Changes in General and Virus-Specific Anxiety During the Spread of COVID-19 in Israel: A 7-Wave Longitudinal Study.

We compared 3 hypothetical trajectories of change in both general and coronavirus disease 2019 (COVID-19)-specific anxiety during the first wave of the spread in the state of Israel: panic (very high anxiety, either from the outset or rapidly increasing), complacency (stable and low anxiety), and threat-sensitive (a moderate, linear increase compatible with the increase in threat). A representative sample of 1,018 Jewish-Israeli adults was recruited online. A baseline assessment commenced 2 days prior to the identification of the first case, followed by 6 weekly assessments. Latent mixture modeling analyses revealed the presence of 3 trajectories: 1) "threat-sensitivity" (29% and 66%, for general and virus-specific anxiety, respectively), 2) panic (12% and 25%), and 3) complacency (29% and 9%). For general anxiety only, a fourth class representing a stable mid-level anxiety was identified ("balanced": 30%). For general anxiety, women and the initially anxious-both generally and specifically from the spread of the virus-were more likely to belong to the panic class. Men and older participants were more likely to belong to the complacency class. Findings indicate a marked heterogeneity in anxiety responses to the first wave of the spread of COVID-19, including a large group evincing a "balanced" response.

The role of phenotype-based search approaches using public online databases in diagnostics of Mendelian disorders.

PURPOSE: To investigate the effectiveness of phenotype-based search approaches using publicly available online databases. METHODS: We included consecutively solved cases from our exome database. For each case, the combination of Human Phenotype Ontology terms reported by the referring clinician was used to perform a search in three commonly used databases: OMIM (first 300 results), Phenolyzer (first 300 results), and Mendelian (all 100 results). RESULTS: One hundred cases were included (43 females; mean age: 10 years). The actual molecular diagnosis identified through exome sequencing was not included in the search results of any of the queried databases in 33% of cases. In 85% of cases it was not found within the top five search results. When included, its median rank was 61 (range: 1-295), 21 (1-270), and 29 (1-92) in OMIM, Phenolyzer and Mendelian, respectively. CONCLUSION: This study demonstrates that, in most cases, phenotype-based search approaches using public online databases is ineffective in providing a probable diagnosis for Mendelian conditions. Genotype-first approach through molecular-guided diagnostics with backward phenotyping may be a more appropriate approach for these disorders, unless a specific diagnosis is considered a priori based on highly unique phenotypic features or a specific facial gestalt.

Does methylphenidate use affect sperm parameters in patients undergoing infertility investigation? A retrospective analysis of 9769 semen samples.

OBJECTIVES: Methylphenidate (MPH) is the most widely prescribed therapy for attention deficit hyperactivity disorder. Animal studies have shown a potential adverse effect of MPH exposure on male fertility. We examined the impact of MPH on human male sperm parameters. DESIGN: Sperm parameters of 9769 samples from patients 18 years of age or older, collected as part of the basic evaluation of couples referred to the Infertility Clinic were analyzed retrospectively. We divided the study population into three groups according to MPH purchasing information: MPH purchased ≤ 90 days prior to sperm analysis-current users (n = 83), MPH purchased > 90 days prior to sperm analysis-past users (n = 293), and MPH-naïve patients (n = 9393). METHODS: All sperm samples were analyzed by the same laboratory technician team for the following routine parameters: semen volume, sperm concentration, percentage of motile sperm, and percentage of normal morphology according to World Health Organization. The analysis of the samples was completed by evaluation of total sperm count, total sperm motility, and percentage of fast and slow motile cells. Sperm morphology was evaluated by a laboratory technician using methodological examination according to the strict Kruger-Tygerberg criteria. RESULTS: Methylphenidate exposure did not affect sperm morphology but was associated with increased sperm concentration as well as increased total sperm count and total sperm motility among current and past users compared with MPH-naïve patients. In particular, progressive motility and total motile sperm count were significantly increased following MPH use. A multivariate analysis adjusting for age and current smoking was conducted, further supporting a positive correlation between current MPH use and increased values of total sperm count and total sperm motility. LIMITATIONS: Our study has several inherent weaknesses, foremost of which is its retrospective nature. Another notable weakness is that medication purchasing data may not accurately reflect MPH exposure in the study population. Patients may be purchasing MPH and not taking it as prescribed. CONCLUSIONS: In the present study, we could not demonstrate a negative impact of methylphenidate treatment on sperm parameters in adults with ADHD. Hence, we may assume that methylphenidate does not negatively affect male fertility.

