The association between duration of breastfeeding and the trajectory of brain development from childhood to young adulthood: an 8-year longitudinal study.

Breastfeeding has been associated with several short- and long-term health benefits, including positive cognitive and behavioral outcomes. However, the impact of breastfeeding on structural brain development over time remains unclear. We aimed to assess the association between breastfeeding duration in childhood and the developmental trajectory of overall cortical thickness, cortical area, and total intracranial volume during the transition from childhood to early adulthood. Participants included 670 children and adolescents with 1326 MRI scans acquired over 8 years from the Brazilian High-Risk Cohort for Mental Conditions (BHRCS). Breastfeeding was assessed using a questionnaire answered by the parents. Brain measures were estimated using MRI T1-weighted images at three time points, with 3-year intervals. Data were evaluated using generalized additive models adjusted for multiple confounders. We found that a longer breastfeeding duration was directly associated with higher global cortical thickness in the left (edf = 1.0, F = 6.07, p = 0.01) and right (edf = 1.0, F = 4.70, p = 0.03) hemispheres. For the total intracranial volume, we found an interaction between duration of breastfeeding and developmental stage (edf = 1.0, F = 6.81, p = 0.009). No association was found between breastfeeding duration and brain area. Our study suggests that the duration of breastfeeding impacts overall cortical thickness and the development of total brain volume, but not area. This study adds to the evidence on the potential impact of breastfeeding on brain development and provides relevant insights into the mechanisms by which breastfeeding might confer cognitive and mental health benefits.

Long-term stability of the cortical volumetric profile and the functional human connectome throughout childhood and adolescence.

There is compelling evidence showing that between-subject variability in several functional and structural brain features is sufficient for unique identification in adults. However, individuation of brain functional connectomes depends on the stabilization of neurodevelopmental processes during childhood and adolescence. Here, we aimed to (1) evaluate the intra-subject functional connectome stability over time for the whole brain and for large scale functional networks and (2) determine the long-term identification accuracy or 'fingerprinting' for the cortical volumetric profile and the functional connectome. For these purposes, we analysed a longitudinal cohort of 239 children and adolescents scanned in two sessions with an interval of approximately 3 years (age range 6-15 years at baseline and 9-18 years at follow-up). Corroborating previous results using short between-scan intervals in children and adolescents, we observed a moderate identification accuracy (38%) for the whole functional profile. In contrast, identification accuracy using cortical volumetric profile was 95%. Among the large-scale networks, the default-mode (26.8%), the frontoparietal (23.4%) and the dorsal-attention (27.6%) networks were the most discriminative. Our results provide further evidence for a protracted development of specific individual structural and functional connectivity profiles.

Repeated subcutaneous esketamine administration for depressive symptoms and pain relief in a terminally ill cancer patient: A case report.

BACKGROUND: Depressive disorders are common among cancer patients. Ketamine can quickly relieve depression, and its subcutaneous administration appears to be as effective as and probably safer than its standard intravenous administration. Herein, we report a case verifying the antidepressant effect of a subcutaneous esketamine formulation. CASE PRESENTATION: A 65-year-old male with metastatic abdominal tumor reported sadness, weight loss, fatigue, hopelessness, insomnia, inattention, and reduced motivation. His scores on the visual analogical scale for pain and Montgomery-Asberg depression rating scale were 8/10 and 30/60, respectively. POSSIBLE COURSES OF ACTION: Monoaminergic antidepressants are effective, but their response is slow for end-of-life care. FORMULATION OF A PLAN: Esketamine was preferred because it possibly contributes to pain relief. It can repeatedly be infused intravenously, but was subcutaneously administered twice a week for safety reasons. OUTCOME: The patient showed continuous mood improvement, achieving depression remission on day 7. Pain relief was observed but without stability. His vital signs remained stable, and he remained calm, without major complaints. LESSONS FROM THE CASE: Repeated subcutaneous esketamine injections are possibly safe and effective in pain and depression relief in palliative care cancer patients. VIEW ON RESEARCH PROBLEMS, OBJECTIVES, OR QUESTIONS GENERATED BY THE CASE: Placebo-controlled studies with similar cases are needed to establish efficacy and safety.

