Post-mortem findings in mood disorders, nightmares and therapeutic approaches of psychiatric diseases

Abstract

Dedicated to post-mortem studies on mood disorders in its first part, this edition opens with Bernstein et al. [1] comparing the pathomorphology of mammillary bodies in patients with major depression disorder (MDD) and bipolar I disorder (BD) to control subjects. Via assessing the mammillary body and fornix volumes, number of neurons and neuronal densities, the group found male control subjects to have significantly larger mammillary bodies compared with females. They furthermore detected a significant reduction of the left mammillary body volume in BD patients compared with those with MDD. Another study of this work group [2] focused on alterations in GABAergic neurotransmission which are assumed to play a crucial role in the pathophysiology of mood disorders. The authors found an accentuated increase in GAD-ir neuropil density in the entorhinal cortex and the hippocampus of MDD compared with BD patients and controls. Another interesting finding was the dorsolateral prefrontal cortex in BD to be the only area showing a significant decrease of GADir neuropil density compared with MDD and controls. The authors suggest a diathesis of the GABAergic system in mood disorders as possibly helpful in differentiating the pathophysiology of MDD from BD. Although protein phosphorylation, involved in specific processes like cellular signaling, might add to unravel the molecular substructure of MDD, psychiatric phosphoproteome studies are rare. Martins-de-Souza et al. [3] aimed at filling this gap with a comparative phosphoproteome analysis of dorsolateral prefrontal cortex tissues in major depression using liquid chromatography mass spectrometry. They could identify more than 5,000 phosphopeptides, corresponding to ca. 800 non-redundant proteins. Compared with controls, 90 of these proteins showed differential levels of phosphorylation in MDD patients, most of them associated with synaptic transmission and cellular architecture. This might point out potential biomarker candidates and thus add to comprehend the pathophysiology of MDD. Due to preliminary evidence from pharmacological studies on verbal and visuospatial subcomponents of working memory (WM) being subject to differential neurotransmitter modulation, Zilles et al. [4] genotyped 20 healthy controls and 80 patients with schizophrenia, BD, or obsessive–compulsive disorder with respect to the dopaminergic and serotonergic systems. While DAT genotype revealed a significant effect on visuospatial WM, and 5-HTT again a significant one on verbal WM task performance, COMT did not show an influence on either domain. This evidently differential impact of genetic polymorphisms on verbal and visuospatial WM functioning adds to prior suppositions about the existence of schizophrenia subgroups with patients exhibiting isolated deficits in only one WM domain and supports the idea of endophenotypically and pathophysiologically distinct patient subgroups needing personalized therapeutic approaches. While behavioral and neuroimaging studies have shown an association of distinct symptom clusters like impulsivity with orbitofrontal cortex (OFC) dysfunction in patients with borderline personality disorder, neither the presence of abnormal OFC activity patterns during resting-state conditions nor a possible specific association of OFC dysfunction with impulsivity has been investigated so far. Accordingly, in an MRI study, Wolf et al. [5] found a significant positive relationship between medial and lateral A. Schmitt (&) P. Falkai Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nusbaumstr. 7, 80336 Munich, Germany e-mail: Andrea.Schmitt@med.uni-muenchen.de