Cingulate Cortex Volume Varies With Severity of Major Depressive Disorder

Caroline Helwick

September 01, 2010

September 1, 2010 (Amsterdam, The Netherlands)— The volume of the cingulate cortex might be progressively affected as major depressive disorder (MDD) worsens over time, investigators reported here at the 23rd European College of Neuropsychopharmacology Congress

Maria Serra, a doctoral candidate in the neuroscience section of the Port d'Informació Científica in Barcelona, Spain, reported the findings of the multicenter study. The senior author was Maria Portella, PhD, from the Institut d'Investigació Biomèdica in Barcelona.

"All the comparisons in our study showed a decrement of cortical volumes of the cingulate cortex in MDD patients vs healthy controls. The decrease seems to begin in the posterior cingulate areas in the more benign stages of depression and progressively become more generalized as the illness becomes more severe," Ms. Serra said.

Previous studies have found morphologic differences between depressed people and healthy control subjects, but these patient populations have been heterogeneous or the studies have only compared control subjects with patients at one stage of the illness. Existing data, therefore, have been somewhat inconsistent, but one finding has been common — that volumetric abnormalities are localized to the prefrontal cortex, the temporal lobe (hippocampus and amygdala), and the cingulate cortex, she said.

The current study focused on the cingulate cortex, which is important in mood disorders and has been shown to be structurally and functionally abnormal in MDD. Most of the abnormalities and volume reductions have been found in the anterior cingulate cortex.

Questions to be answered are "whether only the anterior cingulate is involved, and whether cingulate volume changes over the course of the illness," she said.

The study consisted of 59 patients with MDD — 20 first-episode patients, 19 remitting-recurrent patients, and 20 chronic patients whose current episode had lasted for more than 2 years — and 20 healthy matched control subjects.

Magnetic resonance imaging (MRI) images were obtained and cortical volumes were quantified. The procedure to obtain cingulate volumes occurred in 2 stages: surface segmentation and cortical parcellation, which is the assignment of neuroanatomical labels to each cortical location.

Comparative MRIs showed that the cingulate cortex areas differed in volume according to patient subgroup (ie, by duration/severity of the illness). An increase in cortical volume was observed in the anterior cingulate cortex early on (ie, in first-episode patients), whereas volumetric decreases were observed in later stages in the posterior cingulate cortex, Ms. Serra reported.

Cingulate Cortex Volume Areas Differing by Disease Stage

Cingulate cortex area 1st Ep vs
Control (P Value)
RR vs
Control (P Value)
RR vs
1st Ep (P Value)
Chronic vs
Control (P Value)
Chronic vs
1st Ep (P Value)
Chronic vs
RR (P Value)
Left isthmus cingulate ↓ (.021) ↓ (.00097) ↓ (.0023)   ↓ (.0021) ↓ (.0089)
Right isthmus cingulate       ↓ (.0066) ↓ (.00052) ↓ (.0005)
Right posterior cingulate       ↓ (.0027)    
Left anterior cingulate         ↓ (.0014) ↓ (.0087)
Right anterior cingulate         ↓ (.0074) ↓ (.0013)
Ep, episode; RR, remitting-recurrent MDD; ↓, decreased cortical volume


"Interestingly, the area that is related to the persistence of depressive symptomatology in long-standing patients is the anterior cingulate cortex," she noted, "which is one of the boosting targets of deep brain stimulation for treatment-resistant MDD."

Gregor Hasler, MD, professor of psychiatry at the University of Bern in Switzerland, said that the findings add important information to what has been known about the involvement of the cingulate cortex, specifically, that the reduction in volume is progressive.

"There are several hypotheses, mostly based on animal studies, as to why this might be," Dr. Hasler said. "One is that the glutaminergic system is hyperactive in depression and this causes brain damage. Another is that brain-derived neurotrophic factor, which is protective, is reduced in depression. An older theory is that levels of cortisol are increased in the depressed brain and this causes damage."

"These are the 3 major theories and they have clinical implications," he continued. "In the beginning of depression, we think, stress is important but becomes less important over the course of illness. The episodes of depression begin to occur spontaneously, related to this damage, and therefore it is important to treat patients early and effectively."

The authors and Dr. Hasler have disclosed no relevant financial relationships.

23rd European College of Neuropsychopharmacology (ECNP) Congress: Abstract S.13.05. Presented August 30, 2010.

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