Effects of a brief psychotherapeutic intervention on resilience and behavior in patients with drug-resistant mesial temporal lobe epilepsy and late seizure recurrence after surgery.

Seizure recurrence (SR) after epilepsy surgery in patients with medically resistant temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS) can compromise medical treatment and quality of life (QOL). However, there is a scarcity of interventions specifically addressing this issue in the literature. We aimed to evaluate the impact of a four-week psychotherapeutic intervention on the levels of resilience, behavioral symptoms, and QOL of patients with drug-resistant TLE-MTS who underwent corticoamygdalohippocampectomy (CAH) and who presented with late SR. Fifty patients who had been diagnosed with TLE-TMS, undergone CAH, and presented with late SR were included. The study instruments included a clinical and sociodemographic questionnaire and the Brazilian versions of the Connor-Davidson Resilience Scale (CD-RISC-10), the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), the Interictal Dysphoric Disorder Inventory (IDDI), and the Quality of Life in Epilepsy Inventory (QOLIE-31). Significant reductions in the IDDI (p < 0.001) and NDDI-E (p < 0.001) scores, improvements in the CD-RISC-10 (p < 0.001) and QOLIE-31 (p < 0.001) scores, and positive correlations between resilience levels and QOL (p < 0.01), as well as a negative correlation between depressive symptoms and resilience (p < 0.01) and QOL (p < 0.01), were observed after the psychotherapeutic intervention. Improvements in the resilience levels and QOL, with concomitant reductions in depressive symptoms, were observed in patients with TLE-MTS and late SR after a brief psychotherapeutic intervention. Since there is a lack of studies that measured the impact of interventions in this patient subpopulation, these results may support the development of treatment strategies for this specific group.

Associations between children's family environment, spontaneous brain oscillations, and emotional and behavioral problems.

The family environment in childhood has a strong effect on mental health outcomes throughout life. This effect is thought to depend at least in part on modifications of neurodevelopment trajectories. In this exploratory study, we sought to investigate whether a feasible resting-state fMRI metric of local spontaneous oscillatory neural activity, the fractional amplitude of low-frequency fluctuations (fALFF), is associated with the levels of children's family coherence and conflict. Moreover, we sought to further explore whether spontaneous activity in the brain areas influenced by family environment would also be associated with a mental health outcome, namely the incidence of behavioral and emotional problems. Resting-state fMRI data from 655 children and adolescents (6-15 years old) were examined. The quality of the family environment was found to be positively correlated with fALFF in the left temporal pole and negatively correlated with fALFF in the right orbitofrontal cortex. Remarkably, increased fALFF in the temporal pole was associated with a lower incidence of behavioral and emotional problems, whereas increased fALFF in the orbitofrontal cortex was correlated with a higher incidence.

Default mode network maturation and psychopathology in children and adolescents.

BACKGROUND: The human default mode (DMN) is involved in a wide array of mental disorders. Current knowledge suggests that mental health disorders may reflect deviant trajectories of brain maturation. METHOD: We studied 654 children using functional magnetic resonance imaging (fMRI) scans under a resting-state protocol. A machine-learning method was used to obtain age predictions of children based on the average coefficient of fractional amplitude of low frequency fluctuations (fALFFs) of the DMN, a measure of spontaneous local activity. The chronological ages of the children and fALFF measures from regions of this network, the response and predictor variables were considered respectively in a Gaussian Process Regression. Subsequently, we computed a network maturation status index for each subject (actual age minus predicted). We then evaluated the association between this maturation index and psychopathology scores on the Child Behavior Checklist (CBCL). RESULTS: Our hypothesis was that the maturation status of the DMN would be negatively associated with psychopathology. Consistent with previous studies, fALFF significantly predicted the age of participants (p < .001). Furthermore, as expected, we found an association between the DMN maturation status (precocious vs. delayed) and general psychopathology scores (p = .011). CONCLUSIONS: Our findings suggest that child psychopathology seems to be associated with delayed maturation of the DMN. This delay in the neurodevelopmental trajectory may offer interesting insights into the pathophysiology of mental health disorders.

