White matter predicts tDCS antidepressant effects in a sham-controlled clinical trial study.

Transcranial direct current stimulation (tDCS) has been used as treatment for depression, but its effects are heterogeneous. We investigated, in a subsample of the clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECTTDCS), whether white matter areas associated with depression disorder were associated with tDCS response. Baseline diffusion tensor imaging data were analyzed from 49 patients (34 females, mean age 41.9) randomized to escitalopram 20 mg/day, tDCS (2 mA, 30 min, 22 sessions), or placebo. Antidepressant outcomes were assessed by Hamilton Depression Rating Scale-17 (HDRS) after 10-week treatment. We used whole-brain tractography for extracting white matter measures for anterior corpus callosum, and bilaterally for cingulum bundle, striato-frontal, inferior occipito-frontal fasciculus and uncinate. For the rostral body, tDCS group showed higher MD associated with antidepressant effects (estimate = -5.13 ± 1.64, p = 0.002), and tDCS significantly differed from the placebo and the escitalopram group. The left striato-frontal tract showed higher FA associated with antidepressant effects (estimate = -2.14 ± 0.72, p = 0.003), and tDCS differed only from the placebo group. For the right uncinate, the tDCS group lower AD values were associated with higher HDRS decrease (estimate = -1.45 ± 0.67, p = 0.031). Abnormalities in white matter MDD-related areas are associated with tDCS antidepressant effects. Suggested better white matter microstructure of the left prefrontal cortex was associated with tDCS antidepressant effects. Future studies should investigate whether these findings are driven by electric field diffusion and density in these areas.

A narrative review on invasive brain stimulation for treatment-resistant depression

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Treatment-resistant bipolar depression: concepts and challenges for novel interventions

Treatment-resistant bipolar depression (TRBD) has been reported in about one-quarter of patients with bipolar disorders, and few interventions have shown clear and established effectiveness. We conducted a narrative review of the published medical literature to identify papers discussing treatment-resistant depression concepts and novel interventions for bipolar depression that focus on TRBD. We searched for potentially relevant English-language articles published in the last decade. Selected articles (based on the title and abstract) were retrieved for a more detailed evaluation. A number of promising new interventions, both pharmacological and non-pharmacological, are being investigated for TRBD treatment, including ketamine, lurasidone, D-cycloserine, pioglitazone, N-acetylcysteine, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, cyclooxygenase 2 inhibitors, magnetic seizure therapy, intermittent theta-burst stimulation, deep transcranial magnetic stimulation, vagus nerve stimulation therapy, and deep brain stimulation. Although there is no consensus about the concept of TRBD, better clarification of the neurobiology associated with treatment non-response could help identify novel strategies. More research is warranted, mainly focusing on personalizing current treatments to optimize response and remission rates.

A narrative review on invasive brain stimulation for treatment-resistant depression.

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Treatment-resistant bipolar depression: concepts and challenges for novel interventions.

Treatment-resistant bipolar depression (TRBD) has been reported in about one-quarter of patients with bipolar disorders, and few interventions have shown clear and established effectiveness. We conducted a narrative review of the published medical literature to identify papers discussing treatment-resistant depression concepts and novel interventions for bipolar depression that focus on TRBD. We searched for potentially relevant English-language articles published in the last decade. Selected articles (based on the title and abstract) were retrieved for a more detailed evaluation. A number of promising new interventions, both pharmacological and non-pharmacological, are being investigated for TRBD treatment, including ketamine, lurasidone, D-cycloserine, pioglitazone, N-acetylcysteine, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, cyclooxygenase 2 inhibitors, magnetic seizure therapy, intermittent theta-burst stimulation, deep transcranial magnetic stimulation, vagus nerve stimulation therapy, and deep brain stimulation. Although there is no consensus about the concept of TRBD, better clarification of the neurobiology associated with treatment non-response could help identify novel strategies. More research is warranted, mainly focusing on personalizing current treatments to optimize response and remission rates.

Coadministration of lithium and celecoxib reverses manic-like behavior and decreases oxidative stress in a dopaminergic model of mania induced in rats.

