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1.
medRxiv ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38798344

RESUMEN

The prefrontal cortex (PFC) is a region of the brain that in humans is involved in the production of higher-order functions such as cognition, emotion, perception, and behavior. Neurotransmission in the PFC produces higher-order functions by integrating information from other areas of the brain. At the foundation of neurotransmission, and by extension at the foundation of higher-order brain functions, are an untold number of coordinated molecular processes involving the DNA sequence variants in the genome, RNA transcripts in the transcriptome, and proteins in the proteome. These "multiomic" foundations are poorly understood in humans, perhaps in part because most modern studies that characterize the molecular state of the human PFC use tissue obtained when neurotransmission and higher-order brain functions have ceased (i.e., the postmortem state). Here, analyses are presented on data generated for the Living Brain Project (LBP) to investigate whether PFC tissue from individuals with intact higher-order brain function has characteristic multiomic foundations. Two complementary strategies were employed towards this end. The first strategy was to identify in PFC samples obtained from living study participants a signature of RNA transcript expression associated with neurotransmission measured intracranially at the time of PFC sampling, in some cases while participants performed a task engaging higher-order brain functions. The second strategy was to perform multiomic comparisons between PFC samples obtained from individuals with intact higher-order brain function at the time of sampling (i.e., living study participants) and PFC samples obtained in the postmortem state. RNA transcript expression within multiple PFC cell types was associated with fluctuations of dopaminergic, serotonergic, and/or noradrenergic neurotransmission in the substantia nigra measured while participants played a computer game that engaged higher-order brain functions. A subset of these associations - termed the "transcriptional program associated with neurotransmission" (TPAWN) - were reproduced in analyses of brain RNA transcript expression and intracranial neurotransmission data obtained from a second LBP cohort and from a cohort in an independent study. RNA transcripts involved in TPAWN were found to be (1) enriched for RNA transcripts associated with measures of neurotransmission in rodent and cell models, (2) enriched for RNA transcripts encoded by evolutionarily constrained genes, (3) depleted of RNA transcripts regulated by common DNA sequence variants, and (4) enriched for RNA transcripts implicated in higher-order brain functions by human population genetic studies. In PFC excitatory neurons of living study participants, higher expression of the genes in TPAWN tracked with higher expression of RNA transcripts that in rodent PFC samples are markers of a class of excitatory neurons that connect the PFC to deep brain structures. TPAWN was further reproduced by RNA transcript expression patterns differentiating living PFC samples from postmortem PFC samples, and significant differences between living and postmortem PFC samples were additionally observed with respect to (1) the expression of most primary RNA transcripts, mature RNA transcripts, and proteins, (2) the splicing of most primary RNA transcripts into mature RNA transcripts, (3) the patterns of co-expression between RNA transcripts and proteins, and (4) the effects of some DNA sequence variants on RNA transcript and protein expression. Taken together, this report highlights that studies of brain tissue obtained in a safe and ethical manner from large cohorts of living individuals can help advance understanding of the multiomic foundations of brain function.

2.
Nat Hum Behav ; 8(4): 718-728, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38409356

RESUMEN

Dopamine and serotonin are hypothesized to guide social behaviours. In humans, however, we have not yet been able to study neuromodulator dynamics as social interaction unfolds. Here, we obtained subsecond estimates of dopamine and serotonin from human substantia nigra pars reticulata during the ultimatum game. Participants, who were patients with Parkinson's disease undergoing awake brain surgery, had to accept or reject monetary offers of varying fairness from human and computer players. They rejected more offers in the human than the computer condition, an effect of social context associated with higher overall levels of dopamine but not serotonin. Regardless of the social context, relative changes in dopamine tracked trial-by-trial changes in offer value-akin to reward prediction errors-whereas serotonin tracked the current offer value. These results show that dopamine and serotonin fluctuations in one of the basal ganglia's main output structures reflect distinct social context and value signals.