The effectiveness of acupuncture as a treatment for tinnitus: a randomized controlled trial using (99m)Tc-ECD SPECT.

OBJECTIVE: Investigate the effect of acupuncture on brain perfusion using ethyl cysteinate dimer single-photon emission computed tomography ((99m)Tc-ECD SPECT) in patients with tinnitus. METHODS: This randomized, single-blind, sham-control study examined patients (18-60 years old) with normal hearing and chronic, idiopathic, continuous tinnitus. Fifty-seven subjects were randomly assigned to true (n = 30) or sham (n = 27) acupuncture (ACP); (99m)Tc-ECD SPECT examinations were performed before and after 12 twice-weekly ACP sessions. Secondary outcomes included changes in the Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), Hamilton Anxiety Scale (HAS) and Beck Depression Inventory (BDI). Imaging data were analysed using Statistical Parametric Mapping (SPM8) software. Regression models were used to examine secondary outcomes via two paradigms: intention-to-treat (ITT; where multiple imputations were conducted because of study attrition) and complete cases. RESULTS: No between-group brain perfusion differences were observed. However, a significant improvement in THI scores was observed at the end of true ACP treatment for all domains (all p values < 0.01) except the catastrophic scale. CONCLUSIONS: ACP might reduce the effects of tinnitus on daily life; however, additional studies should be conducted to verify the effects of ACP on the neural architecture and brain function of tinnitus patients. KEY POINTS: • Efficacy of acupuncture on brain perfusion and symptoms of tinnitus patients. • Acupuncture improved the Tinnitus Handicap Inventory scores in tinnitus patients. • No significant changes in brain perfusion were observed after 12 twice-weekly sessions. • Perfusion changes would reflect changes in neuronal function.

Decreased centrality of subcortical regions during the transition to adolescence: a functional connectivity study.

Investigations of brain maturation processes are a key step to understand the cognitive and emotional changes of adolescence. Although structural imaging findings have delineated clear brain developmental trajectories for typically developing individuals, less is known about the functional changes of this sensitive development period. Developmental changes, such as abstract thought, complex reasoning, and emotional and inhibitory control, have been associated with more prominent cortical control. The aim of this study is to assess brain networks connectivity changes in a large sample of 7- to 15-year-old subjects, testing the hypothesis that cortical regions will present an increasing relevance in commanding the global network. Functional magnetic resonance imaging (fMRI) data were collected in a sample of 447 typically developing children from a Brazilian community sample who were submitted to a resting state acquisition protocol. The fMRI data were used to build a functional weighted graph from which eigenvector centrality (EVC) was extracted. For each brain region (a node of the graph), the age-dependent effect on EVC was statistically tested and the developmental trajectories were estimated using polynomial functions. Our findings show that angular gyrus become more central during this maturation period, while the caudate; cerebellar tonsils, pyramis, thalamus; fusiform, parahippocampal and inferior semilunar lobe become less central. In conclusion, we report a novel finding of an increasing centrality of the angular gyrus during the transition to adolescence, with a decreasing centrality of many subcortical and cerebellar regions.

Temporal stability of network centrality in control and default mode networks: Specific associations with externalizing psychopathology in children and adolescents.

