Genetic and Environmental Psychiatric Risk Factors Alter Neuronal Projections During Development

Post by Elisa Guma

The takeaway

Exposure to both a genetic and an environmental risk factor for psychiatric illness causes early developmental changes in hippocampal projections to the prefrontal cortex. This structural and functional alteration may underlie many of the cognitive deficits associated with major mental illness.  

What's the science?

Projections from the hippocampus to the prefrontal cortex form early in development and support cognitive function. Selective disruption of the connections from the hippocampus to the prefrontal cortex has been associated with poor cognitive function in numerous mental illnesses. The developmental timing of these disruptions has yet to be elucidated. This week in the Journal of Neuroscience, Song and colleagues characterize the structural and functional properties of this pathway during development in the presence of genetic and environmental risk factors in mouse models.

How did they do it?

The mouse model of gene-environment (dual-hit) risk factor was generated by exposing mice carrying a DISC1 allele (heterozygous; genetic risk) to maternal immune activation (environmental risk) early in gestation (gestational day 9, equivalent to the end of the human first trimester).  Importantly, DISC 1 mutations have been associated with increased risk for developing schizophrenia, while exposure to maternal immune activation in the womb is a well-recognized risk factor for several neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. Experimental mice of both sexes were tested during neonatal development and pre-juvenile development. 

First, the authors aimed to characterize the effect of the dual-hit on the structure of this circuitry. To do so, they performed tracing experiments by injecting a retrograde tracer in the prefrontal cortex and an anterograde tracer in the hippocampus of the mice. Additionally, in a separate group of mice, they exposed embryos to a fluorescent dye that would stain the same circuits. These complementary experiments allowed them to visualize the fibers projection from the hippocampus to the prefrontal cortex at different stages of development.

In order to test the function of these circuits, the authors performed in vivo electrophysiological recording of prefrontal cortex neurons while stimulating the hippocampus optogenetically, in mice. Additionally, in vitro recordings were performed using the patch-clamp technique to record whole-cells in prelimbic and hippocampal neurons to better characterize single-unit activity, firing rate, membrane properties, and synaptic activity of these neurons.

What did they find?

The authors found that neonatal mice exposed to the dual-hit had the same overall pattern of connectivity, but with sparser projections from the hippocampus (specifically from the CA1 region) to the prelimbic area of the prefrontal cortex. Although connectivity increased overall in the pre-juvenile period relative to the neonatal one, these connectivity deficits were found to persist in the dual-hit mice who displayed less arborized (i.e. branched) connections relative to controls.

Given the structural deficits observed due to the dual genetic and environmental risk factor exposure, the authors wanted to determine whether early neuronal function was also disrupted. Overall, they found that stimulation of the hippocampus activated a smaller number of prelimbic neurons in dual-hit mice relative to controls. Further, these mice had decreased occurrence and more variability in their synaptic activity as measured by spontaneous excitatory postsynaptic currents. These results indicate that the sparser hippocampal to prefrontal cortex projections in the dual-hit mice also leads to an attenuated firing rate. As with the structural deficits, the functional deficits observed in the neonates persisted, but to a lesser extent, in pre-juveniles.

What's the impact?

This study suggests that exposure to known genetic and environmental risk factors for psychiatric illness alters connectivity from the hippocampus to the prefrontal cortex, a pathway critical for supporting cognitive function. These changes are detectable at the earliest stages of life, the neonatal period, and persist, albeit to a lesser extent, in the pre-juvenile period. Future work should investigate the direct link between this early disconnection and cognitive impairments, as well as attempt to explore the clinical validity of these developmental mechanisms.   

Access the original scientific publication here.

Decreased Alertness Influences Brain Activity During Decision-Making

Post by Lincoln Tracy

The takeaway

The decisions we make every day are informed by our surrounding environment and internal processes. Being drowsy means we are slower to react to external information, and we react incorrectly more often than when we are alert due to differences in how our brains process the information.  

What's the science?

Humans make countless decisions each day that are informed by external information, prior knowledge, and evidence. However, we have a limited understanding of how changes in alertness impact neural and cognitive processes. This week in The Journal of Neuroscience, Jagannathan Bareham and Bekinschtein used electroencephalography (EEG), behavioral modeling, and an auditory tone localization task to explore how low alertness modulates evidence accumulation-related processes.

