Epilepsy is a chronic neurological disorder that has complex relations with social, vocational and psychological functioning. Multiple studies showed that frequency of mood disorders in patients with epilepsy is increased and include depression, anxiety and psychosis. We present data from a neurobiological prospective having clinical relevance for epilepsy and comorbidities, including studies in people with late onset epilepsies. Better understanding of neurobiological mechanisms, anatomical, functional, neuroendocrine and molecular basis of psychiatric comorbidities in persons with epilepsy, can advance therapeutic responses. Epilepsy patients have a significantly higher prevalence of depressive symptoms. Many studies showed that depressive symptoms reduce their quality of life. Psychosis in epilepsy is a rare but severe disorder that usually occurs in patients with early onset of seizures, less localised ictal EEG recordings and seizure clustering. Suicide behavior presents an important problem in managing people with epilepsy. Suicidal ideation is not uncommon, and patients also have an increased risk for suicidal attempt or completed suicide. Psychiatric comorbidities present a significant problem and ask for a multidisciplinary approach to optimize treatment of people with epilepsy.

Severe forms of depression have been linked to excessive subcallosal cingulate cortex (SCC) activity. Stimulation of the SCC with surgically implanted electrodes can alleviate depression, but current noninvasive techniques cannot directly and selectively modulate deep targets. We developed a new noninvasive neuromodulation approach that can deliver low-intensity focused ultrasonic waves to the SCC.

Twenty-two individuals with treatment-resistant depression participated in a randomized, double-blind, sham-controlled study. Ultrasonic stimulation was delivered to the bilateral SCC during concurrent functional magnetic resonance imaging to quantify target engagement. Mood state was measured with the Sadness subscale of the Positive and Negative Affect Schedule before and after 40 minutes of real or sham SCC stimulation. Change in depression severity was measured with the 6-item Hamilton Depression Rating Scale at 24 hours and 7 days.

Functional magnetic resonance imaging demonstrated a target-specific decrease in SCC activity during stimulation (p = .028, n = 16). In 7 of 16 participants, SCC neuromodulation was detectable at the individual participant level with a single 10-minute scan (p < .05, small-volume correction). Mood and depression scores improved more with real than with sham stimulation. In the per-protocol sample (n = 19), real stimulation was superior to sham for 6-item Hamilton Depression Rating Scale scores at 24 hours and for Sadness scores (both p < .05, d > 1). Nonsignificant trends were found in the intent-to-treat sample.

This small pilot study indicates that ultrasonic stimulation modulates SCC activity and can rapidly reduce depressive symptoms. The capability to noninvasively and selectively target deep brain areas creates new possibilities for the future development of circuit-directed therapeutics and for the analysis of deep-brain circuit function in humans.

This study assessed whole-brain functional connectivity and network graph theory indices in patients with chronic rhinosinusitis with (CRSwOD) and without (CRSsOD) olfactory dysfunction. We also analyzed correlations between the abnormal network metrics and clinical indices. We acquired resting-state functional magnetic resonance images from 31 patients with CRSsOD, 26 with CRSwOD, and 25 healthy controls (HCs). Functional connectivity was computed and graph theory metrics were evaluated based on the Dosenbach-160 Atlas; relationships between neuroimaging indicators and clinical scales were assessed using Pearson correlation analysis. The results showed that CRSsOD patients had 11 edges with greater strength than HCs, CRSwOD patients had 1 greater edge than HCs, and CRSsOD patients had 5 greater edges than CRSwOD patients. Nodal degree centrality and efficiency in the right posterior occipital region were significantly altered in patients with CRSsOD compared with those in CRSwOD and in HCs. Five and two edges correlated with clinical scales in patients with CRSsOD and CRSwOD, respectively, whereas no correlations in global and nodal indicators were found. These results imply that distinct brain network patterns, particularly in the occipital cortex, could be a valid neuroimaging marker for related diagnosis and prognosis of CRSsOD and CRSwOD patients, and contribute to our better understanding of the central neural mechanisms of CRSwOD, providing new ideas for the clinical management of CRSwOD.

The rising prevalence of depression, with its associated suicide risk, demands effective fast-acting treatments. Ketamine has emerged as promising, demonstrating rapid antidepressant effects. While early studies show swift mood improvements, its precise mechanisms remain unclear. This article aims to compile and synthesize the literature on ketamine's molecular actions. Ketamine primarily works by antagonizing NMDA receptors, reducing GABAergic inhibition, and increasing glutamate release. This enhanced glutamate activates AMPA receptors, triggering crucial downstream cascades, including BDNF-TrkB and mTOR pathways, promoting synaptic proliferation and regeneration. Moreover, neuroimaging studies have demonstrated alterations in brain networks involved in emotional regulation, including the Default Mode Network (DMN), Central Executive Network (CEN), and Salience Network (SN), which are frequently disrupted in depression. Despite the promising findings, the literature reveals significant inaccuracies and gaps in understanding the full scope of ketamine's therapeutic potential. For instance, ketamine engages with opioid receptors, insinuating a permissive role of the opioid system in amplifying ketamine's antidepressant effects, albeit ketamine does not operate as a direct opioid agonist. Further exploration is requisite to comprehensively ascertain its safety profile, long-term efficacy, and the impact of genetic determinants, such as BDNF polymorphisms, on treatment responsiveness.

The aim of this study is to investigate activity and functional connectivity (FC) of Papez circuit networks associated with music processing using functional magnetic resonance imaging (fMRI) in depressed breast cancer patients. Twenty-three breast cancer patients listened to four different Iranian/Persian music paradigms during the resting-state fMRI scanning session: negative stimulation of traditional music, negative stimulation of pop music, positive stimulation of traditional music and positive stimulation of pop music. The amplitude of low-frequency fluctuation (ALFF) was used to evaluate the local characteristics of spontaneous brain activity. FC maps were created using multivariate ROI-to-ROI connectivity (mRRC) and Papez circuit-based regions of interest (ROIs) selection. We found that music increases FC within various brain networks which are involved in memory, emotion, and cognitive function, including the limbic system, the default mode network (DMN), salience network (SN), and central executive network (CEN). Moreover, it seems that the traditional types (both positive and negative) of Iranian music may be more effective to affect brain activity in the patients with breast cancer, than the Iranian pop music. These findings demonstrate that music therapy, as an effective and easily applicable approach, supports the neuropsychological recovery and can contribute to standard treatment protocols in patients with breast cancer.

