Depression is not a single disease. The term refers to a cluster of feelings and behaviors, brought on by a variety of underlying causes. And, unfortunately, it is often difficult to determine which type of depression a person has: a physician cannot take a mouth swab or a blood sample to diagnose the nature and severity of a patient’s psychiatric condition–at least not yet.
According to a new multi-institutional study, published in PNAS, doctors may one day be able gain insight into an individual’s depression by analyzing his or her blood. Rockefeller scientists Bruce McEwen and Carla Nasca, in collaboration with Natalie Rasgon, psychiatry professor at the Stanford University School of Medicine, show that patients with a particular type of depression have decreased blood levels of the molecule acetyl-L-carnitine (LAC)–a finding that may lead to improved diagnosis and treatment of major depressive disorder (MDD).
When LAC is Lacking
Naturally produced by the body, LAC performs a number of crucial tasks in the brain. For example, the molecule regulates energy metabolism and interacts with DNA to promote the expression of important genes. Specifically, it acts on a gene that controls levels of the neurotransmitter glutamate–a chemical implicated in almost everything that the brain does.
McEwen, the Alfred E. Mirsky Professor, and Nasca, a postdoctoral fellow of the American Foundation for Suicide Prevention, have studied the link between LAC and mood disorders using animal models. In one study, they showed that LAC supplements ameliorate depressive symptoms in mice by reversing brain-cell impairment caused by an excess of glutamate. In a separate rodent study, they observed that LAC treatment reduces depressive behavior and stress-associated neural dysfunction in the medial amygdala, a brain region involved in social interactions. These findings strongly suggest that LAC deficits contribute to a depression-like state in mice, leading the scientists to wonder whether the molecule plays a similar role in humans.
Dr David Vilchez and his team at CECAD have made an important step towards understanding the mechanisms that cause the neurodegenerative disorder Huntington’s disease. Particularly, they identified a system blocking the accumulation of toxin protein aggregates, which are responsible for neurodegeneration. The results have now been published in the journal ‘Nature Communications’.
Huntington’s disease is a neurodegenerative disorder that results in the death of brain cells, leading to uncontrolled body movement, loss of speech and psychosis. Mutations in the huntingtin gene cause the disease, resulting in the toxic aggregation of the huntingtin protein. The accumulation of these aggregates causes neurodegeneration and usually leads to the patient’s death within twenty years after the onset of the disease.
To examine the mechanisms underlying Huntington’s disease, Vilchez and his team used so-called induced pluripotent stem cells (iPSC) from Huntington’s disease patients, which are able to differentiate into any cell type, such as neurons. Induced pluripotent stem cells derived from patients with Huntington’s disease exhibit a striking ability to avoid the accumulation of toxic protein aggregates, a hallmark of the disease. Even though iPSCs express the mutant gene responsible for Huntington’s disease, no aggregates were found.
The researchers identified a protein called UBR5 as a protective mechanism for the cells, promoting the degradation of mutant huntingtin. These findings can contribute to a better understanding of Huntington’s disease and could be a step stone to developing further treatment in patients.
The researchers screened immortal iPSCs from patients and derived neurons for differences in their ability to avoid mutant huntingtin aggregation. They found that huntingtin can be degraded by the cellular disposal system known as the proteasome. However, this system is defective in the neurons, which leads to the aberrant aggregation of the mutant huntingtin protein. Vilchez and his team found that UBR5 is increased in pluripotent stem cells to accelerate the degradation of huntingtin in the cells. To examine the role of UBR5 in the regulation of the mutant huntingtin gene (HTT), they reduced the levels of UBR5 and could immediately see an accumulation of aggregated proteins in iPSCs. ‘This was striking to see’, says Vilchez. ‘From nothing, the cells went to huge amounts of aggregates.’
New UK research has found that a new mindfulness based approach to tinnitus could transform the treatment of the condition.
Published in the journals Ear and Hearing and Psychotherapy and Psychosomatics, the research led by Dr Laurence McKenna from University College London Hospitals NHS Foundation Trust (UCLH) and Dr Liz Marks, from Department of Psychology at the University of Bath, found that Mindfulness based Cognitive Therapy (MBCT) helps to significantly reduce the severity of tinnitus compared to relaxation-based treatments, an approach recommended by many tinnitus clinics.
Tinnitus, described as a sensation or awareness of sound that is not caused by an external sound source, affects approximately six million people in the UK – 10 percent of the UK’s population. Approximately 1 in 100 people are very distressed or disabled by it and as many as 1 in 20 people are at least moderately distressed by it. Tinnitus is associated with complaints of emotional stress, insomnia, auditory perceptual problems and concentration problems.
As yet there is no treatment to stop the tinnitus noise but this research, funded by the British Tinnitus Association (BTA), shows clearly that treatment can make it less severe, intrusive and bothersome.
Dr Liz Marks, from the Department of Psychology at the University of Bath, will explore the report’s findings in more detail at the BTA’s annual conference in Birmingham in September. She said: “We compared MBCT to relaxation therapy, a traditional treatment for people with chronic tinnitus, to determine if MBCT was a better option than the current recommended practice.
For decades, clinicians treating multiple sclerosis (MS) have interpreted the appearance of new or expanding brain lesions on magnetic resonance imaging (MRI) scans as a sign that a patient’s disease is getting worse. Now, University at Buffalo researchers are finding that it may be the atrophy or disappearance of these lesions into cerebrospinal fluid (CSF) that is a better indicator of who will develop disability.
The five-year study, conducted by MS researchers in the Jacobs School of Medicine and Biomedical Sciences at UB, was published in the Journal of Neuroimaging. Similar findings also resulted from their 10-year study of 176 patients that they presented at the annual meeting of the American Academy of Neurology (AAN) in Los Angeles in April.
Robert Zivadinov, MD, PhD, first author on the 10-year study and senior author on the five-year study, said: “Using the appearance of new brain lesions and the enlargement of existing ones as the indicator of disease progression, there was no sign of who would develop disability during five or 10 years of follow-up, but when we used the amount of brain lesion volume that had atrophied, we could predict within the first six months who would develop disability progression over long-term follow-up.”
Zivadinov, a professor of neurology in the Jacobs School and director of the Buffalo Neuroimaging Analysis Center (BNAC) in the Jacobs School, also directs the Center for Biomedical Imaging at UB’s Clinical and Translational Science Institute.