Altered local gyrification index and corresponding functional connectivity in female depressed adolescents with suicide attempts and non-suicidal self-injury

Background: Non-suicidal self-injury (NSSI), which commonly occurs during adolescence, often co-occurs with major depressive disorder (MDD). However, the underlying neurobiological mechanisms in adolescents with MDD who engage in NSSI remain unclear. The current study examined the aberrant local neural activity in certain areas of the visual regions and the default mode network (DMN) and the resting-state functional connectivity (rs-FC) in changed brain regions in adolescents with MDD who engage in NSSI and adolescents with MDD only.Methods: A total of 67 adolescents with MDD were divided into two groups based on their NSSI behavior: the NSSI group (n = 31) and an age-, gender-, and education-matched MDD group (n = 36). The Hamilton Depression Rating Scale (HAMD) was used to assess the severity of MDD. Amplitude of low-frequency fluctuation (ALFF) analysis was used to detect alterations in local neural activity. Brain regions with aberrant neural activity were considered regions of interest (ROI). ALFF-based rs-FC analysis was used to further explore the underlying changes in connectivity between ROI and other areas in the NSSI group. Correlation analyses were performed to examine the relationship between neural changes and clinical characteristics.Results: There was no significant difference in HAMD scores between the two groups. ALFF analysis revealed that, compared to adolescents with MDD only, adolescents with MDD who engaged in NSSI displayed significantly enhanced neural activity in the right fusiform gyrus (FFG. R) and the right median cingulate and paracingulate gyri (DCG. R). Significantly reduced rs-FC of the FFG. R-bilateral medial orbital of the superior frontal gyrus (ORBsupmed. L/R)/bilateral medial superior frontal gyrus (SFGmed. L/R), FFG. R-bilateral posterior cingulate gyrus (PCG. L/R), DCG. R-left pallidum (PAL. L), DCG. R-right superior temporal gyrus (STG. R), and DCG. R-right postcentral gyrus (PoCG. R)/right inferior parietal lobule (IPL. R) was found in adolescents with MDD who were engaged in NSSI. Additionally, no significant correlations were observed between ALFF or rs-FC values and the HAMD scores between the two groups.Limitations: Owing to the cross-sectional design, the alterations in ALFF and rs-FC values in the FFG. R and DCG. R could not demonstrate that it was a state or feature in adolescents with MDD who engaged in NSSI. Additionally, the sample size was relatively small.Conclusions: This study highlights changes in regional brain activity and remote connectivity in the FFG. R and DCG. R in adolescents with MDD who engage in NSSI. This could provide a new perspective for further studies on the neurobiological mechanism of NSSI behavior in adolescents with MDD.

Decreased Cortical Folding of the Fusiform Gyrus and Its Hypoconnectivity with Sensorimotor Areas in Major Depressive Disorder

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.

Decreased functional connectivity in patients with major depressive disorder and a history of childhood traumatization through experiences of abuse

BackgroundMajor depressive disorder (MDD) is associated with dysfunction of the reward system. As an important node in the reward system, the resting-state functional connectivity of the nucleus accumbens (NAc) is related to the etiology of MDD. However, an increasing number of recent studies propose that brain activity is dynamic over time, no study to date has examined whether the NAc dynamic functional connectivity (DFC) is changed in patients with MDD. Moreover, few studies have examined the impact of the clinical characteristics of patients with MDD.MethodsA total of 220 MDD patients and 159 healthy controls (HCs), group-matched for age, sex, and education level, underwent resting-state functional magnetic resonance imagining (rs-fMRI) scans. Seed-based resting-state functional connectivity (RSFC) and DFC of the NAc were conducted. Two sample t-tests were performed to alter RSFC/DFC of NAc. In addition, we examined the association between altered RSFC/DFC and depressive severity using Pearson correlation. Finally, we divided patients with MDD into different subgroups according to clinical characteristics and tested whether there were differences between the subgroups.ResultsCompared with the HCs, MDD patients show reduced the NAc-based RSFC with the dorsolateral prefrontal cortex (DLPFC), hippocampus, middle temporal gyrus (MTG), inferior temporal gyrus (ITG), precuneus, and insula, and patients with MDD show reduced the NAc-based DFC with the DLPFC, ventromedial prefrontal cortex (VMPFC), ventrolateral prefrontal cortex (VLPFC), MTG, ITG, and insula. MDD severity was associated with RSFC between the NAc and precentral gyrus (r = 0.288, p = 0.002, uncorrected) and insula (r = 0.272, p = 0.003, uncorrected).ConclusionThis study demonstrates abnormal RSFC and DFC between the NAc and distributed cerebral regions in MDD patients, characterized by decreased RSFC and DFC of the NAc connecting with the reward, executive, default-mode, and salience network. Our results expand previous descriptions of the NAc RSFC abnormalities in MDD, and the altered RSFC/DFC may reflect the disrupted function of the NAc.

