Childhood adversity and adulthood major depressive disorder.

OBJECTIVE: Examine how specific types of childhood adversity are associated with clinical features and treatment in adults with Major Depressive Disorder (MDD). METHOD: This is a secondary analysis of the 35-site VA Augmentation and Switching Treatments for Improving Depression Outcomes study. A 10-item Adverse Childhood Events (ACE) survey was administered at baseline. RESULTS: 83% experienced at least one of the 10 ACEs and 20.7% experienced 6 or more. Participants with childhood adversities were more likely to be younger, female, unemployed, single or divorced, and to have had more severe depression and anxiety, more lifetime episodes, a younger age of first diagnosed MDD, more comorbid PTSD, worse quality of life, and more suicidal ideation than those no or fewer adversities. Neither the overall number nor any of the specific types of adversities were associated with lower remission rates after administration of standard "next-step" treatment strategies, while histories of different specific types were associated with lower depression severity, better quality of life, and less suicidal ideation post-treatment. CONCLUSIONS: Attention to different forms of childhood adversity and to diverse clinical outcomes beyond remission and relapse are important considerations when treating individuals with MDD with histories of childhood maltreatment. CLINICALTRIALS: gov identifier: NCT01421342.

Characterizing the Effects of Quetiapine in Military Post-Traumatic Stress Disorder.

Objectives: A previous randomized placebo-controlled trial in military veterans posttraumatic stress disorder (PTSD) found that quetiapine improved global PTSD symptoms severity, depression and anxiety as well as the re-experiencing and hypearousal clusters. However, it is not known if individual symptoms had a preferential response to this medication. The goal of this study was to analyze the individual symptom response in this group of patients. Methods: Data from a previous trial was re-analyzed. Each of the of the scale items was analyzed individually using Repeated Measures Analysis of Variance. Results: Compared to placebo, there was a significant decline in the Clinician-Administered PTSD Scale intrusive memories and insomnia questions. In the Davidson Trauma Scale, greater improvements were observed on irritability, difficulty concentrating, hyperstartle and a trend was observed on avoiding thoughts or feelings about the event. Greater improvements compared with placebo were noted on the Hamilton Depression (HAM-D) middle and late insomnia items. On the Hamilton Anxiety scale (HAM-A), the insomnia item was significantly improved. Conclusions: Quetiapine demonstrated greater effect than placebo on several symptoms. The strongest response was seen on insomnia, which the highest significance level on the CAPS. The insomnia items of both the HAM-D and HAM-A also demonstrated improvement with quetiapine. These finding indicate quetiapine improved sleep measure. Insomnia can be a difficult problem to treat in PTSD patients, therefore quetiapine should be considered in difficult cases.

Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

IMPORTANCE: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. OBJECTIVE: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. DESIGN, SETTING, AND PARTICIPANTS: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. INTERVENTIONS: Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). MAIN OUTCOMES AND MEASURES: The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS: Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. CONCLUSIONS AND RELEVANCE: Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01421342.

Efficacy of Quetiapine Monotherapy in Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial.

OBJECTIVE: This was a 12-week randomized, placebo-controlled trial to assess the efficacy of quetiapine monotherapy in the treatment of posttraumatic stress disorder (PTSD). METHOD: Eighty patients were randomly assigned to treatment with either quetiapine or placebo. The primary outcome measure was the Clinician-Administered PTSD Scale (CAPS). Secondary efficacy measures included the CAPS subscales, the Davidson Trauma Scale, the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scales for severity of Illness and improvement, the Hamilton Depression Rating Scale (HAM-D), and the Hamilton Anxiety Rating Scale (HAM-A). Safety measurements included adverse events, vital signs, the Abnormal Involuntary Movement Scale, the Barnes Akathisia Scale, the Simpson-Angus Scale, and the Arizona Sexual Experiences Scale. RESULTS: After a 1-week placebo run-in, quetiapine was started at a daily dosage of 25 mg and increased to a maximum of 800 mg; the average was 258 mg (range, 50-800 mg). Reductions in CAPS total, re-experiencing, and hyperarousal scores were significantly greater for the quetiapine group than for the placebo group. Greater improvements were also observed for quetiapine in scores on the Davidson Trauma Scale, CGI severity and improvement ratings, PANSS positive symptom and general psychopathology subscales, HAM-A, and HAM-D than for placebo. Adverse events were generally mild and expected based on prior studies of quetiapine in this and other patient population. There were no differences in safety measures between groups. CONCLUSION: Quetiapine monotherapy was efficacious in the treatment of PTSD. These findings suggest quetiapine as a single agent is effective in treating military PTSD.