The present study intends to investigate the effect of lithium (Li) and celecoxib (Cel) coadministration on the behavioral status and oxidative stress parameters in a rat model of mania induced by dextroamphetamine (d-AMPH). Male Wistar rats were treated with d-AMPH or saline (Sal) for 14 days; on the 8th day of treatment, rats received lithium (Li), celecoxib (Cel), Li plus Cel, or water until day 14. Levels of oxidative stress parameters were evaluated in the serum, frontal cortex, and hippocampus. d-AMPH administration induced hyperlocomotion in rats, which was significantly reversed by Li and Cel coadministration. In addition, d-AMPH administration induced damage to proteins and lipids in the frontal cortex and hippocampus of rats. All these impairments were reversed by treatment with Li and/or Cel, in a way dependent on cerebral area and biochemical analysis. Li and Cel coadministration reversed the d-AMPH-induced decrease in catalase activity in cerebral structures. The activity of glutathione peroxidase was decreased in the frontal cortex of animals receiving d-AMPH, and treatment with Li, Cel, or a combination thereof reversed this alteration in this structure. Overall, data indicate hyperlocomotion and alteration in oxidative stress biomarkers in the cerebral structures of rats receiving d-AMPH. Li and Cel coadministration can mitigate these modifications, comprising a potential novel approach for BD therapy.

Structural and functional neuroimaging studies in generalized anxiety disorder: a systematic review

Objectives: Brain imaging studies carried out in patients suffering from generalized anxiety disorder (GAD) have contributed to better characterize the pathophysiological mechanisms underlying this disorder. The present study reviews the available functional and structural brain imaging evidence on GAD, and suggests further strategies for investigations in this field. Methods: A systematic literature review was performed in PubMed, PsycINFO, and Google Scholar, aiming to identify original research evaluating GAD patients with the use of structural and functional magnetic resonance imaging as well as diffusion tensor imaging. Results: The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex, anterior cingulate, posterior parietal regions, and amygdala in both pediatric and adult GAD patients, mostly in the right hemisphere. However, the literature is often tentative, given that most studies have employed small samples and included patients with comorbidities or in current use of various medications. Finally, different methodological aspects, such as the type of imaging equipment used, also complicate the generalizability of the findings. Conclusions: Longitudinal neuroimaging studies with larger samples of both juvenile and adult GAD patients, as well as at risk individuals and unaffected relatives, should be carried out in order to shed light on the specific biological signature of GAD.

Structural and functional neuroimaging studies in generalized anxiety disorder: a systematic review.

OBJECTIVES: Brain imaging studies carried out in patients suffering from generalized anxiety disorder (GAD) have contributed to better characterize the pathophysiological mechanisms underlying this disorder. The present study reviews the available functional and structural brain imaging evidence on GAD, and suggests further strategies for investigations in this field. METHODS: A systematic literature review was performed in PubMed, PsycINFO, and Google Scholar, aiming to identify original research evaluating GAD patients with the use of structural and functional magnetic resonance imaging as well as diffusion tensor imaging. RESULTS: The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex, anterior cingulate, posterior parietal regions, and amygdala in both pediatric and adult GAD patients, mostly in the right hemisphere. However, the literature is often tentative, given that most studies have employed small samples and included patients with comorbidities or in current use of various medications. Finally, different methodological aspects, such as the type of imaging equipment used, also complicate the generalizability of the findings. CONCLUSIONS: Longitudinal neuroimaging studies with larger samples of both juvenile and adult GAD patients, as well as at risk individuals and unaffected relatives, should be carried out in order to shed light on the specific biological signature of GAD.

Smaller left anterior cingulate cortex in non-bipolar relatives of patients with bipolar disorder

Objective: Bipolar disorder (BD) is highly heritable. The present study aimed at identifying brain morphometric features that could represent markers of BD vulnerability in non-bipolar relatives of bipolar patients. Methods: In the present study, structural magnetic resonance imaging brain scans were acquired from a total of 93 subjects, including 31 patients with BD, 31 non-bipolar relatives of BD patients, and 31 healthy controls. Volumetric measurements of the anterior cingulate cortex (ACC), lateral ventricles, amygdala, and hippocampus were completed using the automated software FreeSurfer. Results: Analysis of covariance (with age, gender, and intracranial volume as covariates) indicated smaller left ACC volumes in unaffected relatives as compared to healthy controls and BD patients (p = 0.004 and p = 0.037, respectively). No additional statistically significant differences were detected for other brain structures. Conclusion: Our findings suggest smaller left ACC volume as a viable biomarker candidate for BD.

Smaller left anterior cingulate cortex in non-bipolar relatives of patients with bipolar disorder.

