Enlargement of the amygdala in patients with a first episode of major depression

Frodl, Thomas; Meisenzahl, Eva; Zetzsche, T.; Bottlender, Ronald; Born, Christine; Groll, Constanze; Jäger, Markus; Leinsinger, Gerda; Hahn, Klaus; Möller, Hans‐Jürgen

doi:10.1016/s0006-3223(01)01359-2

Cited by 294 publications

(167 citation statements)

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“…5 Neuroimaging studies have produced a substantial body of knowledge about alterations of the limbic system in mood disorders. In the amygdala, alterations in cerebral blood flow and metabolism, 6 asymmetry of amygdalar volumes, 7 as well as smaller [8][9][10] and larger volumes [11][12][13][14] have been observed in depressed subjects when compared with normal controls. In the hippocampus, volumetric analysis studies have also revealed reduced volumes in subjects suffering from major depression in some, 7,11,[14][15][16][17][18][19][20] but not all studies 10,[21][22][23] comparing depressed patients versus controls.…”

Section: Introductionmentioning

confidence: 99%

Patterns of gene expression in the limbic system of suicides with and without major depression

et al. 2007

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The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides = 18, non depressed suicides = 8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.

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Section: Introductionmentioning

confidence: 99%

Patterns of gene expression in the limbic system of suicides with and without major depression

et al. 2007

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“…[21][22][23][24] . In contrast, both the size and the activity of the amygdala, a structure critical for fear-associated memories, are increased in depressed patients [25][26][27][28] .Consistent with brain imaging studies, depressed patients exhibit deficits in hippocampus-dependent memory tasks and are more sensitive to stressful events [24,29,30] . Changes in neurotransmitter levels, receptors, and serotonin reuptake transporters have also been found in depressed patients, such as increased glutamate, decreased serotonin 1A receptors and impaired serotonergic neurotransmission [31][32][33][34][35] .…”

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confidence: 57%

“…[21][22][23][24] . In contrast, both the size and the activity of the amygdala, a structure critical for fear-associated memories, are increased in depressed patients [25][26][27][28] .…”

Section: Dysfunctional Neural Plasticity In Depressionmentioning

confidence: 92%

Rapid-onset antidepressant efficacy of glutamatergic system modulators: The neural plasticity hypothesis of depression

et al. 2014

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Depression is a devastating psychiatric disorder widely attributed to defi cient monoaminergic signaling in the central nervous system. However, most clinical antidepressants enhance monoaminergic neurotransmission with little delay but require 4−8 weeks to reach therapeutic efficacy, a paradox suggesting that the monoaminergic hypothesis of depression is an oversimplifi cation. In contrast to the antidepressants targeting the monoaminergic system, a single dose of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine produces rapid (within 2 h) and sustained (over 7 days) antidepressant effi cacy in treatment-resistant patients. Glutamatergic transmission mediated by NMDARs is critical for experience-dependent synaptic plasticity and learning, processes that can be modifi ed indirectly by the monoaminergic system. To better understand the mechanisms of action of the new antidepressants like ketamine, we review and compare the monoaminergic and glutamatergic antidepressants, with emphasis on neural plasticity. The pathogenesis of depression may involve maladaptive neural plasticity in glutamatergic circuits that may serve as a new class of targets to produce rapid antidepressant effects.Keywords: depression; stress; neural plasticity; glutamatergic transmission; monoamine-based antidepressant; ketamine IntroductionDepression is a common psychiatric disorder, with prevalence rates of 19% in Beirut and 16.2% in the UnitedStates [1] . Depression is also one of the leading causes of severe mental disability, suicide, and socioeconomic burden, and its diagnosis sometimes relies on selfreported symptoms in the major depressive inventory [2,3] .The pathogenesis of depression is still not clear, and currently available antidepressants are far from satisfactory.Most antidepressants target the monoaminergic system [4] ; however, 30%-40% of patients are resistant to monoaminebased antidepressants (remittance rates of 13% to 36.8% with citalopram [5] ), and a clinically significant reduction of depressive symptoms in responders usually requires 4−8 weeks of daily treatment [6] . These limitations result in a large proportion of patients at high risk of suicide even after diagnosis. Thus, it is necessary to search for new antidepressants outside the monoaminergic system. R ecent clinical studies have demonstrated that a single dose of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine has rapid antidepressant efficacy within 2 h that can be sustained for over 7 days in patients with treatment-resistant depression [7,8] . This finding suggests that depression could be directly associated with defi cits in glutamatergic synaptic transmission and plasticity. The monoaminergic hypothesis of depression, based on the efficacy of antidepressants that enhance monoaminergic transmission and signaling, has dominated the field of depression research for nearly half a century.However, the primacy of monoaminergic dysfunction in depression is inconsistent with the delay between enhancement of synaptic monoamines confer...

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“…A decrease in hippocampal and prefrontal cortical volumes is reported in patients suffering from recurrent major depression. [7][8][9][10] That morphological changes in the hippocampus can be observed in patients in a first episode of depression remains a matter of debate. 11,12 Structural imaging studies have demonstrated reduced gray matter volumes in areas of the orbital and medial prefrontal cortex, ventral striatum, and hippocampus, and enlargement of the third ventricle of patients with mood disorder.…”

mentioning

confidence: 99%

“…[16][17][18] Although the amygdala appears to shrink with prolonged depression, 19 amygdala enlargement has been reported in the first episode of major depression. 10,20 Neurogenesis in the dentate gyrus of the hippocampal formation may be involved in the mechanism of action of a wide range of antidepressants. [21][22][23] This fascinating finding requires further research in order to understand how the mechanism of antidepressant treatments might converge to regulate common events such as neurogenesis and other forms of structural plasticity.…”

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confidence: 99%

Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine

McEwen

Olie

2005

Mol Psychiatry

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Recent studies have provided evidence that structural remodeling of certain brain regions is a feature of depressive illness, and the postulated underlying mechanisms contribute to the idea that there is more to antidepressant actions that can be explained exclusively by a monoaminergic hypothesis. This review summarizes recent neurobiological studies on the antidepressant, tianeptine (S-1574, [3-chloro-6-methyl-5,5-dioxo-6,11-dihydro-(c,f)-dibenzo-(1,2-thiazepine)-11-yl) amino]-7 heptanoic acid, sodium salt), a compound with structural similarities to the tricyclic antidepressant agents, the efficacy and good tolerance of which have been clearly established. These studies have revealed that the neurobiological properties of tianeptine involve the dynamic interplay between numerous neurotransmitter systems, as well as a critical role of structural and functional plasticity in the brain regions that permit the full expression of emotional learning. Although the story is far from complete, the schema underlying the effect of tianeptine on central plasticity is the most thoroughly studied of any antidepressants. Effects of tianeptine on neuronal excitability, neuroprotection, anxiety, and memory have also been found. Together with clinical data on the efficacy of tianeptine as an antidepressant, these actions offer insights into how compounds like tianeptine may be useful in the treatment of neurobiological features of depressive disorders. Molecular Psychiatry (2005) 10, 525-537.

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Enlargement of the amygdala in patients with a first episode of major depression

Cited by 294 publications

References 36 publications

Patterns of gene expression in the limbic system of suicides with and without major depression

Patterns of gene expression in the limbic system of suicides with and without major depression

Rapid-onset antidepressant efficacy of glutamatergic system modulators: The neural plasticity hypothesis of depression

Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine

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