Epigenetic modifications may underlie the influence of early life experiences on neuronal development and function, yet the molecular mechanisms are poorly understood.  In this paper, Stroud and colleagues report that deposition of repressive mCA marks by the methyltransferase DNMT3A across specific brain genes during early postnatal life is important for their regulation throughout life. DNMT3A preferentially binds across transcribed regions of lowly expressed genes, and changes in gene transcription activity affect this binding. Thus early life gene activity in the brain affects gene methylation and these changes persist into adulthood. This work has implications for drug treatments and other environmental factors which affect early life gene activity in the brain.

Stroud H, Su SC, Hrvatin S, Greben AW, Renthal W, Boxer LD, Nagy MA, Hochbaum DR, Kinde B, Gabel HW, Greenberg ME: Early-Life Gene Expression in Neurons Modulates Lasting Epigenetic States. Cell 171: 1-14 (2017).


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“The acetylcholine arousal system in the brain is needed for robust attention and working memory functions, but the receptor and cellular bases for its beneficial effects are poorly understood in the newly evolved primate brain. The current study found that cholinergic stimulation of nicotinic receptors comprised of α4 and β2 subunits (α4β2-nAChR) enhanced the firing of neurons in the primate prefrontal cortex that subserve top-down attentional control and working memory. α4β2-nAChR stimulation also protected neuronal responding from the detrimental effects of distracters presented during the delay epoch, when information is held in working memory. These results illuminate how acetylcholine strengthens higher cognition and help to explain why genetic insults to the α4 subunit weaken cognitive and attentional abilities.”

Sun Y, Yang Y, Galvin VC, Yang S, Arnsten AF and Wang M: Nicotinic α4β2 Cholinergic Receptor Influences on Dorsolateral Prefrontal Cortical Neuronal Firing during a Working Memory Task. J. Neurosci. 37(21): 5366-5377 (2017).


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“Migration status is one of the best-established risk factors for schizophrenia. An increase in risk is observed in both first- and second-generation immigrants, with a varying magnitude depending on the ethnic background of the individuals. The underlying mechanisms for the increased risk are only recently coming into focus. A causal role for social stress has been widely proposed, and recent work indicated altered neural stress processing in the perigenual anterior cingulate cortex (pACC) in migrants.” Since previous work shows that social stress may lead to enduring changes in the gray matter volume of vulnerable brain regions, this study investigated the impact of migration background on brain structure. Subjects were matched for sociodemographic characteristics including age, gender, urban exposure, and education.  A significant group by gender interaction effect was found in pACC gray matter volume, which was reduced in males with migration background only. This mirrors previous findings in urban upbringing, another risk factor for schizophrenia. The authors concluded that the results show convergent evidence for an impact of environmental risk factors linked to schizophrenia on gray matter volume and highlighted the possibility that” the pACC structure may be particularly sensitive to the convergent risk factors linked to schizophrenia”.

Akdeniz C, Schäfer A, Streit F, Haller L, Wüst S, Kirsch P, Tost H, Meyer-Lindenberg A: Sex-Dependent Association of Perigenual Anterior Cingulate Cortex Volume and Migration Background, an Environmental Risk Factor for Schizophrenia. Schizophr. Bull. 43(4):925-934 (2017).


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The reward generated by social interactions is critical for promoting prosocial behaviors. Here Hung and colleagues present evidence that oxytocin release in the ventral tegmental area, a key component of the brain’s reward circuitry, is necessary to elicit social reward. During social interactions, activity in paraventricular nucleus oxytocin neurons was observed to be increased. Direct activation of these neurons in the paraventricular nucleus or their terminals in the ventral tegmental area also enhanced prosocial behaviors. Conversely, inhibition of paraventricular oxytocin axon terminals in the ventral tegmental area decreased social interactions. Specifically, oxytocin increased excitatory drive onto reward-specific ventral tegmental dopamine neurons. This report demonstrates that oxytocin promotes prosocial behavior through direct effects on dopamine neurons, providing insight into how social interactions can generate rewarding experiences.

Hung LW, Neuner S, Polepalli JS, Beier KT, Wright M, Walsh JJ, Lewis EM, Luo L, Deisseroth K, Dölen G, Malenka RC: Gating of social reward by oxytocin in the ventral tegmental area. Science 357(6358): 1406-1411 (2017).


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Abstract:  Prevention of deterioration of brain function over time is important in the long-term management of chronic brain disorders such as dementia, schizophrenia, and mood disorders. Although the possibility of neurogenesis in the adult human brain is attractive, and there are psychiatric drugs proven to be effective inducers of neurogenesis in animals, we have yet to see their utility in clinical practice. The terms neurodegeneration and neuroregeneration are often used in a nonspecific manner. Neuroregeneration may mean neurogenesis, dendritogenesis, spinogenesis, or axonogenesis. The term “neuroprotection” is attractive clinically and may involve different mechanisms. Many causative and protective factors of neurodegeneration and neuroregeneration have been proposed. However, the specificity of these factors and agents and differential neuronal vulnerability factors have generally been ignored in past studies. It is also hard to separate disease-modifying from “neuroprotective” effects of a drug. The application of stringent long-term neuroanatomical, neurochemical, neurophysiological, and therapeutic efficacy criteria should improve future research in this important area.

Tang SW, Helmeste DM, Leonard BE: Neurodegeneration, Neuroregeneration, and Neuroprotection in Psychiatric Disorders. Modern Trends Pharmacopsychiatry 31: 107-123 (2017).


