Hippocampal Volume in Psychiatric Diagnoses: Should Psychiatry Biomarker Research Account for Comorbidities?

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 = 126/group). Similar comparisons were performed for posttraumatic stress disorder (N = 67), borderline personality disorder (N = 111), and alcohol use disorder (N = 136). RESULTS: Major depressive disorder patients had smaller left (p = 8.79 × 10-3) and right (p = 3.13 × 10-3) hippocampal volumes than healthy control. Posttraumatic stress disorder had smaller left (p = 0.018) and right (p = 8.64 × 10-4) hippocampi than healthy control. Borderline personality disorder had smaller right hippocampus (p = 7.90 × 10-3) and amygdala (p = 1.49 × 10-3) than healthy control. Alcohol use disorder had smaller right hippocampus (p = 0.034) and amygdala (p = .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.

Right temporal pole volume reduction in PTSD.

Previous magnetic resonance imaging studies of post-traumatic stress disorder (PTSD) have reported cortical volume alterations in the parahippocampal, anterior cingulate cortex, and temporal pole. It is unclear, however, if these cortical regions are specifically associated with PTSD or associated with common comorbidities. Here, we present the result of cortical volume differences between PTSD and healthy and psychiatric controls. In this study, healthy controls (n = 67) were matched for demographic characteristics (age, sex, race) and psychiatric controls (n = 67) were matched for demographic characteristics plus all other psychiatric diagnoses (past and current) to a group of PTSD patients (N = 67). We assessed group differences of 34 bilateral cortical structure volumes using statistically defined brain regions-of-interest from FreeSurfer between PTSD patients and healthy controls. We found 10 regions to be significantly different between PTSD and healthy controls and analyzed the group differences between PTSD and psychiatric controls within these regions. The right temporal pole volume in PTSD was found to be significantly smaller than both healthy and psychiatry controls. Our finding suggests only right temporal pole volume reduction is specifically associated with PTSD, and also highlights the need for using appropriate controls in psychiatry research.

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study.

Hearing loss (HL) is an extra-skeletal manifestation of the connective tissue disorder osteogenesis imperfecta (OI). Systematic evaluation of the prevalence and characteristics of HL in COL1A1/COL1A2-related OI will contribute to a better clinical management of individuals with OI. We collected and analyzed pure-tone audiometry data from 312 individuals with OI who were enrolled in the Linked Clinical Research Centers and the Brittle Bone Disorders Consortium. The prevalence, type, and severity of HL in COL1A1/COL1A2-related OI are reported. We show that the prevalence of HL in OI is 28% and increased with age in Type I OI but not in Types III and IV. Individuals with OI Types III and IV are at a higher risk to develop HL in the first decade of life when compared to OI Type I. We also show that the prevalence of SNHL is higher in females with OI compared to males. This study reveals new insights regarding prevalence of HL in OI including a lower general prevalence of HL in COL1A1/COL1A2-related OI than previously reported (28.3 vs. 65%) and high prevalence of SNHL in females. Our data support the need in early routine hearing evaluation in all types of OI that can be adjusted to the severity of the skeletal disease.