Transcranial direct current stimulation (tDCS) has demonstrated benefits in adults with various psychiatric disorders, but its clinical utility in children and young people (CYP) remains unclear. This PRISMA systematic review used published and ongoing studies to examine the effects of tDCS on disorder-specific symptoms, mood and neurocognition in CYP with psychiatric disorders. We searched Medline via PubMed, Embase, PsychINFO via OVID, and Clinicaltrials.gov up to December 2022. Eligible studies involved multiple session (i.e., treatment) tDCS in CYP (≤ 25 years old) with psychiatric disorders. Two independent raters assessed the eligibility of studies and extracted data using a custom-built form. Of 33 eligible studies (participant N = 517), the majority (n = 27) reported an improvement in at least one outcome measure of disorder-specific symptoms. Few studies (n = 13) examined tDCS effects on mood and/or neurocognition, but findings were mainly positive. Overall, tDCS was well tolerated with minimal side effects. Of 11 eligible ongoing studies, many are sham-controlled RCTs (n = 9) with better blinding techniques and a larger estimated participant enrolment (M = 79.7; range 15-172) than published studies. Although encouraging, the evidence to date is insufficient to firmly conclude that tDCS can improve clinical symptoms, mood, or cognition in CYP with psychiatric disorders. Ongoing studies appear of improved methodological quality; however, future studies should broaden outcome measures to more comprehensively assess the effects of tDCS and develop dosage guidance (i.e., treatment regimens).

Transcranial temporal interference stimulation (tTIS) is a new, emerging neurostimulation technology that utilizes two or more electric fields at specific frequencies to modulate the oscillations of neurons at a desired spatial location in the brain. The physics of tTIS offers the advantage of modulating deep brain structures in a non-invasive fashion and with minimal stimulation of the overlying cortex outside of a selected target. As such, tTIS can be effectively employed in the context of therapeutics for the psychiatric disease of disrupted brain connectivity, such as major depressive disorder (MDD). The subgenual anterior cingulate cortex (sgACC), a key brain center that regulates human emotions and influences negative emotional states, is a plausible target for tTIS in MDD based on reports of its successful neuromodulation with invasive deep brain stimulation.

This pilot, single-site, double-blind, randomized, sham-controlled interventional clinical trial will be conducted at St. Michael's Hospital - Unity Health Toronto in Toronto, ON, Canada. The primary objective is to demonstrate target engagement of the sgACC with 130 Hz tTIS using resting-state magnetic resonance imaging (MRI) techniques. The secondary objective is to estimate the therapeutic potential of tTIS for MDD by evaluating the change in clinical characteristics of participants and electrophysiological outcomes and providing feasibility and tolerability estimates for a large-scale efficacy trial. Thirty participants (18-65 years) with unipolar, non-psychotic MDD will be recruited and randomized to receive 10 sessions of 130 Hz tTIS or sham stimulation (n = 15 per arm). The trial includes a pre- vs. post-treatment 3T MRI scan of the brain, clinical evaluation, and electroencephalography (EEG) acquisition at rest and during the auditory mismatch negativity (MMN) paradigm.

This study is one of the first-ever clinical trials among patients with psychiatric disorders examining the therapeutic potential of repetitive tTIS and its neurobiological mechanisms. Data obtained from this trial will be used to optimize the tTIS approach and design a large-scale efficacy trial. Research in this area has the potential to provide a novel treatment option for individuals with MDD and circuitry-related disorders and may contribute to the process of obtaining regulatory approval for therapeutic applications of tTIS.

ClinicalTrials.gov, identifier NCT05295888.

Successful therapy of mental disorders is very important in view of the high level of suffering of those affected. Since established pharmaceutical and psychotherapeutic approaches do not lead to the desired improvement in all cases, complementary or alternative treatment methods are intensively researched. Psilocybin-assisted psychotherapy seems particularly promising, and has been approved in the USA for larger clinical trials. Psilocybin belongs to the group of psychedelics and influences psychological experiences. In assisted therapy, psilocybin is administered in controlled doses under medical supervision to patients with different mental disorders. In the studies conducted so far, longer-term positive effects could be shown after just one or a few doses. In order to provide a better understanding of the potential therapeutic mechanisms, this article will first describe neurobiological and psychological effects of psilocybin. To better assess the potential of psilocybin-assisted psychotherapy for various disorders, clinical studies conducted so far with patients administered psilocybin are reviewed.

EEG neurofeedback (EEG-NFB) is a promising tool for the treatment of depressive disorders. However, many methods for the presentation of neurobiological reactions are available and it is widely unknown which of these feedback options are preferrable. Moreover, the influence of motivation on NFB training success is insufficiently studied. This study analyzed the efficacy of a novel EEG protocol (FC3/Pz) based on findings for NFB in depression. The role of four feedback options (Rumination, Anxiety, Meditation Master, Moving Art) from the NFB software "Brain Assistant" and motivation in EEG-based NFB performance was studied. Regarding "Anxiety" and "Rumination" visual feedback was used to evoke emotions; reinforcement (both negative and positive operant conditioning) was continuous. Regarding "Meditation Master" visual feedback was combined with continuous positive reinforcement. Regarding "Moving Art" 20-min calm nature films with neutral character were used; both visual and auditive feedback were applied. The reinforcement was positive and continuous. 13 healthy participants completed 15 EEG sessions over four months combining simultaneous frontal (aims: reduction of theta-, alpha- and high beta-activity, increase of low and mid beta-activity) and parietal training (aims: reduction of theta-, alpha 1-, mid and high beta-activity, increase of alpha 2- and low beta-activity). We observed significantly more pronounced percentage change in the expected direction for Anxiety than Moving Art (mean difference = 3.32; p = 0.003). The association between motivation and performance was non-significant. Based on these results we conclude that feedback with both negative and positive operant conditioning and emotion evoking effects should be preferred.

Treatment-resistant depression (TRD) occurs more commonly in women. Deep brain stimulation (DBS) is an emerging treatment for TRD, and its efficacy continues to be explored. However, differences in treatment outcomes between males and females have yet to be explored in formal analysis.

A PRISMA-compliant systematic review of DBS for TRD studies was conducted. Patient-level data were independently extracted by two authors. Treatment response was defined as a 50 % or greater reduction in depression score. Percent change in depression scores by gender were evaluated using random-effects analyses.

Of 737 records, 19 studies (129 patients) met inclusion criteria. The mean reduction in depression score for females was 57.7 % (95 % CI, 64.33 %-51.13 %), whereas for males it was 35.2 % (95 % CI, 45.12 %-25.23 %) (p < 0.0001). Females were more likely to respond to DBS for TRD when compared to males (OR = 2.44, 95 % CI 1.06, 1.95). These differences varied in significance when stratified by DBS anatomical target, age, and timeframe for responder classification.

Studies included were open-label trials with small sample sizes.

