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BACKGROUND: Previous studies have suggested that the habenula (Hb) may be involved in the mechanism of obsessive-compulsive disorder (OCD). However, the specific role of Hb in OCD remains unclear. This study aimed to explore the structural and functional abnormalities of Hb in OCD and their relationship with the clinical symptoms. METHODS: Eighty patients with OCD and 85 healthy controls (HCs) were recruited as the primary dataset. The grey matter volume, resting-state functional connectivity (FC), and effective connectivity (EC) of the Hb were calculated and compared between OCD group and HCs. An independent replication dataset was used to verify the stability and robustness of the results. RESULTS: Patients with OCD exhibited smaller Hb volume and increased FC of right Hb-left hippocampus than HCs. Dynamic causal model revealed an increased EC from left hippocampus to right Hb and a less inhibitory causal influence from the right Hb to left hippocampus in the OCD group compared to HCs. Similar results were found in the replication dataset. CONCLUSIONS: This study suggested that abnormal structure of Hb and hippocampus-Hb connectivity may contribute to the pathological basis of OCD.
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BACKGROUND: To investigate the associations between insulin resistance (IR)-related features and cognitive function in type 1 diabetes (T1D). METHODS: A total of 117 adult patients with T1D were recruited in this cross-sectional study. IR-related features include overweight/obesity/central obesity, hypertension, atherogenic dyslipidemia, and decreased estimated insulin sensitivity (eIS). The Wechsler Memory Scale-Chinese Revision, Wisconsin Card Sorting Test, and Sustained Attention to Response Task was used to assess memory, executive function and sustained attention, respectively. A z-score was generated from each test, and a composite measure of global cognitive performance was calculated by averaging the z-scores of all tests. Cognitive differences were measured between T1D patients with and without IR-related features. The associations between IR-related features and and cognitive performance were analyzed using: logistic regression, partial correlation, and multivariate linear regression analysis. RESULTS: A total of 53 (45.3%) T1D patients were defined as having IR-related features. Individuals with IR-related features displayed worse overall cognitive scores compared to those without and had a 4-fold increase in the risk for having global cognitive z-score < 0. Among the IR-related features, higher triglyceride (TG) and lower eIS showed linear correlation with lower global cognitive performance. And the subsequent regression analysis identified eIS as the factor independently associated with global cognitive performance. CONCLUSIONS: We have provided evidence linking IR-related features to deteriorated cognitive function in adult patients with T1D. And eIS showed an independent positive correlation with global cognitive performance. Although no causal relationship can be drawn, IR emerges as an important factor reflecting cognitive function. TRIAL REGISTRATION: ClinicalTrials.gov NCT03610984.
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Although it was acknowledged that patients with obsessive-compulsive disorder (OCD) would exhibit cognitive inflexibility, the underlying neural mechanism has not been fully clarified. Therefore, this study aimed to investigate the neural substrates involved in cognitive inflexibility among individuals with OCD. A total of 42 patients with OCD and 48 healthy controls (HCs) completed clinical assessment and functional magnetic resonance imaging (fMRI) data collection during cued task switching. Behavioral performances and fMRI activation were compared between the OCD group and the HC group. Psychophysiological interactions (PPIs) analyses were applied to explore functional connectivity related to task switching. Pearson correlation was used to investigate the relationships among behavioral performance, fMRI activity, and obsessive-compulsive symptoms in OCD. The OCD group had a greater switch cost than HCs (χ2 = 5.89, p < .05). A significant difference in reaction time was found during switch (χ2 = 17.72, p < .001) and repeat (χ2 = 16.60, p = .018) between the two groups, while there was no significant difference in group accuracy. Comparison of group differences showed that the OCD group had increased activation in the right superior parietal cortex (rSPL) during task switching, and exhibited increased connectivity of frontoparietal network/default mode network (FPN-DMN; i.e., middle frontal gyrus [MFG]/inferior parietal cortex-precuneus, MFG-middle/posterior cingulate gyrus) and within the FPN (inferior parietal cortex-postcentral gyrus). In the OCD group, the compulsion score was positively correlated with accuracy during switch (r = .405, p = .008, FDRq <.05), and negatively correlated with activation of rSPL (r = -.328, p = .034, FDRq >.05). Patients with OCD had impaired cognitive flexibility and cautious response strategy. The neural mechanism of cognitive inflexibility in OCD may involve increased activation in the rSPL, as well as hyperconnectivity within the FPN and between the FPN and DMN.