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The purpose of this paper was to study whether exercise provides protection against new-onset depression and anxiety, to study the intensity and amount of exercise required to gain protection and to determine what mechanisms may underlie these associations. 33,908 adults having no symptoms of common mental disorder or limiting physical health conditions, were prospectively followed for 11 years. Validated measures of exercise, depression, anxiety, and a range of potential confounding and mediating factors were collected.

Undertaking regular leisure-time exercise was associated with reduced incidence of future depression but not anxiety. The majority of this protective effect occurred at low levels of exercise and was observed regardless of intensity. The social and physical health benefits of exercise explained a small proportion of the protective effect. Previously proposed biological mechanisms, such as alterations in parasympathetic vagal tone, did not appear to have a role in explaining the protection against depression. The authors concluded that regular leisure-time exercise of any intensity provides protection against future depression but not anxiety. Relatively modest changes in population levels of exercise may have important public mental health benefits and prevent a significant percentage of new cases of depression.

Harvey SB, Øverland S, Hatch SL, Wessely S, Mykletun A, Hotopf M: Exercise and the Prevention of Depression: Results of the HUNT Cohort Study. Amer. J. Psychiatry  [Epub ahead of print, Oct. 3, 2017; doi: 10.1176/appi.ajp.2017.16111223.]


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Gut bacteria from multiple sclerosis patients were investigated for their immunoregulatory effects in a mouse model of multiple sclerosis. The authors identified specific bacteria that are associated with multiple sclerosis and demonstrated that these bacteria regulate T lymphocyte-mediated adaptive immune responses and contribute to the proinflammatory environment in vitro and in vivo. The results expand understanding of the microbial regulation of immunity and may provide a basis for the development of microbiome-based therapeutics in autoimmune diseases.

Cekanaviciute E, Yoo BB, Runia TF, Debelius JW, Singh S, Nelson CA, Kanner R, Bencosme Y, Lee YK, Hauser SL, Crabtree-Hartman E, Katz Sand I, Gacias M, Zhu Y, Casaccia P, Cree BAC, Knight R, Mazmanian SK and Baranzini SE: Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc. Natl. Acad. Sci. USA [Epub ahead of print, Sept. 11, 2017]; doi: 10.1073/pnas.1711235114.


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Subjective cognitive decline (SCD), or self-perceived worsening of cognitive function in the absence of objective cognitive deficits, has attracted significant scientific attention, because it might reflect the earliest signs of an emerging neurodegenerative disease. Recently, investigators have struggled to standardize the measurement and definition of SCD, a complex problem because of its inherently subjective nature. Although these attempts have not resulted in consistent results, the presence of subjective cognitive decline is often associated with future objective cognitive decline and with conversion from normal cognition to mild cognitive impairment or even dementia. In this study, Buckley and colleagues investigated the independent and interactive effects of Aβ and tau aggregates, on subjective cognitive decline. They found that subjective cognitive decline was associated with accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of Aβ. However, they cautioned that multiple biological factors must be considered when assessing subjective cognitive decline in clinically healthy older adults.

Buckley RF, Hanseeuw B, Schultz AP, Vannini P, Aghjayan SL, Properzi MJ, Jackson JD, Mormino EC, Rentz DM, Sperling RA, Johnson KA, Amariglio RE: Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden. JAMA Neurol. [Epub ahead of print, Oct.2, 2017]; doi: 10.1001/jamaneurol.2017.2216.


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“Some of the most fascinating questions in theology and philosophy are now being tackled by the social and affective neurosciences. For example, are people inherently good? Are our capacities for love, empathy, and altruism uniquely human?  …  The fundamental components of most human traits are shared by other species, in both form and function, indicating a common ancestor and an evolution over time. For example, humans, monkeys, rodents, sheep, and dogs all share mechanisms for bonding with mates or for protecting newborn kin—processes that support acts of kindness. Indeed, the famous social bonding neuropeptide oxytocin can be traced over 500 million years, with analogous peptides found in birds, reptiles, fish, amphibians, and some invertebrates….” Continued……

Preston SD: The rewarding nature of social contact. Science 357(6358): 1353-1354 (2017).


Hung LW, Neuner S, Polepalli JS, Beier KT, Wright M, Walsh JJ, Lewis EM, Luo L, Deisseroth K, Dölen G and Malenka RC: Gating of social reward by oxytocin in the ventral tegmental area. Science 357(6358): 1406-1411 (2017).





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“More than 300 years ago, the philosopher René Descartes asked a disturbing question: If our senses can’t always be trusted, how can we separate illusion from reality? We’re able to do so, a new study suggests, because our brain keeps tabs on reality by constantly questioning its own past expectations and beliefs. Hallucinations occur when this internal fact-checking fails, a finding that could point toward better treatments for schizophrenia and other psychiatric disorders.

The study is “very elegant,” and an important step toward identifying the brain regions that produce hallucinations—and keep them in check, says Georg Northoff, a neuroscientist at the University of Ottawa who was not involved with the work.

We don’t always perceive the world as we see—or hear—it. In an experiment devised at Yale University in the 1890s, for example, researchers repeatedly showed volunteers an image paired with a tone. When the scientists stopped playing the tone, participants still “heard” it when the image appeared. A similar auditory hallucination occurs in daily life: when you think you hear your cellphone ring or buzz, only to find it’s turned off. “People come to expect the sound so much that the brain hears it for them,” says Albert Powers, a psychiatrist at Yale University and an author of the new study. …..” continued…….

Underwood E: How your mind protects you against hallucinations. Video and Commentary in: Science doi:10.1126/science.aan7229 [August 10, 2017].




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