Our findings suggest that females with TRD respond at higher rates to DBS treatment than males. Further research is needed to elucidate the implications of these results, which may include connectomic sexual dimorphism, depression phenotype variations, or unrecognized symptom reporting differences. Methodological standardization of outcome scales, granular demographic data, and individual subject outcomes would allow for more robust comparisons between trials.

Background The subgenual cingulate cortex (SGC) has been identified as a key structure within multiple neural circuits whose dysfunction is implicated in the neurobiology of depression. Deep brain stimulation in the SGC is thought to reduce and normalize local metabolism, causing normalization of circuit behavior and an improvement in depressive symptoms. We hypothesized that nonablative stereotactic radiosurgery (SRS) to the SGC would reduce local metabolism and reduce the severity of depression in patients with treatment-resistant bipolar depression. Methods Under the FDA's Humanitarian Device Exemption program, patients were screened for inclusion and exclusion criteria. Three volunteers meeting the criteria provided informed consent. Bilateral SGC targets were irradiated to a maximum dose of 75 Gy in one fraction. Subjects were followed for one year following the procedure with mood assessments (Hamilton Depression Rating Scale (HDRS), Clinical Global Impression-Improvement, Clinical Global Impression-Severity, and Young Mania Rating Scale), neurocognitive testing (Delis-Kaplan Executive Function System, Wechsler Adult Intelligence Scale III digit span, and California Verbal Learning Test II), and imaging. Further imaging was completed approximately two years after the procedure. Clinical improvement was defined as a ≥50% reduction in HDRS. Results Two of the three subjects showed clinical improvement in depressive symptoms during the follow-up period, while one subject showed no change in symptom severity. One of three subjects was hospitalized for the emergence of an episode of psychotic mania after discontinuing antipsychotic medications against medical advice but promptly recovered with the reinstitution of an antipsychotic. Sequential assessments did not reveal impairment in any cognitive domain assessed. For one of the three subjects, MRI imaging showed evidence of edema at 12 months post-SRS, which resolved at 22 months post-procedure. In a second of three patients, there was evidence of local edema at the target site at long-term follow-up. All imaging changes were asymptomatic. Conclusion Radiosurgical targeting of the SGC may be a noninvasive strategy for the reduction of severe depression in treatment-resistant bipolar disorder. Two out of three patients showed clinical improvement. While these results are promising, further study, including improvements in target selection and dosing considerations, is needed.

Depression is currently one of the most complicated public health problems with the rising number of patients, increasing partly due to pandemics, but also due to increased existential insecurities and complicated aetiology of disease. Besides the tsunami of mental health issues, there are limitations imposed by ambiguous clinical rules of assessment of the symptoms and obsolete and inefficient standard therapy approaches. Here we are summarizing the neuroimaging results pointing out the actual complexity of the disease and novel attempts to detect depression that are evidence-based, mostly related to electrophysiology. It is repeatedly shown that the complexity of resting-state EEG recorded in patients suffering from depression is increased compared to healthy controls. We are discussing here how that can be interpreted and what we can learn about future effective therapies. Also, there is evidence that novel options of treatment, like different modalities of electromagnetic stimulation, are successful just because they are capable of decreasing that aberrated complexity. And complexity measures extracted from electrophysiological signals of depression patients can serve as excellent features for further machine learning models in order to automatize detection. In addition, after initial detection and even selection of responders for further therapy route, it is possible to monitor the therapeutic flow for one person, which leads us to possible tailored treatment for patients suffering from depression.

Transcranial magnetic stimulation (TMS) is entering increasingly widespread use in treating depression. The most common stimulation target, in the dorsolateral prefrontal cortex (DLPFC), emerged from early neuroimaging studies in depression. Recently, more rigorous casual methods have revealed whole-brain target networks and anti-networks based on the effects of focal brain lesions and focal brain stimulation on depression symptoms. Symptom improvement during therapeutic DLPFC-TMS appears to involve directional changes in signaling between the DLPFC, subgenual and dorsal anterior cingulate cortex, and salience-network regions. However, different networks may be involved in the therapeutic mechanisms for other TMS targets in depression, such as dorsomedial prefrontal cortex or orbitofrontal cortex. The durability of therapeutic effects for TMS involves synaptic neuroplasticity, and specifically may depend upon dopamine acting at the D1 receptor family, as well as NMDA-receptor-dependent synaptic plasticity mechanisms. Although TMS protocols are classically considered 'excitatory' or 'inhibitory', the actual effects in individuals appear quite variable, and might be better understood at the level of populations of synapses rather than individual synapses. Synaptic meta-plasticity may provide a built-in protective mechanism to avoid runaway facilitation or inhibition during treatment, and may account for the relatively small number of patients who worsen rather than improve with TMS. From an ethological perspective, the antidepressant effects of TMS may involve promoting a whole-brain attractor state associated with foraging/hunting behaviors, centered on the rostrolateral periaqueductal gray and salience network, and suppressing an attractor state associated with passive threat defense, centered on the ventrolateral periaqueductal gray and default-mode network.

To clarify the neural correlates underlying psychogenic non-epileptic seizures (PNES), we compared glymphatic system activity between patients with PNES and healthy participants using diffusion tensor imaging (DTI)-analysis along the perivascular space (ALPS) method.

The DTI scans were acquired from 16 patients with PNES and 25 healthy participants. We computed the DTI-ALPS index as an index of glymphatic system function and estimated the disease-related changes in the DTI-ALPS index and brain structures in PNES patients.

There were no significant differences in the DTI-ALPS index between patients with PNES and healthy participants. On the other hand, patients with PNES had decreased fractional anisotropy values in the bilateral posterior cingula, a higher mean diffusivity value around the left insula, and a lower gray matter volume in the bilateral amygdalae compared with healthy participants.

Patients with PNES exhibited an impairment of white matter integrity and a reduction of gray matter volume, but no glymphatic-system changes. These findings will play a significant role in our comprehension of this complex illness.

Previous studies have shown disrupted effective connectivity in the large-scale brain networks of individuals with major depressive disorder (MDD). However, it is unclear whether these changes differ between first-episode drug-naive MDD (FEDN-MDD) and recurrent MDD (R-MDD).

This study utilized resting-state fMRI data from 17 sites in the Chinese REST-meta-MDD project, consisting of 839 patients with MDD and 788 normal controls (NCs). All data was preprocessed using a standardized protocol. Then, we performed a granger causality analysis to calculate the effectivity connectivity (EC) within and between brain networks for each participant, and compared the differences between the groups.

Our findings revealed that R-MDD exhibited increased EC in the fronto-parietal network (FPN) and decreased EC in the cerebellum network, while FEDN-MDD demonstrated increased EC from the sensorimotor network (SMN) to the FPN compared with the NCs. Importantly, the two MDD subgroups displayed significant differences in EC within the FPN and between the SMN and visual network. Moreover, the EC from the cingulo-opercular network to the SMN showed a significant negative correlation with the Hamilton Rating Scale for Depression (HAMD) score in the FEDN-MDD group.