Nonsuicidal self-injury (NSSI) is included as conditions for further study in the DSM-5. Therefore, it is necessary to investigate the proposed diagnostic criteria and the diagnostic and clinical correlates for the validity of a diagnostic entity. The authors investigated the characteristics of NSSI disorder and the proposed diagnostic criteria. A sample of 73 female inpatient adolescents and 37 nonclinical adolescents (aged 13 to 19 years) was recruited. Patients were classified into 4 groups (adolescents with NSSI disorder, adolescents with NSSI without impairment/distress, clinical controls without NSSI, and nonclinical controls). Adolescents were compared on self-reported psychopathology and diagnostic cooccurrences. Results indicate that adolescents with NSSI disorder have a higher level of impairment than adolescents with other mental disorders without NSSI. Most common comorbid diagnoses were major depression, social phobia, and PTSD. There was some overlap of adolescents with NSSI disorder and suicidal behaviour and borderline personality disorder, but there were also important differences. Results further suggest that the proposed DSM-5 diagnostic criteria for NSSI are useful and necessary. In conclusion, NSSI is a highly impairing disorder characterized by high comorbidity with various disorders, providing further evidence that NSSI should be a distinct diagnostic entity.

A lot of previous studies have documented that major depressive disorder (MDD) is a developmental disorder. The cortical surface measure, local gyrification index (LGI), can well reflect the fetal and early postnatal neurodevelopmental processes. Thus, LGI may provide new insight for the neuropathology of MDD. The previous studies only focused on the surface structural abnormality, but how the structural abnormality lead to functional connectivity changes is unexplored. In this study, we investigated LGI and corresponding functional connectivity difference in 28 medication-free MDD patients. We found significantly decreased LGI in left lingual gyrus (LING) and right posterior superior temporal sulcus (bSTS), and the changed LGI in bSTS was negatively correlated with disease onset age and anxiety scores. The following functional connectivity analyses identified decreased functional connectivities between LING and right LING, precentral gyrus, and middle temporal gyrus. The decreased functional connectivities were correlated with disease duration, onset, and depression symptoms. Our findings revealed abnormal LGI in LING and bSTS indicating that the abnormal developmental of visual and social cognition related brain areas may be an early biomarker for depression.

The brain's default mode network (DMN) and the executive control network (ECN) switch engagement are influenced by the ventral attention network (VAN). Alterations in resting-state functional connectivity (RSFC) within this so-called triple network have been demonstrated in patients with major depressive disorder (MDD) or anxiety disorders (ADs). This study investigated alterations in the RSFC in patients with comorbid MDD and ADs to better understand the pathophysiology of this prevalent group of patients. Sixty-eight participants (52.9% male, mean age 35.3years), consisting of 25 patients with comorbid MDD and ADs (MDD + AD), 20 patients with MDD only (MDD) and 23 healthy controls (HCs) were investigated clinically and with 3T resting-state fMRI. RSFC utilizing a seed-based approach within the three networks belonging to the triple network was compared between the groups. Compared with HC, MDD + AD showed significantly reduced RSFC between the ECN and the VAN, the DMN and the VAN and within the ECN. No differences could be found for the MDD group compared with both other groups. Furthermore, symptom severity and medication status did not affect RSFC values. The results of this study show a distinct set of alterations of RSFC for patients with comorbid MDD and AD compared with HCs. This set of dysfunctions might be related to less adequate switching between the DMN and the ECN as well as poorer functioning of the ECN. This might contribute to additional difficulties in engaging and utilizing consciously controlled emotional regulation strategies.

