Background: Many research papers claim that patients with specific psychiatric disorders (major depressive disorder, posttraumatic stress disorder, borderline personality disorder, alcohol use disorder, and others) have smaller hippocampi, but most of those reports compared patients to healthy controls. We hypothesized that if psychiatrically matched controls (psychiatric control, matched for demographics and psychiatric comorbidities) were used, much of the biomarker literature in psychiatric research would not replicate. We used hippocampus and amygdala volume only as examples, as these are very commonly replicated results in psychiatry biomarker research. We propose that psychiatry biomarker research could benefit from using psychiatric controls, as the use of healthy controls results in data that are not disorder-specific. Method: Hippocampus/amygdala volumes were compared between major depressive disorder, sex-/age-/race-matched healthy control, and psychiatric control (N ¼ 126/group). Similar comparisons were performed for posttraumatic stress disorder (N ¼ 67), borderline personality disorder (N ¼ 111), and alcohol use disorder (N ¼ 136). Results: Major depressive disorder patients had smaller left (p ¼ 8.79 Â 10 À3 ) and right (p ¼ 3.13 Â 10 À3 ) hippocampal volumes than healthy control. Posttraumatic stress disorder had smaller left (p ¼ 0.018) and right (p ¼ 8.64 Â 10 À4 ) hippocampi than healthy control. Borderline personality disorder had smaller right hippocampus (p ¼ 7.90 Â 10 À3 ) and amygdala (p ¼ 1.49 Â 10 À3 ) than healthy control. Alcohol use disorder had smaller right hippocampus (p ¼ 0.034) and amygdala (p ¼ .024) than healthy control. No differences were found between any of the four diagnostic groups and psychiatric control. Conclusion: When psychiatric controls were used, there was no difference in hippocampal or amygdalar volume between any of the diagnoses studied and controls. This strategy (keeping all possible relevant variables matched between experimental groups) has been used to advance science for hundreds of years, and we propose should also be used in biomarker psychiatry research.

This study aimed to examine habenular resting state functional connectivity (RSFC) abnormalities in tobacco-smoking veterans. The authors explored RSFC in sated smokers (n = 18), overnight deprived smokers (n = 13), and nonsmoker controls (n = 26). Seed-to-voxel analysis was used to explore RSFC in the habenula. Compared to sated smokers, deprived smokers demonstrated higher RSFC between the right habenula and two clusters of voxels: one in the right fusiform gyrus, and one in the left lingual gyrus. To study nicotine withdrawal, the authors used the Shiffman-Jarvik Withdrawal Questionnaire (SJWQ) score as a regressor and found higher RSFC between the right habenula and

Background: Neuroinflammation, a hallmark of frontotemporal dementia, has been sparsely studied in vivo. However, neuroinflammation is a potentially important therapeutic target and biomarkers of inflammation would be welcome. To determine the anatomical specificity of a putative biomarker for inflammation, translocator protein 18 kDa (TSPO) imaging, we used 11 C-PBR28 PET to measure TSPO levels in patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and/or apraxia of speech (AOS).Methods: Sixteen patients with nfvPPP/AOS underwent PET using 11 C-PBR28 and 18 Fflortaucipir. All patients were PET amyloid-negative except two, with a non-AD flortaucipir PET. Thirty healthy controls underwent PET imaging using 11 C-PBR28 (13 controls) or 18 F-flortaucipir (17 controls). Patients (9/16 women, mean age 65±5.9 years) did not differ significantly in age from the controls (17/30 women, mean age 66±9.3 years). V T values for 11 C-PBR28 were calculated with the Logan plot and a metabolitecorrected arterial input function. For 18 F-flortaucipir, the SUV ratio over the cerebellar gray matter was calculated for t = 80-100 min. All images were corrected for partial volume effect. A full factorial analysis was performed on V T and SUVR values between patients and controls at the voxel-wise level.Results: Compared to controls, patients showed increased V T and SUVR values (p < 0.001 uncorrected) in left inferior, middle and superior frontal gyri, as well as in the left putamen and pallidum. However, peak uptake of 18 F-flortaucipir was localized in Broca's area, epicenter of the pathology, while the distribution of 11 C-PBR28 V T was more extensive in the frontal lobe, including precentral gyrus, and other regions outside of the frontal lobe, as the supramarginal gyrus and superior temporal sulcus, as well as a small area in the posterior extent of the right inferior frontal gyrus.Conclusions: 11 C-PBR28 and 18 F-flortaucipir uptake patterns corresponded to anatomical areas known to be related to the specific language functions that are impaired in nfvPPA and apraxia of speech. Thus, 11 C-PBR28 seems to be a suitable radioligand for detecting neuroinflammation in nfvPPA. Furthermore, the more exten-