About one third of people with depression have high levels of inflammation markers in their blood. New research indicates that persistent inflammation affects the brain in ways that are connected with stubborn symptoms of depression, such as anhedonia, the inability to experience pleasure.
The results were published online on Nov. 10 inÂ Molecular Psychiatry.
The findings bolster the case that the high-inflammation form of depression is distinct, and are guiding researchersâ€™ plans to test treatments tailored for it.
Anhedonia is a core symptom of depression that is particularly difficult to treat, says lead author Jennifer Felger, PhD, assistant professor of psychiatry and behavioral sciences at Emory University School of Medicine and Winship Cancer Institute.
“Some patients taking antidepressants continue to suffer from anhedonia,” Felger says. “Our data suggest that by blocking inflammation or its effects on the brain, we may be able to reverse anhedonia and help depressed individuals who fail to respond to antidepressants.”
In a study of 48 patients with depression, high levels of the inflammatory marker CRP (C-reactive protein) were linked with a “failure to communicate”, seen through brain imaging, between regions of the brain important for motivation and reward.
Emory researchers have found that high inflammation in depression is linked to a “failure to communicate” between two parts of the brain: the ventral striatum (VS, vertical cross section) and the ventromedial prefrontal cortex (vmPFC, horizontal). Images from Felger et al, Molecular Psychiatry (2015).
Neuroscientists can infer that two regions of the brain talk to each other by watching whether they light up in magnetic resonance imaging at the same times or in the same patterns, even when someone is not doing anything in particular. They describe this as “functional connectivity.”
A PNAS paper published MondayÂ demonstrates the kinds of insights that can be gleaned from a large scale sequencing project examining the fragile X gene.
Most children (boys, usually) who have fragile X syndrome have a particular mutation. An expanded â€œtriplet repeatâ€ stretch of DNA, which is outside the protein-coding region of the gene, puts the entire gene to sleep.
At Emory,Â geneticist Steve Warren, cell biologist Gary Bassell and colleagues have been identifying less common changesÂ in the fragile X gene by looking in boys who are developmentally delayed, but donâ€™t have the triplet repeat expansion. The first author of the paper is former postdoc Joshua Suhl, now at Booz Allen Hamilton in Massachusetts.
The authors describe two half-brothers who have the same genetic variant, which changes how production of the FMRP protein is regulated.Â These examples show that the fragile X gene is so central to how neurons function that several kinds of geneticÂ glitches in it can make this finely tuned machine break down.
â€œThis is a hot area and not much is known about it,â€ Warren says. Read more
Anesthesiologist Paul Garcia and his colleagues are presenting two posters at the Society of Neuroscience meeting this week, whose findings may raise concerns about two non-stimulant drugs Emory sleep specialists have studied for the treatment of hypersomnia: flumazenil and clarithromycin.
For both, the data is in vitro only, so caution is in order and more investigation may be needed.
With flumazenil, Garcia and colleagues found that when neurons are exposed to a low dose for 24 hours, the cells increase expression of someÂ GABA receptor forms.
This could be part of a mechanism for tolerance. I heard some anecdotes describing how flumazenilâ€™s wake-promoting effects wear off over timeÂ at the Hypersomnia Foundation conference in July, but itâ€™s not clear how common the phenomenon is.
Flumazenilâ€™s utility in hypersomnia became known after the pioneering experience of Anna Sumner, who has reported being able to use the medicine for years. See this 2013 story in Emory Medicine. Read more
In 2013, Brian Dias (at Yerkes) and Kerry Ressler (now at Harvard) describedÂ a surprising example of epigenetic inheritance.
They found that a mouse, exposed to a smell in combination with stress, could transmit the resulting sensitivity to that smell to its offspring. At the time, there wasn’t a lot of information about mechanism.
Now other scientistsÂ haveÂ substantiatedÂ a proposal that micro RNA in playing a role in sperm. See this story (“Sperm RNAs transmit stress”) from Kate Yandell in The ScientistÂ or this one from Rachel Zamzow at Spectrum, the Simons Foundation’s autism news site, for more. An added wrinkle is that thisÂ research showsÂ that descendantsÂ of stress-exposed mice show a muted response to stress.
Note for Emory readers: Dias is scheduled to give a Frontiers in Neuroscience talk on Friday.
This grant announcement from the American Heart Association caught Lab Land’s eye.Â All three of the scientists involved in this project, examining the connections between hypertension, inflammation and the sympathetic nervous system in PTSD, have Emory connections:
*Kerry Ressler, previously Emory Psychiatry/HHMI-supported/Yerkes-based lab/Grady Trauma Project, who moved this summer to Harvard’s McLean Hospital
Related findingÂ that emerged from the Grady Trauma Project: Blood pressure drugs linked with lower PTSD symptoms
*Paul Marvar, who worked with both David Harrison and Kerry Ressler at Emory, and is now at George Washington University
Related item on Marvar’s work: Immune cells required for stress-induced rise in blood pressure in animals
*Jeanie Park, kidney specialist who is here now! The grant is exploring the relationship between the sympathetic nervous system, regulation of blood pressure and PTSD.