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Mapeo Encefálico , Trastorno Obsesivo Compulsivo , Humanos , Mapeo Encefálico/métodos , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Parietal/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Cognición , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: The taxonomy of autogenous- and reactive-type obsessive-compulsive disorder (OCD) (AO vs. RO) is one of the most valid subtyping approaches to the heterogeneity of OCD. The present study aimed to seek evidence of neural substrates supporting the dissociation of cognition inhibition in AO and RO which was revealed by our previous behavioral and electrophysiological work. METHODS: A total of 165 patients with OCD (86 AO versus 79 RO), and 79 healthy controls (HC) underwent resting-state functional magnetic resonance imaging scans. Within-network connectivity, node strength, and edge-wise functional connectivity (FC) in cognition and response inhibition networks were calculated. Results from 3 cognition and 2 response inhibition network atlases were compared to confirm the robustness of the findings. RESULTS: Both AO and RO showed lower within-network connectivity in response inhibition networks, while lower within cognition inhibition network connectivity was only detected in AO. Besides shared weaker node strength in the anterior insula (AI), anterior cingulate cortex (ACC), and supplementary motor area (SMA), AO had a broader range of nodes within cognition inhibition networks exhibiting weaker strength, including nodes in right inferior frontal gyrus (IFG), left parietal and occipital regions. Decreased FC of left AI-CC, left IFG-ACC, and frontal-parietal regions in cognition inhibition networks were found in AO. CONCLUSIONS: Findings indicate that unlike deficits in connectivity within response inhibition networks which may reflect a common pathology in AO and RO, deficits in connectivity within cognition inhibition networks were more pronounced in AO. These findings strengthen our insight into the heterogeneity in OCD.
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Corteza Motora , Trastorno Obsesivo Compulsivo , Humanos , Mapeo Encefálico/métodos , Vías Nerviosas/diagnóstico por imagen , Cognición , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodosRESUMEN
Previous research has identified the contemporaneous association between experiential avoidance, depression, and Internet addiction. However, the mechanisms underlying this association are not well acknowledged. The present study aimed to use cross-lagged panel modeling to examine whether depression mediates the relation between experiential avoidance and Internet addiction and whether gender plays a role in the relation. A total of 2731 participants (934 male, Meanage=18.03) were recruited from a university at the baseline study (December 2019). Data was collected at all 3 time points across one year (2019?2020), using 6-month intervals. Experiential avoidance, depression and Internet addiction were assessed using the Acceptance and Action Questionnaire-II (AAQ-II), the Beck Depression Inventory-II (BDI-II) questionnaire, and Young?s Internet Addiction Test (IAT), respectively. Cross-lagged panel models were used to evaluate the longitudinal association and the mediating effect. Multigroup analyses were conducted to examine gender differences in the models.Cross-lagged models indicated that experiential avoidance significantly predicted subsequent depression, and depression significantly predicted subsequent Internet addiction. Furthermore, mediation analyses showed that depression has a mediating effect in the relation between experiential avoidance and Internet addiction (? = 0.010, 95%CI[0.003, 0.018], p>0.001). Multigroup analyses demonstrated that the pattern of structural relations stayed consistent across gender. The findings indicated that experiential avoidance is indirectly related to Internet addiction through depression, suggesting that treatments targeted at reducing experiential avoidance could help relieve depression and thus decrease the risk of Internet addiction. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04511-6.
