Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Tumor- and treatment-related side effects after multimodal therapy of childhood intracranial germ cell tumors.

UNLABELLED: Multimodality treatment approaches have dramatically improved the outcome of patients with intracranial germ cell tumors and are resulting in an increasing number of long-term survivors. The aim of the present study was to evaluate prospectively the development of side effects in children, adolescents and young adults after treatment for intracranial germ cell tumors. Nine patients with a median age of 14 y at diagnosis and a median follow-up of 7.25 y underwent a detailed long-term evaluation including physical and neuro-ophthalmologic examinations, routine laboratory and endocrine stimulation tests, neuropsychometric testing, audiometry and spirometry at repeated intervals. Endocrine deficiencies requiring hormone replacement therapy occurred in all patients. Neuro-ophthalmologic side effects were observed in 8 of the 9 patients, urinary electrolyte wasting in 4 of the 9, alopecia in 3 of the 9 and high-frequency hearing loss in 2 of the 9. Neuropsychologic examinations revealed pathologic results in all five tested patients. CONCLUSION: The present study indicates that former intracranial germ cell tumor patients suffer from remarkable long-term side effects, and that some of these late effects can develop or worsen months or years after cessation of oncologic therapy. Since life quality is an important parameter of cancer survival, careful follow-up of long-term survivors is mandatory, aimed at counteracting side effects as early as possible and therefore at minimizing long-term morbidity, which may considerably compromise quality of life.