Abnormal connectivity patterns have frequently been reported as involved in pathological mental states. However, most studies focus on "static," stationary patterns of connectivity, which may miss crucial biological information. Recent methodological advances have allowed the investigation of dynamic functional connectivity patterns that describe non-stationary properties of brain networks. Here, we introduce a novel graphical measure of dynamic connectivity, called time-varying eigenvector centrality (tv-EVC). In a sample 655 children and adolescents (7-15 years old) from the Brazilian "High Risk Cohort Study for Psychiatric Disorders" who were imaged using resting-state fMRI, we used this measure to investigate age effects in the temporal in control and default-mode networks (CN/DMN). Using support vector regression, we propose a network maturation index based on the temporal stability of tv-EVC. Moreover, we investigated whether the network maturation is associated with the overall presence of behavioral and emotional problems with the Child Behavior Checklist. As hypothesized, we found that the tv-EVC at each node of CN/DMN become more stable with increasing age (P < 0.001 for all nodes). In addition, the maturity index for this particular network is indeed associated with general psychopathology in children assessed by the total score of Child Behavior Checklist (P = 0.027). Moreover, immaturity of the network was mainly correlated with externalizing behavior dimensions. Taken together, these results suggest that changes in functional network dynamics during neurodevelopment may provide unique insights regarding pathophysiology.

Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts.

Introduction/Objective. Evidence suggests that the prefrontal cortex has been implicated in the pathophysiology of bipolar disorder (BD), but few neurochemical studies have evaluated this region in bipolar patients and there is no information from BD suicide attempters using Proton Magnetic Resonance Spectroscopy (H(+)MRS). The objective was to evaluate the metabolic function of the medial orbital frontal cortex in euthymic BD type I suicide and nonsuicide attempters compared to healthy subjects by H(+)MRS. Methods. 40 euthymic bipolar I outpatients, 19 without and 21 with history of suicide attempt, and 22 healthy subjects were interviewed using the Structured Clinical Interview with the DSM-IV axis I, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Barratt Impulsiveness Scale-11 and underwent H(+)MRS. Results. We did not find any metabolic abnormality in medial orbital frontal regions of suicide and nonsuicide BD patients and BD patients as a group compared to healthy subjects. Conclusions. The combined chronic use of psychotropic drugs with neuroprotective or neurotrophic effects leading to a euthymic state for longer periods of time may improve neurometabolic function, at least measured by H(+)MRS, even in suicide attempters. Besides, these results may implicate mood dependent alterations in brain metabolic activity. However, more studies with larger sample sizes of this heterogeneous disorder are warranted to clarify these data.

Personality traits in juvenile myoclonic epilepsy: evidence of cortical abnormalities from a surface morphometry study.

Cluster B personality disorders (PD), characterized as emotional instability, immaturity, lack of discipline, and rapid mood changes, have been observed among patients with juvenile myoclonic epilepsy (JME) and have been associated with a worse seizure outcome. Proper understanding of the neurobiology of PD associated with JME could contribute to understanding the basis for earlier and more effective interventions. In the present study, volumetric and geometric features of cortical structure were assessed through an automated cortical surface reconstruction method aiming to verify possible structural cortical alterations among patients with JME. Twenty-two patients with JME with cluster B PD, 44 patients with JME without psychiatric disorders, and 23 healthy controls were submitted to a psychiatric evaluation through SCID I and SCID II and to an MRI scan. Significant cortical alterations in mesiofrontal and frontobasal regions, as well as in other limbic and paralimbic regions, were observed mainly in patients with JME with PD. The present study adds evidence to the hypothesis of frontal and limbic involvement in the pathophysiology of cluster B PD in JME, regions linked to mood and affective regulation, as well as to impulsivity and social behavior. Moreover, a multidimensional pattern of frontal, limbic, and paralimbic changes was observed through a method of structural analysis which offers different and simultaneous geometric features, allowing the elaboration of important pathophysiologic insights about cluster B PD in JME.