BOTNet: Deep Learning-Based Bearings-Only Tracking Using Multiple Passive Sensors.

Bearings-only target tracking is commonly used in many fields, like air or sea traffic monitoring, tracking a member in a formation, and military applications. When tracking with synchronous passive multisensor systems, each sensor provides a line-of-sight measurement. They are plugged into an iterative least squares algorithm to estimate the unknown target position vector. Instead of using iterative least squares, this paper presents a deep-learning based framework for the bearing-only target tracking process, applicable for any bearings-only target tracking task. As a data-driven method, the proposed deep-learning framework offers several advantages over the traditional iterative least squares. To demonstrate the proposed approach, a scenario of tracking an autonomous underwater vehicle approaching an underwater docking station is considered. There, several passive sensors are mounted near a docking station to enable accurate localization of an approaching autonomous underwater vehicle. Simulation results show the proposed framework obtains better accuracy compared to the iterative least squares algorithm.

The path to dissociative experiences: A direct comparison of different etiological models.

Severe dissociation is trauma-related, but a range of dissociative experiences are also prevalent in clinical populations that are not necessarily trauma-based (e.g., depression, anxiety disorders, and obsessive-compulsive disorders). These remain poorly understood as the dominant etiological model for dissociation relies on trauma. Importantly, dissociation in such samples predicts poor prognosis and high drop-out rates. We set out to better understand the aetiology of dissociative experiences in a mixed clinical (anxiety and depression) and community sample by exploring between- and within-subjects effects of two domains: psychological distress or negative affectivity (operationalized as anxiety and depression symptoms), and poor sleep quality, including disturbed dreaming. The idea that negative affectivity triggers dissociation (Distress Model) is inspired by the trauma model. The idea that poor sleep and unusual dreaming underlie dissociation (Sleep Model) has been suggested as a competing theory. We examined both models by exploring which domains oscillate alongside dissociative experiences. N = 98 adults, half of them diagnosed with depression and anxiety and half community controls, underwent a structured clinical interview and completed questionnaires monthly for 6 months. Support was found for both models in that each domain had a unique explanatory contribution. Distress evinced consistent effects that could not be explained by sleep or dreaming, both between individuals and across time. Oscillations in dissociation across months, when taking psychological distress into account, were better explained by unusual dreaming than traditional sleep quality measures. These findings cannot be generalized to highly-traumatized samples. A complex, integrated etiological model for dissociative experiences is warranted.

Suicide behavior and meteorological characteristics in hot and arid climate.

BACKGROUND: Suicidal behavior is determined by the consequence of an interaction between biological, psychological and sociological factors, as well as between individual and environmental effects. Fluctuations in meteorological factors can modify human behavior and affect suicidal rates. We hypothesize that high temperatures can be associated with an increase rate of suicidal attempts. METHODS: We included all the patients admitted to Soroka University Medical Center (SUMC) due to suicide attempts between the years 2002-2017 and were residents of Southern Israel. We computed two sets of regression models: first, a time stratified case-crossover design to control for seasonality and individual differences. Results are presented as odds ratio (OR) with confidence interval (CI); and then, time-series analyses to calculate the incidence rate ratio (IRR) and the cumulative effect of temperature on the daily incidences of emergency department (ED) admissions after suicide attempts. We stratified the analyses by demographic variables to identify significant individual differences. RESULTS: We identified 3100 attempts, by 2338 patients who lived in Be'er Sheva between 16 and 90 years of age; 421 patients made 2+ attempts. Suicide attempts were associated with a 5 °C increase during the summer season (OR 1.59, 95% CI 1.22-2.08) and a 5 °C increase in all seasons was associated with those who have made multiple attempts (OR 1.18, 95% CI 1.0005-1.38). The cumulative effect of 5 °C increment is associated with more suicide attempts over 2 days (IRR 1.10, 95% CI 0.98; 1.24) and 5 days (IRR 1.04, 95% CI 1.00; 1.08). The associations were greater for patients with psychiatric diagnosis and patients with multiple attempts. In a stratified analysis by individual characteristics we didn't find significant association. CONCLUSION: High temperatures and low amount of precipitations are evidently of great impact on people's susceptibility to suicidal behavior, especially for individuals who have had a prior suicide attempt. Our findings indicate the need for public health attention in the summer when temperature increases precipitously over days, especially for those who have made a prior suicide attempt.

