Abstract

BackgroundSymptoms of mental diseases can be cross-diagnostic. For example psychosis is not limited to schizophrenia (SZ), but can be also present in bipolar (BPP) and schizoaffective (SA) disorders. Morphometric findings are often also cross-diagnostic, For example, volume decreases of the hippocampus (HP), essential to memory functions, is affected in both schizophrenia and bipolar disorder. Biotyping, grouping of patients according to biomarker-based categories is one attempt to approach cross-diagnostic features in the hope of better classification and ultimately tailored interventions. Here we combine biotyping, in addition to traditional diagnosing, with analysis of the HP volume. Furthermore, we explore the HP according to its anterior (aHP) versus posterior (pHP) anatomical division, following the functional division of this medial temporal lobe structure. Our hypothesis is that aHP and pHP are differentially affected in biotypes and diagnostic groups and reflective of differences in cognitive functions affected in each biotype and/or diagnostic group.MethodsThe sample included 450 probands (age 35±12.0 yo) and 325 healthy controls (HC; 37±12.0 yo). Of the probands 187 were diagnosed with SZ, 150 with BPP (psychosis type), 113 with SA disorders; after biotyping the same probands were categorized into three biotypes: 118 biotype 1 (BP1), 142 biotype 2 (BP2), 187 biotype 3 (BP3). 3T MRI data were quality checked and processed with FreeSurfer 6.0. The HP measures extracted were: the whole HP, and further HP subfields according to aHP and pHP. aHP and pHP subfields were reconstituted into left and right aHP and pHP. BACS cognitive data and PANSS, SAPS, MADRS and mania clinical ratings were collected.ResultsAnalysis According to Diagnoses: There were no aHP or pHP volume differences among diagnostic groups, but all diagnostic groups demonstrated volume decreases of the left and right aHP compared to HC with effect sizes (Cohen’s d) between 0.3 and 0.6. Further, SA had decreases of the left and right pHP as well and SZ of the left pHP (effect sizes 0.3–0.4) compared to HC. BPP pHP volume were not different than pHP volumes measured in HC.Analysis According to Biotyping: Decreases of left and right aHP and pHP volumes were present in BP1 compared to HC while decreases of left pHP and left and right aHP were present in BT2 compared to HC. Only aHP was affected in BT3 compared to HC. Left and right aHP and pHP distinguished BT1 and BT3. BT1 had further decreased left pHP volume compared to BP2. Several anterior portions of the subfields volumes were driving the aHP vs pHP differences among biotypes while differences of the posterior portions of the subfields were fewer. aHP differences between BP1 and BP2 were driven by the anterior portion of the right subiculum.DiscussionBiotypes are more effective than diagnoses in discriminating abnormalities of the HP across psychosis categories. Further, analysis of the aHP versus the pHP demonstrates that the HP should be analyzed not as a whole, or as its subfields, but according to anterior versus posterior divisions of its subfields and to the sum of anterior versus posterior subfields in aHP and pHP. Further studies need to elucidate the cognitive functional correlates of aHP- pHP differences across psychoses and healthy populations.

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