BACKGROUND Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma.

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The continuous need for ion gradient restoration across the cell membrane, a prerequisite for synaptic transmission and conduction, is believed to be a major factor for brain's high oxidative demand. However, do energy requirements of signaling and nonsignaling components of cortical neurons and astrocytes vary with activity levels and across species? We derived oxidative ATP demand associated with signaling (P s ) and nonsignaling (P ns ) components in the cerebral cortex using species-specific physiologic and anatomic data. In rat, we calculated glucose oxidation rates from layer-specific neuronal activity measured across different states, spanning from isoelectricity to awake and sensory stimulation. We then compared these calculated glucose oxidation rates with measured glucose metabolic data for the same states as reported by 2-deoxy-glucose autoradiography. Fixed values for P s and P ns were able to predict the entire range of states in the rat. We then calculated glucose oxidation rates from human EEG data acquired under various conditions using fixed P s and P ns values derived for the rat. These calculated metabolic data in human cerebral cortex compared well with glucose metabolism measured by PET. Independent of species, linear relationship was established between neuronal activity and neuronal oxidative demand beyond isoelectricity. Cortical signaling requirements dominated energy demand in the awake state, whereas nonsignaling requirements were ∼20% of awake value. These predictions are supported by 13 C magnetic resonance spectroscopy results. We conclude that mitochondrial energy support for signaling and nonsignaling components in cerebral cortex are conserved across activity levels in mammalian species.T he brain is one of the most energy demanding tissues in the body (1). 13 C magnetic resonance spectroscopy (MRS) in the rat has shown that, in the resting awake state, ∼80% of cortical energy consumption is used to support signaling as reflected by the rate of glutamate neurotransmitter release and astroglial uptake (2, 3). Cerebral energy demand is also positively correlated with the rate of pyramidal neuron firing in rat cortex (4, 5). 13 C MRS findings in the human cortex have been generally consistent with the rat results (6). However, there remain questions as to how well the energy costs of specific subcellular processes needed to support synaptic transmission and conduction are conserved over different activity levels and/or across species.Recent bottom-up energy budgets for gray matter in the mammalian brain have attempted to understand the energetic costs of neuronal and glial electrical and neurotransmission events occurring in the neuropil (7,8) by calculating the ATP used per neuron for signaling (P s ) and nonsignaling (P ns ) events. In the awake cortex, the total ATP used per unit cortical volume per unit time (E tot ; in units of ATP/s per centimeter 3 ) was determined by multiplying the P s (in units of ATP/neuron per spike) and P ns (in units of ATP/neuron per second) parameter...

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