Lateralized abnormalities in auditory M50 sensory gating and cortical thickness of the superior temporal gyrus in post-traumatic stress disorder: preliminary results.

Auditory sensory gating deficits have been reported in subjects with post-traumatic stress disorder (PTSD), but the hemispheric and neuronal origins of this deficit are not well understood. The objectives of this study were to: (1) investigate auditory sensory gating of the 50-ms response (M50) in patients diagnosed with PTSD by utilizing magnetoencephalography (MEG); (2) explore the relationship between M50 sensory gating and cortical thickness of the superior temporal gyrus (STG) measured with structural magnetic resonance imaging (MRI); and (3) examine the association between PTSD symptomatology and bilateral sensory gating. Seven participants with combat-related PTSD and eleven controls underwent the paired-click sensory gating paradigm. MEG localized M50 neuronal generators to the STG in both groups. The PTSD group displayed impaired M50 gating in the right hemisphere. Thinner right STG cortical thickness was associated with worse right sensory gating in the PTSD group. The right S1 M50 source strength and gating ratio were correlated with PTSD symptomatology. These findings suggest that the structural integrity of right hemisphere STG cortices play an important role in auditory sensory gating deficits in PTSD.

Duloxetine in military posttraumatic stress disorder.

The objective of this prospective study was to assess the efficacy and tolerability of duloxetine in the treatment of in military veterans with posttraumatic stress disorder (PTSD).Twenty subjects were enrolled in this 12-week, open-label trial. Diagnosis and symptom severity were assessed with the Clinician Administered PTSD Scale (CAPS). Depressive symptoms were assessed the Hamilton Depression Rating Scale. All subjects had a CAPS score of at least 60 at baseline. Subjects with lifetime history of psychotic disorders or bipolar illness were excluded. Fifteen participants completed 12 weeks of treatment, five dropped-out from the trial, 3 due to side effects. For patients who discontinued, missing values were estimated using "the last observation carried forward" method. Significant improvements were seen on: CAPS total and all subscales, depression and sleep measures. Most of the improvement was observed by week 2 of treatment. Nine participants (45%) were classified as responders, defined by 20% or greater improvement on CAPS total score. The mean daily dose of duloxetine was 81 mg. The most common side effects were constipation (20%) diarrhea (25%) and nausea (20%). Two subjects developed tachycardia, one withdrew from the trial due to this problem. Duloxetine had a fast onset of action and was effective in about half of the subjects, it was well tolerated in most subjects. These preliminary results in a difficult to treat population warrant the conduction of a double blind, placebo-controlled study of duloxetine in PTSD.

Prospective study to evaluate the efficacy of aripiprazole as a monotherapy in patients with severe chronic posttraumatic stress disorder: an open trial.

The objective of the study was to assess the efficacy and safety of aripiprazole in outpatients with posttraumatic stress disorder (PTSD) on a 12-week, open-label trial. Twenty-two subjects with DSM-IV diagnosis of PTSD participated; 16 were combat veterans. The primary outcome measure was PTSD symptom severity assessed with the Clinician Administered PTSD Scale (CAPS). Secondary outcome measures included the Positive and Negative Symptoms Scale and the Hamilton Depression and Anxiety Scales. All subjects had a CAPS score of > or = 60 at baseline. Lifetime history of psychotic disorders or bipolar illness was exclusionary. The overall analysis across time was Repeated Measures ANOVA, using Bonferroni corrections. Fourteen subjects completed 12 weeks of treatment. Eight subjects dropped-out due to side effects. For patients who discontinued, missing values were estimated using "the last observation carried forward" method. Significant improvements were seen on: CAPS total, all its subscales, positive symptoms, anxiety and depression scores. Fourteen participants were classified as responders, defined by 20% or greater improvement on CAPS total score. Of the 13 subjects who completed final ratings, CAPS total scores improved significantly (P = .011). Two subjects attained remission of PTSD (CAPS < 20), and three had a final CAPS < or = 26. The mean daily dose of aripiprazole was 12.95 mg. The most common side effects were somnolence (54.5%), restlessness (50%), insomnia (36.4%), and asthenia (31.8%). These results indicate that aripiprazole was effective in about two thirds of subjects that tolerated this medication. The initially high dropout rate may be related to intolerability due to a high starting dose (10 mg), suggesting beginning treatment at lower doses. These preliminary results are encouraging; a double blind study seems warranted.