Self-criticism, interpersonal conditions, and biosystemic inflammation in suicidal thoughts and behaviors within mood disorders: A bio-cognitive-interpersonal hypothesis.

We review the theoretical and empirical literature on the role of self-concept in suicidal behavior in the context of mood disorders (i.e., unipolar depression and bipolar spectrum disorders). The main themes emanating from this review are then juxtaposed against (a) the Interpersonal-Psychological Theory of Suicide and (b) biological research on the role of inflammatory processes in suicidality. Such a juxtaposition paves the way for a bio-cognitive-interpersonal hypothesis. Pathologies of the self-concept-primarily self-criticism-propel mood disorder sufferers to generate interpersonal stress that culminates in two proximal causes of suicidality: thwarted belongingness and perceived burdensomeness. In turn, these two interpersonal conditions set in motion systemic biosystemic inflammation, serving as a proximal cause for suicidality in mood disorders. We conclude by describing a research project aimed at testing this hypothesis, and by outlining pertinent implications for assessment, treatment, and prevention.

Depressive personality vulnerability in chronic physical pain: Centrality of sociotropy.

OBJECTIVE: Chronic physical pain is one of modern medicine's principal challenges. Recently, there has been a keen research interest in the role of depressive personality vulnerability (DPV) in the course of chronic pain. This is the first attempt to examine the role of three leading DPV dimensions-sociotropy, autonomy, and self-criticism-in chronic pain. METHOD: Chronic pain patients (N = 428) were assessed four times as to their pain, disability, anxious depression, and pain-based catastrophizing. At Time 1, sociotropy, autonomy, and self-criticism were also assessed. The effects of sociotropy, autonomy, and self-criticism on pain, disability, anxious depression, and pain-based catastrophizing were examined using structural equation modeling analyses. RESULTS: All DPV dimensions uniquely predicted Time 1, but not Time 2, anxious depression. Sociotropy predicted Time 1 pain and catastrophizing over and above anxious depression, as well as an increase in catastrophizing over time. Autonomy predicted a decrease in catastrophizing and disability, and Time 1 anxious depression predicted an increase in self-criticism. CONCLUSIONS: Sociotropy appears to be a unique dimension of DPV in chronic pain.

Longitudinal associations between depression, anxiety, pain, and pain-related disability in chronic pain patients.

OBJECTIVE: The current study sets out to examine the longitudinal relationship between pain, pain-related disability, and symptoms of depression and anxiety. The latter symptoms are highly prevalent in chronic pain and seriously impede functioning and quality of life. Nevertheless, the direction of the relationship involving these variables among individuals with chronic pain is still unclear. METHODS: Four-hundred twenty-eight individuals with chronic pain (238 women, mean age 54.84 years, mean pain duration 85.21 months) treated at two pain clinics completed questionnaires regarding their pain (Short-Form McGill Pain Questionnaire), depression (Center for Epidemiological Studies-Depression Scale), state anxiety (State-Trait Anxiety Inventory), and pain-related disability (Pain Disability Index) at four time points, with an average of 5 months between measurements. Cross-lagged, structural equation modeling analyses were performed, enabling the examination of longitudinal associations between the variables. RESULTS: Significant symptoms of both depression and anxiety were reported by more than half of the sample on all waves. A latent depression/anxiety variable longitudinally predicted pain (ß = .27, p < .001) and pain-related disability (ß = .38, p < .001). However, neither pain (ß = .10, p = .126) nor pain-related disability (ß = -.01, p = .790) predicted depression/anxiety. CONCLUSIONS: Among adult patients with chronic pain treated at specialty pain clinics, high levels of depression and anxiety may worsen pain and pain-related disability.

