News Briefs

March 5, 2015 - 1:14pm

A new study suggests a link between neonatal encephalopathy and cognitive impairment.

March 5, 2015 - 11:10am

According to results of functional MRI studies, disrupted effective connectivity among brain regions involved in attention and interoception may underlie some of the cognitive features of melancholia.

March 5, 2015 - 9:50am

Researchers have discovered potential biomarkers that could aid in diagnosing prevalent neurodegenerative disorders.

March 4, 2015 - 3:30pm

Neuroimaging studies using multivariate pattern recognition have a sensitivity and specificity of 80% for distinguishing people with schizophrenia from healthy controls, a new meta-analysis shows.

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Thu
05
Mar

Cognitive Impairment Persists for School-Aged Children with Neonatal Encephalopathy

By Will Boggs MD

Many children with neonatal encephalopathy have cognitive impairment that persists into the early school years, according to a new study of participants in an earlier hypothermia trial.

"Developmental assessment is important for all patients diagnosed with neonatal encephalopathy," Dr. Athina Pappas from Wayne State University in Detroit, Michigan, told Reuters Health by email. "Centers offering therapeutic hypothermia should provide for outpatient follow-up and early intervention/support services beyond NICU discharge."

"Small clinical and preclinical studies suggest learning impairment and memory problems following perinatal or postnatal hypoxic ischemic brain injury," she explained. "Though not specific to neonatal encephalopathy, cognitive impairment remains an important concern for neonates treated with therapeutic hypothermia."

Dr. Pappas and colleagues used data from the Neonatal Research Network's randomized controlled trial of whole-body hypothermia to describe the spectrum of cognitive outcomes of 110 children with moderate and severe hypoxic ischemic encephalopathy (HIE) with and without cerebral palsy and neuromotor impairment at between six and seven years of age.

At randomization into the hypothermia trial, 78% had moderate encephalopathy and 22% had severe encephalopathy, according to the report, online February 23 in Pediatrics.

At school age, most children (79/110, 72%) remained in the same developmental range. Those who had a low Mental Developmental Index (MDI <70) at 18 to 22 months had, on average, an adjusted IQ at six to seven years that was 42 points lower than that of those with an MDI above 84.

In fact, an MDI below 70 was the best predictor of having an IQ below 70 at age six to seven years, even after adjustment for other risk factors.

About a third of children randomized to hypothermia were receiving early intervention or special educational assistance, compared with 37% to 47% of children randomized to normothermia. Rates were higher among kids with a low IQ, but even among those with normal IQ, 20% received some form of special educational services.

By school age, behavior problems occurred in 7% of children treated with hypothermia and 9% of those in the normothermia group, both of which were less common than had been reported at 18 months (21% and 32%, respectively).

"Though therapeutic hypothermia has improved outcomes for this high risk population, adjuvant therapies targeting neuronal repair and regeneration are still needed," Dr. Pappas said. "Survival without cognitive impairment is reported in ~50% of neonates treated with therapeutic hypothermia in recent trials."

SOURCE: http://bit.ly/1wuvq58

Pediatrics 2015.

(c) Copyright Thomson Reuters 2015. Click For Restrictions - http://about.reuters.com/fulllegal.asp

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Thu
05
Mar

Disrupted Effective Connectivity in the Brain Tied to Melancholia Features

By Will Boggs MD

Disrupted effective connectivity among brain regions involved in attention and interoception may underlie some of the cognitive features of melancholia, according to results of functional MRI studies.

"Through an iterative process, our study first used prototypic symptom- and sign-based features to diagnose melancholic and non-melancholic patient groups," Matthew P. Hyett from University of New South Wales, Australia, told Reuters Health by email. "Our main study findings of brain disconnectivity in melancholia likely underpin such phenotypic features, hence providing clinicians with insight into the biological causes of this disorder."

Melancholia, formerly called endogenous depression, is distinguished from nonmelancholic depression by its loss of pleasure in virtually all activities and its lack of improvement in response to positive events. About a quarter of patients with major depression have melancholic features.

Although melancholia has long been thought to have a strong biological component, there has been limited evidence to support its specific neurobiological origins, Hyett and colleagues write in JAMA Psychiatry, online February 18.

The team used functional MRI to investigate the effective connectivity (a measure of causal interactions) among networks subserving attention, salience, executive function, and internally generated thought in 16 patients with melancholic depression, 16 patients with nonmelancholic depression, and 16 controls with no history of mood or psychotic illness.

The melancholic group had markedly diminished inward connectivity of the right frontoparietal (RFP) component, significantly diminished outgoing connectivity of the insula (INS) to other components, and somewhat fewer outgoing connections from the left frontoparietal (LFP) component, the researchers found.

Specific disruptions in connectivity included reduced connections from the insula component to the right frontoparietal component, and from the insula component to the executive control (EXC) component.

"The involvement of the EXC mode is consistent with disturbances in executive function in melancholia, such as biased decision making," the researchers explain. "Neuroanatomically, our EXC mode overlapped substantially with portions of the ventromedial prefrontal cortex, which has a variety of affective control functions, including those related to self-reference, affect, and visceromotor regulation. Hence, this mode likely contributes to a range of affective control functions in addition to classic cognitive control."

"Our insular component was chosen specifically to incorporate the more anterior regions implicated in interoceptive processes," they add. "We observed a diminished outgoing influence of this anterior insula mode in participants with melancholia compared with healthy controls, particularly on the executive mode, which includes key regions (e.g., ventromedial prefrontal cortex) subserving affective control mechanisms."

"Taken together with the diminished connectivity of the RFP mode, this finding provides support for our hypothesis that melancholia is associated with disruptions to key regions underpinning attention and internalized mood state regulation," the team concludes.

