A meta-analysis of transcranial magnetic stimulation in Tourette syndrome.

There is growing enthusiasm for the treatment of neuropsychiatric disorders using neuromodulation. While some reports claim that transcranial magnetic stimulation (TMS) can be used to treat Tourette Syndrome (TS), little research exists to support this assertion. This meta-analysis examined the efficacy of TMS to reduce tic severity in patients with TS. Additionally, it explored the effect of TMS to reduce premonitory urge severity-the primary mechanism implicated in the frontline evidence-based treatment of TS. Five treatment comparisons were selected using PRISMA guidelines. All studies included were required to be (1) a randomized controlled trial, (2) compare TMS to a sham condition, and (3) have all participants meet diagnostic criteria for a persistent tic disorder and/or TS. A random effects model meta-analysis examined the efficacy of using TMS to reduce tic severity and explored the effect of TMS to reduce premonitory urge severity. TMS did not significantly reduce tic severity (g = 0.44; 95% CI = -0.17, 1.05; z = 1.40; p = 0.16), but a moderate reduction in premonitory urge severity was found (g = 0.63; 95% CI = 0.9, 1.17; z = 2.27; p < 0.02). Trials with larger sample sizes and a preponderance of women were found to have greater therapeutic effects of TMS for tic severity. There is limited support for the use of TMS to reduce tic severity, though reductions in premonitory urge severity were observed. Major limitations of the existing literature are examined, with a call for research investigating newer TMS protocols and their use as a treatment augmentation strategy.

A Meta-analysis of Transcranial Magnetic Stimulation in Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a debilitating illness with substantial morbidity. Although pharmacological and behavioral evidence-based treatments have shown efficacy, many patients remain unresponsive to this first-line care. Repetitive transcranial magnetic stimulation (rTMS) has shown significant promise for patients with treatment-refractory affective disorders. Therefore, we conducted a meta-analysis of randomized controlled trials to examine the therapeutic benefit of rTMS in patients with OCD and explore moderators of its treatment effects. METHODS: PubMed (1997-Dec 31, 2022) and PsycINFO were searched for randomized sham-controlled trials of rTMS to treat OCD using the following terms: "obsessive-compulsive disorder," "transcranial magnetic stimulation," and "randomized controlled trial." Clinical characteristics and effect sizes were extracted from 25 randomized controlled trials (860 participants). A random effects model calculated the effect sizes for treatment efficacy and treatment response using the clinician-rated Yale-Brown Obsessive Compulsive Scale. RESULTS: Across randomized controlled trials, rTMS exhibited a moderate therapeutic effect (g = 0.65) on OCD symptom severity and a 3-fold increased likelihood of treatment response (relative risk = 3.15) compared with sham conditions. Greater improvement in comorbid depression severity corresponded with greater treatment effects of rTMS on OCD symptom severity. In addition, longer rTMS sessions and fewer overall sessions predicted greater clinical improvement. CONCLUSIONS: rTMS is moderately effective for reducing OCD symptom severity. It holds potential to serve as a therapeutic intervention, particularly for patients with OCD who have failed standard treatments and those with comorbid depression. Further research is needed to optimize rTMS protocols and evaluate the long-term efficacy of rTMS for OCD.

A Systematic Review of Fear Learning, Extinction Learning, and Reversal Learning in Obsessive-Compulsive Disorder: Implications for Treatment.

Objective: Given the implications in the etiology and treatment of obsessive-compulsive disorder (OCD), this systematic review examined fear acquisition, extinction learning, and reversal learning processes in individuals with OCD.Data Sources: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, PubMed (1946-October 26, 2021), PsycInfo, and Embase were searched for empirical studies utilizing classical or reversal learning paradigms to compare learning and extinction processes in individuals with and without OCD.Study Selection: A total of 15,603 articles (7,761 from PubMed, 1,128 from PsycInfo, 6,711 from Embase, 3 from citation review) were identified. Articles were screened for duplicates and inclusion/exclusion criteria. Eleven studies met all inclusion/exclusion criteria.Results: Across studies, minimal evidence of abnormal fear learning was found. However, developmental differences emerged for extinction learning. Youth with OCD displayed impaired extinction learning and safety signal discrimination. Meanwhile, adults largely showed deficits in extinction recall. Conflicting findings emerged regarding impairments in reversal learning. Across learning processes, neuroimaging data implicated the importance of the ventromedial prefrontal cortex (vmPFC).Conclusions: The physiological and neuroimaging data suggest that extinction learning impairment varies across development. Notably, key associative learning processes remain largely unexamined. Findings underlying abnormalities in extinction learning suggest the potential of novel therapeutic approaches, such as neuromodulation and psychotherapy augmentation strategies (ie, attention bias modification training), to precisely target and resolve identified deficits.

A prospective examination of sex differences in posttraumatic autonomic functioning.

BACKGROUND: Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic functioning. METHODS: 192 participants were recruited from emergency departments following trauma exposure (Mean age = 35.88, 68.2% female). Skin conductance was measured in the emergency department; fear conditioning was completed two weeks later and included measures of blood pressure (BP), heart rate (HR), and high frequency heart rate variability (HF-HRV). PTSD symptoms were assessed 8 weeks after trauma. RESULTS: 2-week systolic BP was significantly higher in men, while 2-week HR was significantly higher in women, and a sex by PTSD interaction suggested that women who developed PTSD demonstrated the highest HR levels. Two-week HF-HRV was significantly lower in women, and a sex by PTSD interaction suggested that women with PTSD demonstrated the lowest HF-HRV levels. Skin conductance response in the emergency department was associated with 2-week HR and HF-HRV only among women who developed PTSD. CONCLUSIONS: Our results indicate that there are notable sex differences in autonomic functioning among trauma-exposed individuals. Differences in sympathetic biomarkers (BP and HR) may have implications for cardiovascular disease risk given that sympathetic arousal is a mechanism implicated in this risk among PTSD populations. Future research examining differential pathways between PTSD and cardiovascular risk among men versus women is warranted.