Asunto(s)
Dopamina , Enfermedad de Parkinson , Serotonina , Sustancia Negra , Humanos , Serotonina/metabolismo , Dopamina/metabolismo , Sustancia Negra/metabolismo , Masculino , Femenino , Enfermedad de Parkinson/metabolismo , Persona de Mediana Edad , Anciano , Conducta Social , Recompensa
3.
Transl Psychiatry ; 14(1): 87, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38341414

RESUMEN

Although neuroimaging has been widely applied in psychiatry, much of the exuberance in decades past has been tempered by failed replications and a lack of definitive evidence to support the utility of imaging to inform clinical decisions. There are multiple promising ways forward to demonstrate the relevance of neuroimaging for psychiatry at the individual patient level. Ultra-high field magnetic resonance imaging is developing as a sensitive measure of neurometabolic processes of particular relevance that holds promise as a new way to characterize patient abnormalities as well as variability in response to treatment. Neuroimaging may also be particularly suited to the science of brain stimulation interventions in psychiatry given that imaging can both inform brain targeting as well as measure changes in brain circuit communication as a function of how effectively interventions improve symptoms. We argue that a greater focus on individual patient imaging data will pave the way to stronger relevance to clinical care in psychiatry. We also stress the importance of using imaging in symptom-relevant experimental manipulations and how relevance will be best demonstrated by pairing imaging with differential treatment prediction and outcome measurement. The priorities for using brain imaging to inform psychiatry may be shifting, which compels the field to solidify clinical relevance for individual patients over exploratory associations and biomarkers that ultimately fail to replicate.


Asunto(s)
Trastornos Mentales , Psiquiatría , Humanos , Trastornos Mentales/diagnóstico por imagen , Trastornos Mentales/terapia , Neuroimagen/métodos , Imagen por Resonancia Magnética , Psiquiatría/métodos , Encéfalo
4.
Biol Psychiatry ; 96(2): 101-113, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38141909

RESUMEN

BACKGROUND: Deep brain stimulation (DBS) is a promising treatment option for treatment-refractory obsessive-compulsive disorder (OCD). Several stimulation targets have been used, mostly in and around the anterior limb of the internal capsule and ventral striatum. However, the precise target within this region remains a matter of debate. METHODS: Here, we retrospectively studied a multicenter cohort of 82 patients with OCD who underwent DBS of the ventral capsule/ventral striatum and mapped optimal stimulation sites in this region. RESULTS: DBS sweet-spot mapping performed on a discovery set of 58 patients revealed 2 optimal stimulation sites associated with improvements on the Yale-Brown Obsessive Compulsive Scale, one in the anterior limb of the internal capsule that overlapped with a previously identified OCD-DBS response tract and one in the region of the inferior thalamic peduncle and bed nucleus of the stria terminalis. Critically, the nucleus accumbens proper and anterior commissure were associated with beneficial but suboptimal clinical improvements. Moreover, overlap with the resulting sweet- and sour-spots significantly estimated variance in outcomes in an independent cohort of 22 patients from 2 additional DBS centers. Finally, beyond obsessive-compulsive symptoms, stimulation of the anterior site was associated with optimal outcomes for both depression and anxiety, while the posterior site was only associated with improvements in depression. CONCLUSIONS: Our results suggest how to refine targeting of DBS in OCD and may be helpful in guiding DBS programming in existing patients.


Asunto(s)
Estimulación Encefálica Profunda , Cápsula Interna , Trastorno Obsesivo Compulsivo , Humanos , Trastorno Obsesivo Compulsivo/terapia , Estimulación Encefálica Profunda/métodos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Cápsula Interna/diagnóstico por imagen , Estriado Ventral/diagnóstico por imagen , Estriado Ventral/fisiopatología , Resultado del Tratamiento , Adulto Joven
5.
Mol Psychiatry ; 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37919403

RESUMEN

Ongoing experimental studies of subcallosal cingulate deep brain stimulation (SCC DBS) for treatment-resistant depression (TRD) show a differential timeline of behavioral effects with rapid changes after initial stimulation, and both early and delayed changes over the course of ongoing chronic stimulation. This study examined the longitudinal resting-state regional cerebral blood flow (rCBF) changes in intrinsic connectivity networks (ICNs) with SCC DBS for TRD over 6 months and repeated the same analysis by glucose metabolite changes in a new cohort. A total of twenty-two patients with TRD, 17 [15 O]-water and 5 [18 F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) patients, received SCC DBS and were followed weekly for 7 months. PET scans were collected at 4-time points: baseline, 1-month after surgery, and 1 and 6 months of chronic stimulation. A linear mixed model was conducted to examine the differential trajectory of rCBF changes over time. Post-hoc tests were also examined to assess postoperative, early, and late ICN changes and response-specific effects. SCC DBS had significant time-specific effects in the salience network (SN) and the default mode network (DMN). The rCBF in SN and DMN was decreased after surgery, but responder and non-responders diverged thereafter, with a net increase in DMN activity in responders with chronic stimulation. Additionally, the rCBF in the DMN uniquely correlated with depression severity. The glucose metabolic changes in a second cohort show the same DMN changes. The trajectory of PET changes with SCC DBS is not linear, consistent with the chronology of therapeutic effects. These data provide novel evidence of both an acute reset and ongoing plastic effects in the DMN that may provide future biomarkers to track clinical improvement with ongoing treatment.

