“In the winter of 1883, a psychiatric assistant named Julius Wagner-Jauregg was working in an Austrian asylum when he witnessed something curious. While making his rounds, Wagner-Jauregg encountered a woman with psychotic delusions who had caught a skin infection, which caused a high fever. But once her temperature resolved, she became coherent, and her symptoms of psychosis disappeared. Wagner-Jauregg spent the next decades of his career attempting to replicate that observation: he exposed people with mental illness to different types of infection to induce fever. But he had relatively little success until 1917, when he started injecting patients who had developed psychosis as a result of late-stage syphilis with blood from soldiers with malaria. The technique seemed to work, according to reports at the time; upwards of half of patients returned to normal life after they received it. The treatment, referred to as malariotherapy, was used in thousands of patients across the world during the 1920s and 1930s1. It was so well regarded at the time that Wagner-Jauregg won the Nobel Prize in Physiology or Medicine in 1927 for his development of the treatment.” …..continued……

Wetsman N: Inflammatory illness: Why the next wave of antidepressants may target the immune system. Nature Medicine 23(9):1009-1011 (2017).



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Exercise-induced cognitive improvements have traditionally been observed following aerobic exercise interventions; that is, sustained sessions of moderate intensity. Here, researchers tested the effect of a 6 week high-intensity training program on measures of cognitive control and working memory in a multicenter, randomized, placebo-controlled trial.

318 children aged 7-13 years were randomly assigned to high-intensity training or an active control group matched for enjoyment and motivation. The 6-week high-intensity exercise program resulted in improvements on measures of cognitive control and working memory, moderated by BDNF genotype, with met66 carriers showing larger gains post-exercise than val66 homozygotes. The authors suggest that short, intense exercise regimens are promising lifestyle interventions for enhancing cognitive function in children.

Moreau D, Kirk IJ and Waldie KE: High-intensity training enhances executive function in children in a randomized, placebo-controlled trial. Elife 2017 Aug 22;6. pii: e25062. doi: 10.7554/eLife.25062.



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Antipsychotic drugs remain the standard treatment for schizophrenia. Despite their effectiveness in treating hallucinations and delusions, prolonged exposure to antipsychotic drugs leads to cognitive deficits in both schizophrenia patients and animal models. The molecular mechanisms underlying these negative effects on cognition are not known. Here Ibi and colleagues demonstrate that chronic antipsychotic drug exposure increases nuclear translocation of NF-κB in mouse and human frontal cortex, an effect triggered via the 5-HT2A-receptor-dependent downregulation of NF-κB repressor IκBα. Augmented HDAC2 transcription appears to mediate the negative effects of antipsychotic treatment on synaptic remodeling and cognition since deletion of HDAC2 in forebrain pyramidal neurons prevented these effects. Conversely, virally mediated activation of NF-κB signaling decreased cortical synaptic plasticity via HDAC2. This information may aid development of therapeutic strategies to improve cognitive function after antipsychotic treatment.


Ibi D, de la Fuente Revenga M, Kezunovic N, Muguruza C, Saunders JM, Gaitonde SA, Moreno JL et al.: Antipsychotic-induced Hdac2 transcription via NF-κB leads to synaptic and cognitive side effects. Nat Neurosci. Aug. 7, 2017 [Epub ahead of print; doi: 10.1038/nn.4616].



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In a sample of 202 deceased players of American football from a brain donation program, chronic traumatic encephalopathy was neuropathologically diagnosed in 177 players across all levels of play (87%), including 110 of 111 former National Football League players (99%).Neuropathological severity of chronic traumatic encephalopathy was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college, semiprofessionl, and professional players having severe pathology. Among 27 participants with mild pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. The study concludes that football playing is highly associated with chronic traumatic encephalopathy brain damage.

Mez J, Daneshvar DH, Kiernan PT, Abdolmohammdi B, Alvarez VE, Huber BR, Alosco ML, Solomon TM, et al.: Clinocopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football. JAMA 318(4):360-370 (2017).


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“Neuropathic pain involves long-lasting modifications of pain pathways that result in abnormal cortical activity. How cortical circuits are altered and contribute to the intense sensation associated with allodynia is unclear. Here (the authors) report a persistent elevation of layer V pyramidal neuron activity in the somatosensory cortex of a mouse model of neuropathic pain. This enhanced pyramidal neuron activity was caused in part by increases of synaptic activity and NMDA-receptor-dependent calcium spikes in apical tuft dendrites. Furthermore, local inhibitory interneuron networks shifted their activity in favor of pyramidal neuron hyperactivity: somatostatin-expressing and parvalbumin-expressing inhibitory neurons reduced their activity, whereas vasoactive intestinal polypeptide-expressing interneurons increased their activity. Pharmacogenetic activation of somatostatin-expressing cells reduced pyramidal neuron hyperactivity and reversed mechanical allodynia. These findings reveal cortical circuit changes that arise during the development of neuropathic pain and identify the activation of specific cortical interneurons as therapeutic targets for chronic pain treatment.”