Reduced corpus-callosum volume in posttraumatic stress disorder highlights the importance of interhemispheric connectivity for associative memory.

Memory deficits are a common complaint of patients with posttraumatic stress disorder (PTSD). Despite vivid trauma-related memory, previous studies report memory impairment for nontrauma-related stimuli when compared to controls, specifically in associative memory (Guez et al., 2011). Healthy individuals show hemispheric memory asymmetry with left-prefrontal lateralization of encoding and right-prefrontal lateralization of episodic retrieval, suggesting a role for interhemispheric communication in memory-related tasks (Gazzaniga, ; Ringo, Doty, Demeter, & Simard, ). Because brain magnetic resonance imaging (bMRI) studies in PTSD patients report volume changes in various regions, including white matter and corpus callosum (CC), we aimed to test the relationship between memory deficits and CC volume in PTSD patients. We probed for specific alterations in associative memory in PTSD and measured the volume of subportions within the CC employing bMRI. Our main finding was a reduction in CC white-matter volume in PTSD patients, as compared to controls, t(35) = -2.7, p = .010, that was correlated with lower associative performance (r = .76, p = .003). We propose that CC volume reduction is a substrate for the associative memory deficits found in PTSD.

Emotional brain rhythms and their impairment in post-traumatic patients.

Patients with post-traumatic stress disorder (PTSD) suffer from a failure of cognitive control over emotional distracters. The physiological substrates of cognitive-emotional interactions and their breakdown in disease are, however, unknown. Here, we studied brain activity in PTSD patients and healthy controls in response to emotion-provoking pictures using electroencephalography and functional magnetic resonance imaging (fMRI). We demonstrate that in healthy individuals, emotion-induced frontal theta rhythm modulates activity in the beta rhythm mainly in sensory-motor regions. In contrast, in PTSD patients, beta activity is elevated irrespective of emotion, and is not modulated by frontal theta activity in response to negative emotion. EEG source localization and fMRI findings suggest that theta activity is localized to the prefrontal and anterior cingulate cortices while beta activity is localized to sensory-motor regions. We further found that beta activity in sensory-motor regions is related to the emotion-induced slowing of the motor response in healthy controls while the excess frontal theta activity in PTSD is related to the intensity of negative emotional experience. These findings reveal for the first time the importance of brain electrical oscillations and coherence in emotional top-down modulation and point to specific failure of these mechanisms in PTSD.

Anxiety in the face of the first wave of the spread of COVID-19 in Israel: Psychosocial determinants of a "Panic-to-complacency-continuum".

BACKGROUND AND METHODS: Based on an established ongoing prospective-longitudinal study examining anxiety in response to COVID-19, a representative sample of 1018 Jewish-Israeli adults were recruited online. A baseline assessment was employed two days prior to the first spread of COVID-19, followed by six weekly assessments. Three classes of general anxiety and virus-specific anxiety were identified: (1) "Panic" (a very high and stable anxiety throughout the spread), (2) "Complacency" (a very low and stable anxiety throughout the spread), and (3) "Threat-Sensitivity" (a linear increase, plateauing at the 5th wave). For general-anxiety only, a fourth, "Balanced," class was identified, exhibiting a stable, middle-level of anxiety. We tested theory-based, baseline, social-cognitive predictors of these classes: self-criticism, perceived social support, and perceptions/attitudes towards the Israeli Ministry of Health. We also controlled for trait anxiety. Multinomial regression analyses in the context of General Mixture Modeling were utilized. RESULTS: Baseline virus-specific anxiety linearly predicted emerging virus-specific anxiety classes. Virus-specific panic has higher trait anxiety than the other two classes. The general anxiety panic class was over-represented by women and exhibited higher baseline general anxiety and self-criticism than all other classes, and higher baseline virus-specific anxiety along with lower perceived support and less positive perceptions of the ministry of health than two of the three other classes. CONCLUSIONS: Preexisting anxiety shapes subsequent anxious responses to the spread of COVID-19. The general-anxiety panic class may be markedly demoralized, requiring targeted public-health interventions.