How did they do it?

The authors recruited 32 healthy participants (14 males, mean age of 24.5 years), who completed an auditory tone localization task. The task involved listening to a series of guitar chords and indicating whether the sound came from the left or right of their midline. Participants were tested under alert and drowsy conditions. The alert condition was shorter (8 minutes long) and involved participants sitting upright with the lights on and being given specific instructions to stay awake. In contrast, the drowsy session lasted between 1.5 and 2 hours with participants reclined in the dark, given a pillow, and allowed to fall asleep. The number of incorrect responses and reaction times was recorded. Participants wore an EEG cap to record electrical activity in different areas of the brain during the auditory tone localization task.

What did they find?

First, the authors found participants made more localization errors on tones being played on their left-hand side during the drowsy condition compared to the alert condition, confirming the original study from Bareham and colleagues from 2014. Second, they found participants were slower to react during the drowsy condition, meaning the brain required a longer time to process the direction of the auditory tone. Third, they found that the brain activity necessary to decide whether the sounds came from the left or right side was not only less efficient when drowsy, but came later, suggesting a delayed mental process when alertness is decreased. Finally, they found the processing of the auditory began in the frontocentral brain regions before shifting to more central and rear parts of the brain more quickly during the alert condition compared to the drowsy condition, concluding that the brain operated in a different spatial configuration in drowsiness, and at a much later time.

What's the impact?

This study provides new data on how the brain tries to combat decreases in alertness by recruiting additional brain regions to help process external information. These findings shed light on how brain activity tries to adapt to solve problems based on our internal state.

How Has Social Media Impacted Mental Health during COVID-19?

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Post by Lani Cupo

Adapting to a virtual world

Since the beginning of the COVID-19 pandemic, people around the world have largely adapted to a virtual lifestyle. Business meetings, holiday gatherings, and doctor’s appointments now take place through video calls. Recent advances in technology afford clear benefits in facilitating the continuation of such activities. In particular, social media services allow people around the world to access information, spend time with their friends, and engage with their professions from the safety of their homes. However, while such services provide some obvious opportunities for mental health care, such as video-calling with therapists or accessing applications designed to help manage personal mental health like meditation apps for example, recent research also reveals the potential risk of social media usage.

The infodemic

Even as the world has adapted to the global pandemic over the past two years, the more insidious growth of the infodemic has risen to public attention. The infodemic is a term coined to refer to the spread of misinformation in the context of disease outbreak, a process that is fueled not only by mainstream media but also social media platforms.

Examining five social media platforms (Gab, Reddit, Instagram, Twitter, and Youtube), one study found relatively similar patterns of behavior in how users engaged with information across platforms. Assessing the spread of information from either mostly questionable or mostly reliable sources (categorized by the independent fact-checking organization media bias/fact-check), the researchers found similar diffusion patterns for reliable and questionable information. Their findings imply there is no discrimination between the reliability of source information when social media users share information with each other.

Some consequences of the infodemic are tangible—for example, the difficulty average consumers have in determining the accuracy of information complicates the interpretation of public health directives. However, in addition to the overt impact, the overload of information can take a toll on mental health. The stressors accompanying both the pandemic and infodemic can exacerbate psychological disorders, especially against a backdrop of increased isolation. The infodemic contributes to public distrust, increased stress, anxiety, and sleep disorders. In a study examining anxiety and sleep disturbance early in the COVID-19 pandemic, one study found that those most at risk were people who were exceptionally vigilant, constantly seeking information (high monitors) as well as people who sought to distract themselves, avoiding threatening information (high blunters). Their findings indicate the need to account for the interaction between social media use and behavior in assessing the impact of the pandemic on mental health.

COVID-19 and mental health

Beyond the direct health effects of the COVID-19 pandemic, it is imperative to consider the long-term, indirect consequences of the disease outbreak (economic instability, extended isolation and lockdown, delayed treatment for other health issues). The aggressive worldwide response to tackling the disease (lock-downs and curfews) has not been succeeded by equally aggressive policy to combat the mental health crisis primed by increased stressors and decreased access to support. Following increased reports of mental health consequences in Europe and China, a study of 10,368 citizens in the United States of America reports rates of high risk for suicidality and depression higher than averages from previous years, with heightened risk in socially vulnerable populations, such as Blacks, Hispanics, women, and younger respondents.

