Adiponectin in anorexia nervosa and its modifiers: A meta-regression study.

OBJECTIVE: Adiponectin, which is secreted from adipose tissue, is a protein hormone. Although a large body of studies have found that circulating adiponectin levels increase in anorexia nervosa (AN) and caloric restriction, the effect of subtypes of AN and modifiers of adiponectin in AN are not yet known. METHODS: A systematic search of electronic databases was performed using the search terms "adiponectin," "anorexia nervosa," and "eating disorder" up to January 2021. All studies published in peer-reviewed journals, which included cases and control groups, were selected. The main outcome was the pooled standardized mean difference (SMD) in adiponectin levels between cases and controls, using the random-effects model. Modifiers of SMD were tested via meta-regression. Heterogeneity and publication bias were evaluated. RESULTS: Thirty-four studies met all eligibility criteria. The total sample of AN participants (Hedges' g = .765, p < .0001), and specifically the binge-eating/purging (Hedges' g = 1.211, p < .00001) and restrictive subtypes (Hedges' g = .913, p < .00001) of AN have increased adiponectin plasma levels compared with healthy controls. Meta-regression determined that insulin, IGF-1, BMI, triglyceride, resistin, glucose, IL-6 levels are significant modifiers of adiponectin levels. DISCUSSION: Compared with controls, adiponectin levels are higher in AN overall, and specifically in the binge-eating/purging and the restrictive AN subtypes. Many of metabolic parameters of glucose metabolism and pro-inflammatory molecules modify the relationship between AN and adiponectin levels. Adipose tissue is important to maintain metabolic stability. PUBLIC SIGNIFICANCE: Anorexia nervosa is a psychiatric disorder associated with a severe decrease in body weight and multiple metabolic abnormalities, including an increase in the hormone adiponectin. In this paper, we used meta-analysis, a powerful statistical method, to aggregate data from 34 rigorously selected research reports. This enabled us to understand the value of adiponectin to differentiate clinical subtypes of anorexia nervosa and the relations between adiponectin and other important metabolic parameters.

OBJETIVO: La adiponectina, que es secretada del tejido adiposo, es una hormona proteica. Aunque una gran cantidad de estudios han encontrado que los niveles circulantes de adiponectina aumentan en la anorexia nerviosa (AN) y la restricción calórica, el efecto de los subtipos de AN y los modificadores de la adiponectina en la AN aún no se conocen. MÉTODOS: Se realizó una búsqueda sistemática en bases de datos electrónicas utilizando los términos de búsqueda "adiponectina", "anorexia nerviosa" y "trastorno de la conducta alimentaria" hasta enero de 2021. Se seleccionaron todos los estudios publicados en revistas revisadas por pares, que incluían casos y grupos de control. El resultado principal fue la diferencia de medias estandarizada (DME) agrupada en los niveles de adiponectina entre los casos y los controles, mediante el modelo de efectos aleatorios. Los modificadores de DME se probaron mediante metarregresión. Se evaluaron la heterogeneidad y el sesgo de publicación. RESULTADOS: Treinta y cuatro estudios cumplieron todos los criterios de elegibilidad. La muestra total de sujetos con AN (g de Hedges = 0.765, p < 0.0001), y específicamente los subtipos de atracones/purgaciones (g = 1,211 de Hedges, p < 0.00001) y restrictivos (g = 0.913, p < 0.00001) de AN tienen incrementados los niveles plasmáticos de adiponectina en comparación con los controles sanos. La metarregresión determinó que los niveles de insulina, IGF-1, IMC, triglicéridos, resistina, glucosa, IL-6 son modificadores significativos de los niveles de adiponectina. DISCUSIÓN: En comparación con los controles, los niveles de adiponectina son más altos en la AN en general, y específicamente en los subtipos de atracones/purgaciones y AN restrictiva. Muchos de los parámetros metabólicos del metabolismo de la glucosa y las moléculas proinflamatorias modifican la relación entre los niveles de AN y adiponectina. El tejido adiposo es importante para mantener la estabilidad metabólica.