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Cerebellar dysconnectivity has repeatedly been documented in major depressive disorder (MDD). The cerebellum is composed of multiple functionally distinct subunits, and whether those subunits show similar or distinct dysconnectivity patterns with the cerebrum in MDD, is still unclear and needs to be further clarified. In this study, 91 MDD patients (23 male and 68 female) and 59 demographically matched healthy controls (22 male and 37 female) were enrolled to explore the cerebellar-cerebral dysconnectivity pattern in MDD by using the cutting-edge cerebellar partition atlas. Results showed that MDD patients exhibit decreased cerebellar connectivity with cerebral regions of default mode (DMN), frontoparietal networks (FPN), and visual areas. The dysconnectivity pattern was statistically similar across cerebellar subunits, with no significant diagnosis-by-subunit interactions. Correlation analyzes showed that cerebellar-dorsal lateral prefrontal cortex (DLPFC) connectivity is significantly correlated with anhedonia in MDD patients. Such dysconnectivity pattern was not affected by sex, which, however, should be further replicated in larger samples. These findings suggest a generalized disrupted cerebellar-cerebral connectivity pattern in MDD across all cerebellar subunits, which partially accounts for depressive symptoms in MDD, thus highlighting the pivotal role of the disrupted connectivity of cerebellum with DMN and FPN in the neuropathology of depression.
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Trastorno Depresivo Mayor , Humanos , Masculino , Femenino , Adulto Joven , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Cerebelo/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Mapeo Encefálico , Vías Nerviosas/diagnóstico por imagenRESUMEN
As a transdiagnostic symptom, social anhedonia has gained increasing attention. Evidence suggests that obsessive-compulsive disorder (OCD) patients demonstrate social anhedonia. This study examined the psychometric properties of the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS) in an undergraduate sample and Chinese OCD patients. Furthermore, we explored the relationship between clinical symptoms and ACIPS scores. This study involved 3,306 undergraduate students and 293 patients with OCD. Internal consistency and convergent validity of ACIPS were examined. Confirmatory factor analysis (CFA) was applied to determine the best-fitting of potential factor models, and multi-group CFA was used to examine measurement invariance across genders and samples. Additionally, hierarchical linear regression was conducted in order to investigate the relationship between clinical symptoms and ACIPS scores in patients suffering from OCD. ACIPS showed acceptable internal consistency in undergraduate and OCD samples (Cronbach's α = 0.93 and 0.89, respectively). In both samples, the four-factor structure had the best fit index. Scalar invariance was established across undergraduate and OCD samples, while residual invariance was established across genders. In both samples, the ACIPS was significantly correlated with the Revised Social Anhedonia Scale and Beck Depression Inventory. Depression and the severity of obsessive thoughts significantly and negatively correlated with the ACIPS score in OCD patients (p < 0.05). In conclusion, ACIPS is a reliable, effective, simple, and convenient tool for the assessment of social anhedonia. Depression and obsessive thoughts contribute to social anhedonia in OCD patients.
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BACKGROUND/AIM: There is growing awareness that anhedonia plays a critical role in the development of Internet Addictions (IA). However, anhedonia is a multidimensional construct and different aspects of anhedonia may exert different effects on IA. This study was designed to distinguish the effects of social anhedonia and physical anhedonia on the developmental trajectory of IA among college students. METHODS: A total of 3577 Chinese college freshmen (Mage = 18.01, SD = 0.77; 65.4 % girls) participated in a 2-year, four waves longitudinal tracking study. The latent growth curve model (LGCM) was constructed to examine the impacts of different types of anhedonia on the developmental trajectories of IA. Gender was also added to the conditional LGCM as time-invariant variable. RESULTS: The results of unconditional LGCM showed a U-shape developmental trajectory of IA. Social anhedonia significantly affected the intercept (ß = 0.468, p < 0.001) and significantly affected the linear slope (ß = -0.259, p < 0.05), but not the quadratic slope (ß = 0.293, p > 0.05). Physical anhedonia was not significantly associated with intercept, linear slope and quadratic slope. There was no sex difference in both initial levels and change rate of IA. CONCLUSIONS: Social anhedonia while not physical anhedonia has prediction effect on IA. College students with high levels of social anhedonia experienced high levels of IA at baseline, and performed a slower rate in downward trend of IA. The findings of the current study provide implications for prevention of IA in college students.