6.
Nature ; 622(7981): 130-138, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37730990

RESUMEN

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)1. However, achieving stable recovery is unpredictable2, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting3. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.


Asunto(s)
Estimulación Encefálica Profunda , Depresión , Trastorno Depresivo Mayor , Humanos , Inteligencia Artificial , Biomarcadores , Estimulación Encefálica Profunda/métodos , Depresión/fisiopatología , Depresión/terapia , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/terapia , Electrofisiología , Resultado del Tratamiento , Medición de Potencial de Campo Local , Sustancia Blanca , Lóbulo Límbico/fisiología , Lóbulo Límbico/fisiopatología , Expresión Facial
7.
J Neurosurg ; 139(5): 1366-1375, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37119111

RESUMEN

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus interna (GPi) have differential therapeutic effects for Parkinson's disease (PD) that drive patient selection. For example, GPi DBS is preferred for dystonic features and dyskinesia, whereas STN DBS has shown faster tremor control and medication reduction. Connectivity studies comparing these two targets, using patient-specific data, are still lacking. The objective was to find STN and GPi structural connectivity patterns in order to better understand differences in DBS-activated brain circuits between these two stimulation targets and to guide optimal contact selection. METHODS: The authors simulated DBS activation along the main axis of both the STN and GPi by using volume of activated tissue (VAT) modeling with known average stimulation parameters (2.8 V and 60 µsec for STN; 3.3 V and 90 µsec for GPi). The authors modeled VATs in the anterior, middle, and posterior STN and the anterior, midanterior, midposterior, and posterior GPi. The authors generated maps of the connections shared by the patients for each VAT by using probabilistic tractography of diffusion-weighted imaging data obtained in 46 PD patients who underwent DBS (26 with STN and 20 with GPi targeting), and differences between VATs for whole-brain and distal regions of interest (prefrontal cortex, supplementary motor area, primary motor cortex, primary sensory cortex, caudate, motor thalamus, and cerebellum) were generated from structural atlases. Differences between maps were quantified and compared. RESULTS: VATs across the STN and GPi had different structural connectivity patterns. The authors found significant connectivity differences between VATs for all regions of interest. Posterior and middle STN showed stronger connectivity to the primary motor cortex and supplementary motor area (SMA) (p < 0.001). Posterior STN had the strongest connectivity to the primary sensory cortex and motor thalamus (p < 0.001). Posterior GPi showed stronger connectivity to the primary motor cortex (p < 0.001). Connectivity to the SMA was similar for the posterior and midposterior GPi (p > 0.05), which was greater than that for the anterior GPi (p < 0.001). When both nuclei were compared, posterior and middle STN had stronger connectivity to the SMA, cerebellum, and motor thalamus than GPi (all p < 0.001). Posterior GPi and STN had similar connectivity to the primary sensory cortex. CONCLUSIONS: On patient-specific imaging, structural connectivity differences existed between GPi and STN DBS, as measured with standardized electrical field modeling of the DBS targets. These connectivity differences may correlate with the differential clinical benefits obtained by targeting each of the two nuclei with DBS for PD. Prospective work is needed to relate these differences to clinical outcomes and to inform targeting and programming.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Sustancia Blanca , Humanos , Núcleo Subtalámico/diagnóstico por imagen , Globo Pálido/diagnóstico por imagen , Globo Pálido/fisiología , Estimulación Encefálica Profunda/métodos , Estudios Prospectivos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/terapia
9.
J Neural Eng ; 20(2)2023 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-36827705

RESUMEN

Objective. Deep brain stimulation is a treatment option for patients with refractory obsessive-compulsive disorder. A new generation of stimulators hold promise for closed loop stimulation, with adaptive stimulation in response to biologic signals. Here we aimed to discover a suitable biomarker in the ventral striatum in patients with obsessive compulsive disorder using local field potentials.Approach.We induced obsessions and compulsions in 11 patients undergoing deep brain stimulation treatment using a symptom provocation task. Then we trained machine learning models to predict symptoms using the recorded intracranial signal from the deep brain stimulation electrodes.Main results.Average areas under the receiver operating characteristics curve were 62.1% for obsessions and 78.2% for compulsions for patient specific models. For obsessions it reached over 85% in one patient, whereas performance was near chance level when the model was trained across patients. Optimal performances for obsessions and compulsions was obtained at different recording sites.Significance. The results from this study suggest that closed loop stimulation may be a viable option for obsessive-compulsive disorder, but that intracranial biomarkers are patient and not disorder specific.Clinical Trial:Netherlands trial registry NL7486.