Comparison of Sodium Lactate Infusion and Carbon Dioxide Inhalation Panic Provocation Tests: A Meta-analysis.

BACKGROUND: Sodium lactate (NaL) infusion and carbon dioxide (CO2) inhalation are proven to provoke acute panic attacks (PAs) in patients with panic disorder (PD). A systematic literature search and meta-analysis were performed to compare the effect sizes of these methods. METHODS: Odds ratios were calculated for each of the original studies and were pooled using the random-effects model. RESULTS: Either NaL or CO2 provocations significantly increased the rates of PAs in individuals with PD compared to those in healthy controls. However, the effect size of NaL infusion (OR=25.13, 95% CI=15.48-40.80) was significantly greater than that of CO2 inhalation (OR=10.58, 95%CI=7.88-14.21). CONCLUSION: The evidence for the efficacy of the two panic provocation tests is very strong. Yet, the results support the superiority of NaL infusion over CO2 inhalation challenge as a panic provocation test. Thus, lactate seems a much stronger stimulus than CO2 for the brain suffocation detector.

Neuropeptide Y in PTSD, MDD, and chronic stress: A systematic review and meta-analysis.

Previous studies have suggested that neuropeptide Y (NPY) levels may be altered in patients with major depressive disorder (MDD), post-traumatic stress disorder (PTSD) and chronic stress. We investigated, through systematic review and meta-analysis, whether the mean levels of NPY are significantly different in patients with MDD, PTSD or chronic stress, compared to controls. The main outcome was the pooled standardized mean difference (SMD) with 95% confidence intervals between cases and controls, using the random-effects model. Heterogeneity and publication bias were evaluated. Thirty-five studies met eligibility criteria. Meta-regression determined that medication and sex could explain 27% of the between-study variance. Females and participants currently prescribed psychotropic medications had significantly higher levels of NPY. NPY levels were significantly lower in plasma and cerebrospinal fluid (CSF) in PTSD patients versus controls. Patients with MDD had significantly lower levels of NPY in plasma compared to controls, but not in the CSF. The magnitudes of the decrease in plasma NPY levels were not significantly different between PTSD and MDD. However, chronic stress patients had significantly higher plasma NPY levels compared to controls, PTSD or MDD. Our findings may imply a shared role of NPY in trauma and depression: nevertheless, it is not clear that the association is specific to these disorders. Psychotropic medications may help restore NPY levels. Further controlled studies are needed to better delineate the contribution of confounding variables such as type of depression, body mass index, appetite or sleep architecture.

Plasma Neuronal and Glial Markers and Anterior Cingulate Metabolite Levels in Major Depressive Disorder: A Pilot Study.

INTRODUCTION: Neuroglial functions may be deteriorated in major depressive disorder (MDD). OBJECTIVE: To evaluate the markers of glial and neuronal cell turnover and to explore their associations with brain metabolites. METHODS: In 10 participants with MDD and 10 healthy controls (HC) we investigated neuronal and glial plasma markers (the neuron-specific enolase, NSE; and S100beta, S100B) and brain metabolites (N-acetyl aspartate, NAA; total choline, Cho; and total creatine, Cr). Blood was collected for NSE and S100B. NAA, Cho, and Cr metabolite levels were measured in the anterior cingulate cortex (ACC) with proton magnetic resonance spectroscopy (1H-MRS) at 3T. RESULTS: NSE and S100B levels were significantly higher in MDD subjects than in HC. The Cr level was significantly higher in MDD subjects than in HC, but the NAA and Cho levels did not differ between groups. NAA/Cr and Cho/Cr ratios were significantly lower in patients with MDD versus HC. S100B was negatively correlated with the Cho levels. CONCLUSIONS: These results provide supporting evidence of neuronal and glial distress in MDD. Neuronal viability appears decreased, whereas glial regenerative activity and energy metabolism in the ACC increase in acute major depressive episode. Since low concentrations of S100B have neuroplastic effects, these changes may indicate a possible compensatory mechanism.