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Anhedonia , Conducta Adictiva , Femenino , Humanos , Adolescente , Masculino , Trastorno de Adicción a Internet , Conducta Adictiva/epidemiología , Universidades , Estudiantes , InternetRESUMEN
AIMS: In this study, we used neuropsychological tests and neuroimaging to examine the cognitive functions and neuroimaging characteristics to explore the brain mechanism of cognitive deficits in patients with childhood-onset type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: A total of 30 patients with childhood-onset T1DM and 28 healthy controls (HC) participated in the study. Neuropsychological tests were used to assess intelligence quotient, memory, and executive function. Voxel-based morphometry-diffeomorphic anatomical registration through exponential lie algebra analysis and amplitude of low-frequent fluctuation (ALFF) were performed to evaluate the brain grey matter volume and neural spontaneous activity for each participant. RESULTS: Compared with HC, patients with childhood-onset T1DM showed a significant decline in verbal memory (p = 0.001) and visual memory (p = 0.002). Patients with T1DM had smaller grey matter volumes at the midbrain, thalamus, and cerebellar culmen. They demonstrated an increased ALFF value in the left precentral gyrus, left postcentral gyrus, left insula, and left supramarginal gyrus and a decreased ALFF value in the basal ganglia (putamen nucleus), right insula, right superior temporal gyrus, and cerebellar posterior lobe than the healthy control group. In the T1DM group, the ALFF value in the right insula was positively related to the verbal memory scores (r = 0.423, p = 0.025). CONCLUSIONS: Childhood-onset T1DM was associated with cognitive deficits and changes in brain structure and function. These findings suggest that the brain structural and functional alterations in these regions may be the neuropathology of cognitive deficits in patients with T1DM.
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Diabetes Mellitus Tipo 1 , Humanos , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/diagnóstico por imagen , Diabetes Mellitus Tipo 1/patología , Imagen por Resonancia Magnética/métodos , Cognición , Encéfalo/diagnóstico por imagen , Encéfalo/patología , NeuroimagenRESUMEN
The present study investigated the effect of childhood trauma (CT) on amygdala and hippocampus functional connectivity (FC) and the association with clinical presentations of major depressive disorder (MDD). Participants included 73 MDD patients (42 with moderate-to-severe CT and 31 with no or low CT) and 64 healthy controls (HC; 30 with moderate-to-severe CT and 34 with no or low CT). Seed-based whole-brain resting-state FC analyses were performed with seeds located in amygdala and hippocampus. Individuals with moderate-to-severe CT, irrespective of MDD diagnosis, had decreased right amygdala-right precuneus connectivity compared to those with no or low CT. Right amygdala-right precuneus connectivity was significantly correlated with physical and social trait anhedonia in MDD. Mediation effects of this FC on relationship between CT (specifically neglect but not abuse) and trait anhedonia in MDD were significant. MDD patients demonstrated increased right amygdala-left middle frontal gyrus FC, decreased right amygdala-right medial superior frontal gyrus (mSFG) FC and decreased right hippocampus-bilateral mSFG FC relative to HC. Findings highlight the effect of CT on right amygdala-right precuneus FC irrespective of MDD diagnosis. FC of right amygdala-right precuneus may be involved in the mechanism linking CT and depression through its association with trait anhedonia.
