of schizophrenia in adulthood, and another that children who later develop schizophrenia have elevated rates of strabismus, or misalignment of the eyes, compared to the general population.

Dr. Rosen and Steven M. Silverstein, PhD, Director of the Division of Schizophrenia Research at Rutgers University Behavioral Health Care, were the lead authors of the analysis, which examined the results of approximately 170 existing studies and grouped the findings into multiple categories, including changes in the retina vs. other parts of the eye, and changes related to dopamine vs. other neurotransmitters, key brain chemicals associated with the disease.

The newly published review found multiple, replicated, indicators of eye abnormalities in schizophrenia. One of these involves widening of small blood vessels in the eyes of schizophrenia patients, and in young people at high risk for the disorder, perhaps caused by chronic low oxygen supply to the brain. This could explain several key vision changes and serve as a marker of disease risk and worsening. Also important in this regard was thinning of the retinal nerve fiber layer in schizophrenia, which is known to be related to the onset of hallucinations and visual acuity problems in patients with Parkinson’s disease. In addition, abnormal electrical responses by retinal cells exposed to light (as measured by electroretinography) suggest cellular-level differences in the eyes of schizophrenia patients, and may represents a third useful measure of disease progression, according to the authors.

In addition, the review highlighted the potentially detrimental effects of dopamine receptor-blocking medications on visual function in schizophrenia (secondary to their retinal effects), and the need for further research on effects of excessive retinal glutamate on visual disturbances in the disorder.

Interestingly, the analysis found that there are no reports of people with schizophrenia who were born blind, suggesting that congenital blindness may completely or partially protect against the development of schizophrenia. Because congenitally blind people tend to have cognitive abilities in certain domains (e.g., attention) that are superior to those of healthy individuals, understanding brain re-organization after blindness may have implications for designing cognitive remediation interventions for people with schizophrenia.

“The retina develops from the same tissue as the brain,” said Dr. Rosen. “Thus retinal changes may parallel or mirror the integrity of brain structure and function. When present in children, these changes may suggest an increased risk for schizophrenia in later life. Additional research is needed to clarify these relationships, with the goals of better predicting emergence of schizophrenia, and of predicting relapse and treatment response and people diagnosed with the condition.”

Dr. Silverstein points out that, to date, vision has been understudied in schizophrenia, and studies of the retina and other ocular structures in the disorder are in their infancy. However, he added, “because it is much faster and less expensive to obtain data on retinal structure and function, compared to brain structure and function, measures of retinal and ocular structure and function may have an important role in both future research studies and the routine clinical care of people with schizophrenia.”

http://www.eurekalert.org/pub_releases/2015-08/tmsh-rcm081715.php