These findings suggest that first-episode and recurrent MDD have distinct effects on the effective connectivity in large-scale brain networks, which could be potential neural mechanisms underlying their different clinical manifestations.

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.

Severe forms of depression have been linked to hyperactivity of the subcallosal cingulate cortex. The ability to stimulate the subcallosal cingulate cortex or associated circuits noninvasively and directly would maximize the number of patients who could receive treatment. To this end, we have developed an ultrasound-based device for effective noninvasive modulation of deep brain circuits. Here we describe an application of this tool to an individual with treatment-resistant depression.

A 30-year-old Caucasian woman with severe treatment-resistant non-psychotic depression was recruited into a clinical study approved by the Institutional Review Board of the University of Utah. The patient had a history of electroconvulsive therapy with full remission but without sustained benefit. Magnetic resonance imaging was used to coregister the ultrasound device to the subject's brain anatomy and to evaluate neural responses to stimulation. Brief, 30-millisecond pulses of low-intensity ultrasound delivered into the subcallosal cingulate cortex target every 4 seconds caused a robust decrease in functional magnetic resonance imaging blood-oxygen-level-dependent activity within the target. Following repeated stimulation of three anterior cingulate targets, the patient's depressive symptoms resolved within 24 hours of the stimulation. The patient remained in remission for at least 44 days afterwards.

This case illustrates the potential for ultrasonic neuromodulation to precisely engage deep neural circuits and to trigger a durable therapeutic reset of those circuits. Trial registration ClinicalTrials.gov, NCT05301036. Registered 29 March 2022, https://clinicaltrials.gov/ct2/show/NCT05301036.

Non-suicidal self-injury (NSSI) is a major mental health problem among youth worldwide. Dysfunction in emotion regulation contributes to NSSI, but research on the underlying neurobiological mechanisms of NSSI is limited. Adolescents with emotion regulation difficulties are vulnerable to stress, making them susceptible to maladaptive coping mechanisms such as NSSI.

This study examined the functional neurocircuitry relevant to emotion regulation and stress coping in individuals with NSSI compared with healthy controls. This case-control study included 34 adolescents with NSSI (15.91 years) and 28 (16.0 years) unaffected controls. Participants underwent a functional magnetic resonance imaging scan before and after completing a laboratory stress-induction paradigm (the Montreal Imaging Stress Test). The effects of stress induction were quantified by both physiological measures and self-reports.

Participants with NSSI showed distinctive alterations in functional resting-state following stress induction, which differentiated them from unaffected controls. Results show a reduction in functional connectivity between frontoparietal regions and the angular gyrus within the patient group compared to controls, as well as an increase in functional connectivity between visual regions, the insular cortex, the planum polare, and the central opercular cortex. After conditions of acute stress, adolescents with NSSI show changes in functional connectivity of regions associated with sensorimotor alertness, attention, and effortful emotion regulation.

The patient group showed both NSSI and suicidal behavior, therefore results might be partly due to suicidality.

The findings emphasize the importance of targeting emotion regulation within therapeutic approaches to enhance stress coping capacity, which in turn may contribute to counteracting self-injurious behavior.

The current study is the first meta-analysis to examine grey matter volume (GMV) changes in adolescents and across the lifespan in major depressive disorder (MDD). Seed-based d mapping-with permutation of subject images (SDM-PSI) has advantages over previous coordinate-based meta-analytical methods (CBMA), such as reducing bias (via the MetaNSUE algorithm) and including non-statistically significant unreported effects. SDM-PSI was used to analyze 105 whole-brain GMV voxel-based morphometry (VBM) studies comparing 6,530 individuals with MDD versus 6,821 age-matched healthy controls (HC). A laterality effect was observed in which adults with MDD showed lower GMV than adult HC in left fronto-temporo-parietal structures (superior temporal gyrus, insula, Rolandic operculum, and inferior frontal gyrus). However, these abnormalities were not statistically significant for adolescent MDD versus adolescent HC. Instead, adolescent MDD showed lower GMV than adult MDD in right temporo-parietal structures (angular gyrus and middle temporal gyrus). These regional differences may be used as potential biomarkers to predict and monitor treatment outcomes as well as to choose the most effective treatments in adolescents versus adults. Finally, due to the paucity of youth, older adult, and longitudinal studies, future studies should attempt to replicate these GMV findings and examine whether they correlate with treatment response and illness severity.

Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and (es)ketamine are used to treat major depressive disorder (MDD). These different types of medication may involve common neural pathways related to glutamatergic and GABAergic neurotransmitter systems, both of which have been implicated in MDD pathology. We conducted a systematic review of pharmacological proton Magnetic Resonance Spectroscopy (1H-MRS) studies in healthy volunteers and individuals with MDD to explore the potential impact of these medications on glutamatergic and GABAergic systems. We searched PubMed, Web of Science and Embase and included randomized controlled trials or cohort studies, which assessed the effects of SSRIs, SNRIs, or (es)ketamine on glutamate, glutamine, Glx or GABA using single-voxel 1H-MRS or Magnetic Resonance Spectroscopic Imaging (MRSI). Additionally, studies were included when they used a field strength > 1.5 T, and when a comparison of metabolite levels between antidepressant treatment and placebo or baseline with post-medication metabolite levels was done. We excluded animal studies, duplicate publications, or articles with 1H-MRS data already described in another included article. Twenty-nine studies were included in this review. Fifteen studies investigated the effect of administration or treatment with SSRIs or SNRIs, and fourteen studies investigated the effect of (es)ketamine on glutamatergic and GABAergic metabolite levels. Studies on SSRIs and SNRIs were highly variable, generally underpowered, and yielded no consistent findings across brain regions or specific populations. Although studies on (es)ketamine were also highly variable, some demonstrated an increase in glutamate levels in the anterior cingulate cortex in a time-dependent manner after administration. Our findings highlight the need for standardized study and acquisition protocols. Additionally, measuring metabolites dynamically over time or combining 1H-MRS with whole brain functional imaging techniques could provide valuable insights into the effects of these medications on glutamate and GABAergic neurometabolism.

