To the depressed brain, it’s all the same

If you’re among the 8-12% of the population who will suffer from depression during their lifetime 1, you’re painfully aware of its debilitating symptoms – hopelessness, indifference, emptiness. While it’s clear how depression radically affects one’s emotional state, emerging research is showing that the reaches of depression extend far beyond our mood. In fact, depression can disrupt basic cognitive functions, with a particularly devastating impact on memory 2. However, at present we don’t fully understand the brain processes that give rise to depression, never mind how they contribute to the disorder’s associated cognitive impairments. A recent study published by neuroscientists at Brigham Young University suggests that depression is associated with problems with a particular memory operation known as pattern separation.

Can you tell Buddy from Fuzzy? Thank your hippocampus

Yassa & Stark, 2011

Imagine your two neighbors both have black labs, one slightly smaller and fuzzier than the other. A part of your brain called the hippocampus registers the subtle differences between the dogs and creates distinct representations of the two. You recognize Buddy and Fuzzy as unique because your brain effectively pattern separated them, forming distinct memories of each. It is this process that the researchers speculated might go awry in depression.

Earlier studies have shown that depressed individuals have smaller 4 and less active 5 hippocampi during memory formation than non-depressed people. Although pattern separation is not the only memory function mediated by the hippocampus, depression symptoms can manifest as a tendency to overgeneralize, the opposite of pattern separating. The authors therefore wondered whether diminished pattern separation might lie at the heart of depression-related memory problems.

Pattern separation to the test

To test their hypothesis, they had 98 adults perform a memory test that demanded pattern separation, and complete questionnaires evaluating depression, anxiety, sleep and exercise. Participants with higher depression scores performed significantly worse on the memory test than those with low depression scores, consistent with past studies. Critically, the depressed group had particular difficulty distinguishing a new item they had never seen from a similar one they previously encountered, indicating that they were pattern separating poorly. Furthermore, they found that the higher an individual’s depression score, the worse their pattern separation performance. Importantly, there was no correlation between pattern separation and anxiety, sleep or exercise, suggesting that the memory deficit was specifically related to depression, and not confounded by other associated factors.

But why don’t depressed brains pattern separate?

This study goes a step beyond prior work to identify what specific memory function is compromised in depression. Although the study didn’t examine the neurobiological processes underlying the pattern separation deficit, its findings provide a clear direction for further research.

Past studies suggest that newly born neurons in the hippocampus, produced by neurogenesis, contribute to pattern separation 6 and an association between reduced neurogenesis and “depression” in animals 7. If there are links between pattern separation and neurogenesis, neurogenesis and depression, and now depression and pattern separation, might a causal relationship exist among the three? The authors propose that depression could inhibit neurogenesis, thus impairing pattern separation. Alternatively, reduced neurogenesis (which can be regulated by numerous factors such as exercise, drugs or a rich environment) may induce depressive symptoms. Given the invasive nature of currently available methods to study neurogenesis, examining the effect of neurogenesis on human depression and memory is no easy feat (although some innovative folks recently devised a clever way to document human neurogenesis).

Can poor pattern separation make you sad?

But this study raises another, possibly more accessible, question over how pattern separation is involved in emotional regulation. Whereas the average person might readily discriminate between similar objects or experiences, someone suffering from depression would emphasize the similarities. A pathological tendency to excessively generalize could account for an unwarranted negative outlook.

“That last party was so awkward, I should just stop trying to be social.”

“I was bad at my last job, so I’ll certainly fail at any job I try”.

We’ll have to wait on future research to fully understand whether poor pattern separation contributes to a negative outlook, as well as the brain basis of memory impairments in depression. In the meantime, take a moment to notice the subtle differences around you – it just might make you happy.


1. Andrade L et al. 2003. The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int J Methods Psychiatr Res. 12:3-21.
2. Zakzanis KK et al. 1998. On the nature and pattern of neurocognitive function in major depressive disorder. Neuropsychiatry Neuropsychol Behav Neurol. 11:111-9.
3. Shelton DJ & Kirwan CB. 2013. A possible negative influence of depression on the ability to overcome memory interference. Behav Brain Research.
4. Videbech P & Ravnkilde B. 2004. Hippocampal volume and depression: A meta-analysis of MRI studies. Am J Psychiatry. 161:1957-66.
5. Fairhall SL et al. 2010. Memory related dysregulation of hippocampal function in major depressive disorder. Biol Psychol. 85:499-503.
6. Clelland CD et al. 2009. A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science. 325:210-3.
7. Petrik D et al. 2012. The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking the scaffolding for the building? Neuropharmacology. 62:21-34.
Shelton DJ & Kirwan CB (2013). A possible negative influence of depression on the ability to overcome memory interference Behavioral Brain Research DOI: 10.1016/j.bbr.2013.08.016

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