Proton magnetic resonance spectroscopic analysis of changes in brain metabolites following electroconvulsive therapy in patients with major depressive disorder.

Objectives: The aim of this study was to evaluate the metabolic changes in the anterior cingulate cortex (ACC) induced by electroconvulsive therapy (ECT) in patients with MDD via 1H-MRS.Methods: The study was conducted on 13 MDD patients receiving ECT treatment and 14 healthy controls matched in terms of age, gender and education. The patients underwent six sessions of ECT. 1H-MRS imaging and psychometric evaluations obtained before 1st and after the 6th sessions. The control group also went through the same procedures except for ECT. N-Acetyl aspartate (NAA), choline (Cho) and creatine (Cr) metabolite levels and the creatine to metabolite ratios were measured.Results: There was no significant difference in the ACC metabolite levels of the patients and those of the controls at the baseline. ECT associated with a statistically significant decrease in the NAA/Cr ratio in ACC. All of the patients had responded to ECT treatment as measured with the clinical scales.Conclusions: The results has suggested that indirect proof of an increase in energy metabolism without any evidence of impaired neuronal viability in the ACC induced by ECT. The relative increase in Cr levels following ECT in MDD seems to be associated with improvement in clinical severity.Key pointsECT is one the most effective method in the treatment of acute MDD.The mechanism of ECT's antidepressant activity remains unclear but it is thought to be related to the regulation of prefrontal cortical or cingulate areas.In this study the patients underwent six sessions of ECT and after 1H-MRS imaging.The study revealed that baseline levels of metabolites in patients with MDD were not significantly different than those of control group.

The Prevalence of Mitral Valve Prolapse in Panic Disorder: A Meta-Analysis.

BACKGROUND: Although most studies have suggested that mitral valve prolapse (MVP) is more prevalent in patients with panic disorder (PD) than in healthy controls, there is a substantial uncertainty in the rates of MVP across studies. OBJECTIVE: To investigate, through systematic review and meta-analysis, the relative risk of MVP in patients with PD compared to controls. METHODS: Embase, Proquest, Pubmed, and Google Scholar electronic databases were searched up to September 2018. All studies published in peer-reviewed journals, which included both PD and controls groups, were selected. Events (presence of MVP) and nonevents (absence of MVP) in PD and control groups were recorded. The main outcome was the measure of relative risk (RR) pooled with 95% confidence intervals, using fixed-effects model. Heterogeneity, small publication effect, and publication bias were evaluated. RESULTS: Fourteen studies, including 1146 participants, met eligibility criteria. There was no significant heterogeneity or publication bias. The prevalence of MVP in PD and healthy controls was 27.20% and 9.21%, respectively. Patients with PD had a significantly increased relative risk of MVP compared to controls in the pooled sample (RR = 2.469, 95% confidence interval = 1.848-3.300). Age did not significantly modify the RR. CONCLUSIONS: MVP is significantly more prevalent in patients with PD than in controls. This meta-analysis of published studies is sufficient to establish an association between PD and MVP; nevertheless, it is not clear that the association is specific to PD. Patients with PD should be evaluated for MVP to decrease possible negative adverse consequences of MVP.

The prevalence of childhood psychopathology in Turkey: a cross-sectional multicenter nationwide study (EPICPAT-T).

AIM: The aim of this study was to determine the prevalence of childhood psychopathologies in Turkey. METHOD: A nation-wide, randomly selected, representative population of 5830 children (6-13 years-old) enrolled as a 2nd,3rd or 4th grade student in 30 cities were evaluated for presence of a psychiatric or mental disorder by a Sociodemographic Form, Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL), and DSM-IV-Based Screening Scale for Disruptive Behavior Disorders in Children and Adolescents scales. Impairment criterion was assessed via a 3 point-Likert scale by the parent and the teacher independently. RESULTS: Overall prevalence of any psychopathology was 37.6% without impairment criterion, and 17.1% with impairment criterion. Attention-deficit hyperactivity disorder was the most frequent diagnosis, followed by anxiety (19.5% and 16.7% without impairment, 12.4% and 5.3% with impairment, respectively). Lower education level and presence of a physical or psychiatric problem of the parents were independent predictors of any psychopathology of the offspring. CONCLUSION: This is the largest and most comprehensive epidemiological study to determine the prevalence of psychopathologies in children and adolescents in Turkey. Our results partly higher than, and partly comparable to previous national and international studies. It also contributes to the literature by determining the independent predictors of psychopathologies in this age group.

