Archive for the ‘schizophrenia’ Category

A pair of new studies links childhood cat ownership and infection with the parasite Toxoplasma gondii (T. gondii) with later onset schizophrenia and other mental illness. Researchers published their findings in the online Schizophrenia Research and Acta Psychiatrica Scandinavica.

In the Schizophrenia Research study, investigators compared two previous studies that suggested childhood cat ownership could be a possible risk factor for schizophrenia or another serious mental illness with a third, even earlier survey on mental health to see if the finding could be replicated.

“The results were the same,” researchers reported, “suggesting that cat ownership in childhood is significantly more common in families in which the child later becomes seriously mentally ill.”

If accurate, the researchers expect the culprit to be infection with T. gondii, a parasite commonly carried by cats. At this point, though, they are urging others to conduct further studies to clarify the apparent link between cat ownership and schizophrenia.

The Acta Psychiatrica Scandinavica study was a meta-analysis of 50 previously published studies to investigate the prevalence of t. gondii infection in people diagnosed with psychiatric disorders compared with healthy controls.

In cases of schizophrenia, researchers said evidence of an association with T. gondii was “overwhelming,” CBS News reported. Specifically, people infected with T. gondii were nearly twice as likely to be diagnosed with schizophrenia as people never infected with the parasite, according to the report.

The meta-analysis also suggested associations between T. gondii infection and bipolar disorder, obsessive-compulsive disorder, and addiction. No association, however, was found for major depression.

—Jolynn Tumolo

References

1. Fuller Torrey E, Simmons W, Yolken RH. Is childhood cat ownership a risk factor for schizophrenia later in life? Schizophrenia Research. 2015 April 18. [Epub ahead of print].

2. Sutterland AL, Fond G, Kuin A, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatrica Scandinavica. 2015 April 15. [Epub ahead of print].

http://www.psychcongress.com/article/studies-link-cat-ownership-schizophrenia-other-mental-illness

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katharine-thakkar

People with schizophrenia have different levels of the neurotransmitters glutamate and gamma-aminobutyric acidergic (GABA) than healthy people do, and their relatives also have lower glutamate levels, according to a study published online in Biological Psychiatry.

Using magnetic resonance spectroscopy, researchers discovered reduced levels of glutamate — which promotes the firing of brain cells — in both patients with schizophrenia and healthy relatives. Patients also showed reduced levels of GABA, which inhibits neural firing. Healthy relatives, however, did not.

Researchers are unsure why healthy relatives with altered glutamate do not show symptoms of schizophrenia or how they maintain normal GABA levels despite a predisposition to the illness.

“This finding is what’s most exciting about our study,” said lead investigator Katharine Thakkar, PhD, assistant professor of clinical psychology at Michigan State University, East Lansing. “It hints at what kinds of things have to go wrong for someone to express this vulnerability toward schizophrenia. The study gives us more specific clues into what kinds of systems we want to tackle when we’re developing new treatments for this very devastating illness.”

The study included 21 patients with chronic schizophrenia, 23 healthy relatives of other people with schizophrenia not involved in the study, and 24 healthy nonrelatives who served as controls.

Many experts believe there are multiple risk factors for schizophrenia, including dopamine and glutamate-GABA imbalance. Drugs that regulate dopamine do not work for all patients with schizophrenia. Dr. Thakkar believes magnetic resonance spectroscopy may help clinicians target effective treatments for specific patients.

“There are likely different causes of the different symptoms and possibly different mechanisms of the illness across individuals,” said Dr. Thakkar.

“In the future, as this imaging technique becomes more refined, it could conceivably be used to guide individual treatment recommendations. That is, this technique might indicate that one individual would benefit more from treatment A and another individual would benefit more from treatment B, when these different treatments have different mechanisms of action.”

—Jolynn Tumolo

References

Thakkar KN, Rösler L, Wijnen JP, et al. 7T proton magnetic resonance spectroscopy of GABA, glutamate, and glutamine reveals altered concentrations in schizophrenia patients and healthy siblings [publisehd online ahead of print April 19, 2016]. Biological Psychiatry.
Study uncovers clue to deciphering schizophrenia [press release]. Washington, DC: EurekAlert!; June 7, 2016.

An international team of researchers has linked specific symptoms of schizophrenia with various anatomical characteristics in the brain, according to research published in NeuroImage.

By analyzing the brain’s anatomy with magnetic resonance imaging (MRI), researchers from the University of Granada, Washington University in St. Louis, and the University of South Florida have demonstrated the existence of distinctive subgroups among patients with schizophrenia who suffer from different symptoms.

These findings could herald a significant step forward in diagnosing and treating schizophrenia.

To perform the study, the researchers conducted the MRI technique “diffusion tensor imaging” on 36 healthy participants and 47 schizophrenic participants.

The researchers found that tests on schizophrenic participants revealed various abnormalities in parts of the corpus callosum, a bundle of neural fibers that connects the left and right cerebral hemispheres and is essential for effective interhemispheric communication.

Different anomalies in the corpus callosum were associated with different symptoms in the schizophrenic participants. An anomaly in one part of the brain structure was associated with strange and disorganized behavior; another anomaly was associated with disorganized thought and speech, as well as negative symptoms such as a lack of emotion; and other anomalies were associated with hallucinations.