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Experiencias Adversas de la Infancia , Trastorno Depresivo Mayor , Humanos , Niño , Trastorno Depresivo Mayor/diagnóstico por imagen , Anhedonia , Depresión , Imagen por Resonancia Magnética , Amígdala del Cerebelo/diagnóstico por imagen , Lóbulo Parietal/diagnóstico por imagenRESUMEN
BACKGROUND: Despite the several researches on the correlates of insight in psychosis, less is known regarding the specificity of disease diagnosis on the relationship between insight and the correlates. The current study sought to explore the effects of insight and disease diagnosis on those in patients with obsessive-compulsive disorder (OCD) and patients with schizo-obsessive disorder (SOD). METHODS: We evaluated clinical symptoms and neurocognitions among 111 patients (including 41 OCD with good insight, 40 OCD with poor insight, 14 SOD with good insight and 16 SOD with poor insight. Gray matter volume and spontaneous neural activity were also examined by analyzing the voxel-based morphometry and amplitude of low frequency fluctuation (ALFF), respectively. RESULTS: Interactive effects of insight and diagnosis was found on working memory and the gray matter volume in right superior and middle temporal gyrus. Main effect of insight was found on working and visual memory, compulsion and obsession, and ALFF in right middle and superior occipital cortex. Main effect of diagnosis was found on severity of compulsion, relative verbal IQ, executive function, verbal and visual memory, working memory and ALFF in precuneus, medial superior frontal gyrus, anterior cingulate and paracingulate gyri, and inferior parietal, postcentral gyrus, paracentral lobule. CONCLUSIONS: As a common feature in mental disorders, insight has its own special influence on neurocognition and possible structural/functional alterations in brain, and the influence is partly dependent of disease diagnosis.
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Imagen por Resonancia Magnética , Trastorno Obsesivo Compulsivo , Humanos , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Sustancia Gris , Encéfalo/diagnóstico por imagen , Mapeo EncefálicoRESUMEN
BACKGROUND/AIM: There is growing awareness that specific childhood trauma (CT) may confer to the unique risk of depression, but little is known about this. The present study seeks to provide insight into how CT subtypes may impact distinct depressive symptoms over time based on the dimensional model of adversity (DMA). METHODS: A total of 3535 college freshmen participated in a 2-year, four waves longitudinal tracking study. A conditional parallel latent growth curve model (LGCM) was constructed to examine the impacts of different types of CT (threat and deprivation) on the development of depressed mood and anhedonia, and whether these relationships vary across gender. RESULTS: Our findings revealed that threat and deprivation could differentially relate to depressed mood and anhedonia. Both threat and deprivation predicted initial depressed mood levels (ß = 0.309, p < 0.001; ß = 0.175, p < 0.001, respectively) and its trajectory (ß = -0.139, p = 0.068; ß = -0.168, p < 0.05, respectively). Only deprivation predicted anhedonia levels (ß = 0.318, p < 0.001) and trajectory (ß = -0.218, p < 0.001). This pattern of relationships between CT and depressive symptoms varied across gender. CONCLUSION: These findings highlight specific pathways and symptomatic manifestations of the impacts of different CT subtypes on depression and are consistent with the hypothesis of DMA. Threat and deprivation predicted more severe depressed mood, whereas deprivation uniquely conferred to the risk of depression via elevated anhedonia. Meanwhile, the deleterious effects of CT would persist during early adulthood. Gender differences were also discussed.
