Anxiety: Persistent Across Animals, Situations, and Ages

The research conducted by Ned Kalin on anxiety and depression includes children and adults.  He has found that anxious temperament (AT), a phenotype, appears around ages 2-3; these children show behavioral inhibition.  Behavioral inhibition is a fancy way of saying that these kids are really, really shy.  Lots of kids are shy, and in fact about 50% of them, according to Kalin, grow to develop anxiety or depression problems.  Of the other 50%, some stay anxious but it does not develop into a disorder, and the others just “grow out of it.”  Additionally, a longitudinal study that followed children until the age of 15 or 16 revealed that chronically low levels of AT can result in ADHD or other ‘external’ disorders. 

Anxious temperament (AT) may result from an altered prefrontal cortex.  In humans, the prefrontal cortex is the area of decision-making and reasoning.  It therefore makes sense that anxiety could result in an altered prefrontal cortex.  Those who develop anxiety characteristically show ‘stable anxiety,’ which is a persistence of the disease across situations and areas of life.  High levels of brain activity in the amygdala occur during stressful situations when someone is anxious across situations.   

Genetically, Kalin’s lab has found that some SNPs can predict anxiety in children.  Single Nucleotide Polymorphisms, SNPs, are changes in DNA at a single nucleotide (A, C, G, T).  As a result there is a mismatch pair that can result in: no change to phenotypes, a change which does not greatly affect the quality of life, or a change that does indeed affect the quality of life.

Kalin has extended his research to behavioral and fieldwork with chimpanzees.  He has found striking parallels to humans.  When a human intruder paradigm was introduced to a young child and monkey (in separate in environments), their responses were exactly the same.  When left to play in an area they are comfortable and happy, but when a stranger enters the area the monkey and child freeze up, refusing to move or make any eye contact.  This freezing behavior is characteristic of AT, therefore people who are consistently  

acting like the monkey and child (when scared), are seen as perpetually anxious.

Monkeys who present consistent AT also show some parallels to humans with anxiety disorders.  Kalin’s research has looked at neural circuits that underlie socialized anxiety disorder, as well as temperamental anxiety, in humans.  These same circuits are present in chimps exhibiting high levels of AT; the circuits are trait-like in nature, further indicating some genetic component to anxiety.

A recent article published in Scientific American (April 2013) touches on “how over-generalization within the brain might influence the development of anxiety disorders.”  Although a different branch than Kalin’s work, the concepts discussed do tie in.  Kalin’s research has shown that many people with anxiety or depression exhibit signs since the womb; high levels of AT make for very shy children.  Anxious temperament is, in itself, a very general diagnosis and commonly occurs in children at low levels.  The brains of those who develop severe, chronic anxiety may be experiencing an overgeneralization i.e. becoming fearful across many situations, instead of in specific situations.  Even those without chronic anxiety get nervous sometimes, but not across most situations.

The study discussed in this article, “Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders” (Kheirbek et al., 2012), proposes that pattern separation, which occurs in the hippocampus, can relate to anxiety, although previously thought to relate only to memory.  Pattern separation is not difficult to understand, but an example, using PTSD, is useful for first-time exposure to this concept: normally, if you’re walking around downtown Chicago and hear a loud noise, maybe a car crash, you might glance over your shoulder to detect the source of the sound, but this is not an earth-shattering event.  For people who suffer from PTSD, this car crash could trigger memories of guns, bombs, a home invasion, or hand-to-hand combat, sending them into an anxiety attack; they struggle with pattern separation in this instance.  This is also applicable to other anxiety disorders, where people cannot discern between events that should truly make them anxious, and those that should.  It is not uncommon, even for the most confident person, to become nervous, anxious, or excited to give a presentation, but people who suffer from anxiety may even get nervous just raising their hand in class or speaking up in a meeting, because they generalize this to be public speaking. 

This Scientific American article goes on to describe neurological consequences of the hippocampus, focusing on neurogenesis as a possible mechanism behind pattern separation.  Neurogenesis is the generation of new neurons, only seen in the olfactory bulb and hippocampus, so far, and is a process that is reduced greatly by aging and stress.  Therefore, those who suffer from anxiety disorders show impaired pattern separation and sensory input, resulting in this generalization we see that goes with anxiety.  Chronic antidepressants are one solution to improve brain plasticity. 

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Kalin, Ned. "Developmental Risk for Anxiety and Depression: A Translational Neuroscience Approach." University of Wisconsin. Loyola University Chicago, Chicago, IL. 25 April 2014. Guest speaker. 

Scicurious. “The Overgeneralization of Generalized Anxiety Disorder.” Scientific American. 29 April 2013. Web. 9 April 2014.