Science Bites seeks to compile the latest scientific research updates in bite-sized forms.

1. Brain imaging distinguishes four neurophysiological subtypes of depression

Depression is a neuropsychiatric disorder that is diagnosed when five out of a list of nine symptoms are identified. The possible heterogeneous combinations of symptoms suggest that depression can manifest in multiple forms, which inadvertently reflect why patients respond divergently to treatment.

Using brain functional magnetic resonance imaging (fMRI), researchers from Canada and USA assessed the strength of connections between neural circuits in the brains of 1,188 participants, of whom 40% had depression, and studied 258 regions of the brain in each individual.

Computer analysis revealed differences between the brain connectivity in the limbic and frontostriatal networks of participants with depression and those without, but also found disparities within the group with depression, revealing four distinct subtypes of depression. Each subtype corresponds with differing clinical-symptom profiles – patients categorised in the first two subtypes reported fatigue, while those in the third and fourth subtypes reported anhedonia.

Neurotypes 1 through 4, in this figure called clusters 1 through 4. This study maps each neurotype in two dimensions: anxiety and anhedonia. At left, a scatter plot of subjects classed into each neurotype. At right, demonstration of how tightly subjects tended to cluster around each neurotype, shaded by number of participants (pale areas denote lower frequency of symptom overlap, while yellow places denote lots of participants with very similar symptoms). Figures credit: Liston et al, 2016
Neurotypes 1 through 4, in this figure called clusters 1 through 4. This study maps each neurotype in two dimensions: anxiety and anhedonia. At left, a scatter plot of subjects classed into each neurotype. At right, demonstration of how tightly subjects tended to cluster around each neurotype, shaded by number of participants (pale areas denote lower frequency of symptom overlap, while yellow places denote lots of participants with very similar symptoms). Figures credit: Liston et al, 2016


The subtypes, researchers also found, were “prognostically informative” and could predict which group of patients responded to a targeted neurostimulation therapy known as transcranial magnetic stimulation (TMS). For instance, those with subtype one depression were found to be thrice as likely to benefit from TMS targeted at the dorsomedial prefrontal cortex, compared to those in subtype two and four.

The findings can be used to adjust TMS when treating patients with different subtypes of depression, according to Weill Cornell psychiatrist Marc Dubin. Doctors could fine-tune and target the TMS magnet at specific brain areas with abnormal connectivity in each patient.

“In the next five years we could be doing that,” he says.

2. Intracerebral production of fructose linked to diabetic neurological complications

Cells require glucose for energy, but when the metabolic process becomes saturated, the sugar is converted into fructose via the polyol pathway in the body. Unlike glucose, which is metabolised in all cells in the body, fructose – a sugar found in fruits and honey that is associated with the development of type 2 diabetes and obesity – plays a less important physiological role, and is mostly metabolised in the liver as well as in the semen.

Previous studies suggested that brain function can be altered with exposure to fructose, with evidence of altered gene expressions in the brain, including genes that influence metabolism, cell communication and inflammation. Though the circulating plasma levels of fructose are usually low, some studies found significant levels of fructose in the central nervous system (CNS).

Using magnetic resonance spectroscopy scanning, researchers at Yale University measured the intracerebral glucose and fructose levels of eight healthy individuals who underwent a four-hour hyperglycemic clamp.

After just 20 minutes of glucose infusion, the researchers found a marked increase of intracerebral glucose and fructose levels in all eight volunteers. The changes were not related to the fructose levels in the blood, providing evidence that that the brain was capable of endogenously converting excess glucose to fructose via the polyol pathway.

Though the study involves a small sample size, the findings are intriguing, as the brain relies heavily on glucose as fuel. In patients with poorly controlled diabetes for instance, prolonged elevated plasma glucose can lead to conversion of fructose in the brain, and may be the reason for brain changes observed in type 2 diabetics. Results of the study suggest that CNS effects of fructose may extend beyond direct dietary consumption of the sugar, and more studies should be conducted to better understand neurological complications of diabetes.

3. Autoimmune disorders associated with higher dementia risk

Researchers at the University of Oxford have found that individuals with autoimmune disorders are 20% more likely to develop dementia. An analysis of 1.8 million hospital cases in England between 1999 and 2012 revealed that chronic inflammatory diseases, including autoimmune disorders and diabetes, can lead to damage of healthy brain tissue which may result in dementia and Alzheimer’s disease.

Individuals with psoriasis were associated with a 29% increase in dementia risk, while the risk was 46% higher in those with systemic lupus erythematosus. However, patients with rheumatoid arthritis had a 10% lower risk of dementia, possibly due to the long-standing use of non-steroidal anti-inflammatory drugs.

“They reduce inflammation and that could explain why there’s less spillover, at least in principle,” said lead researcher Michael Goldacre.

Individuals with autoimmune disease were also at higher risk of circulatory disease, and have a 53% and 46% increased likelihood of being admitted in hospital for a coronary heart disease and stroke respectively.

"This research reinforces earlier evidence that shows the immune system plays an important role in developing dementia, opening up new avenues to find effective treatments,” said Dr Clare Walton, Research Manager at Alzheimer’s Society.

“Targeting immune and inflammatory responses is a promising approach for researchers working on new dementia treatments,” added Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK. MIMS

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Sources:
https://www.scientificamerican.com/article/brain-imaging-identifies-different-types-of-depression/
http://www.nature.com/articles/nm.4246.epdf?referrer_access_token=La3T8CBSnOSJRUUb6qZ02NRgN0jAjWel9jnR3ZoTv0PfCsRp9TbZ9t7hiPoiMtvYT4juKJBfJe2HRkhf2wKWi4qnxjcrt4P-QvHwPrX01kUX
4EqDHNy5IkmWnf6ymISfkzRm-HKSdk_7bF9s_eeANAv3J9vhqo2FwSok84u3FQ2ig1IsgMJn427g1RBvnk
XZ4YjqumLouBKfzIZyEP5IUkArGtSwXO8QypKN1obqsLJ9TkAFXh6WrhdY5HCRFecWQGqoJtEu0_W2a8Iop4O-dA%3D%3D&tracking_referrer=www.scientificamerican.com
https://theconversation.com/the-human-brain-makes-fructose-researchers-discover-heres-why-that-might-be-a-big-deal-73258
http://insight.jci.org/articles/view/90508#top
https://www.newscientist.com/article/2123274-autoimmune-disorders-linked-to-an-increased-risk-of-dementia/
http://www.telegraph.co.uk/science/2017/03/01/autoimmune-disease-may-raise-risk-dementia-oxford-study-shows/
https://www.extremetech.com/extreme/241222-groundbreaking-fmri-study-weill-cornell-finds-four-distinct-neurological-subtypes-depression