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Experiencias Adversas de la Infancia , Trastorno Depresivo , Humanos , Adulto , Anhedonia , Depresión/epidemiología , Depresión/diagnóstico , Estudios LongitudinalesRESUMEN
OBJECTIVE: Childhood trauma (CT) has been supported to be a high-risk factor for major depressive disorder (MDD), but the neural mechanism linking CT and depression remains unclear. The aim of this study is to deepen our understanding of this issue by establishing the neuroimaging correlations between CT and depression. METHODS: A sample of 123 MDD patients (91 with moderate-to-severe CT and 32 with no or low CT) and 79 healthy controls (HC, 33 with moderate-to-severe CT and 46 with no or low CT) participated. All participants completed assessments of depression level, anxiety, recent perceived stress, and resting-state functional MRI scan. RESULTS: Participants with moderate-to-severe CT showed elevated depression level and trait anxiety, and reduced spontaneous neural activity in left inferior temporal gyrus (ITG). Abnormalities of seed-based functional connectivity (FC) of left ITG - bilateral precuneus/posterior cingulate cortex (PCC), left middle temporal gyrus (MTG), left medial orbitofrontal cortex (mOFC), and bilateral medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC) were observed. CT was associated with decreased FCs in MDD, but with increased FCs in HC. The total altered FCs of left ITG - bilateral precuneus/PCC and left mOFC mediated relationship between CT and depression in MDD, and total altered FCs and trait anxiety have a significant chain mediation effect in the association between CT and depression in HC. CONCLUSION: These findings highlight the changes of default mode network (DMN) functions and trait anxiety as targets of CT. The decreased functional coupling within DMN may be involved in the mechanism of MDD following CT.
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Experiencias Adversas de la Infancia , Trastorno Depresivo Mayor , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Red en Modo Predeterminado , Trastorno Depresivo Mayor/diagnóstico por imagen , Giro del Cíngulo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
ABSTRACT: Insight is a complex and multidimensional concept, and has a complex relationship with cognition. A meta-analysis of 102 studies of 9396 patients was conducted to determine the magnitude of the relationship between insight and neurocognition, higher-order cognition in multiple mental disorders. Insight has been found moderately related to higher-order cognition, but only weakly related to neurocognition. The different relationship has been found between the dimensions of insight and higher-order cognition. Almost none of the correlational coefficients of insight and cognitive domains were found to differ significantly among the different diagnostic groups. In conclusion, insight may be essentially related to higher-order cognition, but not to neurocognition. The orientation and expression of different dimensions of insight might be different, and the relationship of insight and cognition might not be explained by specific diagnosis.
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Trastornos del Conocimiento , Metacognición , Esquizofrenia , Cognición , Trastornos del Conocimiento/psicología , Humanos , Pruebas Neuropsicológicas , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Cognición SocialRESUMEN
The present study tested the effects of childhood trauma (CT) on trait social anhedonia (SA) and on gray matter volume (GMV) and explored the possible relationships among CT, SA and brain GMV. Forty-three healthy individuals with experience of moderate-to-severe CT and sixty-eight individuals with no or low CT participated in the present study. Trait SA was evaluated using the Revised Social Anhedonia Scale. GMV was measured using voxel-based morphometry. Participants with moderate-to-severe CT had elevated trait SA, as well as brain volumetric differences in left inferior parietal lobule (IPL), left precuneus, right insula, left superior temporal gyrus, and left middle occipital gyrus extending into middle temporal gyrus relative to participants with no or low level of CT. CT was also found to be positively correlated with GMV in right dorsolateral prefrontal cortex (DLPFC) and bilateral precuneus. Partial mediation effect of GMV in left IPL and right DLPFC on the relationship between CT and trait SA was significant. These findings suggest that CT may have effects on trait SA and on GMV of widespread brain regions. GMV differences in DLPFC and left IPL may mediate the effect of CT on trait SA, although this needs to be verified by future longitudinal studies.