Asunto(s)
Trastorno Obsesivo Compulsivo , Estriado Ventral , Humanos , Conducta Obsesiva/diagnóstico , Conducta Obsesiva/terapia , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/terapia
10.
Clin Neurophysiol ; 148: 109-117, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36774324

RESUMEN

OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD) yet neural markers of optimized stimulation parameters are largely unknown. We aimed to describe (sub-)cortical electrophysiological responses to acute DBS at various voltages in OCD. METHODS: We explored how DBS doses between 3-5 V delivered to the ventral anterior limb of the internal capsule of five OCD patients affected electroencephalograms and intracranial local field potentials (LFPs). We focused on theta power/ phase-stability, given their previously established role in DBS for OCD. RESULTS: Cortical theta power and theta phase-stability did not increase significantly with DBS voltage. DBS-induced theta power peaks were seen at the previously defined individualized therapeutic voltage. Although LFP power generally increased with DBS voltages, this occurred mostly in frequency peaks that overlapped with stimulation artifacts limiting its interpretability. Though highly idiosyncratic, three subjects showed significant acute DBS effects on electroencephalogram theta power and four subjects showed significant carry-over effects (pre-vs post DBS, unstimulated) on LFP and electroencephalogram theta power. CONCLUSIONS: Our findings challenge the presence of a consistent dose-response relationship between stimulation voltage and brain activity. SIGNIFICANCE: Theta power may be investigated further as a neurophysiological marker to aid personalized DBS voltage optimization in OCD.


Asunto(s)
Estimulación Encefálica Profunda , Trastorno Obsesivo Compulsivo , Humanos , Trastorno Obsesivo Compulsivo/terapia , Resultado del Tratamiento , Electroencefalografía , Cápsula Interna
11.
Brain Stimul ; 16(1): 82-87, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36681239

RESUMEN

BACKGROUND: Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is effective for refractory obsessive-compulsive disorder (OCD), but patients typically require high stimulation voltages and DBS comes with a risk for adverse events (AE). OBJECTIVE: The aim of the present study was to advance DBS for OCD by optimizing energy efficiency and minimize adverse events using a cyclic form of stimulation METHODS: This double blind, randomized crossover trial compares 2 weeks of continuous versus cyclic DBS (0.1 s ON, 0.2 s OFF) in 16 patients with OCD. We compared OCD symptoms (Yale-Brown Obsessive-Compulsive Scale, Y-BOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), AEs, battery life, cognitive performance and quality of life. RESULTS: Average Y-BOCS scores at baseline increased significantly with 5.5 points (p = 0.006) in the cyclic condition. Average HAM-D and HAM-A scores increased with 2.2 (p = 0.088) and 2.8 points (p = 0.018). The overall health scale of quality of life worsened during cyclic DBS (p = 0.044). Patients reported on average 3.3 AEs during continuous stimulation and 4.4 AEs during cyclic stimulation (p = 0.175), though stimulation-related AEs such as headache and concentration problems reduced during cyclic DBS. Battery usage during continuous DBS was 0.021 V per hour compared to 0.008 V per hour during cyclic DBS. CONCLUSION: Though specific stimulation-related AEs improved, cyclic stimulation (0.1 s ON, 0.2 s OFF) comes with a high relapse risk in patients with DBS for OCD. Cyclic DBS is no alternative for standard DBS treatment, but applicable in case of debilitating AEs.


