June has brought us some interesting findings: new therapeutic targets and drugs, tips on how to prevent cognitive decline, and great technological innovations. But it also brought us some bad news. I share the best and worst news with which I came across in June. These are personal opinions, presented in no particular order and we welcome your comments and suggestions. If you have come across any interesting studies, let us know in the comment section.

THE BEST

Lifestyle changes to prevent cognitive decline

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a big randomized controlled trial ran over the course of two years to assess the effect of modifiable vascular and lifestyle-related risk factors on the prevention of cognitive decline in at-risk elderly people from the general population. This study analyzed the effect of diet, exercise, cognitive training, and vascular risk monitoring and evaluated change in cognition scores. Their results were now published in The Lancet and demonstrate that such lifestyle interventions can indeed improve or maintain cognitive functioning in at-risk elderly people.

Promising new drugs for multiple sclerosis

One of the hallmarks of multiple sclerosis (MS) is the progressive failure of remyelination in the central nervous system. In order to effectively prevent neurodegeneration and the associated disability, remyelination is required. One approach would be the generation of new oligodendrocytes, the glial cells that produce myelin in the central nervous system. Oligodendrocyte progenitor cells are stem cells that are abundant in demyelinated regions of patients with MS, but that fail to differentiate into mature, myelin-producing oligodendrocyte, thereby being a potential therapeutic target.

A study published in Nature aimed to discover therapeutic compounds for enhancing myelination from endogenous oligodendrocyte progenitor cells, by screening the effect of a library of bioactive molecules on these cells. They were able to identify a couple of molecules that may enhance the generation of mature oligodendrocytes and enhance remyelination, resulting in striking reversal of disease severity.

Nanothechnology for neuroscience

A multidisciplinary team from Harvard and from Beijing’s National Center for Nanoscience and Technology has developed a new type of brain implant made from a rolled-up, silky mesh covered with tiny electronic devices. It can be injected into the brain, where it then unfolds to monitor and stimulate individual neurons. The mesh integrates with the neural tissue, and, so far, no signs of adverse immune responses have been reported. The applications are countless: from understanding brain processes in great detail to being able to interfere with those processes and directly stimulate the brain in a minimally invasive way. Their findings were published in Nature Nanotechnology.

A new therapeutic target for Huntington’s disease

Huntington’s disease is still an incurable neurodegenerative disease. In a large-scale screening of potential therapeutic targets, a team of researchers from the UK, Germany, Luxembourg and Italy identified new modifiers of mutant Huntingtin (HTT), the protein that causes Huntington’s disease. 

After validating their results in Drosophila, they found that the inhibition of the protein glutaminyl cyclase (QPCT) was able to reduce the aggregation of multiple proteins. In the study published in Nature Chemical Biology, they argue that this may be a new Huntington’s disease druggable target affecting mutant HTT aggregation. They also generated new QPCT inhibitors that may eventually be effective in the treatment of the disease.

Medical marijuana legalization does not increase adolescent use

The relationship between medical marijuana laws in the US and adolescent use of marijuana were reviewed and published In The Lancet Psychiatry. Arguments against the use of marijuana for medical purposes have included the claim that it could increase the use of marijuana by adolescents. To test this claim, the authors used 24 years of national data from the USA to examine the relationship between state medical marijuana laws and adolescent use of marijuana.

They concluded that although there is an overall higher adolescent use in states that ever passed medical marijuana laws, the passage of those laws did not lead to an increase in adolescent use of marijuana. This is most likely associated to a local cultural background that contributes to both marijuana use and the passage of medical marijuana laws.

THE WORST

The increase of disability in the world

The Global Burden of Disease Study 2013 was published last month in The Lancet. That study aimed at estimating trends in disease and injury incidence, prevalence, and years lived with disability for acute and chronic diseases and injuries. Data from 188 countries between 1990 and 2013 was analysed.

The study found a surprisingly high prevalence of disease and injury worldwide. Leading causes of disability include low back pain and major depressive disorder. The highest increases in disability were observed as a consequence of musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases. Furthermore, in sub-Saharan Africa, HIV/AIDS was also a significant contributor to increased disability. The study concludes that ageing of the world’s population is leading to a substantial increase in disease and injury incidence and prevalence. Since the disability rates are declining much more slowly than mortality rates, health systems will most likely have to adjust.

The effects of anesthesia in young children’s brain

Anesthetics are known to produce some detrimental neurological effects in immature animals, raising concerns about the possibility of similar effects occurring in young children. To address this issue, research published in Pediatrics compared participants of a language development study aged 5 to 18 years who had undergone surgery with anesthesia before 4 years of age with participants with no exposure to anesthesia. Children who had received anesthesia showed lower scores in listening comprehension and performance IQ. These decreased scores were associated with lower gray matter density in the occipital cortex and cerebellum. These findings suggest that general anesthesia in early childhood may affect language abilities and cognition.