Double Blind Controlled Study of Adding Folic Acid to Fluoxetine in the Treatment of OCD.

BACKGROUND: Folate is important for the synthesis of serotonin the neurotransmitter which plays a main role in OCD. We, therefore, explored the efficacy of folic acid as add on treatment to fluoxetine in a double blind study among patients with OCD. SUBJECTS AND METHODS: A double blind, 12-week study comparing the efficacy of folic acid as add on treatment and placebo in patients with OCD was conducted on thirty six (36) patients. Patients were randomly assigned to folic acid (5 mg/day) or placebo group in addition to fluoxetine (40 mg/day). After the baseline assessment, on week 2, 4, 6, 8 and 12 assessments were performed by using YBOCS, HAM-D, HAM-A and CGI-S. Serum folate, erythrocyte folate, serum homocysteine and B12 levels were measured both baseline and the end of study. RESULTS: A mixed model repeated measures ANCOVA on Y-BOCS scores were used to determine the difference between folic acid and placebo groups. No significant differences were found in the ratios of gender or in the mean age, serum folic acid level, erythrocyte folate level, serum homocysteine level and serum B12 level between the treatment groups at the baseline. Consecutively scores collected over six measurements on YBOCS, HAM-D, HAM-A and CGI showed non-significant differences between folic acid and placebo groups. CONCLUSION: None of the biological markers of one carbon metabolism were associated with the change in YBOCS scores. It may be assumed that there is no beneficial effect of folic acid addition to fluoxetine in the treatment of OCD.

Efficacy of Transcranial Photobiomodulation on Depressive Symptoms: A Meta-Analysis.

Background: Transcranial photobiomodulation (tPBM) is a novel, noninvasive, device-based intervention, which has been tested as a possible treatment for various neurological and psychiatric conditions. Recently, it has been investigated as an innovative treatment for major depressive disorder (MDD). There have been several animal and clinical studies that evaluated the underlying mechanism and the efficacy of its antidepressant effects, but results have been conflicting. Objective: Thus, we conducted the first meta-analysis on effects of tPBM on depressive symptoms. Materials and methods: Thirty original articles on tPBM were retrieved, eight of them met criteria for inclusion to a random effects meta-analysis. Results: tPBM appeared effective in decreasing depressive symptom severity regardless of diagnosis (Hedges' g = 1.415, p < 0.001, k = 8), but a significant heterogeneity has been found. The meta-analysis of single-arm studies (baseline to endpoint changes) limited to participants with MDD has supported the significant effect of tPBM in reducing the depression severity, without a significant heterogeneity (Hedges' g = 1.142, 95% confidence interval = 0.780-1.504, z = 6.19, p < 0.001, k = 5). However, the meta-analysis of the few double-blind, sham-controlled studies in MDD has not supported the statistically significant superiority of tPBM over sham (Hedges' g = 0.499, p = 0.211, k = 3), although a sample size bias is likely present. Conclusions: Overall, this meta-analysis provides weak support for the promising role of tPBM in the treatment of depressive symptoms. Dose finding studies to determine optimal tPBM parameters followed by larger, randomized, sham-controlled studies will be needed to fully demonstrate the antidepressant efficacy of tPBM.

Comparison of Adiponectin Levels in Anorexia Nervosa, Bulimia Nervosa, Binge-Eating Disorder, Obesity, Constitutional Thinness, and Healthy Controls: A Network Meta-Analysis.