2015Â TV interview with Park on her chronic kidney disease research
Those of us who are old enough to remember vinyl records will recall how a scratch can cause the same sounds to repeat many times. A similar type of genetic glitch causes neurodegenerative diseases such as Huntingtonâ€™s and several forms of spinocerebellar ataxia.
Huntingtonâ€™s and the spinocerebellar ataxias are known as â€œpolyglutamineâ€ diseases. In each, the affected gene has a stretch where the same three DNA letters are repeated several times — more than usual. As a result, the protein encoded by the affected gene has a patch, where only the building block glutamine can be found, disrupting that proteinâ€™s usual functions in the body.
Geneticist Xiao-Jiang Li and colleagues recently published a paper in Cell Reports that may explain why more aggressive juvenile-onset forms of polyglutamine diseases have different symptoms and pathology. Read more
These days, it sounds a bit old-fashioned to ask the question: â€œWhere is consciousness located in the brain?â€ The prevailing thinking is that consciousness lives in the network, rather than in one particular place. Still, neuroscientists sometimes get an intriguing glimpse of a critical link in the network.
A recent paper in the journal Epilepsy & Behavior describes an epilepsy patient who had electrodes implanted within her brain at Emory University Hospital, because neurologists wanted to understand where her seizures were coming from and plan possible surgery. Medication had not controlled her seizures and previous surgery elsewhere hadÂ not either.
MRI showing electrode placement. Yellow outline indicates the location of the caudate and thalamus. Image from Leeman-Markowsi et al, Epilepsy & Behavior (2015).
During intracranial EEG monitoring, implanted electrodes detected a pattern of signals coming from one part of the thalamus, a central region of the brain. The pattern was present when the patient was conscious, and then stopped as soon as seizure activity made her lose awareness.
The pattern of signals had a characteristic frequency â€“ around 35 times per second â€“ so it helps to think of the signal as an auditory tone. Lead author Beth Leeman-Markowski, director of EUHâ€™s Epilepsy Monitoring Unit at the time when the patient was evaluated, describes the signal as a â€œbuzz.â€
â€œThat buzz has something to do with maintenance of consciousness,â€ she says. Read more
Last week on Friday, Lab Land attended the annual Regenerative Engineering & Medicine center get-together to hear about progress in this exciting area.
During his talk, Tony Kim of Georgia Tech mentioned a topic that Rose Eveleth recently explored in The Atlantic: why arenâ€™t doctors using amazing â€œnanorobotsâ€ yet? Or as Kim put it, citing a recent review, â€œSo many papers and so few drugs.â€
[A summary: scaling up is difficult, testing pharmacokinetics, toxicity and efficacy is difficult, and so is satisfying the FDA.]
TheÂ talks Friday emerged from REM seed grants; manyÂ paired an Emory medical researcher with a Georgia Tech biomedical engineer. All of these projects take on challenges in delivering regenerative therapies: getting cells or engineered particles to the right place in the body.
For example, cardiologist W. Robert Taylor discussed the hurdles his team had encountered in scaling up his cells-in-capsules therapies for cardiovascular diseases to pigs, in collaboration with Luke Brewster. The pre-pig phase of this research is discussed in more detail here and here. Read more
A visitor might not realize this was a meeting devoted to people who experience excessive daytime sleepiness. The 2015 Hypersomnia Foundation ConferenceÂ on Saturday was full of energy, with:
*more than 245 attendees, about twice as many people as last yearâ€™s conference
*medical experts from France, Wisconsin and Louisiana — in addition to Emory
*data from several recent clinical trials
*some signs of industry interest in hypersomnia
Hypersomnia is a sleep disorder in which individuals feel frequent or constant sleepiness and need to sleep for long portions of the day (more than 70 hours per week). It is distinct from other sleep disorders such as narcolepsy and sleep apnea, but its prevalence is still unclear. Conventional stimulants such as amphetamine or modafinil often can be used to treat the sleepiness, but some with hypersomnia find these drugs ineffective or hard to tolerate.
Previous research at Emory has shown that many individuals with hypersomnia have a substance in their spinal fluid that acts like a sleeping pill, enhancing the action of the neurotransmitter GABA. The identity of this mysterious substance is unknown, but Emory researchers report that they are close to identifying it. That could give hypersomnia a â€œmolecular handleâ€ likeÂ what narcolepsy has, with loss of hypocretin-producing neurons.
The terminology is still up in the air — keynote speaker Isabelle Arnulf from the PitiÃ©-SalpÃªtriÃ¨re University Hospital in Paris said, â€œThe term â€˜idiopathic hypersomniaâ€™ does not mean that you are an idiot.â€ Rather, she said, it means that even specialists can have trouble distinguishing hypersomnia from other sleep disorders, and â€œidiopathicâ€ signifies that the detailed cause is still under investigation.