The Personification of Chronic Pain: An Examination Using the Ben-Gurion University Illness Personification Scale (BGU-IPS).

Objective: Relying on anthropomorphism research, Illness Personification Theory (ILL-PERF) posits that individuals living with a chronic illness ascribe human-like characteristics to their illness. Herein we examine the personification of chronic pain using a new measure: the Ben-Gurion University Illness Personification Scale (BGU-IPS). Method: Three samples of chronic pain patients (Sample 1 and 2 are distinct samples sharing similar characteristics, collected in the context of a cross-sectional design, Ns = 259, 263; Sample 3: a 2-waves longitudinal, N =163) completed the 12-item BGU-IPS, and measures of pain and related factors. Results: An orthogonal, two-factor structure was revealed for the BGU-IPS pertaining to negative vs. positive personifications. Negative personification was associated with pain intensity and illness-related distress (e.g., depression and low adjustment to pain). Positive personification was correlated with hope, pain-related sense of control, and low depression. However, positive personification also augmented the associations between negative personification and several risk factors. Conclusions: Pain personification, particularly as assessed via the BGU-IPS, plays a major role in (mal)adaptation to chronic pain.

Pursuing personalized medicine for depression by targeting the lateral or medial prefrontal cortex with Deep TMS.

BACKGROUNDMajor depressive disorder (MDD) can benefit from novel interventions and personalization. Deep transcranial magnetic stimulation (Deep TMS) targeting the lateral prefrontal cortex (LPFC) using the H1 coil was FDA cleared for treatment of MDD. However, recent preliminary data indicate that targeting the medial prefrontal cortex (MPFC) using the H7 coil might induce outcomes that are as good or even better. Here, we explored whether Deep TMS targeting the MPFC is noninferior to targeting the LPFC and whether electrophysiological or clinical markers for patient selection can be identified.METHODSThe present prospective, multicenter, randomized study enrolled 169 patients with MDD for whom antidepressants failed in the current episode. Patients were randomized to receive 24 Deep TMS sessions over 6 weeks, using either the H1 coil or the H7 coil. The primary efficacy endpoint was the change from baseline to week 6 in Hamilton Depression Rating Scale scores.RESULTSClinical efficacy and safety profiles were similar and not significantly different between groups, with response rates of 60.9% for the H1 coil and 64.2% for the H7 coil. Moreover, brain activity measured by EEG during the first treatment session correlated with clinical outcomes in a coil-specific manner, and a cluster of baseline clinical symptoms was found to potentially distinguish between patients who can benefit from each Deep TMS target.CONCLUSIONThis study provides a treatment option for MDD, using the H7 coil, and initial guidance to differentiate between patients likely to respond to LPFC versus MPFC stimulation targets, which require further validation studies.TRIAL REGISTRATIONClinicalTrials.gov NCT03012724.FUNDINGBrainsWay Ltd.

Blood-brain barrier dysfunction in brain diseases: clinical experience.

The blood-brain barrier, a unique feature of the cerebral vasculature, is gaining attention as a feature in common neurologic disorders including stroke, traumatic brain injury, epilepsy, and schizophrenia. Although acute blood-brain barrier dysfunction can induce cerebral edema, seizures, or neuropsychiatric symptoms, epileptogenesis and cognitive decline are among the chronic effects. The mechanisms underlying blood-brain barrier dysfunction are diverse and may range from physical endothelial damage in traumatic brain injury to degradation of extracellular matrix proteins via matrix metalloproteinases as part of an inflammatory response. Clinically, blood-brain barrier dysfunction is often detected using contrast-enhanced imaging. However, these techniques do not give any insights into the underlying mechanism. Elucidating the specific pathways of blood-brain barrier dysfunction at different time points and in different brain diseases using novel imaging techniques promises a more accurate blood-brain barrier terminology as well as new treatment options and personalized treatment.