In 2014, this same research group proved that schizophrenia is not a single illness. The team demonstrated the existence of 8 genetically distinct disorders, each with its own symptoms. Igor Zwir, PhD, and Javier Arnedo from the University of Granada’s Department of Computer Technology and Artificial Intelligence found that different sets of genes were strongly linked with different clinical symptoms.

“The current study provides further evidence that schizophrenia is a heterogeneous group of disorders, as opposed to a single illness, as was previously thought to be case,” Dr Zwir said in a statement.

While current treatments for schizophrenia tend to be generic regardless of the symptoms exhibited by each patient, the researchers believe that in the future, analyzing how specific gene networks are linked to various brain features and specific symptoms will help develop treatments that are adapted to each patient’s individual disorder.

To conduct the analysis of the gene groups and brain scans, the researchers developed a new, complex analysis of the relationships between different types of data and recommendations regarding new data. The system is similar to that used by companies such as Netflix to determine what movies they want to broadcast.

“To conduct the research, we did not begin by studying individuals who had certain schizophrenic symptoms in order to determine whether they had the corresponding brain anomalies,” said Dr Zwir in a statement. “Instead, we first analyzed the data, and that’s how we discovered these patterns. This type of information, combined with data on the genetics of schizophrenia, will someday be of vital importance in helping doctors treat the disorders in a more precise and effective way.”

Reference
Arnedo J, Mamah D, Baranger DA, et al. Decomposition of brain diffusion imaging data uncovers latent schizophrenias with distinct patterns of white matter anisotropy. NeuroImage. 2015; doi:10.1016/j.neuroimage.2015.06.083.

http://www.psychiatryadvisor.com/schizophrenia-and-psychoses/types-subgroups-schizophrenia-linked-various-different-brain-anomalies-corpus-callosum/article/470226/?DCMP=EMC-PA_Update_rd&cpn=psych_md&hmSubId=&hmEmail=5JIkN8Id_eWz7RlW__D9F5p_RUD7HzdI0&NID=&dl=0&spMailingID=13630678&spUserID=MTQ4MTYyNjcyNzk2S0&spJobID=720090900&spReportId=NzIwMDkwOTAwS0

Excessive activity in complement component 4 (C4) genes linked to the development of schizophrenia may explain the excessive pruning and reduced number of synapses in the brains of patients with schizophrenia, according to a study published in Nature.

The study, co-funded by the Office of Genomics Research Coordination at the National Institute of Mental Health and the Stanley Center for Psychiatric Research at the Broad Institute in Cambridge, Massachusetts, analyzed various structurally diverse versions of the C4 gene.

Led by Steve McCarroll, PhD, of the Broad Institute of Harvard and MIT, researchers analyzed the genomes of 65 000 study participants and 700 postmortem brains, detecting a link between specific gene versions and the biological process that causes some cases of schizophrenia.

The team—including Beth Stevens, PhD; Michael Carroll, PhD; and Aswin Sekar, BBS— determined that C4 genes generate varying levels of C4A and C4B proteins; the more C4A found in a person, the higher his or her risk of developing schizophrenia. The researchers found that during critical periods of brain maturation, C4 identifies synapses for pruning. Overexpression of C4 results in higher amounts of C4A, which could cause excessive pruning during the late teens and early adulthood, “conspicuously corresponding to the age-of-onset of schizophrenia symptoms,” the researchers noted.

“It has been virtually impossible to model [schizophrenic] disorder in cells or animals,” said Dr McCarroll. “The human genome is providing a powerful new way into this disease. Understanding these genetic effects on risk is a way of prying open that black box, peering inside, and starting to see actual biological mechanisms.”

Research suggests that future schizophrenia treatments may be developed to target and suppress excessive levels of pruning, halting a process that has the potential to develop into psychotic illness.

Reference

Sekar A, Bialas AR, de Rivera H, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016; doi: 10.1038/nature16549.

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

Forum Pharmaceuticals announced that the FDA has granted Fast Track designation to encenicline for the treatment of cognitive impairment in schizophrenia.

Forum recently completed patient enrollment for the COGNITIV SZ phase 3 clinical trial program which includes two randomized, double-blind, placebo-controlled studies. The program is evaluating the safety and efficacy of two oral doses of once-daily treatment with encenicline as a pro-cognitive treatment compared to placebo when added to chronic, stable, atypical antipsychotic therapy in people with schizophrenia.

Primary endpoints of the trials include effect on cognitive function and effect on clinical function. The two global 26-week trials enrolled a total of more than 1,500 patients at approximately 200 clinical sites.

Encenicline is an orally administered, selective, and potent agonist of the alpha 7 receptor found in hippocampal and cortical neurons involved in cognition.

In a phase 2 trial, which was sponsored by Forum and results of which were released in March, 319 schizophrenia patients were randomized to receive either encenicline in one of two doses daily, or a placebo, for 12 weeks.

Patients in both encenicline dose groups showed significant cognitive improvement based on various measures, according to a presentation made at the 15th International Congress on Schizophrenia Research. In a subset of 154 patients, the improvement was greater in the higher-dose group (0.9 mg) than the lower-dose cohort (0.27 mg).