Asunto(s)
Estimulación Encefálica Profunda , Trastorno Obsesivo Compulsivo , Humanos , Estimulación Encefálica Profunda/efectos adversos , Calidad de Vida , Trastorno Obsesivo Compulsivo/psicología , Cápsula Interna , Método Doble Ciego , Resultado del Tratamiento
12.
bioRxiv ; 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38187733

RESUMEN

Background: A critical advance in depression research is to clarify the hypothesized role of interoceptive processing in neural mechanisms of treatment efficacy. This study tests whether cortical interoceptive processing, as indexed by the heartbeat-evoked potential (HEP), is modulated by deep brain stimulation (DBS) to the subcallosal cingulate (SCC) for treatment resistant depression (TRD). Methods: Eight patients with TRD were enrolled in a study of SCC DBS safety and efficacy. Electroencephalography (EEG) and symptom severity measures were sampled in a laboratory setting over the course of a six-month treatment protocol. The primary outcome measure was an EEG-derived HEP, which reflects cortical processing of heartbeat sensation. Cluster-based permutation analyses were used to test the effect of stimulation and time in treatment on the HEP. The change in signal magnitude after treatment was correlated with change in depression severity as measured by the 17-item Hamilton Depression Rating Scale. Results: HEP amplitude was greater after 24 weeks of treatment ( t (7)=-4.40, p =.003, g= -1.38, 95% Cl [-2.3, -0.42]), and this change was inversely correlated with latency of treatment response (rho = -0.75, 95% Cl [-0.95, -0.11], p= .03). An acute effect of DBS was also observed, but as a decrease in HEP amplitude ( t (6) =6.66, p <.001, g= 2.19, 95% Cl [0.81, 3.54]). HEP differences were most pronounced over left posterior sensors from 405-425 ms post-stimulus. Conclusion: Brain-based evidence substantiates a theorized link between interoception and depression, and suggests an interoceptive contribution to the mechanism of treatment efficacy with deep brain stimulation for severe depression.

13.
Neurotherapeutics ; 19(4): 1229-1245, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35817944

RESUMEN

Deep brain stimulation has been extensively studied as a therapeutic option for treatment-resistant depression (TRD). DBS across different targets is associated with on average 60% response rates in previously refractory chronically depressed patients. However, response rates vary greatly between patients and between studies and often require extensive trial-and-error optimizations of stimulation parameters. Emerging evidence from tractography imaging suggests that targeting combinations of white matter tracts, rather than specific grey matter regions, is necessary for meaningful antidepressant response to DBS. In this article, we review efficacy of various DBS targets for TRD, which networks are involved in their therapeutic effects, and how we can use this information to improve targeting and programing of DBS for individual patients. We will also highlight how to integrate these DBS network findings into developing adaptive stimulation and optimal trial designs.


Asunto(s)
Estimulación Encefálica Profunda , Trastorno Depresivo Resistente al Tratamiento , Sustancia Blanca , Humanos , Estimulación Encefálica Profunda/métodos , Depresión/terapia , Trastorno Depresivo Resistente al Tratamiento/terapia , Antidepresivos
15.
Compr Psychiatry ; 117: 152329, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35679658

RESUMEN

BACKGROUND: While a growing body of research highlights a bi-directional link between diabetes and mood disorders, little is known about the relationship between diabetes and obsessive-compulsive disorder (OCD). The aim of the present review is to investigate current evidence linking OCD, insulin-signaling and diabetes. METHODS: A PubMed search was conducted to review all the available studies assessing diabetes, glucose metabolism and insulin-signaling in OCD patients and vice versa. RESULTS: Some clinical and epidemiological studies show a higher prevalence of diabetes in OCD and vice versa compared to the general population. Animal and genetic studies suggest a possible role of insulin-signaling in the pathophysiology of OCD. Deep brain stimulation (DBS) studies suggest that abnormal dopaminergic transmission in the striatum may contribute to impaired insulin sensitivity in OCD. While DBS seems to increase insulin sensitivity, a possible protective role of serotonin reuptake-inhibitors on diabetic risk needs further studies. CONCLUSION: Despite their preliminary nature, these data highlight the importance of further investigations aimed at assessing metabolic features in OCD patients and OCD symptoms in diabetes patients to understand the impact of each condition on the pathophysiology and course of the other. Understanding the role of insulin in the obsessive-compulsive brain could open new treatment pathways for OCD.


Asunto(s)
Diabetes Mellitus , Resistencia a la Insulina , Trastorno Obsesivo Compulsivo , Animales , Humanos , Insulina/uso terapéutico , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Encéfalo , Comorbilidad , Diabetes Mellitus/epidemiología
16.
Front Neuroanat ; 16: 795231, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35370568

RESUMEN

Recently, the abuse of ketamine has soared. Therefore, it is of great importance to study its potential risks. The effects of prolonged ketamine on the brain can be observationally studied in chronic recreational users. We performed a systematic review of studies reporting functional and structural brain changes after repeated ketamine abuse. We searched the following electronic databases: Medline, Embase and PsycINFO We screened 11,438 records and 16 met inclusion criteria, totaling 440 chronic recreational ketamine users (2-9.7 years; mean use 2.4 g/day), 259 drug-free controls and 44 poly-drug controls. Long-term recreational ketamine use was associated with lower gray matter volume and less white matter integrity, lower functional thalamocortical and corticocortical connectivity. The observed differences in both structural and functional neuroanatomy between ketamine users and controls may explain some of its long-term cognitive and psychiatric side effects, such as memory impairment and executive functioning. Given the effect that long-term ketamine exposure may yield, an effort should be made to curb its abuse.