Hippocampal atrophy and memory dysfunction in patients with juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a well-defined idiopathic generalized epilepsy (IGE) syndrome, being the most common IGE in adults and accounting for 5-11% of patients with epilepsy. While neuropsychological and neuroimaging studies have discussed the thalamofrontal dysfunction as the major pathophysiologic mechanism of JME, investigation on memory is scarce in patients with JME, with lack of objective assessments addressing common complaints and daily difficulties such as recalling telephone numbers, messages to pass on, and taking antiepileptic drugs regularly. The aim of this study was to objectively assess memory deficits in a group of patients with JME using neuropsychological examination combined with structural MRI of the hippocampi. After informed consent, a cohort of 56 consecutive patients with JME (29 males; mean age ± SD = 26.5 ± 9.01 years; range = 14.0-55.0 years) was included. The control group consisted of 42 healthy volunteers (18 males; mean age ± SD = 31.0 ± 8.54 years; range=20.0-56.0 years) without a family history of neuropsychiatric disorders. Patients and controls were submitted to a MRI and to a neuropsychological assessment, and comparisons between groups were performed, as well as a correlation study between hippocampal atrophy and neuropsychological performance in a group of patients with JME. The level of statistical significance was set at p<0.05. Significant hippocampal atrophy among patients with JME was observed, which was correlated with memory dysfunctions. The present findings reinforce the existence of functional-anatomic ictogenic networks that are not limited to frontal lobes, providing further support towards the concept of 'system epilepsies' in JME.

Is there an association between cortical thickness, age of onset, and duration of illness in schizophrenia?

OBJECTIVE: Several studies have shown cortical volume loss in frontotemporal regions in schizophrenia patients, and it is known that these reductions may be associated with disease symptoms and cognitive deficits. The aim of this study was to investigate possible cortical thickness correlations in frontotemporal regions in relation to age at onset and duration of illness. METHODS: One hundred forty-eight schizophrenia patients (97 males; age and SD 36.30 ± 10.06) and 87 (57 males; age and SD 36.48 ± 10.10) age-matched healthy subjects underwent a brain MRI scan. Cortical segmentation and surface statistical analysis were performed using the FreeSurfer software package. Results were corrected for multiple comparisons using the Monte Carlo method considering a cluster-corrected Type I Error of 5%. RESULTS: Compared to controls, schizophrenia patients presented significant cortical thinning in the frontotemporal, parietal, and occipital cortices. No correlation between prefrontal cortex thickness and duration of illness in patients with schizophrenia or between frontotemporal cortical thickness and age at onset was found. However, a significant interaction between age and diagnosis was observed on frontal cortical thickness with patients presenting a thinner cortex than expected for age. CONCLUSION: Although there was no correlation between age of onset and duration of illness with brain volume, our findings suggest that there is an accelerated cortical loss in schizophrenia, thus reinforcing the progressive processes of the disease.

Efficacy and safety of ketamine for the treatment of depressive symptoms in palliative care: A systematic review.

OBJECTIVES: Ketamine has a fast onset of action that may offer a paradigm change for depression management at the end of life. We aimed to synthesize evidence regarding the safety and efficacy of ketamine in depression treatment within a broad palliative care concept. METHODS: We searched seven databases and included studies on the safety and efficacy of ketamine for depression treatment in patients diagnosed with any life-threatening disease. We also conducted a narrative review of the evidence. RESULTS: Among 2,252 screened titles and abstracts, we included 32 studies in our final synthesis: 14 case reports, two case series, two quasi-experimental studies, and seven randomized clinical trials (RCTs), as well as data from three unpublished clinical trials and seven cases from four larger case series. Most case reports reported a robust effect; however, the larger studies reported conflicting findings. Five RCTs reported positive outcomes; however, four of them were focused on a perioperative setting. Two negative studies did not primarily focus on depression and did not apply severity cutoffs. CONCLUSIONS: Although ketamine is generally safe and potentially useful, its efficacy in palliative care settings remains unclear. It may be a reasonable alternative for perioperative depression in oncological patients.

Generalizability of 3D CNN models for age estimation in diverse youth populations using structural MRI.