Normal visual acuity in 17--18 year olds.

PURPOSE: The aim of this work was to establish visual acuity norms in 17-18-year-olds. METHODS: In a previous, population-based study carried out in 1998, a total of 1046 12-13-year-old children were examined with a full eye examination. In 2003, 25% (n=262) of these children were randomly selected and invited to a re-examination; 147 subjects agreed to participate and 116 attended. The examined group did not significantly differ from the original sample in terms of the prevalence of ocular and visual disorders. Best corrected monocular visual acuity (VA) was assessed with the revised 2000 ETDRS logMAR chart. RESULTS: Mean best corrected VA was -0.10 logMAR across the examined group. There was no significant difference between right and left eyes. By excluding nine subjects who had significant ametropia and/or ocular or visual pathology, mean VA increased to -0.12 logMAR (SD 0.07). The mean interocular difference in VA among normal subjects was 0.04 logMAR. CONCLUSIONS: Visual acuity in teenagers is significantly better than 0.0 logMAR and the interocular difference is low in healthy eyes.

Reduced area of the corpus callosum in posttraumatic stress disorder.

Magnetic resonance imaging (MRI) studies have revealed decreases in the mid-sagittal area of the corpus callosum (CC) in pediatric posttraumatic stress disorder (PTSD), but at present no data are available in adult PTSD patients. We have previously reported decreased whole-brain white matter (WM) volume in adults with PTSD and now report corpus callosum area from the same sample. MRI was used to obtain whole-brain images in 12 adult patients with PTSD and 10 matched controls. Total parenchyma (white matter plus gray matter [GM]) volume, mid-sagittal area of the CC and seven sub-regions of this structure were calculated. In PTSD patients, the total CC area, absolute and normalized to total brain parenchyma, was smaller compared with control values. Several absolute and normalized CC sub-regions were also smaller in PTSD patients: genu (region 2), mid-body (region 5) and isthmus (region 6). There was also a trend for the anterior mid-body (area 4) to be smaller in PTSD patients. No differences were found in the rostrum (region 1), rostral body (region 3) or splenium (region 7). Adult patients with PTSD had decreased CC area after correcting for total brain tissue, indicating that these differences are not attributable to generalized white matter atrophy. These findings are similar to previous results in children with PTSD and suggest specific changes in the CC.

Prevalence of myopia among 12- to 13-year-old schoolchildren in northern Mexico.

PURPOSE: The aim of this article was to report the prevalence of refractive errors, mainly myopia, among 12- to 13-year-old children in a metropolitan setting in Mexico. METHODS: A total of 1035 schoolchildren were examined in a field study in Monterrey, Mexico. The examination included best-corrected visual acuity and refraction during cycloplegia. A sample of the children was sent to a pediatric eye clinic and underwent cycloplegic refraction with an autorefractor. RESULTS: We found a prevalence of myopia (>/=-0.5 D SE) of 44%, whereas bilateral myopia was present in 37% of the children. In the total sample, high myopia (>/=-5D) was found in 1.4%. The prevalence of myopia was significantly higher in girls. Only 20% of children with bilateral myopia used prescription glasses; 8% had prescribed glasses, but did not use them. Hyperopia (>/=+1 D) was present in 6.0% of the total population, and astigmatism (>/=-1.5 D) was present in 9.5%. CONCLUSIONS: The prevalence of myopia among 12- to 13-year-old children in Mexico is high. The majority of cases are low grade, and a large number of the myopic children do not have, or do not use, prescription glasses.

Visual acuity, amblyopia, and ocular pathology in 12- to 13-year-old children in Northern Mexico.

PURPOSE: The aim of this study was to establish visual acuity (VA) and the prevalence of amblyopia and other ocular disorders in a population of 12- to 13-year-old children in Mexico who have not been vision screened. METHODS: A total of 1,035 12- to 13-year-old children were examined in a field study. The examination included VA, stereopsis, cover testing, refractive retinoscopy, and examination of the red reflex and posterior pole. In cases with unexplained subnormal VA, visually evoked potential/visually evoked response was also performed. RESULTS: A >or=20/20 in at least one eye was found in 93% of the subjects. Bilateral VA

Proton magnetic resonance spectroscopy of the hippocampus and occipital white matter in PTSD: preliminary results.

