Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression

Quteineh, Lina; Preisig, Martin; Rivera, Margarita; Milaneschi, Yuri; Castelao, Enrique; Gholam‐Rezaee, Mehdi; Vandenberghe, Frederik; Saigí-Morgui, Núria; Delacrétaz, Aurélie; Cardinaux, Jean‐René; Willemsen, Gonneke; Boomsma, Dorret I.; Penninx, Brenda W. J. H.; Ching-López, Ana; Conus, Philippe; Eap, Chin B.

doi:10.1016/j.jad.2016.03.031

Cited by 19 publications

(20 citation statements)

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“…Recent evidence collected in Crtc1 −/− mice has established that not only the lack of CRTC1 induces hyperphagic obesity 6 , 7 , but it also triggers a depressive-like phenotype, which suggests that CRTC1 plays a role in mood disorder etiology and antidepressant response 8 – 10 . In agreement with these animal studies, two human investigations have highlighted an association of CRTC1 polymorphisms with body mass index and fat mass, and have suggested that CRTC1 is involved in the high prevalence of overweight and obesity observed in psychiatric patients and in subjects from the general population with major depressive disorder 22 , 23 . Altogether, these findings suggest that CRTC1 is a transcriptional coactivator reciprocally involved in the bidirectional relation between obesity and depression.…”

Section: Introductionmentioning

confidence: 55%

Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

et al. 2017

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Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 −/− mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 −/− mice was further characterized by investigating CRTC1’s role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity. Crtc1 −/− mice showed a strong gender difference in the homeostatic regulation of energy balance. Mutant males were hyperphagic and rapidly developed obesity on normal chow diet, whereas Crtc1 −/− females exhibited mild late-onset obesity without hyperphagia. Overeating of mutant males was accompanied by alterations in the expression of several orexigenic and anorexigenic hypothalamic genes, thus confirming a key role of CRTC1 in the central regulation of food intake. No alteration in preference and conditioned response for saccharine was observed in Crtc1 − /− mice, suggesting that mutant males’ hyperphagia was not due to an altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a hyperphagic behavior only during the resting (diurnal) phase of the light cycle. This abnormal feeding behavior was associated with a higher diurnal locomotor activity indicating that the lack of CRTC1 may affect circadian rhythmicity. Collectively, these findings highlight the male-specific involvement of CRTC1 in the central control of energy balance and circadian locomotor activity.

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Section: Introductionmentioning

confidence: 55%

Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

et al. 2017

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“…In addition, a human study suggested that CRTC1 polymorphisms are associated with obesity markers in individuals with major depression but not in non‐depressive individuals (Quteineh et al . ).…”

Section: Discussionmentioning

confidence: 97%

Adeno‐associated virus‐mediated over‐expression of CREB‐regulated transcription coactivator 1 in the hippocampal dentate gyrus ameliorates lipopolysaccharide‐induced depression‐like behaviour in mice

Huang

et al. 2019

Journal of Neurochemistry

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Depression is a highly complex global disabling psychiatric disorder. Unfortunately, the currently available antidepressants are not effective in a significant percentage of patients. Therefore, the underlying mechanisms of depression must be explored at the molecular level to discover new candidate molecular targets for depression treatment. Behavioural and molecular depression‐like endophenotypes have been observed in cyclic AMP response element‐binding protein‐regulated transcription coactivator 1 (Crtc1) knockout mice; however, the underlying mechanism for these endophenotypes remains unclear. This work investigated the role of hippocampal CREB‐regulated transcription coactivator 1 (CRTC1) in depression using a recombinant adeno‐associated virus (AAV) system to alter Crtc1 gene expression and explore its potential mechanism. We found that shRNA‐mediated Crtc1 gene knockdown (AAV‐shCRTC1) in the dentate gyrus regions of the ventral hippocampus directly resulted in depression‐like behaviours and down‐regulation of brain‐derived neurotrophic factor and neuropeptide VGF levels. A widely used depression model induced by lipopolysaccharide administration (0.5 mg/kg, i.p.) was applied in our study and was validated by increased immobility time in the tail‐suspension and forced swim tests and decreased sucrose consumption in the sucrose preference test. Importantly, CRTC1 over‐expression mediated by AAV‐CRTC1 in the ventral dentate gyrus regions prevented lipopolysaccharide‐induced depressive‐like behaviours, the down‐regulation of brain‐derived neurotrophic factor and VGF, and the accumulation of pro‐inflammatory cytokines such as interleukin‐6, interleukin 1‐β and tumour necrosis factor α in mice. Together, our findings indicate that CRTC1 is a key factor in depression‐like behaviour and provide an important reference for finding a novel drug target in the neuroinflammatory and neurotrophic pathways for curing depressive disorders. Cover Image for this issue: doi: .

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“…Indeed, epidemiological evidence supports the association of depression and obesity in both Western and non-Western countries, with a robust bidirectional relationship, independently of antidepressant medications [5,70]. In fact, weight gain related to psychotropic medications appears more to be linked to polygenic risk more than comorbid depression/obesity mechanisms [71]. Despite these limitations, other reports have demonstrated similar spatial correlations in linked pathologies (e.g.…”

Section: Discussionmentioning

confidence: 99%

Depression and obesity, data from a national administrative database study: Geographic evidence for an epidemiological overlap

et al. 2019

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BackgroundDepression and obesity are two major conditions with both psychological and somatic burdens. Some data suggest strong connections between depression and obesity and more particularly associated prevalence of both disorders. However, little is known about the geographical distribution of these two diseases. This study aimed to determine if there is spatial overlap between obesity and depression using data from the entire French territory.MethodsData for 5,627 geographic codes for metropolitan France were collected from the two national hospital databases (PMSI-MCO and RIM-P) for the year 2016. We identified people who were depressed, obese or both registered in the two public medico-administrative databases, and we assessed their location. In addition, a multivariable analysis was performed in order to determine geographic interactions between obesity and depression after controlling for age, sex, environmental and socio-economic factors (social/material deprivation, urbanicity/rurality).Results1,045,682 people aged 18 years and older were identified. The mapping analysis showed several cold and hot regional clusters of coinciding obesity and depression. The multivariable analysis demonstrated significant geographic interactions, with an increasing probability of finding a high prevalence of obesity in regions with major depression (OR 1.29 95% CI 1.13–1.49, p = 0.0002) and an increased probability of finding a high prevalence of depression in regions with a high ration of obesity (OR 1.32, 95% CI 1.15–1.52, p<0.0001).ConclusionOur study confirms the significant bidirectional relationships between obesity and depression at a group level. French geographic patterns reveal a partial overlap between obesity and depression, suggesting these two diseases can be included in a common approach. Further studies should be done to increase the understanding of this complex comorbidity.

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Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression

Cited by 19 publications

References 44 publications

Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

Adeno‐associated virus‐mediated over‐expression of CREB‐regulated transcription coactivator 1 in the hippocampal dentate gyrus ameliorates lipopolysaccharide‐induced depression‐like behaviour in mice

Depression and obesity, data from a national administrative database study: Geographic evidence for an epidemiological overlap

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