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Experiencias Adversas de la Infancia , Sustancia Gris , Humanos , Sustancia Gris/diagnóstico por imagen , Anhedonia , Voluntarios Sanos , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagenRESUMEN
BACKGROUND: Acceptance and commitment therapy (ACT), a third-generation cognitive behavioral therapy (CBT), has proved its efficacy amidst various mental disorders. A growing body of studies has shown that ACT can improve obsessive-compulsive disorder (OCD) severity in recent years. To assess the effect of ACT on OCD, we carried out a systematic review and meta-analysis to provide a basis for therapists to use different psychological dimensions of ACT for OCD. METHODS: PubMed, the Cochrane Library, EMBASE, EBSCO Host, and literature references were searched until May 2021. Randomized controlled trials (RCTs) and other study designs assessing the effect of ACT among adults suffering from OCD were examined. RESULTS: Fourteen studies, including 413 participants, published between 2010 and 2021 were identified. ACT made statistically significant progress in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) compared with control conditions. CONCLUSION: After reviewing all the ACT studies, we acknowledge the plausibility of ACT in treating OCD and improving its symptoms for the clinical population. ACT can also be an adjunct therapy for other well-established treatments. It also favors targeting psychological inflexibility. Further well-controlled and high-quality RCTs are required for a better conclusion in further studies.
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Objective: Early life adversity is a risk factor for depression in adulthood; however, the underlying mechanisms are not well understood. This study aims to investigate the effect of DNA methylation of DRD2 gene on early life stress-induced depression in adult rats. Methods: Newborn Sprague-Dawley rats were randomly assigned to four groups: maternal deprivation group (MD), chronic unpredictable stress (CUS) group, maternal deprivation plus chronic unpredictable stress (MD/CUS) group, and normal control group (NOR). Behaviors were measured by open field test (OFT), sucrose preference test (SPT), and Original Research Article forced swimming test (FST). Fecal CORT level was detected by ELISA. Bisulfite amplicon sequencing PCR was used to assess methylation levels of DRD2 promoter. Results: CUS and MD/CUS rats had a significantly shorter total distance, longer immobility time, and higher CORT level, while MD and MD/CUS rats had a significantly lower percentage of central distance, more feces, lower rate of sucrose preference, and lower levels of DRD2 protein and mRNA in the VTA than NOR rats. CUS rats showed a significantly higher DRD2 mRNA and protein levels in the VTA than NOR rats. CUS, MD, and MD/CUS rats showed a significantly higher level of DRD2 promoter methylation than NOR rats. CORT level was significantly correlated with the sucrose preference rate in SPT, the immobility time in FST, the total distance, and the number of fecal pellets in OFT. DRD2 protein level was significantly correlated with the sucrose preference rate and the number of fecal pellets. DRD2 mRNA level was significantly correlated with the percentage of central distance and the number of fecal pellets in OFT. The level of DRD2 promoter methylation was significantly correlated with the sucrose preference rate, immobility time, total distance, the percentage of central distance, and the number of fecal pellets. Conclusions: Early life MD increased vulnerability to stress-induced depressive-like behavior in adult rats. Enhanced DRD2 promoter methylation in the VTA may increase the susceptibility to depression.
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BACKGROUND: Accumulating evidence indicated that anhedonia as a transdiagnostic construct might be an inherent feature of obsessive-compulsive disorder(OCD). Moreover, our recent study demonstrated that OCD patients exhibited consummatory anhedonia but not anticipatory anhedonia. However, neural mechanisms of consummatory anhedonia in OCD has not been explored. This study aimed to investigate this issue using resting-state functional magnetic resonance imaging (fMRI). METHODS: 44 OCD patients with high consummatory anhedonia(OCD-HCA), 41 OCD patients with low consummatory anhedonia(OCD-LCA) and 47 healthy controls (HC) underwent fMRI scan. Spontaneous neural activity was analyzed and compared among the three groups by adopting the amplitude of low-frequency fluctuation (ALFF). Relationships between the consummatory anhedonia levels and regional ALFFs were examined in OCD patients. RESULTS: Compared with HC, OCD-HCA showed decreased ALFF in the right putamen and right thalamus, and OCD-LCA showed increased ALFF in the right orbitofrontal cortex and decreased ALFF in the right fusiform gyrus, left Precentral/postcentral gyrus. Notably, ALFF values differed between the two patient groups in the right putamen (OCD-HCA < OCD-LCA), and right fusiform gyrus (OCD-HCA > OCD-LCA). Further analysis revealed that the consummatory anhedonia was positively correlated with ALFF values in the right fusiform, and negatively correlated with ALFFs in the right putamen. CONCLUSIONS: Spontaneous neural activity in right fusiform gyrus and right putamen is associated with consummatory anhedonia in OCD. The findings provided first insights into neural mechanism of consummatory anhedonia in OCD and confirmed the importance of exploring the transdiagnostic role of anhedonia.