Researchers speculate it is still too early to understand the full brunt of the psychological impact of the COVID-19 pandemic, however, they call for an examination of some consequences that ought to be considered now. These include the fact that those with pre-existing mental health conditions may be at increased risk of exposure to and contraction of COVID-19, the potential of increased anxiety and depressive symptoms in those who did not previously report mental health conditions and the fact that mental health care providers themselves will likely be at heightened risk for contracting the virus, further straining the professional support system. Even as vaccines are developed for the virus and the world learns to adapt to the global presence of the disease, the impact of the psychological consequences is just beginning to be systematically investigated.

What role does social media play?

Several studies have already begun to investigate the potential mediating role of social media usage in the impact of the pandemic on mental health. A study in Chinese citizens revealed increased exposure to social media may increase anxiety or the combination of anxiety and depression in respondents. Another study focused specifically on those who were not infected by COVID-19 and found that while social media usage did not cause mental health issues, it did mediate the experience of traumatic emotions in response to COVID-19 news, increasing reports of stress, anxiety, depression, and vicarious trauma. Nevertheless, many participants also used social media to receive COVID-19 updates and peer support.

Adolescents may be a particularly vulnerable population to the disruption of their social lives. During adolescence, humans are uniquely sensitive to the perspectives of their peers, often making them the ideal consumer for social media platforms. As schools and extracurricular activities are closed, teenagers turn increasingly to social media for connecting with their peers. Much of the previous research investigating teenagers’ mental health and social media usage collapsed across websites, online activities, and applications, making it difficult to disentangle the consequences beyond “screen time”. It may be that screen time itself is less important than the activities teenagers are engaging in. During COVID-19, teenagers can use social media to share creative outlets, learn new skills, engage with their coursework, and connect with their peers. Nevertheless, they may also be more at risk of exposure to misinformation, and time engaging with social media may exacerbate negative emotional responses to the COVID-19 crisis.

Social media does present positive benefits to a world facing social separation, easing interpersonal connection and allowing for the fast transmission of information. Nevertheless, it also poses potential risks that should be considered as well. In order to fully establish the impact of COVID-19 on mental health and the role social media plays in the relationship, continued research must survey individuals from multiple age groups, cultural backgrounds, and countries to understand the impact on diverse populations. Preliminary research provides evidence that social media may increase stress and anxiety, potentially exacerbating underlying mental health issues, however, further research will need to establish the continued impact in coming years.

References +

Fitzpatrick, K. M., Harris, C. & Drawve, G. How bad is it? Suicidality in the middle of the COVID-19 pandemic. Suicide Life Threat. Behav. 50, 1241–1249 (2020). Access the original scientific article here.

Cullen, W., Gulati, G. & Kelly, B. D. Mental health in the COVID-19 pandemic. QJM 113, 311–312 (2020). Access the original scientific article here.

Gao, J. et al. Mental health problems and social media exposure during COVID-19 outbreak. PLoS One 15, e0231924 (2020). Access the original scientific article here.

Rathore, F. A. & Farooq, F. Information Overload and Infodemic in the COVID-19 Pandemic. J. Pak. Med. Assoc. 70(Suppl 3), S162–S165 (2020). Access the original scientific article here.

Hamilton, J. L., Nesi, J. & Choukas-Bradley, S. Teens and social media during the COVID-19 pandemic: Staying socially connected while physically distant. (2020) doi:10.31234/osf.io/5stx4. Access the original scientific article here.

Cheng, C., Ebrahimi, O. V. & Lau, Y.-C. Maladaptive coping with the infodemic and sleep disturbance in the COVID-19 pandemic. J. Sleep Res. 30, e13235 (2021). Access the original scientific article here.

Cinelli, M. et al. The COVID-19 social media infodemic. Sci. Rep. 10, 16598 (2020). Access the original scientific article here.

Zhong, B., Jiang, Z., Xie, W. & Qin, X. Association of Social Media Use With Mental Health Conditions of Nonpatients During the COVID-19 Outbreak: Insights from a National Survey Study. J. Med. Internet Res. 22, e23696 (2020). Access the original scientific article here.