Deep brain stimulation (DBS) has shown therapeutic benefits for treatment resistant depression (TRD). Stimulation of the subcallosal cingulate gyrus (SCG) aims to alter dysregulation between subcortical and cortex. However, the 50% response rates for SCG-DBS indicates that selection of appropriate patients is challenging. Since stimulation influences large-scale network function, we hypothesized that network features can be used as biomarkers to inform outcome. In this pilot project, we used resting-state EEG recorded longitudinally from 10 TRD patients with SCG-DBS (11 at baseline). EEGs were recorded before DBS-surgery, 1-3 months, and 6 months post surgery. We used graph theoretical analysis to calculate clustering coefficient, global efficiency, eigenvector centrality, energy, and entropy of source-localized EEG networks to determine their topological/dynamical features. Patients were classified as responders based on achieving a 50% or greater reduction in Hamilton Depression (HAM-D) scores from baseline to 12 months post surgery. In the delta band, false discovery rate analysis revealed that global brain network features (segregation, integration, synchronization, and complexity) were significantly lower and centrality of subgenual anterior cingulate cortex (ACC) was higher in responders than in non-responders. Accordingly, longitudinal analysis showed SCG-DBS increased global network features and decreased centrality of subgenual ACC. Similarly, a clustering method separated two groups by network features and significant correlations were identified longitudinally between network changes and depression symptoms. Despite recent speculation that certain subtypes of TRD are more likely to respond to DBS, in the SCG it seems that underlying brain network features are associated with ability to respond to DBS. SCG-DBS increased segregation, integration, and synchronizability of brain networks, suggesting that information processing became faster and more efficient, in those patients in whom it was lower at baseline. Centrality results suggest these changes may occur via altered connectivity in specific brain regions especially ACC. We highlight potential mechanisms of therapeutic effect for SCG-DBS.

Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are effective neuromodulation therapies for treatment-resistant depression (TRD). While ECT is generally considered the most effective antidepressant, rTMS is less invasive, better tolerated and leads to more durable therapeutic benefits. Both interventions are established device antidepressants, but it remains unknown if they share a common mechanism of action. Here we aimed to compare the brain volumetric changes in patients with TRD after right unilateral (RUL) ECT versus left dorsolateral prefrontal cortex (lDLPFC) rTMS.

We assessed 32 patients with TRD before the first treatment session and after treatment completion using structural magnetic resonance imaging. Fifteen patients were treated with RUL ECT and seventeen patients received lDLPFC rTMS.

Patients receiving RUL ECT, in comparison with patients treated with lDLPFC rTMS, showed a greater volumetric increase in the right striatum, pallidum, medial temporal lobe, anterior insular cortex, anterior midbrain, and subgenual anterior cingulate cortex. However, ECT- or rTMS-induced brain volumetric changes were not associated with the clinical improvement.

We evaluated a modest sample size with concurrent pharmacological treatment and without neuromodulation therapies randomization.

Our findings suggest that despite comparable clinical outcomes, only RUL ECT is associated with structural change, while rTMS is not. We hypothesize that structural neuroplasticity and/or neuroinflammation may explain the larger structural changes observed after ECT, whereas neurophysiological plasticity may underlie the rTMS effects. More broadly, our results support the notion that there are multiple therapeutic strategies to move patients from depression to euthymia.

To explore the correlation between the incidence rates of depression and anxiety and cerebral glucose metabolism in cancer patients.

The experiment subjects consisted of patients with lung cancer, head and neck tumor, stomach cancer, intestinal cancer, breast cancer and healthy individuals. A total of 240 tumor patients and 39 healthy individuals were included. All subjects were evaluated by the Hamilton depression scale (HAMD) and Manifest anxiety scale (MAS), and were examined by whole body Positron Emission Tomography/Computed Tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG). Demographic, baseline clinical characteristics, brain glucose metabolic changes, emotional disorder scores and their relations were statistically analyzed.

The incidence rates of depression and anxiety in patients with lung cancer were higher than those in patients with other tumors, and Standard uptake values (SUVs) and metabolic volume in bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were lower than those in patients with other tumors. We also found that poor pathological differentiation, and advanced TNM stage independently associated with depression and anxiety risk. SUVs in the bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were negatively correlated with HAMD and MAS scores.

This study revealed the correlation between brain glucose metabolism and emotional disorders in cancer patients. The changes in brain glucose metabolism were expected to play a major role in emotional disorders in cancer patients as psychobiological markers. These findings indicated that functional imaging can be applied for psychological assessment of cancer patients as an innovative method.

In patients affected by Parkinson's disease (PD), up to 50% of them experience cognitive changes, and psychiatric disturbances, such as anxiety and depression, often precede the onset of motor symptoms and have a negative impact on their quality of life. Pathologically, PD is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and the presence of intracellular inclusions, called Lewy bodies and Lewy neurites, composed mostly of α-synuclein (α-Syn). Much of PD research has focused on the role of α-Syn aggregates in the degeneration of SNc DA neurons due to the impact of striatal DA deficits on classical motor phenotypes. However, abundant Lewy pathology is also found in other brain regions including the midbrain raphe nuclei, which may contribute to non-motor symptoms. Indeed, dysfunction of the serotonergic (5-HT) system, which regulates mood and emotional pathways, occurs during the premotor phase of PD. However, little is known about the functional consequences of α-Syn inclusions in this neuronal population other than DA neurons. Here, we provide an overview of the current knowledge of α-Syn and its role in regulating the 5-HT function in health and disease. Understanding the relative contributions to α-Syn-linked alterations in the 5-HT system may provide a basis for identifying PD patients at risk for developing depression and could lead to a more targeted therapeutic approach.

We attempted to explore the common and distinct long- and short-range functional connectivity (FC) patterns of melancholic and non-melancholic major depressive disorder (MDD) and their associations with clinical characteristics.

Fifty-nine patients with first-episode drug-naïve MDD, including 31 patients with melancholic features and 28 patients with non-melancholic features, underwent resting-state functional magnetic resonance imaging (fMRI) scanning to examine long- and short-range FC. Thirty-two healthy volunteers were recruited as controls. The support vector machines (SVM) was applied to distinguish the melancholic patients from the non-melancholic patients by using the FC of abnormal brain regions.

Compared to healthy volunteers, patients with MDD showed increased long-range positive FC (lpFC) in the right insula/inferior frontal gyrus and left insula. Relative to non-melancholic patients, melancholic patients displayed decreased lpFC in the right lingual gyrus, decreased short-range positive FC (spFC) in the right middle temporal gyrus and right superior parietal lobule, increased lpFC in the left inferior parietal lobule, and increased spFC in the left middle occipital gyrus/inferior occipital gyrus, left cerebellum VII/IX, and bilateral cerebellum CrusII. Increased lpFC in the left inferior parietal lobule in melancholic patients was correlated with the TEPS abstract anticipatory scores. SVM results showed that FCs of five combinations within different brain regions could distinguish melancholic patients from non-melancholic patients.

FC abnormalities in the default mode network and parietal-occipital brain regions may underlie the neurobiology of melancholic MDD. An increased lpFC in the left inferior parietal lobule correlated with anhedonia may be a distinctive neurobiological feature of melancholic MDD.

