Chronicity in Depression

Major depressive disorder is unremitting in 15% of cases

Major depressive disorder is recurrent in 35%.

About half of those with a first-onset episode recover and have no further episodes.

53% of those with a lifetime episode of depressive disorder either do not recover at all or have at least 1 recurrence.

What is new in this research?

The focus of this analysis is the group of 92 participants who experienced an episode of depression (meeting criteria for DSM-IV) for the first time in their life during the follow-up. Seventy-one first lifetime episodes occurred between the baseline and 1993 follow-up, and 21 occurred between the 1993 and 2004 follow-ups. The comparison group for onset consists of the 1739 participants followed up through the 1993 wave who also had the opportunity for onset but for whom onset did not occur.

This way the Neyman bias and the Berkson bias (A special example of selection bias)are avoided. The first bias is also called the “clinician’s illusion. Clinicians only see a subsample of patients with depression, those with chronic or recurrent episodes.

The Berkson Bias occurs when the combination of exposure and disease under study increases the risk of hospital admission, thus leading to a higher exposure rate among the hospital cases than the hospital controls. So the natural history of depression is best studied using a population based sample, in which individuals are selected from the general population without regard to treatment.Both these biases lead to exaggeration of the chronicity of depression. This research avoids these biases.

Besides the above mentioned results, more common findings in this research were:
the 92 participants with first lifetime onset of depressive disorder were:

  • more likely to be women
  • younger of age
  • those with 1 or 2 short 5HTT alleles. This polymorphism has also been shown to be of importance for evidence of interaction between a functional genetic variant in the serotonin transporter gene and life events
  • persons with a history of drug or alcohol disorders and
    panic attacks were at a higher risk.

These factors raised the risk of first lifetime onset of depressive disorder.

That is somewhat different but also show some overlap with the risk factor for recurrence of depression

What is more important is that the data suggest little or no acceleration or amplification of the course through time.

Another important finding in this research was the intriguing result of the paradoxical effects of the 5HTT on the natural history of MDD. Individuals
with 2 long alleles are protected from the occurrence of first lifetime onset of depressive disorder,consistent with other research. However, the same configuration
is related to longer, not shorter, episodes of depression.

Our speculative explanation is based on the notion that depressive disorder has multiple causes which
endure in varying degrees throughout the course of life.Individuals with the protective genetic configuration sometimes are exposed to other causes whose force is sufficient to break through this protective effect, and presumably these other causes are stronger than in individualswith first episodes and a less protective genetic constellation. After the occurrence of the first episode, these causal forces remain
in place, producing longer episodes andmore difficult recovery.

The serotonin transporter gene

There is evidence of interaction between a functional genetic variant in the serotonin transporter gene and life events.

Serotonin is an important neurotransmitter believed to play an important role in depression. The variant of this gene affects how much serotonin transporter protein is produced. This protein is involved in reuptake of serotonin in the synaps. Individuals with the short allelic form of this variant showed an increased risk of depression compared to those carrying the long allele but only when exposed to adverse life events or maltreatment. There have been some nonreplications, but these have been outnumbered by the number of replicated findings.

These results are not very different from the results of patient samples from clinics and studies whose samples include cases late in the course.

Eaton, W.W. (2008). Population-Based Study of First Onset
and Chronicity in Major Depressive Disorder. Archives of GeneralPsychiatry, 65(5), 513-520.