Thalamic volume and fear extinction interact to predict acute posttraumatic stress severity.

Posttraumatic stress disorder (PTSD) is associated with lower gray matter volume (GMV) in brain regions critical for extinction of learned threat. However, relationships among volume, extinction learning, and PTSD symptom development remain unclear. We investigated subcortical brain volumes in regions supporting extinction learning and fear-potentiated startle (FPS) to understand brain-behavior interactions that may impact PTSD symptom development in recently traumatized individuals. Participants (N = 99) completed magnetic resonance imaging and threat conditioning two weeks following trauma exposure as part of a multisite observational study to understand the neuropsychiatric effects of trauma (AURORA Study). Participants completed self-assessments of PTSD (PTSD Checklist for DSM-5; PCL-5), dissociation, and depression symptoms two- and eight-weeks post-trauma. We completed multiple regressions to investigate relationships between FPS during late extinction, GMV, and PTSD symptom development. The interaction between thalamic GMV and FPS during late extinction at two weeks post-trauma predicted PCL-5 scores eight weeks (t (75) = 2.49, ß = 0.28, p = 0.015) post-trauma. Higher FPS predicted higher PCL-5 scores in the setting of increased thalamic GMV. Meanwhile, lower FPS also predicted higher PCL-5 scores in the setting of decreased thalamic GMV. Thalamic GMV and FPS interactions also predicted posttraumatic dissociative and depressive symptoms. Amygdala and hippocampus GMV by FPS interactions were not associated with posttraumatic symptom development. Taken together, thalamic GMV and FPS during late extinction interact to contribute to adverse posttraumatic neuropsychiatric outcomes. Multimodal assessments soon after trauma have the potential to distinguish key phenotypes vulnerable to posttraumatic neuropsychiatric outcomes.

Cortical Thickness and Subcortical Gray Matter Volume in Pediatric Anxiety Disorders.

Perturbations in the prefrontal cortex (PFC), hippocampus, and amygdala are implicated in the development of anxiety disorders. However, most structural neuroimaging studies of patients with anxiety disorders utilize adult samples, and the few studies in youths examine small samples, primarily with volume-based measures. This study tested the hypothesis that cortical thickness of PFC regions and gray matter volume of the hippocampus and amygdala differ between pediatric anxiety disorder patients and healthy volunteers (HVs). High-resolution 3-Tesla T1-weighted MRI scans were acquired in 151 youths (75 anxious, 76 HV; ages 8-18). Analyses tested associations of brain structure with anxiety diagnosis and severity across both groups, as well as response to cognitive-behavioral therapy in a subset of 53 patients. Cortical thickness was evaluated both within an a priori PFC mask (small-volume corrected) and using an exploratory whole-brain-corrected (p<0.05) approach. Anxious relative to healthy youths exhibited thicker cortex in the left ventromedial PFC (vmPFC) and left precentral gyrus. Both anxiety diagnosis and symptom severity were associated with smaller right hippocampal volume. In patients, thinner cortex in parietal and occipital cortical regions was associated with worse treatment response. Pediatric anxiety was associated with structural differences in vmPFC and hippocampus, regions implicated in emotional processing and in developmental models of anxiety pathophysiology. Parietal and occipital cortical thickness were related to anxiety treatment response but not baseline anxiety.

Comparing Brain Morphometry Across Multiple Childhood Psychiatric Disorders.

OBJECTIVE: In both children and adults, psychiatric illness is associated with structural brain alterations, particularly in the prefrontal cortex (PFC). However, most studies compare gray matter volume (GMV) in healthy volunteers (HVs) to one psychiatric group. We compared GMV among youth with anxiety disorders, bipolar disorder (BD), disruptive mood dysregulation disorder (DMDD), attention-deficit/hyperactivity disorder (ADHD), and HVs. METHOD: 3-Tesla T1-weighted magnetic resonance imaging scans were acquired in 184 youths (39 anxious, 20 BD, 52 DMDD, 20 ADHD, and 53 HV). Voxel-based morphometry analyses were conducted. One-way analysis of variance tested GMV differences with whole-brain familywise error (p < .05) correction; secondary, exploratory whole-brain analyses used a threshold of p < .001, ≥200 voxels. Given recent frameworks advocating dimensional approaches in psychopathology research, we also tested GMV associations with continuous anxiety, irritability, and inattention symptoms. RESULTS: Specificity emerged in the left dorsolateral PFC (dlPFC), which differed among youth with BD, anxiety, and HVs; GMV was increased in youth with anxiety, but decreased in BD, relative to HVs. Secondary analyses revealed BD-specific GMV decreases in the right lateral PFC, right dlPFC, and dorsomedial PFC, and also anxiety-specific GMV increases in the left dlPFC, right ventrolateral PFC, frontal pole, and right parahippocampal gyrus/lingual gyrus. Both BD and DMDD showed decreased GMV relative to HVs in the right dlPFC/superior frontal gyrus. GMV was not associated with dimensional measures of anxiety, irritability, or ADHD symptoms. CONCLUSION: Both disorder-specific and shared GMV differences manifest in pediatric psychopathology. Some differences were specific to anxiety disorders, others specific to BD, and others shared between BD and DMDD. Further developmental research might map commonalities and differences of structure and function in diverse pediatric psychopathologies.