Postpartum depression (PPD) and PPD comorbid with anxiety (PPD-A) are highly prevalent and severe mental health problems in postnatal women. PPD and PPD-A share similar pathopsychological features, leading to ongoing debates regarding the diagnostic and neurobiological uniqueness. This paper aims to delineate common and disorder-specific neural underpinnings and potential treatment targets for PPD and PPD-A by characterizing functional dynamics with resting-state functional magnetic resonance imaging in 138 participants (45 first-episode, treatment-naïve PPD; 31 PDD-A patients; and 62 healthy postnatal women [HPW]). PPD-A group showed specifically increased dynamic amplitude of low-frequency fluctuation in the subgenual anterior cingulate cortex (sgACC) and increased dynamic functional connectivity (dFC) between the sgACC and superior temporal sulcus. PPD group exhibited specifically increased static FC (sFC) between the sgACC and ventral anterior insula. Common disrupted sFC between the sgACC and middle temporal gyrus was found in both PPD and PPD-A patients. Interestingly, dynamic changes in dFC between the sgACC and superior temporal gyrus could differentiate PPD, PPD-A, and HPW. Our study presents initial evidence on specifically abnormal functional dynamics of limbic, emotion regulation, and social cognition systems in patients with PDD and PPD-A, which may facilitate understanding neurophysiological mechanisms, diagnosis, and treatment for PPD and PPD-A.

It has been demonstrated that the anterior cingulate cortex (ACC) has three subregions, involved in behavior, cognition, and emotion. However, the intrinsic connectivity of the ACC subregions in patients with major depressive disorder (MDD) is still unclear. In this study, functional magnetic resonance imaging (fMRI) data was used to detect the functional connectivity (FC) of ACC subregions and the correlation with the disease severity in young and middle-aged patients with MDD.

A total of 36 young and middle-aged patients with first-episode MDD and 36 healthy controls (HCs) were enrolled in this study. FC was applied to investigate altered connectivity of the ACC subregion in MDD patients compared to HCs. Correlation analysis was then used to assess possible relationship between the neuroimaging findings and clinical symptoms in the patient group.

Compared to HCs, young and middle-aged patients had significantly decreased FC between the emotional subregion of the ACC and the hippocampus, thalamus, insula, angular gyrus, and posterior cingulate cortex. The FC between the ACC emotional subregion and the insula, the AG, the RPHG was negatively correlated with depression index. The FC between the ACC emotional subregion and the putamen was positively correlated with depression index.

The present findings indicate that abnormal ACC subregions-seeded FC may be implicated in the MDD-related abnormalities of emotion regulation and information processing. And there is a correlation between the above FC changes and the clinical symptoms of young and middle-aged MDD patients. This study may provide preliminary evidence for the ACC-related neural mechanism in young and middle-aged MDD patients and enhance the understanding of the pathophysiology of MDD.

Anhedonia is a core symptom of major depressive disorder (MDD) resulting from maladaptive reward processing. Electroconvulsive therapy (ECT) is an effective treatment for patients with MDD. No previous neuroimaging studies have taken a dimensional approach to assess whether ECT-induced volume changes are specifically related to improvements in anhedonia and positive valence emotional constructs. We aimed to assess the relationship between ECT-induced brain volumetric changes and improvement in anhedonia and reward processing in patients with MDD.

We evaluated 15 patients with MDD before and after ECT. We used magnetic resonance imaging, clinical scales (i.e., Quick Inventory of Depressive Symptomatology for syndromal depression severity and Snaith-Hamilton Pleasure Scale for anhedonia) and the Temporal Experience of Pleasure Scale for anticipatory and consummatory experiences of pleasure. We identified 5 regions of interest within the reward circuit and a 6th control region relevant for MDD but not core to the reward system (Brodmann Area 25).

Anhedonia, anticipatory and consummatory reward processing improved after ECT. Volume increases within the right reward system separated anhedonia responders and non-responders. Improvement in anticipatory (but not consummatory) reward correlated with increases in volume in hippocampus, amygdala, ventral tegmental area and nucleus accumbens.

We evaluated a modest sample size of patients with concurrent pharmacological treatment using a subjective psychometric assessment.

We highlight the importance of a dimensional and circuit-based approach to understanding target engagement and the mechanism of action of ECT, with the goal to define symptom- and circuit-specific response biomarkers for device neuromodulation therapies.

The major depressive disorder (MDD) can be a threat to the health of people all over the world. Although governments have developed and implemented evidence-based interventions and prevention programs to prevent MDD and maintain mental health in adolescents, the number of adolescents with this condition has been on the rise for the past 10 years.

A total of 60 adolescents were recruited, including 32 drug-naive adolescents with first-episode MDD and 28 healthy controls (HCs). Alterations in the intrinsic cerebral activity of the adolescents with MDD were explored using arterial spin labeling (ASL) while differences in the regional cerebral blood flow (rCBF) of the two groups were assessed based on voxel-based whole-brain analysis. Finally, correlations between the regional functional abnormalities and clinical variables were investigated for adolescents with MDD.

Compared with HCs, MDD patients had a lower rCBF in the left triangular part of the inferior frontal gyrus (IFGtriang) but a higher one in the right Precental gyrus (PreCG). Negative correlations were also noted between the CBF in the left IFGtriang and the Hamilton depression scale (HAMD) scores of MDD patients.

Elucidating the neurobiological features of adolescent patients with MDD is important to adequately develop methods that can assist in early diagnosis, precaution and intervention.

The use of deep brain stimulation (DBS) in treatment resistant patients with schizophrenia is of considerable current interest, but where to site the electrodes is challenging. This article reviews rationales for electrode placement in schizophrenia based on evidence for localized brain abnormality in the disorder and the targets that have been proposed and employed to date. The nucleus accumbens and the subgenual anterior cingulate cortex are of interest on the grounds that they are sites of potential pathologically increased brain activity in schizophrenia and so susceptible to the local inhibitory effects of DBS; both sites have been employed in trials of DBS in schizophrenia. Based on other lines of reasoning, the ventral tegmental area, the substantia nigra pars reticulata and the habenula have also been proposed and in some cases employed. The dorsolateral prefrontal cortex has not been suggested, probably reflecting evidence that it is underactive rather than overactive in schizophrenia. The hippocampus is also of theoretical interest but there is no clear functional imaging evidence that it shows overactivity in schizophrenia. On current evidence, the nucleus accumbens may represent the strongest candidate for DBS electrode placement in schizophrenia, with the substantia nigra pars reticulata also showing promise in a single case report; the ventral tegmental area is also of potential interest, though it remains untried.

