Background: Patients with Major Depressive Disorder (MDD) often experience unexpected relapses, despite achieving remission. This study examines the utility of a single multidimensional measure that captures variance in patient-reported Depressive Symptom Severity, Functioning, and Quality of Life (QOL), in predicting MDD relapse.
Methods: Complete data from remitted patients at the completion of 12 weeks of citalopram in the STAR D study were used to calculate the Individual Burden of Illness index for Depression (IBI-D), and predict subsequent relapse at six (n = 956), nine (n = 778), and twelve months (n =479) using generalized linear models.
Results: Depressive Symptom Severity, Functioning, and QOL were all predictors of subsequent relapse. Using Akaike information criteria (AIC), the IBI-D provided a good model for relapse even when Depressive Symptom Severity, Functioning, and QOL were combined in a single model. Specifically, an increase of one in the IBI-D increased the odds ratio of relapse by 2.5 at 6 months (/3=0921 - 0194, z=476, p <2 x 10-6), by 284 at 9 months (/3=1045 - 022, z=474, p <2.2 x 10-6), and by 4.1 at 12 months (/3=141 - 029, z=479, p < 1.7 x 10-6).
Limitations: Self-report poses a risk to measurement precision. Using highly valid and reliable measures could mitigate this risk. The IBI-D requires time and effort for filling out the scales and index calculation. Technological solutions could help ease these burdens. The sample suffered from attrition. Separate analysis of dropouts would be helpful.
Conclusions: Incorporating patient-reported outcomes of Functioning and QOL in addition to Depressive Symptom Severity in the IBI-D is useful in assessing the full burden of illness and in adequately predicting relapse, in MDD.
The amygdala is a key structure mediating emotional processing. Few studies have used direct electrical stimulation of the amygdala in humans to examine stimulation-elicited physiological and emotional responses, and the nature of such effects remains unclear. Determining the effects of electrical stimulation of the amygdala has important theoretical implications for current discrete and dimensional neurobiological theories of emotion, which differ substantially in their predictions about the emotional effects of such stimulation. To examine the effects of amygdala stimulation on physiological and subjective emotional responses we examined epilepsy patients undergoing intracranial EEG monitoring in which depth electrodes were implanted unilaterally or bilaterally in the amygdala. Nine subjects underwent both sham and acute monopolar electrical stimulation at various parameters in electrode contacts located in amygdala and within lateral temporal cortex control locations. Stimulation was applied at either 50 Hz or 130 Hz, while amplitudes were increased stepwise from 1 to 12 V, with subjects blinded to stimulation condition. Electrodermal activity (EDA), heart rate (HR), and respiratory rate (RR) were simultaneously recorded and subjective emotional response was probed after each stimulation period. Amygdala stimulation (but not lateral control or sham stimulation) elicited immediate and substantial dose-dependent increases in EDA and decelerations of HR, generally without affecting RR. Stimulation elicited subjective emotional responses only rarely, and did not elicit clinical seizures in any subject. These physiological results parallel stimulation findings with animals and are consistent with orienting/defensive responses observed with aversive visual stimuli in humans. In summary, these findings suggest that acute amygdala stimulation in humans can be safe and can reliably elicit changes in emotion physiology without significantly affecting subjective emotional experience, providing a useful approach for investigation of amygdala-mediated modulatory effects on cognition.
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Gregory A. Fonzo;
Madeleine S. Goodkind;
Desmond J. Oathes;
Yevgeniya V. Zaiko;
Meredith Harvey;
Kathy K. Peng;
M. Elizabeth Weiss;
Allison L. Thompson;
Sanno E. Zack;
Colleen E. Mills-Finnerty;
Benjamin M. Rosenberg;
Raleigh Edelstein;
Rachael N. Wright;
Carena A. Kole;
Steven E. Lindley;
Bruce A. Arnow;
Booil Jo;
James J. Gross;
Barbara Rothbaum;
Amit Etkin
Objective: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms. Method: Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or awaiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively. Results: Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayeda greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum. Conclusions: Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.
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Krishnapriya Ramanujam;
Michael B. Himle;
Loran P. Hayes;
Douglas W. Woods;
Lawrence Scahill;
Denis G. Sukhodolsky;
Sabine Wilhelm;
Thilo Deckersbach;
Alan L. Peterson;
Matt Specht;
John T. Walkup;
Susanna Chang;
John Piacentini
Although tics are the defining feature of chronic tic disorders (CTD), many children experience comorbid internalizing and externalizing problems that contribute to impairment across several domains, including family functioning. The current study examined clinical correlates and predictors of caregiver strain in parents of children with CTD. Participants were 123 children and adolescents diagnosed with a CTD who participated in a randomized-controlled trial of behavior therapy for reducing tics. Results showed that a combination of disruptive behavior, inattention/hyperactivity, and tic intensity best explained objective strain, and a combination of inattention/hyperactivity and tic intensity were the best predictors of subjective caregiver strain. Implications of these findings for care providers are discussed.
