Jorge Julio González Olvera

Cocaine use disorder (CUD) presents high comorbidity with mood symptoms that impair recovery processes and facilitate relapses. Peripheral brain-derived neurotrophic factor (BDNF) is negatively correlated with mood symptoms in depressive disorders. However, whether a correlation exists between BDNF and mood in CUD is still unknown. Thus, in this cross-sectional study, we explored the potential relationship between peripheral BDNF levels and depression and anxiety symptoms in CUD. Serum peripheral BDNF was determined by the ELISA method. Standardized Hamilton Depression (HDRS) and Anxiety (HARS) inventories were administered. Twenty-nine seeking-treatment CUD participants under stable medication (female = 3) were enrolled. According to the mood severity, 34.48% of participants were classified as normal, 24.14% as moderate, and 41.38% as severe symptoms (p < 0.001). Peripheral BDNF was similar between the different mood severity groups (p > 0.05). No correlation between BDNF and HDRS and BDNF and HARS was detected regardless of the severity of mood symptoms (p > 0.05). Different from what has been observed in depressive disorders, independence between peripheral BDNF levels and mood symptoms in CUD was observed. This finding suggests a singular, intricate regulation of peripheral BDNF and mood as part of CUD-related maladaptations that might disrupt the expected antidepressant response and perpetuate mood symptoms in CUD.

In amnestic mild cognitive impairment (aMCI), neuroinflammation evolves during disease progression, affecting microglial function and potentially accelerating the pathological process. Currently, no effective treatment exists, leading to explorations of various symptomatic approaches, though few target the underlying physiological mechanisms. Modulating inflammatory processes may be critical in slowing disease progression. Cognitive stimulation (CS) and transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (l-DLPFC) show promise, but the results are heterogeneous. Thus, a randomized, double-blind, placebo-controlled clinical trial is currently underway. The first-stage results were examined after three weeks of intervention in two groups: active tDCS combined with CS and sham tDCS combined with CS. Twenty-two participants underwent two assessments: T0 (baseline) and T1 (after 15 sessions of tDCS, active or sham, and 9 sessions of CS). The results demonstrated that CS improved cognition, increased brain-derived neurotrophic factor (BDNF) levels, and reduced peripheral proinflammatory cytokine levels (interleukin IL-6 and chemokine CX3CL1) in serum. This decrease in IL-6 may promote microglial proliferation and survival as a modulatory effect response, while the increase in BDNF might suggest a regulatory mechanism in microglia–neuron interaction responses. However, tDCS did not enhance the cognitive or modulatory effects of CS, suggesting that longer interventions might be required to achieve substantial benefits.

Background. Abuse in early life stages has been proposed as an etiological risk factor for developing menstrually-related mood disorders (MRMDs). Objetive. To evaluate whether there is a relation between the occurrence of physical and/or sexual violence in childhood and/or adolescence and the development of MRMDs in adulthood. Method. A systematic search was conducted in PubMed, Web of Science, and ScienceDirect, with the route (“Premenstrual Syndrome”[Mesh]) OR (“Premenstrual Dysphoric Disorder”[MeSH]) AND (“Violence”[Mesh]) / (“menstrually-related mood disorders” AND “abuse”). Fifty-four articles were initially reviewed and 32 were excluded based on the criteria. Twenty-two articles were thoroughly reviewed. Finally, five articles (publication years 2014, 2013, 2012, 2007, and 2003) were included in the systematic review and submitted to a meta-analysis. Results. Results indicate that having been exposed to physical and/or sexual violence in childhood and/or adolescence increases 1.99 times the risk of experiencing MRMDs in adulthood in comparison with women who did not experience that type of violence (odds ratio [OR] = 1.99; 95% confidence interval [1.58, 2.51]). Discussion and conclusion. The present work provides evidence that a woman who experienced violence through physical and/or sexual abuse during childhood and/or adolescence has a greater risk of developing MRMDs in adulthood.

BACKGROUND: Cocaine use disorder (CUD) is a global condition lacking effective treatment. Repeated magnetic transcranial stimulation (rTMS) may reduce craving and frequency of cocaine use, but little is known about its efficacy and neural effects. METHODS: Using a double-blind placebo-controlled randomized clinical trial (RCT) [ NCT02986438 ], we sought to elucidate short- and long-term clinical benefits of 5-Hz rTMS as an add-on to standard treatment in CUD patients and discern underlying functional connectivity effects using magnetic resonance imaging. Forty-four randomly assigned CUD patients completed the 2-week double-blind acute phase [Sham (n=20, 2f/18m) and Active (n=24, 4f/20m)], in which they received 2 daily sessions of rTMS (5,000 pulses) on the left dorsolateral prefrontal cortex. Subsequently, n=20 CUD patients continued to open-label maintenance (2 weekly sessions for up to 6 months). Measures were acquired at baseline, 2 weeks, 3 months and 6 months. RESULTS: Overall, 5-Hz rTMS plus standard treatment for 2 weeks significantly reduced craving and impulsivity in the Active group; decreased impulsivity correlated with improvements in functional connectivity in executive control and default mode networks. Clinical and functional connectivity effects were maintained for 3 months but they dissipated by 6 months. We did not observe reduction of positive cocaine urine tests, however, self-reported frequency and grams consumed for 6 months were reduced. CONCLUSIONS: With this RCT we show that 5-Hz rTMS has potential promise as an adjunctive treatment for CUD and merits further research.