Adiponectin is a protein hormone that is produced and secreted primarily by adipose tissue. The levels of adiponectin in those with eating disorders, obesity, and healthy controls have been extensively studied. However, the general picture of the differences in adiponectin levels across the mentioned conditions is still unclear and fragmented. In this study, we pooled previous studies and performed a network meta-analysis to gain a global picture of comparisons of adiponectin levels across eating disorders, obesity, constitutional thinness, and healthy controls. Electronic databases were searched for anorexia nervosa, avoidant restrictive food intake disorder, binge-eating disorder, bulimia nervosa, healthy controls, night eating syndrome, obesity, and constitutional thinness in studies where adiponectin levels were measured. A total of 4262 participants from 50 published studies were included in the network meta-analysis. Adiponectin levels were significantly higher in participants with anorexia nervosa than in healthy controls (Hedges' g = 0.701, p < 0.001). However, adiponectin levels in constitutionally thin participants were not significantly different from those of healthy controls (Hedges' g = 0.470, p = 0.187). Obesity and binge-eating disorder were associated with significantly lower adiponectin levels compared to those of healthy controls (Hedges' g = -0.852, p < 0.001 and Hedges' g = -0.756, p = 0.024, respectively). The disorders characterized by excessive increases or decreases in BMI were associated with significant changes in adiponectin levels. These results suggest that adiponectin may be an important marker of severely disequilibrated homeostasis, especially in fat, glucose, and bone metabolisms. Nonetheless, an increase in adiponectin may not simply be associated with a decrease in BMI, as constitutional thinness is not associated with a significant increase in adiponectin.

Personality characteristics, not clinical symptoms, are associated with anhedonia in a community sample: A preliminary investigation.

Anhedonia is a salient transdiagnostic psychiatric symptom associated with increased illness severity and chronicity. Anhedonia is also present to varying degrees in non-clinical cohorts. Here, we sought to examine factors influencing expression of anhedonia. Participants (N = 335) were recruited through the Nathan Kline Institute-Rockland Sample, an initiative to deeply phenotype a large community sample across the lifespan. Utilizing a data-driven approach, we evaluated associations between anhedonia severity, indexed by Snaith-Hamilton Pleasure Scale (SHAPS), and 20 physical, developmental, and clinical measures, including Structured Clinical Interview for DSM-IV, Beck Depression Inventory, State-Trait Anxiety Inventory, NEO Five-Factor Inventory-3 (NEO-FFI-3), BMI, Hemoglobin A1C, and demography. Using a bootstrapped AIC-based backward selection algorithm, seven variables were retained in the final model: NEO-FFI-3 agreeableness, extraversion, and openness to experience; BMI; sex; ethnicity; and race. Though median SHAPS scores were greater in participants with psychiatric diagnoses (18.5) than those without (17.0) (U = 12238.5, z = 2.473, p = 0.013), diagnosis and symptom measures were not retained as significant predictors in the final robust linear model. Participants scoring higher on agreeableness, extraversion, and openness to experience reported significantly lower anhedonia. These results demonstrate personality as a mild-to-moderate but significant driver of differences in experiencing pleasure in a community sample.

Stigma: a core factor on predicting functionality in bipolar disorder.

OBJECTIVE: Extant literature indicates that bipolar disorder (BD) is associated with significant poor psychosocial functioning. However, the relationship between functioning and demographic and clinical variables is unclear. The aim of this study is to investigate the predictors of functioning such as demographic and clinical variables, social support, self-perceived stigma, and insight in remitted patients with BD. METHODS: Eighty patients with a diagnosis of BD, complete remission according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were included in the final assessment. Bipolar Disorder Functioning Questionnaire, Beck Depression Inventory, Young Mania Rating Scale, Internalized Stigma of Mental Illness Scale, Multidimensional Scale of Perceived Social Support, and Schedule for Assessing the Three Components of Insight were used. Student t test, Pearson correlation analyses, and linear regression analyses were used to assess the pathways effecting on functioning. RESULTS: The 3 predictors of functioning were severity of depression, perceived social support, and internalized stigmatization. Severity of depression is considered the strongest predictor, whereas internalized stigmatization has a core role in predicting functioning. Clinical variables such as years of education and number of hospitalization probably have indirect effects on functioning. CONCLUSION: Interventions that oppose stigmatization and consideration of mild depressive symptoms will positively affect functioning in remitted patients with BD.