Hyett said the "findings contribute to more detailed understanding of the neurobiology of melancholia, and if consensus is gained in future studies may assist in the development of more targeted physical treatments."

"There has been a significant shift in our understanding of brain function, which is likely to have a vast impact on the way we understand the neurobiology of psychiatric conditions," Hyett added.

SOURCE: http://bit.ly/1JUNTO2

JAMA Psychiatry 2015.

(c) Copyright Thomson Reuters 2015. Click For Restrictions - http://about.reuters.com/fulllegal.asp

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Thu
05
Mar

Potential Biomarkers Identified for Alzheimer’s, Parkinson’s

Skin biopsies of patients with Alzheimer’s and Parkinson’s diseases showed elevated levels of specific proteins, according to a study scheduled to be presented at the American Academy of Neurology annual meeting in Washington, DC, in April.

The findings suggest potential biomarkers that could allow physicians to diagnose the two most prevalent neurodegenerative disorders sooner.

“Until now, pathological confirmation was not possible without a brain biopsy, so these diseases often go unrecognized until after the disease has progressed,” said researcher Ildefonso Rodriguez-Leyva, MD, at Central Hospital at the University of San Luis Potosi, San Luis Potosi, Mexico. “We hypothesized that since skin has the same origin as brain tissue while in the embryo, that they might also show the same abnormal proteins.”

After analyzing skin biopsies from 20 patients with Alzheimer’s disease, 16 patients with Parkinson’s disease, 17 patients with non-neurodegenerative dementia, and 12 healthy controls, Dr. Rodriguez-Leyva and colleagues discovered that compared to the control group, patients with Alzheimer’s and Parkinson’s diseases had 7 times higher levels of the tau protein. In addition, patients with Parkinson’s disease had 8 times higher levels of the alpha-synuclein protein.

“More research is needed to confirm these results,” said Dr. Rodriguez-Leyva, “but the findings are exciting because we could potentially begin to use skin biopsies from living patients to study and learn more about these diseases.”

—Jolynn Tumolo

References

1. Rodriguez-Leyva I, Chi-Ahumada E, Calderon-Garciduenas AL, et al. Skin cells express altered proteins that characterize the most common neurodegenerative diseases [press release/abstract]. American Academy of Neurology: Washington, DC; Feb. 24, 2015.

2. Skin test may shed new light on Alzheimer’s and Parkinson’s diseases [press release]. American Academy of Neurology: Washington, DC; Feb. 24, 2015.

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Wed
04
Mar

Pattern Recognition Advances Brain Imaging for Schizophrenia

By Reuters Staff

Neuroimaging studies using multivariate pattern recognition have a sensitivity and specificity of 80% for distinguishing people with schizophrenia from healthy controls, a new meta-analysis shows.

But before this approach can be used in clinical practice, more detailed information on patients' clinical characteristics is needed to evaluate these imaging methods, Dr. Joseph Kambeitz of Ludwig-Maximilians University Munich and colleagues conclude.

Several studies have identified functional and structural brain abnormalities in schizophrenic individuals, but it has not yet been possible to use them as biomarkers for diagnosis, Dr. Kambeitz and his team write in Neuropsychopharmacology.

Multivariate statistical approaches have identified distinct patterns of brain changes in schizophrenia, with 60% to 100% accuracy for distinguishing patients from healthy controls, they add, and could potentially be used in diagnosing the disease.

"However, these studies differ with respect to multiple aspects such as the demographic characteristics of the investigated populations, the clinical symptoms of the patient samples, the imaging modalities employed, the preprocessing of neuroimaging data prior to analysis, the statistical models, as well as the evaluation scheme of the models' performance," Dr. Kambeitz and his team write. "As a result, the sensitivity and specificity of the reported predictive models differ widely, making it difficult to compare the classification of neuroimaging-based biomarkers across studies."

To evaluate the performance of these multivariate pattern recognition approaches, the researchers analyzed 38 studies including a total of 1,602 patients with schizophrenia and 1,637 healthy controls.

Twenty studies used structural MRI, 11 used resting state functional MRI (rsfMRI), four used functional MRI, three used PET, and one used diffusion tensor imaging. All of the analyzed studies used a neuroimaging-based multivariate classification model to distinguish schizophrenia patients from healthy controls.

Overall, the models had a sensitivity of 80.3% and a specificity of 80.3%. They were more sensitive in older patients, and more specific for patients with predominantly positive symptoms. The models were also more sensitive in patients with chronic schizophrenia than for first-episode patients. Studies using rsfMRI were more sensitive than those using structural MRI. Tests were also more specific in patients who had received more chlorpromazine equivalents.

"To further disentangle possible effects of antipsychotic medication on diagnostic classification measures from the impact of the disease process itself, future meta-analyses have to cover a critical mass of patient samples having well-documented prospective medication data," Dr. Kambeitz and colleagues write.

Most of the studies did not provide detailed information on patients, they note. "As pointed out by Deville et al (Deville et al, 2002), a detailed description of the patient's disease status, symptoms length and course of illness, current medication, or comorbidities is crucial for evaluating the potential of such models to enter clinical practice in the future," the researchers write.

"Although the present analysis indicates a discriminative pattern of brain alterations associated with schizophrenia," they conclude, "our results underline the importance of an exhaustive assessment of clinical characteristics during the investigation of such biomarkers."

SOURCE: http://bit.ly/1vHsykH

Neuropsychopharmacol 2015.

(c) Copyright Thomson Reuters 2015. Click For Restrictions - http://about.reuters.com/fulllegal.asp

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