OBJECTIVE: Previous proton magnetic resonance spectroscopy (1H-MRS) studies in posttraumatic stress disorder (PTSD) report decreased hippocampal N-acetylaspartate (NAA), an indicator of neuronal integrity. However, other areas of the brain need to be explored. The objective of this study was to investigate the specificity of hippocampal NAA concentration changes in PTSD by also examining a control region, the occipital white matter (OWM). METHODS: Eight patients with PTSD and 5 control subjects underwent single-voxel 1H-MRS of the hippocampi and bilateral OWM. Absolute neurometabolite concentrations were determined. PRELIMINARY RESULTS: Trends toward reduced left hippocampal NAA and creatine (Cre) were found in the PTSD group. PTSD subjects also had reduced bilateral OWM Cre. CONCLUSIONS: The preliminary results of our study in civilians with PTSD replicate previous MRS studies and are consistent with decreased hippocampal neuronal integrity without effects in the OWM. Replication of our findings is needed.

Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder.

BACKGROUND: Reduced hippocampal volumes in posttraumatic stress disorder (PTSD) patients are thought to reflect specific changes of this structure. Previous magnetic resonance imaging (MRI) studies have not consistently examined indices of overall brain atrophy, therefore it cannot be completely ruled out that hippocampal changes are explained by whole-brain atrophy. The purpose of this study was to assess hippocampal and whole-brain volume in civilian PTSD. METHODS: Twelve subjects with PTSD and 10 control subjects underwent brain MRI. Hippocampal volumes were visually quantified using a computerized volumetric program. Whole-brain volumes were obtained with automated k-means-based segmentation. RESULTS: No differences were found in intracranial volumes (ICV). Subjects with PTSD had higher cerebrospinal fluid (CSF)/ICV ratios and lower white matter/ICV ratios, consistent with generalized white matter (WM) atrophy. The effect of age on CSF/ICV was more pronounced in the PTSD group. Subjects with PTSD had smaller absolute and normalized bilateral hippocampal volumes. These differences persisted after adjusting for lifetime weeks of alcohol intoxication. Posttraumatic stress disorder and depression scores correlated negatively with left hippocampal volume, but PTSD scores were a better predictor of hippocampal volumes. CONCLUSIONS: Our results replicate previous findings of reduced hippocampal volume in PTSD but also suggest independent, generalized, white matter atrophy.

Screening for amblyopia and strabismus with the Lang II stereo card.

PURPOSE: To evaluate the effectiveness of the Lang II stereo card as a screening test for amblyopia and/or strabismus. METHODS: A total of 1046 children aged 12-13 years were examined in a field study in the Göteborg area, Sweden. In addition to the Lang II stereo card, the examination included visual acuity, cover testing, cycloplegic refraction, and inspection of the optical media and posterior pole. RESULTS: If every incorrect subject response was considered a reason for referral, the Lang II test would have correctly identified 82% (23 subjects) of the 28 children with manifest strabismus and 38% (11 subjects) of the 29 children with amblyopia. The test failed to refer 45% (21 subjects). Of all subjects referred, 44 (63%) were found to be ophthalmologically normal. CONCLUSIONS: The Lang II stereo card is neither a reliable nor an efficient method of screening for amblyopia and/or strabismus.

Alteraciones en la memoria de pacientes con crisis de angustia, y efecto del tratamiento farmacológico con alprazolam e imipramina / Changes in the memory of patients with anxiety crisis and effect of pharmacological treatment with alprazolam and imipramine

Para evaluar si los pacientes con crisis de angustia (ataques de pánico) cursan con alteraciones de los procesos mnésicos, se usó la Escala de Memoria de Wechsler en 38 pacientes antes y después de tratamiento farmacológico y se comparó su desempeño con el de un grupo de 20 voluntários sanos. Los pacientes recibieron en forma doble ciega tratamiento con alprazolam, imipramina o placebo. Antes del tratamiento los coeficientes de memoria del grupo de pacientes fueron significativamente inferiores a los del grupo control (p <0.001). Las correlaciones entre la severidad de los síntomas del padecimiento y el puntaje total en los pacientes antes y después del tratamiento no fueron estadísticamente significativas. Sin embargo, se observó que los pacientes que mejoraron su calificación en la escala después de 3 semanas de tratamiento lograron una mayor reducción en el número de crisis de angustia por semana en comparación con los que bajaron su calificación (p <0.05). Estos hallazgos indican que los pacientes con crisis de angustia cursan con alteraciones mnésicas, cuya mejoría se asocia con una disminución en el número de crisis que presentan, independientemente del fármaco que hayan recibido