Effect of depression on recovery from PTSD.

It has been suggested that the treatment strategy needs to be reviewed and changed if depression occurs in patients with posttraumatic stress disorder (PTSD). We analyzed data extracted from the Marmara Epidemiological Survey (MES) which had examined 683 survivors at 3 years after a devastating earthquake. Fifty three cases (40.5%) out of the 131 cases with PTSD had also been diagnosed with MDD. Comorbid PTSD and MDD group has significantly lower rates of recovery from PTSD in comparison to PTSD without MDD (26.4% vs. 47.4% respectively). Rates of past psychiatric disorder and past traumatic experience were significantly more frequent among the comorbid group. Moreover, comorbidity of PTSD and MDD was clearly associated with greater psychological distress, more severe PTSD, and diminished perceived social support. Past psychiatric disorder, General Health Questionnaire (GHQ-12) and Multidimensional Scale of Perceived Social Scale (MSPSS) total scores succeeded in predicting the comorbidity of PTSD and MDD significantly.

Separate pathways to violent behavior in schizophrenia and in the general population.

Violence in schizophrenia is best investigated within the broader context of violent behavior in the general population. Two important domains of general pathology which allow us to take such an approach include impairment in emotion processing, as manifested by faulty facial emotion recognition, and aggressive reactivity which consists of heightened sensitivity to provocation. To test this approach, we included 135 subjects: 38 violent (VS's) and 33 nonviolent patients with schizophrenia, 32 healthy controls and 32 non-psychotic violent subjects (NPV's). We measured violence with the Life History of Aggression Scale, recognition of facial emotions with the Emotion Recognition Task, and aggressive reactivity through the Buss-Perry Aggression Questionnaire. Adolescent antisocial behavior was evaluated as a potential precursor to these deficits. We found that impairment in fear recognition (IFR) and aggressive reactivity have a significant effect on violence in the violent groups. These two impairments interact in different ways in these groups. In NPV's they contribute in an additive fashion to violence, whereas in VS's they represent separate pathways; aggressive reactivity leads to violence only when there is no IFR. Adolescent antisocial behavior has a differential effect on these 2 impairments in the 2 groups. Thus, these findings provide insights on the differential role of IFR and aggressive reactivity for violence in schizophrenia compared to the general population. In NPV's, both dysfunctions represent antisocial features and contribute jointly to violence. In schizophrenia, they have different etiologies and constitute alternative pathways to violence. This has important implications for the conceptualization and treatment of violence.

Correlation between S100B and severity of depression in MDD: A meta-analysis.

BACKGROUND: Previous studies have demonstrated elevated levels of the S100B protein (located in glial cells) in major depressive disorder (MDD) as compared to healthy controls. However, studies reporting correlation between S100B levels and depression severity have been conflicting. METHODS: We investigated, through systematic review and meta-analysis, whether the correlation between S100B levels and depression severity is significant in patients with MDD. Pearson correlation coefficients reported in the individual studies were converted to Fisher's Z scores, then pooled using the random effects model. Meta-regression was used to test modifiers of the effect size. RESULTS: Sixteen studies including 658 patients with MDD met eligibility criteria. No publication bias was observed. There was a significant and positive correlation between serum S100B level and depression severity (r = 0.204, z = 2.297, p = 0.022). A meta-regression determined that onset age of MDD and percentage of female participants are significant modifiers of this correlation. A moderate, but non-significant heterogeneity was observed in serum studies (44%). CONCLUSION: As many studies have reported significantly increased levels of S100B in MDD compared to controls, this meta-analysis supports the assumption that the increase in S100B correlates with the severity of MDD. Additional studies investigating the precise biological connection between S100B and MDD are indicated.

