Dysfunctional hippocampal activity affects emotion and cognition in mood disorders

Femenía, Teresa; Gómez-Galán, Marta; Lindskog, Maria; Magara, Salvatore

doi:10.1016/j.brainres.2012.03.053

Cited by 115 publications

(74 citation statements)

References 164 publications

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“…TLR2, but not TLR4, has also been implicated in the perpetuation of inflammatory responses in the CNS after pro-inflammatory stimulation of astrocytes [70] and involved in hippocampal neurogenesis as mice lacking TLR2 displayed impaired hippocampal and neuronal differentiation, which was not observed for TLR4 [71]. These observations could be related to the TLR2 specificity of our findings especially as hippocampal alterations have been repeatedly reported in adults with a history of childhood traumatic experiences and are suggested to be involved in the pathophysiology of BD [72][73][74].…”

Section: Discussionmentioning

confidence: 50%

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Oliveira

Étain

Lajnef

et al. 2015

European Psychiatry

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Gene-environment interactions may play an important role in modulating the impact of earlylife stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.

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Section: Discussionmentioning

confidence: 50%

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Oliveira

Étain

Lajnef

et al. 2015

European Psychiatry

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“…In AD, increased salience network connectivity relates to neuropsychiatric hyperactivity symptoms (e.g., agitation, irritability, aberrant motor behavior, disinhibition, and euphoria) (31). Neurodegeneration of medial temporal structures that support emotion inhibition (27,28) and lateral temporal structures that promote socioemotional processes, including evaluation of faces (32), prosody (33), intention (34), and trustworthiness (35), may alter affective physiology, behavior, and experience in MCI and AD.Emotional contagion is a basic affective mechanism by which an organism automatically synchronizes its physiological and behavioral states with those of another to promote affective simulation and altruistic behavior (e.g., helping) (36, 37). Via salience network structures and emotion generators (26), emotions can unfold without conscious awareness (36) and travel rapidly from organism to organism through the activation of visceromotor mirroring mechanisms (36-38).…”

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confidence: 99%

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confidence: 99%

“…The hippocampus, although most prominently known for its role in cognitive processes such as episodic memory and spatial navigation (22,23), is also implicated in emotion. The anterior hippocampus, in particular, has rich connections with the hypothalamus and amygdala (24,25), which are structures important for emotion reactivity (26), and plays an inhibitory role in affective behavior via its projections to autonomic and endocrine emotion generation systems (24,27,28). As default mode network integrity deteriorates in AD, there is a concomitant connectivity increase within an emotion-relevant salience network (14).…”

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confidence: 99%

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Heightened emotional contagion in mild cognitive impairment and Alzheimer’s disease is associated with temporal lobe degeneration

Sturm

Yokoyama

Seeley

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

148

133

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Emotional changes are common in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Intrinsic connectivity imaging studies suggest that default mode network degradation in AD is accompanied by the release of an emotion-relevant salience network. We investigated whether emotional contagion, an evolutionarily conserved affect-sharing mechanism, is higher in MCI and AD secondary to biological alterations in neural networks that support emotion. We measured emotional contagion in 237 participants (111 healthy controls, 62 patients with MCI, and 64 patients with AD) with the Interpersonal Reactivity Index Personal Distress subscale. Depressive symptoms were evaluated with the Geriatric Depression Scale. Participants underwent structural MRI, and voxel-based morphometry was used to relate whole-brain maps to emotional contagion. Analyses of covariance found significantly higher emotional contagion at each stage of disease progression [controls < MCI (P < 0.01) and MCI < AD (P < 0.001)]. Depressive symptoms were also higher in patients compared with controls [controls < MCI (P < 0.01) and controls < AD (P < 0.0001)]. Higher emotional contagion (but not depressive symptoms) was associated with smaller volume in right inferior, middle, and superior temporal gyri (P FWE < 0.05); right temporal pole, anterior hippocampus, parahippocampal gyrus; and left middle temporal gyrus (all P < 0.001, uncorrected). These findings suggest that in MCI and AD, neurodegeneration of temporal lobe structures important for affective signal detection and emotion inhibition are associated with up-regulation of emotion-generating mechanisms. Emotional contagion, a quantifiable index of empathic reactivity that is present in other species, may be a useful tool with which to study emotional alterations in animal models of AD.empathy | social behavior | simulation | affective resonance P rogressive deterioration of memory and other cognitive functions characterizes Alzheimer's disease (AD) (1) and its prodromal stage, mild cognitive impairment (MCI) (2). Deposition of beta-amyloid plaques and neurofibrillary tangles, the hallmark pathological changes in AD (3), is hypothesized to begin decades before the emergence of cognitive symptoms and subsequent functional decline (4). Emotional symptoms are also common and have been found in 35-85% of patients with MCI (5-7) and up to 75% of patients with AD (8), with depression and anxiety the most frequent symptoms seen. Individuals with MCI who have comorbid emotional complaints are more likely to progress to dementia than those without such symptoms (9-13). Taken together, these studies suggest that a clinical presentation that includes both cognitive decline and emotion dysregulation may point to an underlying AD process and that emotional symptoms themselves may portend or even exacerbate disease progression (9,11,14).The medial temporal lobe is among the earliest sites of disease in MCI and AD (2, 15), and hippocampal atrophy is associated with worse episodic memory performance on standardi...

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“…MR blockade has to be shown to inhibit this shift (Vogel et al, 2015). Interestingly, there is compelling evidence for dysfunctional activation of the prefrontal cortex and hippocampus in MDD, possibly due to exaggerated HPA axis function (Femenia et al, 2012). Accordingly, in patients with MDD, MR blockade might strengthen or normalize frontal cortex-based cognitive evaluation strategies and, thus, normalize cognitive evaluation of emotional stimuli.…”

Section: Discussionmentioning

confidence: 99%

Effects of mineralocorticoid receptor blockade on empathy in patients with major depressive disorder

Wingenfeld

Kuehl

Dziobek

et al. 2016

Cogn Affect Behav Neurosci

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Background The mineralocorticoid receptor (MR) is highly expressed in the hippocampus and prefrontal cortex and is involved in social cognition. We recently found that pharmacological stimulation of the MR enhances emotional empathy but does not affect cognitive empathy. In the current study, we examined whether blockade of the MR impairs empathy in patients with major depressive disorder (MDD) and healthy individuals. Methods In a placebo-controlled study, we randomized 28 patients with MDD without psychotropic medication and 43 healthy individuals to either placebo or 300 mg spironolactone, a MR antagonist. Subsequently, all participants underwent two tests of social cognition, the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC), measuring cognitive and emotional facets of empathy. Results In the MET, we found no significant main effect of treatment or main effect of group for cognitive empathy but a highly significant treatment by group interaction (p < 0.01). Patients had higher cognitive empathy scores compared to controls in the placebo condition but not after spironolactone. Furthermore, in the spironolactone condition reduced cognitive empathy was seen in MDD patients but not in controls.Emotional empathy was not affected by MR blockade. In the MASC, no effect of spironolactone could be revealed. Conclusion Depressed patients appear to exhibit greater cognitive empathy compared to healthy individuals. Blockade of MR reduced cognitive empathy in MDD patients to the level of healthy individuals. Future studies should further clarify the impact of MR functioning on different domains of social cognition in psychiatric patients.

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Dysfunctional hippocampal activity affects emotion and cognition in mood disorders

Cited by 115 publications

References 164 publications

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Heightened emotional contagion in mild cognitive impairment and Alzheimer’s disease is associated with temporal lobe degeneration

Effects of mineralocorticoid receptor blockade on empathy in patients with major depressive disorder

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