OBJECTIVE: Bipolar disorder (BD) is highly heritable. The present study aimed at identifying brain morphometric features that could represent markers of BD vulnerability in non-bipolar relatives of bipolar patients. METHODS: In the present study, structural magnetic resonance imaging brain scans were acquired from a total of 93 subjects, including 31 patients with BD, 31 non-bipolar relatives of BD patients, and 31 healthy controls. Volumetric measurements of the anterior cingulate cortex (ACC), lateral ventricles, amygdala, and hippocampus were completed using the automated software FreeSurfer. RESULTS: Analysis of covariance (with age, gender, and intracranial volume as covariates) indicated smaller left ACC volumes in unaffected relatives as compared to healthy controls and BD patients (p = 0.004 and p = 0.037, respectively). No additional statistically significant differences were detected for other brain structures. CONCLUSION: Our findings suggest smaller left ACC volume as a viable biomarker candidate for BD.

Skin picking disorder: prevalence, correlates, and associations with quality of life in a large sample.

OBJECTIVE: Evidence suggests that skin picking disorder (SPD) could be a prevalent condition associated with comorbidity and psychosocial dysfunction. However, just a few studies have assessed the prevalence and correlates of SPD in samples from low- and middle-income countries. In addition, the impact of SPD on quality of life (QoL) dimension after multivariable adjustment to potential confounders remains unclear. METHODS: Data were obtained from a Brazilian anonymous Web-based research platform. Participants provided sociodemographic data and completed the modified Skin Picking-Stanford questionnaire, the Hypomania Checklist (HCL-32), the Patient Health Questionnaire-9 (PHQ-9), the Fagerström Test for Nicotine Dependence, Alcohol Use Disorder Identification Test (AUDIT), Symptom Checklist-90-Revised inventory (SCL-90R), early trauma inventory self report-short form, and the World Health Organization quality of life abbreviated scale (WHOQOL-Bref). Associations were adjusted to potential confounders through multivariable models. RESULTS: For our survey, 7639 participants took part (71.3% females; age: 27.2±7.9 years). The prevalence of SPD was 3.4% (95% CI: 3.0-3.8%), with a female preponderance (P<0.001). In addition, SPD was associated with a positive screen for a major depressive episode, nicotine dependence, and alcohol dependence, as well as suicidal ideation. Physical and psychological QoL was significantly more impaired in participants with SPD compared to those without SPD, even after adjustment for comorbidity. CONCLUSIONS: In this large sample, SPD was a prevalent condition associated with co-occurring depression, nicotine, and alcohol dependence. In addition, SPD was independently associated with impaired physical and psychological QoL. Public health efforts toward the early recognition and treatment of SPD are warranted.

An exploratory study of the heterogeneity of the jealousy phenomenon and its associations with affective temperaments and psychopathological dimensions in a large Brazilian sample.

BACKGROUND: Jealousy is a heterogenous emotion on a spectrum from normality to psychopathology. The relationship between different jealousy subtypes/dimensions and affective temperaments remain unknown. In addition, few large surveys have investigated the associations between jealousy subtypes and psychopathological dimensions. METHODS: A Brazilian Portuguese version of the "Questionario della Gelosia" (QUEGE) was developed. We obtained data from an anonymous web-based research platform. Socio-demographic data was obtained and participants answered the QUEGE, the TEMPS-Rio de Janeiro, and the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: 2042 participants (29% men, 71% female, mean age+SD: 28.9±8.8 years), took part in this survey. Confirmatory factor analysis provided a five-factor model for the QUEGE with self-esteem, paranoia, interpersonal sensitivity, fear of being abandoned, and obsessive dimensions. The anxious, irritable, cyclothymic, and depressive temperaments were independently associated with jealousy dimensions, whereas the hyperthymic temperament was associated with lower scores on the self-esteem jealousy dimension (N=2042, P<0.001). Jealousy subtypes were dissimilarly associated with SCL-90R psychopathological dimensions, whereas the 'obsessive' jealousy dimension was not significantly associated with SCL-90R dimension scores. We found no independent influence of gender across any jealousy dimension. LIMITATIONS: A convenience web-based sample was employed. Cross-sectional design precludes the establishment of causal inferences. CONCLUSIONS: Our data indicate that a five-factor solution may provide the best-fit model for the QUEGE. Different jealousy subtypes were independently associated with affective temperaments and psychopathological dimensions. These associations reported herein should be confirmed in prospective studies.