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Mapeo Encefálico , Trastorno Obsesivo Compulsivo , Anhedonia , Encéfalo , Mapeo Encefálico/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Putamen/diagnóstico por imagen , Lóbulo TemporalRESUMEN
Based on the "oxidative stress hypothesis" of major depressive disorder (MDD), cells regulate their structure through the Wnt pathway. Little is known regarding the interactions of dishevelled 3 (DVL3) and glycogen synthase kinase 3 beta (GSK3ß) polymorphisms with MDD. The aim of the current study was to verify the relationship between DVL3 and GSK3ß genetic variants in a Chinese Han population and further to evaluate whether these interactions exhibit gender-specificity. A total of 1136 participants, consisting of 541 MDD patients and 595 healthy subjects, were recruited. Five single-nucleotide polymorphisms (SNPs) of DVL3/GSK3ß were selected to assess their interaction by use of a generalized multifactor dimensionality reduction method. The genotype and haplotype frequencies of DVL3/GSK3ß polymorphisms were significantly different between patients and controls for DVL3 rs1709642 (P < 0.01) and GSK3ß rs334558, rs6438552, and rs2199503 (P < 0.01). In addition, our results also showed that there were significant interaction effects between DVL3 and GSK3ß polymorphisms and the risk of developing MDD, particularly in women. The interaction between DVL3 (rs1709642) and GSK3ß (rs334558, rs6438552) showed a cross-validation (CV) consistency of 10/10, a P value of 0.001, and a testing accuracy of 59.22%, which was considered as the best generalized multifactor dimensionality reduction (GMDR) model. This study reveals the interaction between DVL3 and GSK3ß polymorphisms on MDD susceptibility in a female Chinese Han population. The effect of gender should be taken into account in future studies that seek to explore the genetic predisposition to MDD relative to the DVL3 and GSK3ß genes.
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Pueblo Asiatico/genética , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Proteínas Dishevelled/genética , Predisposición Genética a la Enfermedad/genética , Glucógeno Sintasa Quinasa 3 beta/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Estudios de Casos y Controles , China/epidemiología , Femenino , Frecuencia de los Genes , Sitios Genéticos , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Reducción de Dimensionalidad Multifactorial/métodos , Factores SexualesRESUMEN
BACKGROUND: Previous studies examining potential relationships of impaired insight with severity obsessive-compulsive (O-C) symptoms and depressive symptoms in patients diagnosed with obsessive-compulsive disorder (OCD) have produced mixed results. Here, we examined differences in these clinical characteristics and their changes after treatment in adult patients with OCD who have poor insight (OCD-PI) versus in those who have good insight (OCD-GI). METHODS: Fifty-nine full-text articles were screened for eligibility with 20 studies ultimately being included in the present meta-analysis. RESULTS: The OCD-PI and OCD-GI groups differed from each other with respect to O-C symptom (p < 0.001, g > 0.7) and depressive symptom (p < 0.001, g = 0.614) severity. Significant and moderate correlations were observed between insight and treatment outcomes (O-C symptoms, r = 0.33; depressive symptoms, r = 0.47). Exploratory meta-regression showed that methodological factors influenced the magnitudes of inter-group O-C symptom differences. CONCLUSIONS: The current meta-analysis indicates that poorer insight is associated with more severe O-C and depression, and less improvement of symptoms in patients with OCD. Insight impairment may be a critical and core OCD-related deficit.