Introduction. Inhalant use disorder has increased in spite of its adverse medical consequences. Due to the inherent difficulties of working with this population, so far there has been no quantifiable clinical evidence of the cognitive characteristics of inhalants users in early withdrawal and the clinic effect of consumption time. Objective. To evaluate the clinical and cognitive performance of inhalant users and the clinic effects of consumption time. Method. A cross-sectional study in which 28 adult users of inhalants were included, divided in two groups according to their consumption time: less than or greater than seven years. They were all evaluated in terms of clinical and neuropsychological values. Results. Consumers of inhalant showed presence of craving (M = 479.14, .5D = 213.51), altered frontal behavior before (M = 119.18, SD = 29.53) and now (M = 130, SD = 33.03), sleeping problems (M = 8.93, SD = 3.4), and cognitive difficulties (inhibitory control, planning, decision-making, working memory, verbal fluency, and cognitive flexibility); all these tasks were statistically significant (p = < .05). Discussion and conclusion. Executive functioning is impaired with inhalant use disorder; these alterations increase with withdrawal and craving and changes remain independent from the use time.

Introduction. Currently, misuse inhalants is increasing: addictive potential has been demonstrated in several studies. Until now there was no quantifiable clinical evidence of behavioral characteristics inhalant users. Main objective was to evaluate craving, impulsivity, frontalized behaviors and recognition of emotions in young inhalant users. Method. Eleven male, aged 15-22 years (17.73 +/- 2.14), schooling 3-12 years (8.18 +/- 2.56) were evaluated. Results. Evaluation showed that inhalant users exhibit signs of craving, high ranges of impulsivity, frontal behavioral deficits and difficulties detection of emotional expressions. Conclusions. In inhalants addiction, symptoms of craving and behavioral alterations are exhibited, time use increases frontal behaviors.

Borderline personality disorder (BPD) is a chronic condition characterized by high levels of impulsivity, affective instability, and difficulty to establish and manage interpersonal relationships. This paper assessed differences in performance on social cognitive paradigms (MASC, RMTE) and how it related to child abuse. Specifically, it evaluated the relationship between performance on cognitive paradigms and baseline brain connectivity in patients with BPD, compared to healthy controls. BPD patients had higher levels of childhood maltreatment, increased impulsivity and aggression, and more dissociative symptoms than control subjects. For the sexual abuse subdimension, there were no differences between the BPD and the control groups, but there was a negative correlation between MASC scores and total childhood maltreatment levels, as well as between physical abuse, physical negligence, and MASC. Both groups showed that the higher the level of childhood maltreatment, the lower the performance on the MASC social cognitive test. Further, in the BPD group, there was hypoconnectivity between the structures responsible for emotion regulation and social cognitive responses that have been described as part of the frontolimbic circuitry. The more serious the child abuse, the lower the connectivity.

Substance addiction is regarded as an important public health problem, perpetuated by fronto-striatal circuit pathology. A usual finding in neuroimaging human and murine studies is cortical thinning and lower volume when compared to healthy controls. In this study we wished to replicate cortical thinning findings and find if striatum morphology may explain the cortical pathology. For this we analyzed T1w neuroimaging data from an ongoing addiction Mexican dataset. This dataset includes cocaine addicts diagnosed by expert psychiatrists and healthy controls. For the analysis we used voxel-based morphometry, cortical thickness and volumetric analysis of the basal ganglia, and we correlated striatum volume with cortical thickness to find pathological patterns. Our group contrast showed cortical thinning and striatum volume differences in cocaine addicts correlated to their years of substance use, craving and age. Our correlation between striatum-cortex morphology showed higher significant correlations in healthy controls, not observed in cocaine addicts. The correlation between striatum volume and cortical thickness in healthy controls involved similar areas as those shown with less cortical thickness in cocaine addicts. We suggest that striatum morphological changes in addiction may explain the pattern of cortical thinning observed across several substances addiction studies. Research Data Related to this Submission: Data set https://zenodo.org/record/1409808#.W5E3oCOZPIF Patterns of reduced cortical thickness and striatum pathological morphology in cocaine addiction This dataset includes all the data and scripts needed to reproduce the analysis and results on the manuscript “Patterns of reduced cortical thickness and striatum pathological morphology in cocaine addiction” (link). The brain data is not raw, as T1w were not defaced. We will do so in the near future for version 2.0. Instead we include only the “output/thickness” files used in the final analysis. For the use of raw T1w images, please contact the main author EAGV.

Objective: Borderline personality disorder (BPD) is present in 19% of cocaine dependence (CD) cases; however, this dual pathology (DP) is poorly understood. We assessed impulsivity, emotional dysregulation (ED) and amygdala functional connectivity in this DP. Methods. We recruited 69 participants divided into 4 groups: DP (n = 20), CD without BPD (n = 19), BPD without CD (n = 10) and healthy controls (HC, n = 20). We used self-reported instruments to measure impulsivity and ED. We acquired resting state fMRI and performed seed-based analyses of functional connectivity (FC) of bilateral amygdalas. Results. BPD and CD factors had opposing effects in impulsivity and ED, as well as on FC between left amygdala and medial prefrontal cortex. For the FC between right amygdala and left insula, the effect of having both disorders was additive, reducing FC strength. Significant FC clusters were correlated with impulsivity and ED. Conclusions. In this preliminary study, we found that clinical scores of DP patients were closer to those of BPD without CD than to those of CD without BPD, while amygdala to medial prefrontal cortex FC patterns in DP patients were closer to HC than expected.