Chronic stress and decreased longevity

Stress is known to be associated with accelerated aging and premature death. However, the link between chronic stress and these effects remains largely unknown. Klotho is a molecule that regulates the ageing process and has neuroprotective effects.

A study published in Translational Psychiatry looked at a possible link between stress and klotho levels in women with chronic stress and found that they had significantly lower levels of klotho compared with low-stress women. It was also found that this decrease was age-dependent. Additionally, the levels of klotho were even lower in women who reported more depressive symptoms. These results suggest that klotho levels may be directly influenced by stress and that this may play a part in disease development associated with stress.

Bullying and mental health

Bullying has been shown to have long-term adverse psychological effects. A study published in The Lancet Psychiatry aimed to determine whether bullying has unique adverse mental health effects compared to other forms of childhood maltreatment, including physical, emotional, or sexual abuse, or severe maladaptive parenting.

The authors found that being bullied by peers in childhood had generally worse long-term adverse effects on young adults’ mental health. An increased risk for depression in young adulthood was found for children who were only maltreated. By contrast, those who were both maltreated and bullied or only bullied were at increased risk for overall mental health problems, anxiety, depression, and self-harm.

Nicotine and depression

Depression and nicotine dependence go hand in hand: around 50% of individuals with major depressive disorder are smokers. Nicotine dependence is likely to persist even after the clinical symptoms of depression subside. This may be due to an impaired reward response associated with depression. Given nicotine’s know ability to enhance reward responsiveness, it has been hypothesized that smoking may be a way to compensate for this reward deficit. To test this hypothesis, a study published in Neuropsychopharmacology evaluated reward responsiveness in individuals with and without remissive depression who were or were not nicotine dependent. Results showed that nonsmokers had lower reward responsiveness, and that smokers with remissive depression showed behavioral patterns comparable to individuals with no history of depression. To effectively treat both depression and nicotine dependence, reward response mechanisms will most likely have to be targeted.

References

Backeljauw B, Holland SK, Altaye M, & Loepke AW (2015). Cognition and Brain Structure Following Early Childhood Surgery With Anesthesia. Pediatrics, 136 (1) PMID: 26055844

Global Burden of Disease Study 2013 Collaborators (2015). Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet (London, England) PMID: 26063472

Hasin, D., Wall, M., Keyes, K., Cerdá, M., Schulenberg, J., O’Malley, P., Galea, S., Pacula, R., & Feng, T. (2015). Medical marijuana laws and adolescent marijuana use in the USA from 1991 to 2014: results from annual, repeated cross-sectional surveys The Lancet Psychiatry, 2 (7), 601-608 DOI: 10.1016/S2215-0366(15)00217-5

Janes AC, Pedrelli P, Whitton AE, Pechtel P, Douglas S, Martinson MA, Huz I, Fava M, Pizzagalli DA, & Evins AE (2015). Reward Responsiveness Varies by Smoking Status in Women with a History of Major Depressive Disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 40 (8), 1940-6 PMID: 25662839

Jimenez-Sanchez M, Lam W, Hannus M, Sönnichsen B, Imarisio S, Fleming A, Tarditi A, Menzies F, Ed Dami T, Xu C, Gonzalez-Couto E, Lazzeroni G, Heitz F, Diamanti D, Massai L, Satagopam VP, Marconi G, Caramelli C, Nencini A, Andreini M, Sardone GL, Caradonna NP, Porcari V, Scali C, Schneider R, Pollio G, O’Kane CJ, Caricasole A, & Rubinsztein DC (2015). siRNA screen identifies QPCT as a druggable target for Huntington’s disease. Nature chemical biology, 11 (5), 347-54 PMID: 25848931

Lereya, S., Copeland, W., Costello, E., & Wolke, D. (2015). Adult mental health consequences of peer bullying and maltreatment in childhood: two cohorts in two countries The Lancet Psychiatry, 2 (6), 524-531 DOI: 10.1016/S2215-0366(15)00165-0

Liu J, Fu TM, Cheng Z, Hong G, Zhou T, Jin L, Duvvuri M, Jiang Z, Kruskal P, Xie C, Suo Z, Fang Y, & Lieber CM (2015). Syringe-injectable electronics. Nature nanotechnology, 10 (7), 629-36 PMID: 26053995

Najm FJ, Madhavan M, Zaremba A, Shick E, Karl RT, Factor DC, Miller TE, Nevin ZS, Kantor C, Sargent A, Quick KL, Schlatzer DM, Tang H, Papoian R, Brimacombe KR, Shen M, Boxer MB, Jadhav A, Robinson AP, Podojil JR, Miller SD, Miller RH, & Tesar PJ (2015). Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature, 522 (7555), 216-20 PMID: 25896324

Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, Bäckman L, Hänninen T, Jula A, Laatikainen T, Lindström J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, & Kivipelto M (2015). A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet (London, England), 385 (9984), 2255-63 PMID: 25771249

Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, & Dubal DB (2015). Longevity factor klotho and chronic psychological stress. Translational psychiatry, 5 PMID: 26080320

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