18.
J Clin Psychiatry ; 82(6)2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34727424

RESUMEN

Background: Deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) is effective in half of patients, but also is invasive and labor-intensive.Objective: Selecting probable responders beforehand would more optimally allocate treatment resources and prevent patients' disappointment. Some centers use clinical and demographic predictors to exclude patients from DBS treatment, but the evidence base remains uncertain.Methods: This observational cohort study examined the association of baseline demographic and disease characteristics with a 1-year prospective course of OCD and depressive symptoms in a cohort of 70 consecutive patients who received DBS of the ventral anterior limb of the internal capsule (vALIC-DBS) for OCD according to DSM-IV or DSM-5 criteria between April 2005 and October 2017. Baseline characteristics and symptom decrease were analyzed using Fisher exact tests and binary logistic regression to examine whether they could predict individual response (> 35% reduction in Yale-Brown Obsessive Compulsive Scale score and 50% reduction in Hamilton Depression Rating Scale score, respectively).Results: Insight into illness was the only significant predictor of individual response, with a positive predictive value of 84.4%, while the negative predictive value was 44.0% (b = 0.247, χ21 = 5.259, P = .022). Late-onset OCD was associated with more symptom decrease (ß = -0.29; 95% CI, -0.53 to -0.04; P = .023) and comorbid personality disorder with less symptom decrease over time (ß = 0.88; 95% CI -0.29 to 1.47; P = .004), but they could not significantly predict vALIC-DBS response. A later age at onset, comorbid personality disorder, and insight into illness were associated with clinical outcomes after vALIC-DBS, but predictive values were not large enough to facilitate clinical patient selection.Conclusions: Clinical and demographic factors cannot yet predict outcome and should not be used to exclude patients from treatment with vALIC-DBS. These first individual prediction analyses for vALIC-DBS response in OCD are important, given that some centers up until now still exclude patients based on clinical characteristics such as comorbid personality disorders.


Asunto(s)
Estimulación Encefálica Profunda , Trastorno Obsesivo Compulsivo , Adulto , Estudios de Cohortes , Comorbilidad , Estimulación Encefálica Profunda/efectos adversos , Estimulación Encefálica Profunda/métodos , Demografía , Depresión/diagnóstico , Depresión/etiología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Resistencia a la Enfermedad , Femenino , Humanos , Masculino , Países Bajos/epidemiología , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/psicología , Trastorno Obsesivo Compulsivo/terapia , Selección de Paciente , Valor Predictivo de las Pruebas , Pronóstico , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad
20.
Biol Psychiatry ; 90(10): 678-688, 2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34482949

RESUMEN

Obsessive-compulsive disorder is among the most disabling psychiatric disorders. Although deep brain stimulation is considered an effective treatment, its use in clinical practice is not fully established. This is, at least in part, due to ambiguity about the best suited target and insufficient knowledge about underlying mechanisms. Recent advances suggest that changes in broader brain networks are responsible for improvement of obsessions and compulsions, rather than local impact at the stimulation site. These findings were fueled by innovative methodological approaches using brain connectivity analyses in combination with neuromodulatory interventions. Such a connectomic approach for neuromodulation constitutes an integrative account that aims to characterize optimal target networks. In this critical review, we integrate findings from connectomic studies and deep brain stimulation interventions to characterize a neural network presumably effective in reducing obsessions and compulsions. To this end, we scrutinize methodologies and seemingly conflicting findings with the aim to merge observations to identify common and diverse pathways for treating obsessive-compulsive disorder. Ultimately, we propose a unified network that-when modulated by means of cortical or subcortical interventions-alleviates obsessive-compulsive symptoms.


Asunto(s)
Conectoma , Estimulación Encefálica Profunda , Trastorno Obsesivo Compulsivo , Encéfalo/diagnóstico por imagen , Humanos , Trastorno Obsesivo Compulsivo/terapia , Resultado del Tratamiento
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