Post-traumatic stress disorder (PTSD) develops in only some people following trauma exposure, but the mechanisms differentially explaining risk versus resilience remain largely unknown. PTSD is heritable but candidate gene studies and genome-wide association studies (GWAS) have identified only a modest number of genes that reliably contribute to PTSD. New gene-based methods may help identify additional genes that increase risk for PTSD development or severity. We applied gene-based testing to GWAS data from the Grady Trauma Project (GTP), a primarily African American cohort, and identified two genes (NLGN1 and ZNRD1-AS1) that associate with PTSD after multiple test correction. Although the top SNP from NLGN1 did not replicate, we observed gene-based replication of NLGN1 with PTSD in the Drakenstein Child Health Study (DCHS) cohort from Cape Town. NLGN1 has previously been associated with autism, and it encodes neuroligin 1, a protein involved in synaptogenesis, learning, and memory. Within the GTP dataset, a single nucleotide polymorphism (SNP), rs6779753, underlying the gene-based association, associated with the intermediate phenotypes of higher startle response and greater functional magnetic resonance imaging activation of the amygdala, orbitofrontal cortex, right thalamus and right fusiform gyrus in response to fearful faces. These findings support a contribution of the NLGN1 gene pathway to the neurobiological underpinnings of PTSD.
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Maureen S. Durkin;
Mayada Elsabbagh;
Josephine Barbaro;
Melissa Gladstone;
Francesca Happe;
Rosa A. Hoekstra;
Li-Ching Lee;
Alexia Rattazzi;
Jennifer Stapel-Wax;
Wendy L. Stone;
Helen Tager-Flusberg;
Audrey Thurm;
Mark Tomlinson;
Andy Shih
The Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scale (WMS) are 2 of the most common psychological tests used in clinical care and research in neurology. Newly revised versions of both instruments (WAIS-IV and WMS-IV) have recently been published and are increasingly being adopted by the neuropsychology community. There have been significant changes in the structure and content of both scales, leading to the potential for inaccurate patient classification if algorithms developed using their predecessors are employed. There are presently insufficient clinical data in neurologic populations to insure their appropriate application to neuropsychological evaluations. We provide a perspective on these important new neuropsychological instruments, comment on the pressures to adopt these tests in the absence of an appropriate evidence base supporting their incremental validity, and describe the potential negative impact on both patient care and continuing research applications.
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Naomi R Wray;
Stephan Ripke;
Manuel Mattheisen;
Maciej Trzaskowski;
Enda M Byrne;
Abdel Abdellaoui;
Mark J Adams;
Esben Agerbo;
Tracy M Air;
Elisabeth Binder
Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.
The last 25 years have seen profound changes in neurocognitive rehabilitation that continue to motivate its evolution. Although the concept of nervous system plasticity was discussed by William James (1890), the foundation for experience-based plasticity had not reached the critical empirical mass to seriously impact rehabilitation research until after 1992. The objective of this review is to describe how the emergence of neural plasticity has changed neurocognitive rehabilitation research. Method: The important developments included (a) introduction of a widely available tool that could measure brain plasticity (i.e., functional MRI); (b) development of new structural imaging techniques that could define limits of and opportunities for neural plasticity; (c) deployment of noninvasive brain stimulation to leverage neural plasticity for rehabilitation; (d) growth of a literature indicating that exercise has positively impacts neural plasticity, especially for older persons; and (e) enhancement of neural plasticity by creating interventions that generalize beyond the boundaries of treatment activities. Given the massive literature, each of these areas is developed by example. Results: The expanding influence of neural plasticity has provided new models and tools for neurocognitive rehabilitation in neural injuries and disorders, as well as methods for measuring neural plasticity and predicting its limits and opportunities. Early clinical trials have provided very encouraging results. Conclusion: Now that neural plasticity has gained a firm foothold, it will continue to influence the evolution of neurocognitive rehabilitation research for the next 25 years and advance rehabilitation for neural injuries and disease.
Physical activity (PA) interventions constitute a critical component of cardiovascular disease (CVD) risk reduction programs. Objective mobile health (mHealth) software applications (apps) and wearable activity monitors (WAMs) can advance both assessment and integration of PA counseling in clinical settings and support community-based PA interventions. The use of mHealth technology for CVD risk reduction is promising, but integration into routine clinical care and population health management has proven challenging. The increasing diversity of available technologies and the lack of a comprehensive guiding framework are key barriers for standardizing data collection and integration. This paper reviews the validity, utility and feasibility of implementing mHealth technology in clinical settings and proposes an organizational framework to support PA assessment, counseling and referrals to community resources for CVD risk reduction interventions. This integration framework can be adapted to different clinical population needs. It should also be refined as technologies and regulations advance under an evolving health care system landscape in the United States and globally.