Over the past 15 years, deep brain stimulation (DBS) has been actively investigated as a groundbreaking therapy for patients with treatment-resistant depression (TRD); nevertheless, outcomes have varied from patient to patient, with an average response rate of ∼50%. The engagement of specific fiber tracts at the stimulation site has been hypothesized to be an important factor in determining outcomes, however, the resulting individual network effects at the whole-brain scale remain largely unknown. Here we provide a computational framework that can explore each individual's brain response characteristics elicited by selective stimulation of fiber tracts. We use a novel personalized in-silico approach, the Virtual Big Brain, which makes use of high-resolution virtual brain models at a mm-scale and explicitly reconstructs more than 100 000 fiber tracts for each individual. Each fiber tract is active and can be selectively stimulated. Simulation results demonstrate distinct stimulus-induced event-related potentials as a function of stimulation location, parametrized by the contact positions of the electrodes implanted in each patient, even though validation against empirical patient data reveals some limitations (i.e., the need for individual parameter adjustment, and differential accuracy across stimulation locations). This study provides evidence for the capacity of personalized high-resolution virtual brain models to investigate individual network effects in DBS for patients with TRD and opens up novel avenues in the personalized optimization of brain stimulation.

The differences in brain activity between patients with major depressive disorder (MDD) and healthy adults have been confirmed by functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG). The prefrontal lobe and posterior cingulate cortex (PCC) are related to emotional regulation in patients with MDD. However, the high cost and poor time resolution of fMRI and PET limit their clinical application. Recently, researchers have used high time resolution of standardized weighted low-resolution electromagnetic tomography (swLORETA) to investigate deep brain activity. This study aimed to convert raw EEG signals into swLORETA images and explore deep brain activity in patients with MDD and healthy adults.

BrainMaster EEG equipment with a 19-channel EEG cap was used to collect resting EEG data with eyes closed for 5 min. NeuroGuide software was used to remove the EEG artifacts, and the swLORETA software was used to analyze 12,700 voxels of current source density (CSD) for 139 patients with MDD and co-morbid anxiety symptoms (mean age = 43.08, SD = 13.76; 28.78% were male) and 134 healthy adults (mean age = 40.60, SD = 13.52; 34.33% were male). Deep brain activity in the frontal lobe and PCC at different frequency bands was analyzed, including delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), beta (12-24 Hz), beta1 (12-14 Hz), beta2 (15-17 Hz), beta3 (18-24 Hz), and high beta (25-29 Hz).

There was lower delta and theta and higher beta, beta1, beta2, beta3, and high-beta activity at the prefrontal lobe (dorsal medial prefrontal cortex [dmPFC], ventral medial prefrontal cortex [vmPFC], and dorsal lateral prefrontal cortex [dlPFC], ventral lateral prefrontal cortex [vlPFC], orbital frontal cortex [OFC]) and PCC in MDD patients compared with healthy adults. There was no significant difference in alpha activity between the two groups.

This study indicates brain hyperactivity in the right prefrontal lobe (dlPFC and vmPFC) and PCC in patients with MDD with co-morbid anxiety symptoms, and the dlPFC and PCC were also related to emotion regulation in MDD. Inhibiting high-beta activity or restoring delta and theta activity to the normal range in the right frontal lobe and PCC may be possible in z-score neurofeedback protocols for patients with MDD in future studies.

Escitalopram is a selective serotonin reuptake inhibitor (SSRIs) antidepressant, drug that is currently used as first-line agents for the treatment of depression and it is also used in the treatment of other psychiatric disorders. The main goal of this study was to identify which brain areas are affected by escitalopram administration. This study was carried out on male Wistar rats that received escitalopram daily over 14 days and that were studied by 2-deoxy-2[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG)-PET on the last day of treatment. Computed tomography (CT) images were acquired immediately before each PET scan and the main effects of drug administration were elucidated by Statistical Parametric Mapping. The results obtained indicated that repeated exposure to escitalopram increased metabolic activity in the retrosplenial and posterior cingulate cortices, while it decreased such activity in the ventral hippocampus, cerebellum, brainstem and midbrain regions, including the raphe nuclei and ventral tegmental area. Therefore, repeated exposure to escitalopram alters the activity of several brain areas closely related to the serotonergic system, and previously identified as key regions in the antidepressant effect induced by SSRIs. Furthermore, some of the changes found, such as the dampened metabolism in the ventral tegmental area, are similar to changes that have been described after treating with other fast-acting antidepressant approaches.

Major depressive disorder (MDD) and anxiety disorders (ANX) share core symptoms such as negative affect and often co-exist. Magnetic-resonance imaging (MRI) research suggests shared neuroanatomical/neurofunctional underpinnings. So far, studies considering transdiagnostic and disorder-specific neural alterations in MDD and ANX as well as the comorbid condition (COM) have not been reviewed systematically.

Following PRISMA guidelines, the literature was screened and N = 247 articles were checked according to the PICOS criteria: MRI studies investigating transdiagnostic (across MDD, ANX, COM compared to healthy controls) and/or disorder-specific (between MDD, ANX, COM) neural alterations. N = 35, thereof n = 13 structural MRI and diffusion-tensor imaging studies and n = 22 functional MRI studies investigating emotional, cognitive deficits and resting state were included and quality coded.

Results indicated transdiagnostic structural/functional alterations in the orbitofrontal cortex/middle frontal cortex and in limbic regions (amygdala, cingulum, hippocampus). Few and inconsistent disorder-specific alterations were reported. However, depression-specific functional alterations were reported for the inferior frontal gyrus and dorsolateral prefrontal cortex during emotional tasks, and limbic regions at rest. Preliminary results for anxiety-specific functional alterations were found in the insula and frontal regions during emotional tasks, in the inferior parietal lobule, superior frontal gyrus and superior temporal gyrus during cognitive tasks, and (para)limbic alterations at rest.

This review provides evidence to support existing transdiagnostic fronto-limbic neural models in MDD and ANX. On top, it expands existing knowledge taking into account comorbidity and comparing MDD with ANX. Heterogeneous evidence exists for disorder-specific alterations. Research focusing on ANX sub-types, and the consideration of COM would contribute to a better understanding of basic neural underpinnings.

