An investigation of medial temporal lobe changes and cognition following antidepressant response: a prospective rTMS study.

BACKGROUND: Major depressive disorder (MDD) is often resistant to treatment with standard approaches. Repetitive transcranial magnetic stimulation (rTMS) is a new treatment that has proven antidepressant efficacy in treatment resistant MDD (TRD). Preliminary evidence also raises the possibility of rTMS enhancing neuronal plasticity; with demonstrated increases in serum levels of brain derived neurotrophic factor (BDNF) found. This is of most relevance to volumetric reductions associated with MDD, particularly in the hippocampus and related structures. Extensive preclinical literature suggests that hippocampal volume reductions from MDD induced suppression of adult neurogenesis can be reversed by different types of classical antidepressant treatments which increase expression of BDNF. OBJECTIVE: The aims of this study were to investigate whether antidepressant response to rTMS has similar therapeutic potential as antidepressant pharmacotherapy in promoting neurogenesis in the HC and surrounding structures and facilitating related neurocognitive improvements. METHODS: Magnetic resonance imaging and neurocognitive assessments were conducted on 29 patients prior to rTMS treatment (baseline) and at three months post baseline (endpoint). RESULTS: Over time, antidepressant response was associated with a near significant increase in left amygdala volume (6.58%), whilst treatment non-responders showed significant declines in left hippocampus volumes (-2.64%) from baseline. Functionally, there was no cognitive deterioration following rTMS treatment. The results are limited, however, by sample size. CONCLUSIONS: These preliminary findings suggest that rTMS may promote neurogenesis or other effects that favour neuronal plasticity and may also be neuroprotective for patients with TRD but these findings need replication in a larger sample.

Cognitive and volumetric predictors of response to repetitive transcranial magnetic stimulation (rTMS) - a prospective follow-up study.

As the prevalence of treatment resistant depression (TRD) continues to rise, it remains a clinically important issue to identify neurobiological-, patient- and treatment-related factors that could potentially predict response to treatment. Medial temporal lobe (MTL) structures, in particular the hippocampus and amygdala have been implicated in inferior treatment response. The role of related structures such as the entorhinal cortex and the impact of MTL abnormalities on neurocognitive function, however, have not been systematically examined. The current study investigated MTL abnormalities and neurocognitive characteristics of eventual treatment responders and non-responders to a course of repetitive transcranial magnetic stimulation (rTMS) in order to identify potential predictors of treatment outcome. Prior to rTMS treatment all patients underwent magnetic resonance imaging (MRI) and neuropsychological assessment. MRI analysis was conducted using FreeSurfer 5.0. There was a 50% response rate following up to a 6-week course of daily rTMS treatments. Treatment response was defined as 50% reduction in Hamilton Depression Rating Scale and BDI-II scores from baseline. There was no difference in pre-treatment neurocognitive profiles and MTL volumes between eventual treatment responders and non-responders. Smaller pre-treatment left hippocampus volume showed a trend towards predicting eventual subjective improvement in depressive symptomatology. Although preliminary, our findings suggest that structural abnormalities may have some potential for predicting outcome to rTMS.

A magnetic resonance imaging study of the entorhinal cortex in treatment-resistant depression.

Despite a growing interest in this area, we continue to lack an understanding of the pathophysiology of depression and of treatment-resistant depression (TRD) in particular. The role of the medial temporal lobe, particularly the hippocampus, has been widely implicated in the aetiology of depression. However, related structures such as the entorhinal cortex have not been systematically examined. This research study aimed to examine possible abnormalities in the volume of the entorhinal cortex (ERC) in TRD patients. A group of 45 TRD patients and 30 healthy age- and sex-matched controls underwent magnetic resonance imaging (MRI). ERC volumes were manually traced from MRI data using ANALYZE software. An analysis of variance was conducted between subject groups and in the sexes separately while controlling for the effects of brain size via intracranial volume (ICV). Results revealed significant reductions in the volume of the left ERC of female patients. Although preliminary, our findings suggest that anatomical abnormalities in the ERC may confer vulnerability to treatment resistance. Confirmatory longitudinal studies are required to determine whether these abnormalities predate the onset of depression or are the result of a more chronic, treatment-resistant course of illness.