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<h5 class="section-title" id="d7383170e453">Importance</h5>
<p id="d7383170e455">More than half of all patients with major depressive disorder
(MDD) experience a relapse
within 2 years after recovery. It is unclear how relapse affects brain morphologic
features during the course of MDD.
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<h5 class="section-title" id="d7383170e458">Objective</h5>
<p id="d7383170e460">To use structural magnetic resonance imaging to identify morphologic
brain changes
associated with relapse in MDD.
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<h5 class="section-title" id="d7383170e463">Design, Setting, and Participants</h5>
<p id="d7383170e465">In this longitudinal case-control study, patients with acute
MDD at baseline and healthy
controls were recruited from the University of Münster Department of Psychiatry from
March 21, 2010, to November 14, 2014, and were reassessed from November 11, 2012,
to October 28, 2016. Depending on patients’ course of illness during follow-up, they
were subdivided into groups of patients with and without relapse. Whole-brain gray
matter volume and cortical thickness of the anterior cingulate cortex, orbitofrontal
cortex, middle frontal gyrus, and insula were assessed via 3-T magnetic resonance
imaging at baseline and 2 years later.
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<h5 class="section-title" id="d7383170e468">Main Outcomes and Measures</h5>
<p id="d7383170e470">Gray matter was analyzed via group (no relapse, relapse, and
healthy controls) by
time (baseline and follow-up) analysis of covariance, controlling for age and total
intracranial volume. Confounding factors of medication and depression severity were
assessed.
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<h5 class="section-title" id="d7383170e473">Results</h5>
<p id="d7383170e475">This study included 37 patients with MDD and a relapse (19 women
and 18 men; mean
[SD] age, 37.0 [12.7] years), 23 patients with MDD and without relapse (13 women and
10 men; mean [SD] age, 32.5 [10.5] years), and 54 age- and sex-matched healthy controls
(24 women and 30 men; mean [SD] age, 37.5 [8.7] years). A significant group-by-time
interaction controlling for age and total intracranial volume revealed that patients
with relapse showed a significant decline of insular volume (difference, −0.032; 95%
CI, −0.063 to −0.002;
<i>P</i> = .04) and dorsolateral prefrontal volume (difference, −0.079; 95% CI, −0.113
to
−0.045;
<i>P</i> < .001) from baseline to follow-up. In patients without relapse, gray
matter volume
in these regions did not change significantly (insula: difference, 0.027; 95% CI,
−0.012 to 0.066;
<i>P</i> = .17; and dorsolateral prefrontal volume: difference, 0.023; 95% CI, −0.020
to 0.066;
<i>P</i> = .30). Volume changes were not correlated with psychiatric medication or
with severity
of depression at follow-up. Additional analysis of cortical thickness showed an increase
in the anterior cingulate cortex (difference, 0.073 mm; 95% CI, 0.023-0.123 mm;
<i>P</i> = .005) and orbitofrontal cortex (difference, 0.089 mm; 95% CI, 0.032-0.147
mm;
<i>P</i> = .003) from baseline to follow-up in patients without relapse.
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<h5 class="section-title" id="d7383170e497">Conclusion and Relevance</h5>
<p id="d7383170e499">A distinct association of relapse in MDD with brain morphologic
features was revealed
using a longitudinal design. Relapse is associated with brain structures that are
crucial for regulation of emotions and thus needs to be prevented. This study might
be a step to guide future prognosis and maintenance treatment in patients with recurrent
MDD.
</p>
</div><p class="first" id="d7383170e502">This nonrandomized longitudinal study uses
structural magnetic resonance imaging to
identify morphologic brain changes associated with relapse in patients with major
depressive disorder.
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<h5 class="section-title" id="d7383170e508">Question</h5>
<p id="d7383170e510">Is relapse in major depressive disorder associated with morphologic
brain changes?</p>
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<h5 class="section-title" id="d7383170e513">Findings</h5>
<p id="d7383170e515">In this longitudinal, case-control, magnetic resonance imaging
study, patients with
major depressive disorder showed different trajectories of cortical gray matter changes
depending on whether they experienced a relapse during the follow-up interval. These
changes were not significantly associated with psychiatric medication or with severity
of depression at follow-up.
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<h5 class="section-title" id="d7383170e518">Meaning</h5>
<p id="d7383170e520">Relapse in major depressive disorder is associated with morphologic
changes in brain
regions that are crucial for regulation of emotions and cognitive control.
</p>
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