Relationships between Diffusion Tensor Imaging and Resting State Functional Connectivity in Patients with Schizophrenia and Healthy Controls: A Preliminary Study.

Schizophrenia is widely seen as a disorder of dysconnectivity. Neuroimaging studies have examined both structural and functional connectivity in the disorder, but these modalities have rarely been integrated directly. We scanned 29 patients with schizophrenia and 25 healthy control subjects, and we acquired resting state fMRI and diffusion tensor imaging. We used the Functional and Tractographic Connectivity Analysis Toolbox (FATCAT) to estimate functional and structural connectivity of the default mode network. Correlations between modalities were investigated, and multimodal connectivity scores (MCS) were created using principal component analysis. Of the 28 possible region pairs, 9 showed consistent (>80%) tracts across participants. Correlations between modalities were found among those with schizophrenia for the prefrontal cortex, posterior cingulate, and lateral temporal lobes, with frontal and parietal regions, consistent with frontotemporoparietal network involvement in the disorder. In patients, MCS correlated with several aspects of the Positive and Negative Syndrome Scale, with higher multimodal connectivity associated with outward-directed (externalizing) behavior and lower multimodal connectivity related to psychosis per se. In this preliminary sample, we found FATCAT to be a useful toolbox to directly integrate and examine connectivity between imaging modalities. A consideration of conjoint structural and functional connectivity can provide important information about the network mechanisms of schizophrenia.

Affective and somatic symptom clusters in depression and their relationship to treatment outcomes in the STAR*D sample.

BACKGROUND: The heterogenous nature of depression continues to stymie efforts to identify biomarkers or predict treatment response. Efforts leveraging large datasets to define more uniform subtypes of depression or subgroups of depressed patients have considered only small subsets of symptoms. We aimed to understand how inclusion of more diverse complaints would impact data-emergent symptom and patient clusters. METHODS: We applied principal components analysis to baselineInventory of Depressive Symptomatology data from 1491 patients with major depressive disorder to derive naturally co-occurring symptom subsets before utilizing k-means clustering to divide patients into groups based on standardized residuals of each symptom subset score. We evaluated the clinical utility of our approach by comparing how cluster membership impacted response to citalopram. RESULTS: Prinicpal components analysis identified nine naturally co-occurring symptom subsets: core affective symptoms, appetite/weight loss, anxiety, somatic symptoms, insomnia, negative intrusive thoughts, leaden paralysis/mood quality, diurnal mood variation, and irritability. Cluster analysis identified two patient groups, differing significantly in 7 of 9 c symptom subsets. Patients distinguished by the prominence of somatic versus core affective symptoms exhibited less reduction in depression severity with citalopram treatment. LIMITATIONS: Results depend not only on raw data, but also parameter selection, and interpretation. Replication is indicated. CONCLUSIONS: Findings are consistent with previous reports linking somatic symptoms to treatment resistance and demonstrating that SSRIs are most effective in treating affective symptoms. A novel distinction between physical somatic symptoms and psychic anxiety highlights the utility of assessing a broad spectrum of symptoms when exploring heterogeneity in depression and the need for treatments targeting physical somatic symptoms specifically.

Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder: The ELATED-3 Multicenter, Randomized, Sham-Controlled Trial.