Cichon J, Blanck TJJ, Gan WB, Yang G: Activation of cortical somatostatin interneurons prevents the development of neuropathic pain. Nature Neurosci. 20(8):1122-1132 (2017).


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“The human brain is plastic, i.e. it can show structural changes in response to the altered environment. Physical activity is a lifestyle factor which has significant associations with the structural and functional aspects of the human brain, as well as with the mind and body health. Many studies have reported regional/global brain volume increments due to exercising; however, a map which shows the overall extent of the influences of physical activity on brain structure is not available. In this study, (the authors) collected all the reports on brain structural alterations in association with physical activity in healthy humans, and next, a brain map of the extent of these effects is provided. The results of this study showed that a large network of brain areas, equal to 82% of the total grey matter volume, were associated with physical activity. This finding has important implications in utilizing physical activity as a mediator factor for educational purposes in children, rehabilitation applications in patients, improving the cognitive abilities of the human brain such as in learning or memory, and preventing age-related brain deteriorations.”


Batouli SAH and Saba V: At least eighty percent of brain grey matter is modifiable by physical activity: A review study. Behav. Brain Res. 332: 204-217 (2017).



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As the world’s elderly population rises, an understanding of brain aging becomes increasingly crucial. This review highlights recent findings in the study of neurocognitive aging, with special focus on episodic memory. Topics include dysfunction in neural circuits, the roles of neurogenesis and inhibitory signaling, vulnerability in the entorhinal cortex, individual differences, and comorbidities.

The first point describes volumetric brain changes with age. This is thought to reflect synaptic degradation rather than frank neuronal loss in the absence of disease. Memory functions are also under tight inhibitory control by small interneurons which can become dysregulated with age. The authors suggest that analysis of these different factors will help evaluate brain health trajectory with age.


Reagh Z and Yassa M: Selective vulnerabilities and biomarkers in neurocognitive aging. F1000Res. 6:491 (2017); doi: 10.12688/f1000research.10652.1. eCollection 2017.



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“No one likes a con artist. People avoid dealing with characters who have swindled them in the past, and—according to new research—birds avoid those people, too. Ravens, known more for their intelligence, but only slightly less for their love of cheese, were trained by researchers to trade a crust of bread for a morsel of cheese with human partners. When the birds then tried to broker a trade with “fair” and “unfair” partners—some completed the trade as expected, but others took the raven’s bread and kept (and ate) the cheese—the ravens avoided the tricksters in separate trials a month later. This suggests that ravens can not only differentiate between “fair” and “unfair” individuals, but they retain that ability for at least a month, the researchers write this month in Animal Behavior. Ravens have a complex social life involving friendships and rivalries. Their ability to recognize and punish dishonest individuals, even after a single encounter, may help explain how cooperation evolved in this group of birds. For people, though, the moral of the story is simple: Be nice to ravens.”  Written by K. Langin.

Müller JJA, Massen JJM, Bugnyar T, Osvath M: Ravens remember the nature of a single reciprocal interaction sequence over 2 days and even after a month. Animal Behaviour 128: 69-78 (2017).



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This viewpoint article describes the brain as a central organ responding to stress, which is vulnerable but also resilient. It receives information not only from the outside world but also reciprocally with the rest of the body. The article explains the concepts of allostasis and allostatic loads as they epigenetically affect neural and systemic processes over the lifecourse. McEwen explains how the brain and body influence each other during the course of psychiatric disorders with frequent multimorbidity   – a point the author thinks needs more emphasis in the Research Domain Criteria matrix.

McEwen Bruce S.:  Allostasis and the Epigenetics of Brain and Body Health over the Life Course – The Brain on Stress. JAMA Psychiatry 74(6):551-552 (2017).


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Cognitive dysfunction may be observed in depression during both acute episodes and remission. Vortioxetine is a novel multimodal antidepressant that has improved cognitive function including executive function in depressed patients in randomised placebo-controlled clinical trials. However, it is unclear whether vortioxetine is able to target directly the neural circuitry implicated in the cognitive deficits in depression. Remitted depressed and healthy volunteers were randomised to receive 14 days treatment with 20 mg vortioxetine or placebo in a double-blind design. The effects of vortioxetine on fMRI responses during an N-back working memory task were assessed at baseline and at the end of treatment. Vortioxetine reduced BOLD signal during performance of the N-back working memory task. This action of vortioxetine was opposite in direction of effect to the increases in BOLD signal described in MDD patients able to maintain task performance. The authors suggest that vortioxetine increased efficiency during effortful working memory performance.

Smith J, Browning M, Conen S, Smallman R, Buchbjerg J, Larsen KG, Olsen CK, Christensen SR, Dawson GR, Deakin JF, Hawkins P, Morris R, Goodwin G, Harmer CJ: Vortioxetine reduces BOLD signal during performance of the N-back working memory task: a randomised neuroimaging trial in remitted depressed patients and healthy controls. Molecular Psychiatry [Epub ahead of print, May 23, 2017; doi: 10.1038/mp.2017.104].



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