Anxiety and deterioration of quality of life factors associated with recurrent miscarriage in an observational study.

OBJECTIVES: To examine the relationship of anxiety and quality of life and sleep variables to recurrent miscarriages (RMs) in patients during two stages of their treatment in an RM-dedicated clinic ­ before and after the evaluation ­ and determine what factors could aggravate anxiety and worsen global well-being outcomes. STUDY DESIGN: Thirty-nine women who had experienced two or more RMs were measured before and after their evaluation and investigation in the RM clinic. A battery of questionnaires including the STAI scale and various instruments were administered to record anxiety, mental, and physical components of quality of life and sleep quality. Several statistical tests including canonical correlation were performed. RESULTS: All the patients revealed a mild to moderate level of anxiety, low numbers of physical and mental health but reasonably normal values of the global quality of sleep. The evaluation in the RM clinic and investigation for possible causes accounting for RM did not significantly change anxiety levels. The children-to-pregnancies ratio introduced into the analysis proved to correlate significantly with the sleep quality and mental health. Summarized anxiety in a given RM woman could be predicted based on the set of the variables, characterizing the woman's reproductive status and her psychological health. CONCLUSIONS: This study establishes anxiety as a common response in RM patients, and suggests factors that predict it. Knowing these factors may help clinicians to identify more accurately those RM patients who would be prone to a high level of anxiety and therefore need more attention and reassurance.

Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized, Double-Blind, Sham-Controlled Proof-of-Concept Trial Targeting the Medial Prefrontal and Anterior Cingulate Cortices.

BACKGROUND: Alcohol addiction is associated with a high disease burden, and treatment options are limited. In a proof-of-concept study, we used deep repetitive transcranial magnetic stimulation (dTMS) to target circuitry associated with the pathophysiology of alcohol addiction. We evaluated clinical outcomes and explored associated neural signatures using functional magnetic resonance imaging. METHODS: This was a double-blind, randomized, sham-controlled trial. A total of 51 recently abstinent treatment-seeking patients with alcohol use disorder (moderate to severe) were randomized to sham or active dTMS, using an H7 coil targeting midline frontocortical areas, including the medial prefrontal and anterior cingulate cortices. Treatment included 15 sessions over 3 weeks, followed by five sessions over 3 months of follow-up. Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, obtained using timeline follow-back interviews. Secondary analyses included self-reports of craving, ethyl glucuronide in urine, and brain imaging measures. RESULTS: Both craving after treatment and percentage of heavy drinking days during follow-up were significantly lower in the active versus sham control group (percentage of heavy drinking days = 2.9 ± 0.8% vs. 10.6 ± 1.9%, p = .037). Active dTMS was associated with decreased resting-state functional connectivity of the dorsal anterior cingulate cortex with the caudate nucleus and decreased connectivity of the medial prefrontal cortex to the subgenual anterior cingulate cortex. CONCLUSIONS: We provide initial proof-of-concept for dTMS targeting midline frontocortical structures as a treatment for alcohol addiction. These data strongly support a rationale for a full-scale confirmatory multicenter trial. Therapeutic benefits of dTMS appear to be associated with persistent changes in brain network activity.

Traumatic stress is linked to a deficit in associative episodic memory.

Individuals with posttraumatic stress disorder (PTSD) are haunted by persistent memories of the trauma, but ironically are impaired in memories of daily life. The current set of 4 experiments compared new learning and memory of emotionally neutral content in 2 groups of patients and aged- and education-matched controls: 20 patients diagnosed with chronic posttraumatic stress disorder (C-PTSD) and 20 patients diagnosed with acute stress disorder (ASD). In all experiments, participants studied a list of stimuli pairs (words or pictures) and were then tested for their memory of the items, or for the association between items in each pair. Results indicated that both types of patients showed associative memory impairment compared to a control group, although their item memory performance was relatively intact. Potential mechanisms underlying such associative memory deficits in posttraumatic patients are discussed.

