Depression: from psychopathology to pathophysiology

Belzung, Catherine; Willner, Paul; Philippot, Pierre

doi:10.1016/j.conb.2014.08.013

Cited by 147 publications

(123 citation statements)

References 53 publications

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“…Pertinent to the current findings, brain regions associated with emotion processing and memory, such as the amygdala and hippocampus, are believed to be involved in FKBP5-related vulnerability to psychopathology (Zannas et al, 2016). Interestingly, rumination has also been associated with increased activation of the default mode network, which includes the amygdala and hippocampus (Belzung et al, 2015). Future studies are needed to determine whether this association between these brain regions and rumination and catastrophizing are moderated by FKBP5 genotype.…”

Section: Discussionsupporting

confidence: 61%

FKBP5 moderation of the relationship between childhood trauma and maladaptive emotion regulation strategies in adolescents

Halldorsdottir

Matos

Awaloff

et al. 2017

Psychoneuroendocrinology

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A B S T R A C TMaladaptive emotion regulation strategies, such as rumination and catastrophizing, are transdiagnostic risk factors for psychopathology. FK506-binding protein 51 (FKBP5) has been found to moderate the relationship between stressful life events and various psychiatric disorders. Given the cross-disorder moderation effect of FKBP5 at the diagnostic level, the aim of the current study was to examine whether the relationship between exposure to childhood trauma and transdiagnostic maladaptive emotion regulation processes would also be moderated by genetic FKBP5 variation in a community sample of adolescents. We hypothesized that adolescent carriers of the FKBP5 CATT haplotype composed of rs9296158, rs3800373, rs1360780, and rs9470080, that has been associated with increased risk for psychiatric disorders in adulthood, would also show higher levels of rumination and catastrophizing. Participants included 1345 genotyped adolescents (M age = 13.95, 64.2% female; 100% European Caucasians of Portuguese descent) who completed self-report measures on exposure to childhood trauma and emotion regulation strategies. Genotypes of rs9296158, rs3800373, rs1360780, and rs9470080 were used to estimate the CATT haplotype (carriers versus non-carriers). Consistent with our hypotheses and previous findings, adolescent CATT haplotype carriers with higher levels of childhood trauma endorsed higher levels of both rumination and catastrophizing compared to non-carriers. Given the association of these maladaptive emotion regulation processes and psychiatric disorders, the findings suggest possible psychological mechanisms why FKBP5 haplotype carriers exposed to childhood trauma are more vulnerable to developing a psychiatric disorder later in life.

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Section: Discussionsupporting

confidence: 61%

FKBP5 moderation of the relationship between childhood trauma and maladaptive emotion regulation strategies in adolescents

Halldorsdottir

Matos

Awaloff

et al. 2017

Psychoneuroendocrinology

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“…This issue appears relevant, regarding the modulatory role of the LHb upon dopaminergic and serotonergic transmissions (Bernard and Veh, 2012;Ji and Shepard, 2007;Wang and Aghajanian, 1977), as well the cholinergic septo-hippocampal pathway (Nilsson et al, 1990), which are key systems involved in memory processes. It is also relevant because dysfunction of the LHb has been evidenced in disorders such as depression (Aizawa et al, 2013a;Sartorius and Henn, 2007), which encompasses alterations of hippocampal networks, as well as memory impairments (Trivedi and Greer, 2014;Belzung et al, 2015;Lecca et al, 2014). In rats, LHb electric stimulation prevented avoidance learning (Shumake et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Excitatory Transmission to the Lateral Habenula Is Critical for Encoding and Retrieval of Spatial Memory

Mathis

Cosquer

Avallone

et al. 2015

Neuropsychopharmacol

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The lateral habenula (LHb) is viewed as a relay between the limbic system, the basal ganglia (BG), and monoaminergic neurons of the midbrain. If a prominent role has been evidenced in BG-mediated functions such as value-based decision-making, very little is known about the involvement of the LHb in limbic functions such as memory processing. In the present study, we used two pharmacological approachesLHb reversible inactivation with intra-LHb infusion of muscimol, an agonist of the GABA-A receptor, or blockade of excitatory inputs with intra-LHb infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of the glutamatergic AMPA receptor-to investigate the involvement of the LHb in encoding, consolidation, and retrieval of spatial memory in the water maze (WM) in rats. We found that intra-LHb infusion of muscimol or CNQX prevented encoding and retrieval, but not consolidation of spatial information. In addition, muscimol but not CNQX induced impairments during a cued version of the WM task, and marked anxiety in the elevated plus maze. These results confirm the involvement of the LHb in higher cognitive functions. They further suggest a dichotomy between the role of glutamatergic and other inputs to the LHb in hippocampus-dependent memory processing, as well as in emotional aspects of goal-directed behaviors.

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“…1) Flexibility of the mood is lost in patients, thereby causing it to decrease and to no longer be influenced by favorable external events.…”

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confidence: 99%

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Madrigal-Bujaidar

Álvarez-González

Morales-González

2015

Biological & Pharmaceutical Bulletin

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Duloxetine is a widely used antidepressant worldwide. In the present report, we evaluated its capacity to induce micronucleated polychromatic erythrocytes (MNPEs) and micronucleated normochromatic erythrocytes (MNNEs) in mice. Two assays were performed, one with a single chemical administration and the other with daily chemical administration. In the first, we administered the antidepressant once to groups of 5 mice by the intragastric (i.g.) route (2, 20, and 200 mg/kg) and performed the analysis at 24, 48, and 72 h postadministration. A control group administered i.g. distilled water was included in the assay, as well as another treated with the micronuclei-inducing chemical daunorubicin (2.5 mg/kg, injected intraperitoneally (i.p.)). In this assay, we found significant damage induced by duloxetine starting from the first time evaluated, showing the highest MNPE increase at the end of the assay. We observed a saturation effect as well, suggested by a decreasing relative efficiency with respect to each tested dose. In a second assay, we administered the antidepressant i.g. every day for 5 weeks (2, 6, and 12 mg/kg), and micronuclei analysis was performed at the end of each week. In this study, we also found a significant increase in both MNPEs and MNNEs which was clear by the second week of administration. Our results suggest that short-term as well as cumulative damage is produced by duloxetine. Thus, confirmation of the observed genotoxic potential in other models seems advisable, as well as caution when prescribing this antidepressant.

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Depression: from psychopathology to pathophysiology

Cited by 147 publications

References 53 publications

FKBP5 moderation of the relationship between childhood trauma and maladaptive emotion regulation strategies in adolescents

FKBP5 moderation of the relationship between childhood trauma and maladaptive emotion regulation strategies in adolescents

Excitatory Transmission to the Lateral Habenula Is Critical for Encoding and Retrieval of Spatial Memory

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

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