Katherine Reding, Ph.D., Winner of the 2017 NIMH Three-Minute Talks Competition

Transcript

>> KATHERINE REDING: I want to talk to you about puberty and psychopathology.

Puberty is a time of increase onset of several neuropsychiatric disorders.

However, across the pubertal transition - demarcated here by the white dashed-line - there is a demonstrable sex difference in disease prevalence, such that girls show a 2 to 3 fold increase in onset of mood and anxiety disorders compared to boys.

So, one hypothesis is that the activation of the reproductive axis - and production of gonadal hormones including estrogen - increases disease vulnerability for girls at this time.

However, to understand how puberty itself may affect disease vulnerability, one must first understand how puberty affects neurodevelopment.

So, to begin to answer this question, I asked a very simple first question:

Prior to the onset of puberty - at that first dashed-line - are there any visible sex differences in brain function?

To do this I studied a cohort of typically developing 8-year-old children prior to onset of puberty using a neuroimaging paradigm which allows me to look at brain function.

Specifically, how brain areas communicate with each other by measuring their "functional connectivity" while children rested in an MRI scanner.

I then used an analysis tool which allowed me to go through the brain voxel by voxel to identify those that show the greatest differences between boys and girls.

The results of this analysis identified a region in the medial prefrontal cortex.

An area associated with autobiographical memory and part of a larger systems-level network called the default mode network.

Importantly the default mode network is often dysregulated it in both mood and anxiety disorders in adulthood.

We then hypothesized that girls might actually be showing increased connectivity within the default-mode network compared to boys, which might elevate their disease vulnerability.

However, as our first analysis only identified the voxels that showed the greatest differences, we had to conduct a second analysis to understand the directionality and magnitude of those differences.

The results of the second analysis are at the bottom.

We found seven regions that showed greater medial prefrontal cortex connectivity in girls compared to boys, and none where boys were greater than girls.

When you identify these regions, what you see is two-fold.

One, increased connectivity between the prefrontal cortex and other regions in the same 'default mode network.' And then two, increased connectivity in regions within a secondary-network called the 'executive control network' which is responsible for decision making, working memory, and cognitive control.

The key take home here is that prior to the onset of puberty, girls show greater within network and between network connectivity in a circuit that is associated with both mood and anxiety disorders in adults.

This highlights the connectivity of these circuits as a key point of vulnerability that may confer risk to girls across the pubertal transition and may be altered by activation of the reproductive axis and/or gonadal hormones at this time.