The ADNP gene affects brain formation, development, and function, and the protein produced from it helps control the expression of other genes. ADNP mutations are one of the most common single-gene causes of autism. Ketamine was approved in the United States in 1970 and is used for anesthesia and pain management, and more recently as a treatment for depression. Studies in animal models suggest that low-dose ketamine may be neuroprotective and increase expression of the ADNP gene.

“We were intrigued by the preclinical evidence suggesting that low-dose ketamine may increase levels of the ADNP protein and compensate for its loss in ADNP syndrome, so we designed this study to evaluate the safety, tolerability, and behavioral outcomes of low-dose ketamine in children with the syndrome,” says Alexander Kolevzon, MD, Clinical Director of the Seaver Autism Center. “We also sought to explore the feasibility of using electrophysiological biomarkers and computerized eye-tracking to assess sensitivity to treatment.”

In order to evaluate the effect of ketamine, the Mount Sinai research team used a single-dose (0.5mg/kg), open-label design, with ketamine infused intravenously over 40 minutes. Ten children with ADNP syndrome, ages six to 12 years, were enrolled. They found ketamine was generally well-tolerated, and there were no serious adverse events. The most common adverse events were elation/silliness (50 percent), fatigue (40 percent), and increased aggression (40 percent). Using parent-report instruments to assess treatment effects, ketamine was associated with improvements in a wide array of domains, including social behavior, attention deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities, a week after administration.

Results from the clinician-rated assessments indicated improvement based on the Clinical Global Impression-Improvement scale, a seven-point scale commonly used by clinicians to assess how much a patient’s illness has improved or worsened relative to a baseline state at the beginning of an intervention. Importantly, results across clinician-rated and caregiver-rated assessments were largely consistent. The results also highlight the potential of assessing early changes in social attention with computerized eye-tracking and the electrophysiological measurement of a listening task known as auditory steady-state response.

“We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome,” Dr. Kolevzon says. “Future studies using a placebo-controlled design and studying the effects of repeated dosing over a longer duration of time and in a larger cohort of participants are needed before ketamine is used clinically, but our study is a promising first step in that process.”

Ongoing studies are using RNA sequencing to measure change in ADNP expression and other genes, as well as DNA methylation analysis, which has been previously described as relevant in ADNP syndrome. DNA methylation regulates and silences the expression of genes and is vital for embryonic development. Increased occurrence of rare and extreme DNA methylation levels have been linked with neurodevelopmental disorders and congenital anomalies.

To achieve causal evidence, the researchers from the Lise Meitner Group for Environmental Neuroscience examined brain activity in regions involved in stress processing in 63 healthy volunteers before and after a one-hour walk in Grunewald forest or a shopping street with traffic in Berlin using functional magnetic resonance imaging (fMRI). The results of the study revealed that activity in the amygdala decreased after the walk in nature, suggesting that nature elicits beneficial effects on brain regions related to stress.

“The results support the previously assumed positive relationship between nature and brain health, but this is the first study to prove the causal link. Interestingly, the brain activity after the urban walk in these regions remained stable and did not show increases, which argues against a commonly held view that urban exposure causes additional stress,” explains Simone Kühn, head of the Lise Meitner Group for Environmental Neuroscience.

The authors show that nature has a positive impact on brain regions involved in stress processing and that it can already be observed after a one-hour walk. This contributes to the understanding of how our physical living environment affects brain and mental health. Even a short exposure to nature decreases amygdala activity, suggesting that a walk in nature could serve as a preventive measure against developing mental health problems and buffering the potentially disadvantageous impact of the city on the brain.

The results go in line with a previous study (2017, Scientific Reports) which showed that city dwellers who lived close to the forest had a physiologically healthier amygdala structure and were therefore presumably better able to cope with stress. This new study again confirms the importance for urban design policies to create more accessible green areas in cities in order to enhance citizens’ mental health and well-being.

In order to investigate benedicial effects of nature in different populations and age groups, the researchers are currently working on a study examining how a one-hour walk in natural versus urban environments impacts stress in mothers and their babies.

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A team led by the University of Exeter tested bee behaviour and built bee’s-eye-view simulations to work out how they see flowers.

Honeybees have low-resolution vision (about 100 times lower than human vision), so they can only see a flower’s pattern clearly when they are within few centimetres.

However, the new study shows bees can very effectively distinguish between different flowers by using a combination of colour and pattern.

In a series of tests, bees rarely ignored pattern — suggesting colour alone does not lead them to flowers.

This may help to explain why some colours that are visible to bees are rarely produced by flowers in nature.

“We analysed a large amount of data on plants and bee behaviour,” said Professor Natalie Hempel de Ibarra, from Exeter’s Centre for Research in Animal Behaviour.

“By training and testing bees using artificial patterns of shape and colour, we found they relied flexibly on their ability to see both of these elements.

“Showing how insects see colour and learn colour patterns is important to understand how pollinators may, or may not, create evolutionary ‘pressures’ on the colours and patterns that flowers have evolved.

“Our findings suggest that flowers don’t need to evolve too many different petal colours, because they can use patterns to diversify their displays so bees can tell them apart from other flowers.”

One consistent feature identified in the study is that the outside edges of flowers usually contrast strongly with the plant’s foliage — while the centre of the flower does not have such a strong contrast with the foliage colour.

This could help bees quickly identify colour differences and navigate to flowers.

While flowers may be beautiful to humans, Professor Hempel de Ibarra stressed that understanding more about bees — and the threats they face — meant we need to see the world “through the eyes of a bee and the mind of a bee.”

The research, by a team including the Free University of Berlin and the University of Auckland, was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).

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