GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

Abstract

Post-mortem morphometric studies report reductions in the average density and size of cortical neurons in the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (ORB) in major depressive disorder (MDD). The contribution of specific neuronal phenotypes to this general pathology in depression is still unclear. Post-mortem sections from the dlPFC and ORB regions of 14 subjects with MDD and 11 controls were immunostained to visualize calbindin-immunoreactive (CB-IR) and parvalbumin-immunoreactive (PV-IR) presumptive GABAergic neurons. A three-dimensional cell counting probe was used to assess the cell packing density and size of CB-IR neurons in layers II + IIIa and PV-IR neurons in layers III-VI. The density of CB-IR neurons was significantly reduced by 50% in depression in the dlPFC and there was a trend toward reduction in the ORB. The size of CB-IR somata was significantly decreased (18%) in depression in the dlPFC with a trend toward reduction in the ORB. In contrast, there was no difference in the density of PV-IR neurons between the depressed and control groups in the dlPFC. The size of PV-IR neuronal soma was unchanged in depressed compared to control subjects in either dlPFC or ORB. In depression, subpopulations of GABAergic neurons may be affected differently in dlPFC and ORB. A significant reduction in the density and size of GABAergic interneurons immunoreactive for calcium binding proteins was found predominantly in the dlPFC region. These cellular changes are consistent with recent neuroimaging studies revealing a reduction in the cortical levels of GABA in depression.

Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

“…Interneuron-related disorders may arise when cortical development goes awry (Levitt et al, 2004;Di Cristo, 2007). An aberrant number and/or distribution of specific subsets of cortical interneurons have been linked to several major neurological disorders, including epilepsy (Powell et al, 2003;Garbelli et al, 2006), schizophrenia (Reynolds et al, 2002;Lewis et al, 2005;Daskalakis et al, 2007), and depression (Rajkowska et al, 2007). In a rat model of fetal alcohol syndrome, one outcome of ethanol exposure during the first postnatal week is an increase in the number of cortical calretinin-IR neurons in the adult (Granato, 2006).…”

“…The heterogeneity of cortical interneuron morphology and neurochemistry presents a complex, incompletely understood picture of neural development (Wonders and Anderson, 2006). Moreover, cortical interneuron dysfunction has been implicated in several neurological disorders with developmental origins (Levitt et al, 2004;Di Cristo, 2007), including epilepsy (Powell et al, 2003;Garbelli et al, 2006), schizophrenia (Reynolds et al, 2002;Lewis et al, 2005;Daskalakis et al, 2007), and depression (Rajkowska et al, 2007). The current study examined a subpopulation of rat cortical interneurons that produced tyrosine hydroxylase (TH), the first, rate-limiting catecholaminergic enzyme.…”

Resting-state brain activation correlates with short-time antidepressant treatment outcome in drug-naïve patients with major depressive disorder

“…29 In addition, imaging studies have identified reductions in occipital cortex g-aminobutyric acid (GABA) levels in patients with MDD. 30,31 We hypothesize that patients with END may have a greater imbalance in concentrations of GABA than those with ERD, resulting in a poor response to SSRI antidepressants. There were no differences between either of the patient groups and the control subjects in ALFF of the lingual gyrus, in the present study, but there was a difference between patients with ERD and those with END.…”

El papel del ácido gamma-aminobutírico en la depresión de la mujer

“…Existen estudios que reportan un incremento del GABA en la corteza occipital después de un tratamiento antidepresivo efectivo con terapia electroconvulsiva 53 , y estudios que reportan concentraciones GABAérgicas normales en pacientes deprimidos recuperados y sin medicación 54 . El estudio de la depresión, como hemos mencionado con anterioridad, implica una correlación multidisciplinaria para poder desentrañar la compleja gama de causas que la integran, por lo que en un intento de continuar dilucidando la relación del GABA con la depresión se han realizado estudios post mortem que reportan una reducción en el tamaño y la densidad de las neuronas en la corteza prefrontal dorsolateral en pacientes con depresión mayor, relacionándolo con la reducción de las concentraciones corticales de GABA 55 .…”