From brooding to detachment: Rumination longitudinally predicts an increase in depersonalization and derealisation.

OBJECTIVES: Depersonalization-derealization (DEP-DER) is a dissociative experience which is related to psychopathology and distress. Yet, the aetiological factors leading to DEP-DER are not sufficiently clear. In this study, we suggest rumination as one possible antecedent. Thus, the goal of the study was to explore the longitudinal relationship between rumination and DEP-DER. DESIGN: Longitudinal self-report study; mixed clinical and community sample. METHODS: The study was conducted on 98 participants, 49 of them were diagnosed with depression, anxiety disorders, or obsessive-compulsive disorder, and the other 49 were healthy, matched community controls. The participants underwent a structured clinical interview and completed a battery of questionnaires. Then, the participants completed the same battery again once a month, for five additional assessment points (6 months in total). The data were analysed using multilevel linear modelling with time-lag analysis. RESULTS: We found that levels of rumination and DEP-DER increased and decreased simultaneously, meaning that on assessments in which people reported that they tended to ruminate, they also reported higher levels of DEP-DER symptoms. In addition, we found support for a unidirectional association, consistent with our theoretical hypothesis. Specifically, rumination levels on a certain month longitudinally predicted a higher likeliness for reporting DEP-DER on the following month, even when controlling for the contemporaneous relationship. Conversely, DEP-DER symptoms did not longitudinally predict increased rumination. CONCLUSIONS: These findings suggest that rumination may be an antecedent of DEP-DER, but not vice versa. Possible mechanisms to explain this link are discussed. PRACTITIONER POINTS: Rumination and DEP-DER oscillate together over time; additionally, rumination predicts a longitudinal increase in DEP-DER. Clinicians noticing ruminative thought followed by decreased emotionality should distinguish between an authentic decrease of distress versus detachment. The findings provide one possible explanation for the frequency of DEP-DER symptoms in anxiety and depressive disorders. Poor sleep quality and emotion regulation difficulties should be explored as potential mediators explaining this link.

Alleviation of ADHD symptoms by non-invasive right prefrontal stimulation is correlated with EEG activity.

Attention deficit hyperactivity disorder (ADHD) is a prevalent disorder with effective pharmacological treatment that benefits most patients. However, about one-third fail to benefit while others search non-pharmacological alternatives, and for those options are scarce. One alternative treatment option is to alter abnormal right prefrontal cortex (rPFC) activity, given that rPFC abnormality has been repeatedly implicated in ADHD neurophathology. Here, we evaluated whether targeting the rPFC with multiple sessions of repetitive transcranial magnetic stimulation (rTMS), which can modulate neuronal excitability, activity, and plasticity in a non-invasive manner, will affect clinical symptoms in adults suffering from ADHD. Concomitantly, we used EEG to characterize electrophysiological alterations induced by treatment and to search for correlation between baseline neuronal activity and clinical response. Forty-three drug free adults with ADHD were randomized to receive either Real, Active Control, or Sham treatment (13 females, age ranging 21-46; n = 15, 14, 14, respectively), and underwent three weeks of daily high-frequency (18 Hz) stimulation sessions. We found that Real treatment was safe and resulted in significant improvement of symptoms (η2p = 0.34; Cohen's d(against Sham) = 0.96; Cohen's d(against AC) = 0.68; p = 0.00085). Furthermore, based on EEG recorded within the first treatment session we established a novel biomarker, composed of the Alpha and Low-gamma power, which highly correlated the magnitude of the clinical outcome (r = 0.92, p = 0.0001). Taken together, the results of this pilot study indicate safety and effectiveness of rTMS directed to the rPFC for treatment of adult ADHD patients. The biomarker is suggested to reflect the responsiveness of the cortex to this rTMS intervention. Following validation of the results in larger samples, this study may represent a step towards a non-pharmacological treatment for adults with ADHD using EEG-based selection of optimal candidates for treatment.