IntroductionThe pathogenesis of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD) remains uncertain. Our work sought to examine the cortical gyrification pattern and its corresponding functional connectivity alterations, along with the underlying neurotransmitter information, in LID of PD.MethodsWe included 30 PD patients with LID (PD-LID group), 30 without LID (PD-NLID group), and 30 age- and gender-matched healthy controls (HC group). Regional cortical gyrification computed by local gyrification index (LGI) and seed-based resting-state functional connectivity (RSFC) were employed. We adopted the JuSpace toolset to further validate whether the spatial patterns in RSFC changes were linked with specific neurotransmitters.ResultsCompared to PD-NLID, PD-LID demonstrated lower regional LGI in the right inferior frontal gyrus (rIFG) (pars opercularis) and decreased RSFC between the rIFG and the left inferior parietal lobule (IPL). The decreased RSFC was correlated with the spatial distribution of the serotonin transporter (SERT) in the serotonergic system. In particular, the level of rIFG (pars opercularis) LGI was negatively related to the severity of LID and demonstrated good performance in detecting patients with PD-LID.ConclusionOur main findings indicated that the hypogyrification of rIFG and its corresponding functional connectivity reduction with left IPL, as well as the underlying serotonergic neurotransmitter distribution, could underlie the neurobiological underpinnings of LID.

Resting-state functional connectivity (RSFC) has been proposed as a potential indicator of repetitive negative thinking (RNT) in depression. However, identifying the specific functional process associated with RSFC alterations is challenging, and it remains unclear whether alterations in RSFC for depressed individuals are directly related to the RNT process or to individual characteristics distinct from the negative thinking process per se. To investigate the relationship between RSFC alterations and the RNT process in individuals with major depressive disorder (MDD), we compared RSFC with functional connectivity during an induced negative-thinking state (NTFC) in terms of their predictability of RNT traits and associated whole-brain connectivity patterns using connectome-based predictive modeling (CPM) and connectome-wide association (CWA) analyses. Thirty-six MDD participants and twenty-six healthy control participants underwent both resting state and induced negative thinking state fMRI scans. Both RSFC and NTFC distinguished between healthy and depressed individuals with CPM. However, trait RNT in depressed individuals, as measured by the Ruminative Responses Scale-Brooding subscale, was only predictable from NTFC, not from RSFC. CWA analysis revealed that negative thinking in depression was associated with higher functional connectivity between the default mode and executive control regions, which was not observed in RSFC. These findings suggest that RNT in depression involves an active mental process encompassing multiple brain regions across functional networks, which is not represented in the resting state. Although RSFC indicates brain functional alterations in MDD, they may not directly reflect the negative thinking process.

Trait repetitive negative thinking in depression is associated with functional connectivity in negative thinking state rather than resting state

AimsThis research aimed to explore alterations in the local gyrification index (GI) and resting-state functional connectivity (RSFC) in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI).MethodsIn this study, 126 T2DM patients with MCI (T2DM-MCI), 154 T2DM patients with normal cognition (T2DM-NC), and 167 healthy controls (HC) were recruited. All subjects underwent a battery of neuropsychological tests. A multimodal approach combining surface-based morphometry (SBM) and seed-based RSFC was used to determine the structural and functional alterations in patients with T2DM-MCI. The relationships among the GI, RSFC, cognitive ability, and clinical variables were characterized.ResultsCompared with the T2DM-NC group and HC group, T2DM-MCI patients showed significantly reduced GI in the bilateral insular cortex. Decreased RSFC was found between the left insula and right precuneus, and the right superior frontal gyrus (SFG). The altered GI was correlated with T2DM duration, global cognition, and episodic memory. The mediation effects of RSFC on the association between GI and cognition were not statistically significant.ConclusionOur results suggest that GI may serve as a novel neuroimaging biomarker to predict T2DM-related MCI and help us to improve the understanding of the neuropathological effects of T2DM-related MCI.