Recently, several studies have investigated the neurodevelopment of psychiatric disorders using brain data acquired via structural magnetic resonance imaging (sMRI). These analyses have shown the potential of sMRI data to provide a relatively precise characterization of brain structural biomarkers. Despite these advances, a relatively unexplored question is how reliable and consistent a model is when assessing subjects from other independent datasets. In this study, we investigate the performance and generalizability of the same model architecture trained from distinct datasets comprising youths in diverse stages of neurodevelopment and with different mental health conditions. We employed models with the same 3D convolutional neural network (CNN) architecture to assess autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), brain age, and a measure of dimensional psychopathology, the Child Behavior Checklist (CBCL) total score. The investigated datasets include the Autism Brain Imaging Data Exchange II (ABIDE-II, N = 580), Attention Deficit Hyperactivity Disorder (ADHD-200, N = 922), Brazilian High-Risk Cohort Study (BHRCS, N = 737), and Adolescent Brain Cognitive Development (ABCD, N = 11,031). Models' performance and interpretability were assessed within each dataset (for diagnosis tasks) and inter-datasets (for age estimation). Despite the demographic and phenotypic differences of the subjects, all models presented significant estimations for age (p value < 0.001) within and between datasets. In addition, most models showed a moderate to high correlation in age estimation. The results, including the models' brain regions of interest (ROI), were analyzed and discussed in light of the youth neurodevelopmental structural changes. Among other interesting discoveries, we found that less confounded training datasets produce models with higher generalization capacity.

Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample.

Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN. We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation.

The relationship between recent PTSD secondary to sexual assault, hippocampal volume and resting state functional connectivity in adolescent girls.

Objective: Improved understanding of the time course of neural changes associated with adolescent PTSD would elucidate the development of the disorder and could inform approaches to treatment. We compared hippocampal volumes and resting state functional connectivity (RSFC) in adolescent girls with post-traumatic stress disorder (PTSD) secondary to sexual assault, within six months of onset and age- and gender-matched, non-trauma exposed healthy controls (HCs) in São Paulo, Brazil. We also examined the relationship between pre- and post-treatment PTSD symptoms and RSFC. Method: We collected brain structure, RSFC, and PTSD symptoms in 30 adolescents with PTSD (mean age: 15.7 ± 1.04 years) and 21 HCs (mean age: 16.2 ± 1.21 years) at baseline. We collected repeated measures in 21 participants with PTSD following treatment; 9 participants dropped out. Hippocampal volume and RSFC from hippocampal and default mode network (DMN) seeds were compared between participants with PTSD and HCs. We examined associations between within-subject changes in RSFC and PTSD symptoms following treatment. Results: No hippocampal volumetric differences between groups were found. Compared to HCs, adolescents with recent PTSD had reduced RSFC between hippocampus and the lateral parietal node of the DMN, encompassing the angular gyrus, peak coordinates: -38, -54, 16; 116 voxels; peak F 1,47 = 31.76; FDR corrected p = 0.038. Improvements in PTSD symptoms were associated with increased RSFC between hippocampus and part of the lateral parietal node of the DMN, peak coordinates: -38, -84, 38; 316 voxels; peak F 1,47 = 40.28; FDR corrected p < 0.001. Conclusion: Adolescents with recent PTSD had reduced hippocampal-DMN RSFC, while no group differences in hippocampal volume were found, suggesting that hippocampal function, but not structure, is altered early in the course of PSTD. Following treatment, hippocampal-DMN RSFC increased with symptom improvement and may indicate an important neural mechanism related to successful PTSD treatment.

A pioneering FreeSurfer volumetric study of a series of patients with mesial temporal lobe epilepsy and hippocampal sclerosis with comorbid depression.