Background: Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light might represent a treatment for major depressive disorder (MDD). However, the dosimetry of administered t-PBM varies widely. We tested the efficacy of t-PBM with low irradiance, low energy per session, and low number of sessions in individuals with MDD.Methods: A 2-site, double-blind, sham-controlled study was conducted of adjunct t-PBM NIR (830 nm; continuous wave; 35.8 cm2 treatment area; 54.8 mW/cm2 irradiance; 65.8 J/cm2 fluence, 20 min/session; ~2 W total power; 2.3 kJ total energy per session), delivered to the prefrontal cortex, bilaterally, twice a week for 6 weeks, in subjects diagnosed with MDD per the DSM-IV criteria. Subjects were recruited between August 2016 and May 2018. A sequential parallel comparison design was used: 18 nonresponders to sham in phase 1 (6 weeks) were re-randomized in phase 2. The primary outcome was reduction in depression severity (Hamilton Depression Rating Scale [HDRS-17] and Quick Inventory of Depressive Symptomatology-Clinician Rating [QIDS-C] scores) from baseline. Statistical analyses used R package SPCDAnalyze2, including all subjects with ≥ 1 post-randomization evaluation.Results: Of the 54 subjects recruited, we included 49 MDD subjects in the analysis (71% female, mean ± SD age 40.8 ± 16.1 years). There were no significant differences between t-PBM and sham with respect to the change in HDRS-17 (t = -0.319, P = .751) or QIDS-C (t = -0.499, P = .620) scores. The sham effect was reasonably low.Conclusions: Mostly uncontrolled studies suggest the efficacy of t-PBM for MDD; however, its optimal dose is still to be defined. A minimal dose threshold is likely necessary, similarly to other neuromodulation techniques in MDD (electroconvulsive therapy, transcranial magnetic stimulation). We established a threshold of inefficacy of t-PBM for MDD, based on combined low irradiance, low energy per session, and low number of sessions.Trial Registration: ClinicalTrials.gov identifier: NCT02959307.

Effect of Impairment on the Prevalence and Comorbidities of Attention Deficit Hyperactivity Disorder in a National Survey: Nation-Wide Prevalence and Comorbidities of ADHD.

OBJECTIVE: This study aimed to determine the prevalence and comorbidities of attention-deficit hyperactivity disorder (ADHD) by evaluating a large-scale nation-wide sample of children. METHOD: The inclusion criterion was being enrolled as a 2nd, 3rd, or 4th-grade student. A semi-structured diagnostic interview (K-SADS-PL), DSM-IV-Based Screening Scale for Disruptive Behavior Disorders, and assessment of impairment (by both parents and teachers) were applied to 5,842 participants. RESULTS: The prevalence of ADHD was 19.5% without impairment and 12.4% with impairment. Both ADHD with and without impairment groups had similar psychiatric comorbidity rates except for oppositional defiant disorder (ODD) and conduct disorder (CD) diagnoses. Impairment in the ADHD group resulted in significantly higher ODD and CD diagnoses. CONCLUSION: Even when impairment is not described, other psychiatric disorders accompany the diagnosis of ADHD and may cause impairment in the future. Impairment in the diagnosis of ADHD significantly increases the likelihood of ODD and CD.

Comparison of alprazolam versus captopril in high blood pressure: a randomized controlled trial.

UNLABELLED: OBJECTIVE. Anxiety is an important cause of acute blood pressure (BP) elevation. However, the role of anxiolysis in this situation is still controversial. In this study, the relationship of anxiety with BP and the effect of anxiolytic treatment on BP were investigated. METHODS. Emergency department (ED) patients with an initial systolic BP (SBP) ≥ 160 mmHg or diastolic BP (DBP) ≥ 100 mmHg but no end organ damage were approached for inclusion in the study. In those consenting to participate, anxiety levels were measured using the State-Trait Anxiety Index (STAI) and Visual Analog Scale for Anxiety (VAS-A). Patients were randomly assigned to receive oral alprazolam 0.5 mg or captopril 25 mg. BP and anxiety levels were measured at baseline and at 1 and 2 h after administration of the study medication. RESULTS. Of 133 patients meeting inclusion criteria, 53 patients agreed to participate. Of these, 27 patients (50.9%) received captopril and 26 patients (49.1%) received alprazolam. The majority of the patients had a high-level trait (96.2%, n = 51) and state anxiety (81.1%, n = 43). The mean SBP and VAS-A values of both patient groups dropped significantly over the 2 h, with no significant difference between the two groups. A significant association between SBP and VAS-A scores was found (F((2,50)) = 6.27, p = 0.004). CONCLUSION: A significant association exists between the level of BP and anxiety in hypertensive ED patients. Alprazolam is as effective as captopril in lowering BP in ED patients with an initial SBP > 160 mmHg.