IntroductionEarly neurodevelopmental deviations, such as abnormal cortical folding patterns, are a candidate biomarker for major depressive disorder (MDD). Previous studies on patterns of abnormal cortical gyrification in MDD have provided valuable insights; however, the findings on cortical folding are controversial.ObjectivesWe aimed to investigate the association of MDD with the local gyrification index (LGI) in each cortical region at the whole-brain level and the association of the LGI with clinical characteristics of MDD, including recurrence, remission status, illness duration, severity of depression, and medication status of patients with MDD.MethodsWe obtained T1-weighted images of 234 patients with MDD and 215 healthy controls (HCs). LGI values were automatically calculated using the FreeSurfer software according to the Desikan–Killiany atlas. LGI values from 66 cortical regions in the bilateral hemispheres were analyzed. We compared the LGI values between the MDD and HC groups using the analysis of covariance, including patients’ age, sex, and years of education as covariates. The association between clinical characteristics and LGI values was investigated in the MDD group.ResultsCompared with HCs, patients with MDD showed significantly decreased LGI values in the cortical regions, including the bilateral ventrolateral and dorsolateral prefrontal cortices, medial and lateral orbitofrontal cortices, insula, right rostral anterior cingulate cortex, and several temporal and parietal regions, with the highest effect size in the left pars triangularis (Cohen’s f = 0.361; P = 1.78 × 10-13). As for the association of clinical characteristics with LGIs within the MDD group, recurrence and longer illness duration of MDD were associated with increased gyrification in several occipital and temporal regions, which showed no significant difference in LGIs between MDD and HC groups.ConclusionsConsidering that the aforementioned cortical regions are involved in emotion regulation, abnormal cortical folding patterns in such regions may be associated with the dysfunction of emotion regulation-related neural circuits, which may lead to MDD. These findings suggest that LGI may be a relatively stable neuroimaging marker associated with the trait of MDD predisposition.Disclosure of InterestNone Declared

Disruption of resting-state functional connectivity of right posterior insula in adolescents and young adults with major depressive disorder

BackgroundThere have been numerous studies investigating the relationship between nonsuicidal self-injury (NSSI) and suicidality. On the one side, NSSI is an important risk factor for suicidality, including suicidal thoughts and behaviors. On the other side, it has been suggested that one function of NSSI might be as a coping mechanism that can help individuals in the short term avoid suicide. The present study investigated the relationship between suicidality and NSSI in female inpatient adolescents, focusing on NSSI as an anti-suicide strategy.MethodsSubjects were 56 female adolescents, aged 12–18 years (M = 15.95 years, SD = 1.27), recruited from different inpatient child and adolescent psychiatric units. All participants fulfilled the DSM-5 research criteria for nonsuicidal self-injury disorder (NSSI-D). To assess suicidality, NSSI-D, and current and past diagnoses, a structured clinical interview was conducted.ResultsNSSI as a short-term coping strategy for avoiding suicide was indicated by one third (32.1%) of the participants. Before participants engaged in NSSI, the anti-suicide function was reported more frequently than reducing interpersonal problems (d = -.59). Getting relief from negative emotions and inducing positive feelings were reported at the same frequency as avoiding suicide before NSSI. Participants engaging in NSSI to avoid suicide and those reporting other functions did not significantly differ regarding other NSSI characteristics, suicidality, or psychopathology. Results indicate that the anti-suicide function significantly predicts the duration of current suicidal ideation (β = .557).ConclusionThis study provides preliminary support for the idea that NSSI is frequently used by female adolescents with NSSI-D to avoid suicide. Given the high co-occurrence of NSSI and suicidality, our results underline the importance of clinical assessment of suicidality and several NSSI functions, including the anti-suicide function, in adolescents with NSSI.