Depression is the most frequent psychiatric comorbidity in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). This study aimed to confirm whether patients with comorbid depression have different volumetric patterns on magnetic resonance imaging, analysing the influence of HS sides. Psychiatrists conducted semi-structured interviews with 75 patients, who were divided into non-depression group (NDG, n = 52) and depression group (DG, n = 23), and compared with 98 controls. The FreeSurfer software was used in the volumetric analysis of the estimated total intracranial volume (eTIV), bilateral cortical and subcortical regions of interest (ROIs), and for presence of left (L-, n = 41) or right (R-, n = 34) MTLE-HS. Twenty-three (30.7%) patients had depression, of whom 14 (34.1%) had l-MTLE-HS and 9 (26.5%) had R-MTLE-HS. No difference was observed between DG and NDG vs. controls in terms of eTIV and cortical ROIs, regardless of the severity of depression. In patients with l-MTLE-HS, the eTIV in the DG was reduced in comparison with that in the NDG and control group, with a small effect size. Hippocampal reduction occurred ipsilateral to HS in the l-MTLE-HS and R-MTLE-HS subgroups when DG and NDG were compared with controls, as expected according to Enhancing Neuro Imaging Genetics through Meta-Analysis (2018).

Obsessive-Compulsive Symptoms, Polygenic Risk Score, and Thalamic Development in Children From the Brazilian High-Risk Cohort for Mental Conditions (BHRCS).

Background: Thalamic volume measures have been linked to obsessive-compulsive disorder (OCD) in children and adolescents. However, it is unclear if alterations in thalamic volumes occur before or after symptom onset and if there is a relation to the presence of sub-clinical obsessive-compulsive symptoms (OCS). Here, we explore the relationship between OCS and the rate of thalamic volume change in a cohort of children and youth at high risk to develop a mental disorder. A secondary aim was to determine if there is a relationship between OCS and the individual's OCD polygenic risk score (OCD-PRS) and between the rate of thalamic volume change and the OCD-PRS. Methods: The sample included 378 children enrolled in the longitudinal Brazilian High-Risk Cohort for Mental Conditions. Participants were assessed for OCS and the symmetrized percent change (SPC) of thalamic volume across two time-points separated by 3 years, along with the OCD-PRS. Zero-altered negative binomial models were used to analyze the relationship between OCS and thalamic SPC. Multiple linear regressions were used to examine the relationship between thalamic SPC and OCD-PRS. Results: A significant relationship between OCS and the right thalamus SPC (p = 0.042) was found. There was no significant relationship between changes in thalamic volume SPC and OCD-PRS. Conclusions: The findings suggest that changes in the right thalamic volume over the course of 3 years in children may be associated to OCS. Future studies are needed to confirm these results and further characterize the specific nature of OCS symptoms associated with thalamic volumes.

The probability of response after each subcutaneous injection of esketamine in treatment-resistant depression.

INTRODUCTION: The administration of multiple esketamine doses has shown efficacy for unipolar and bipolar treatment-resistant depression (TRD). Nevertheless, the probability of responding or not after each dose in the real-world remains unknown. This study aimed to estimate it throughout four doses of esketamine, administrated via subcutaneous (SC). MATERIAL AND METHODS: We conducted a retrospective analysis of a case series of 70 patients with TRD who received treatment from the esketamine assistance program at Federal University of Sao Paulo, between April 2017 and December 2018. The SC injections were administrated weekly at a dose of 0.5-1.0mg/kg, in conjunction with patients' psychotropic drugs. Response was defined as a decrease of at least 50% in the Montgomery-Åsberg Depression Rating Scale between baseline and 24h after dose. We used hidden Markov modeling in order to estimate de probability of response after each esketamine injection. RESULTS: The probability of a patient that was a "non-responder" to become a "responder" following a SC injection of esketamine was 17.30% and the probability that this patient remains a "non-responder" was 82.70%. The probability of a patient that was a "responder" to remain as a "responder" was 95%. CONCLUSIONS: Patients with TRD who had not responded after the first dose of esketamine, still had a chance of responding after the subsequent dose administrated via SC.