The Zn²⁺ receptor GPR39 is proposed to be involved in the pathophysiology of depression. GPR39 knockout (KO) animals show depressive- and anxiety-like behaviour, and resistance to conventional monoamine-based antidepressants. However, it is unclear as to which brain regions are involved in the pro-depressive phenotype of GPR39KO mice and the resistance to monoamine-targeting antidepressant treatment. Our current study confirmed previous results, showing that mice lacking GPR39 display enhanced passive coping-like behaviour compared with their wild-type controls. Furthermore, this study shows for the first time that GPR39KO displayed aberrant challenge-induced neuronal activity in key brain regions associated with passive coping behaviour. Imipramine induced only a marginal reduction in the enhanced passive coping behaviour in GPR39KO mice, which was associated with attenuation of the hyperactive prefrontal cortex. Similarly, the aberrant activity within the amygdalar subregions was normalized following imipramine treatment in the GPR39KO mice, indicating that imipramine mediates these effects independently of GPR39 in the prefrontal cortex and amygdala. However, imipramine failed to modulate the aberrant brain activity in other brain regions, such as the anterior CA3 and the dentate gyrus, in GPR39KO mice. Normalization of aberrant activity in these areas has been shown previously to accompany successful behavioural effects of antidepressants. Taken together, our data suggest that monoamine-based antidepressants such as imipramine exert their action via GPR39-dependent and -independent pathways. Failure to modulate passive-coping related aberrant activity in important brain areas of the depression circuitry is proposed to mediate/contribute to the greatly reduced antidepressant action of monoamine-based antidepressants in GPR39KO mice.

Subclinical depression (ScD) is a prevalent condition associated with relatively mild depressive states, and it poses a high risk of developing into major depressive disorder (MDD). However, the neural pathology of ScD is still largely unknown. Identifying the spontaneous neural activity involved in ScD may help clarify risk factors for MDD and explore treatment strategies for mild stages of depression.

A total of 34 ScD subjects and 40 age-, sex-, and education-matched healthy controls were screened from 1105 college students. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of resting-state fMRI were calculated to reveal neural activity. Strict statistical strategies, including Gaussian random field (GRF), false discovery rate (FDR), and permutation test (PT) with threshold-free cluster enhancement (TFCE), were conducted. Based on the altered ALFF and ReHo, resting-state functional connectivity (RSFC) was further analyzed using a seed-based approach.

The right precuneus and left middle frontal gyrus (MFG) both showed significantly increased ALFF and ReHo in ScD subjects. Moreover, the left hippocampus and superior frontal gyrus (SFG) showed decreased ALFF and increased ReHo, respectively. In addition, ScD subjects showed increased RSFC between MFG and hippocampus compared to healthy controls, and significant positive correlation was found between the Beck Depression Inventory-II (BDI-II) score and RSFC from MFG to hippocampus in ScD group.

Spontaneous neural activities in the right precuneus, left MFG, SFG, and hippocampus were altered in ScD subjects. Functional alterations in these dorsolateral prefrontal cortex and default mode network regions are largely related to abnormal emotional processing in ScD, and indicate strong associations with brain impairments in MDD, which provide insight into potential pathophysiology mechanisms of subclinical depression.

The spatial functional chronnectome is an innovative mathematical model designed to capture dynamic features in the organization of brain function derived from resting-state functional magnetic resonance imaging (rs-fMRI) data. Measurements of dynamic functional connectivity (dFC) have been developed from this model to quantify the brain dynamical self-reconfigurations at different spatial and temporal scales. This study examined whether two spatiotemporal dFC quantifications were linked to late adolescence-onset major depressive disorder (AO-MDD), and scaled with depression and symptom severity measured with the Montgomery-Asberg depression rating scale (MADRS) Methods: Thirty-five AO-MDD patients (21±6y) and fifty-three age- and gender-matched healthy young participants (20±3y) underwent 3T MRI structural and rs-fMRI acquisitions. The chronnectome here comprised seven individualized functional networks portrayed along 132 temporal overlapping windows, each framing 110s of resting brain activity Results: Based on voxelwise analyses, AO-MDD patients demonstrated significantly reduced temporal variability within the bilateral prefrontal cortex in five functional networks including the limbic network, the default-mode network (DMN) and frontoparietal network (FPN). Furthermore, the limbic network appeared to be particularly involved in this sample, and was associated with MADRS scores, and its progressive dynamic inflexibility was linked to sadness. DMN and FPN dynamics scaled with negative thoughts and neurovegetative symptoms, respectively Conclusions: This triple-network imbalance could delay spatiotemporal integration, while across-subject symptom variability would be network-specific. Therefore, the present approach supports that brain network dynamics underlie patients' symptom heterogeneity in AO-MDD.

Repurposing ketamine in the therapy of depression could well represent a breakthrough in understanding the etiology of depression. Ketamine was originally used as an anesthetic drug and later its use was extended to other therapeutic applications such as analgesia and the treatment of addiction. At the same time, the abuse of ketamine as a recreational drug has generated a concern for its psychotropic and potential long-term effects; nevertheless, its use as a fast acting antidepressant in treatment-resistant patients has boosted the interest in the mechanism of action both in psychiatry and in the wider area of neuroscience. This article provides a comprehensive overview of the actions of ketamine and intends to cover: (i) the evaluation of its clinical use in the treatment of depression and suicidal behavior; (ii) the potential use of ketamine in pediatrics; (iii) a description of its mechanism of action; (iv) the involvement of specific brain areas in producing antidepressant effects; (v) the potential interaction of ketamine with the hypothalamic-pituitary-adrenal axis; (vi) the effect of ketamine on neuronal transmission in the bed nucleus of stria terminalis and on its output; (vii) the evaluation of any gender-dependent effects of ketamine; (viii) the interaction of ketamine with the inflammatory processes involved in depression; (ix) the evaluation of the effects observed with single or repeated administration; (x) a description of any adverse or cognitive effects and its abuse potential. Finally, this review attempts to assess whether ketamine's use in depression can improve our knowledge of the etiopathology of depression and whether its therapeutic effect can be considered an actual cure for depression rather than a therapy merely aimed to control the symptoms of depression.

Our previous study identified a significant association between a single nucleotide polymorphism (SNP) located in the neurogenin3 (NEUROG3) gene and post-stroke depression (PSD) in Chinese populations. The present work explores whether polymorphism rs144643855 affects regional brain activity and clinical phenotypes in major depressive disorder (MDD).

A total of 182 participants were included: 116 MDD patients and 66 normal controls. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning at baseline. Spontaneous brain activity was assessed using amplitude of low-frequency fluctuation (ALFF). The Hamilton Depression Scale-24 (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess participants at baseline. Two-way analysis of covariance (ANCOVA) was used to explore the interaction between diagnostic groups and NEUROG3 rs144643855 on regional brain activity. We performed correlation analysis to further test the association between these interactive brain regions and clinical manifestations of MDD.

Genotype and disease significantly interacted in the left inferior frontal gyrus (IFG-L), right superior frontal gyrus (SFG-R), and left paracentral lobule (PCL-L) (P < 0.05). ALFF values of the IFG-L were found to be significantly associated with anhedonia in MDD patients.

These findings suggest a potential relationship between rs144643855 variations and altered frontal brain activity in MDD. NEUROG3 may play an important role in the neuropathophysiology of MDD.