A randomized comparison trial of culturally adapted HIV prevention approaches for Native Americans reducing trauma symptoms versus substance misuse: The Healing Seasons protocol.

Native Americans (NA) experience interrelated risks of trauma exposure, substance use, and HIV risk behaviors that put them at increased risk for HIV infection. Despite these known risk factors, there are very few published randomized trials testing interventions to reduce trauma-related symptoms and substance misuse among NA. METHODS: The Healing Seasons study is a randomized comparsion trial of two counseling strategies, Narrative Exposure Therapy (NET) addressing PTSD or Motivational interviewing with cognitive behavioral therapy skills training (MIST) addressing substance misuse as a means to prevent HIV among NA. Using a community-based participatory research approach, we adapted both evidence-based interventions to be specific to the risk contexts and realities of NA and to include psychoeducational and skill-building components that include cultural-specific stories, virtues, and traditional treatment strategies. Participants, 16 years and older, were recruited from a Pacific Northwest tribal community, screened over the phone, enrolled in person, and randomized in equal numbers to NET or MIST. We stratified by age (16-29 years and 30 or older) and gender (male or female identified) to ensure balance between treatment arms. The primary outcomes were number of sex partners and frequency of sexual acts (with and without condoms), sex under the influence of substances, frequency of substance use, and PTSD severity. DISCUSSION: Behavioral interventions for NA are needed to prevent HIV risk behaviors when faced with trauma symptoms and substance misuse. This study will provide evidence to determine feasibility and efficacy of addressing related risk factors as part of counseling-based HIV prevention intervention to reduce sexual risk among this population. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03112369, registered April 12, 2017.

Interventions to treat posttraumatic stress disorder in partnership with primary care: A review of feasibility and large randomized controlled studies.

OBJECTIVE: Evidence-based therapies for posttraumatic stress disorder are underutilized and at times unavailable in specialty settings. We reviewed the literature on interventions to treat PTSD within primary care to make recommendations on their effectiveness as treatment modalities or ways to improve engagement in specialty care. METHOD: We searched PubMed, PsychInfo, CINHAL, and Cochrane Reviews databases using search terms related to PTSD and primary care. We excluded clinical guidelines and studies of screening only or subthreshold PTSD. RESULTS: 524 articles were identified. Twenty-one papers on 15 interventions met review criteria. Seven interventions focus on individual therapies studied via small feasibility studies to prepare for full-scale intervention research. Eight describe treatment programs in primary care based on collaborative care that included medication management, tracking outcomes, referral services, and for some psychotherapy (versus psychotherapy referral). Ten interventions were feasibility studies which precludes meaningful comparison of effect sizes. Of the four RCTs of treatment programs, only two including some psychotherapy found improvements in PTSD symptoms. CONCLUSION: More research is needed to adapt treatment for PTSD to primary care. Collaborative care may be a promising framework for improving the reach of PTSD treatments when psychotherapy is offered within the collaborative care team.

The impact of Cognitive Processing Therapy on stigma among survivors of sexual violence in eastern Democratic Republic of Congo: results from a cluster randomized controlled trial.

BACKGROUND: Sexual violence is associated with a multitude of poor physical, emotional, and social outcomes. Despite reports of stigma by sexual violence survivors, limited evidence exists on effective strategies to reduce stigma, particularly in conflict-affected settings. We sought to assess the effect of group Cognitive Processing Therapy (CPT) on stigma and the extent to which stigma might moderate the effectiveness of CPT in treating mental health problems among survivors of sexual violence in the Democratic Republic of Congo. METHODS: Data were drawn from 405 adult female survivors of sexual violence reporting mental distress and poor functioning in North and South Kivu. Women were recruited through organizations providing psychosocial support and then cluster randomized to group CPT or individual support. Women were assessed at baseline, the end of treatment, and again six months later. Assessors were masked to women's treatment assignment. Linear mixed-effect regression models were used to estimate (1) the effect of CPT on feelings of perceived and internalized (felt) stigma, and (2) whether felt stigma and discrimination (enacted stigma) moderated the effects of CPT on combined depression and anxiety symptoms, posttraumatic stress, and functional impairment. RESULTS: Participants receiving CPT experienced moderate reductions in felt stigma relative to those in individual support (Cohen's D = 0.44, p = value = 0.02) following the end of treatment, though this difference was no longer significant six-months later (Cohen's D = 0.45, p = value = 0.12). Neither felt nor enacted stigma significantly moderated the effect of CPT on mental health symptoms or functional impairment. CONCLUSIONS: Group cognitive-behavioral based therapies may be an effective stigma reduction tool for survivors of sexual violence. Experiences and perceptions of stigma did not hinder therapeutic effects of group psychotherapy on survivors' mental health. TRIAL REGISTRATION: ClinicalTrials.gov NCT01385163.

PTSD symptoms, substance use, and vipassana meditation among incarcerated individuals.

The present study evaluated whether Posttraumatic Stress Disorder (PTSD) symptom severity was associated with participation and treatment outcomes comparing a Vipassana meditation course to treatment as usual in an incarcerated sample. This study utilizes secondary data. The original study demonstrated that Vipassana meditation is associated with reductions in substance use. The present study found that PTSD symptom severity did not differ significantly between those who did and did not volunteer to take the course. Participation in the Vipassana course was associated with significantly greater reductions in substance use than treatment as usual, regardless of PTSD symptom severity levels. These results suggest that Vipassana meditation is worthy of further study for those with comorbid PTSD and substance use problems.

Quantitative magnetic resonance imaging of human brain development: ages 4-18.

Brain magnetic resonance images (MRI) of 104 healthy children and adolescents, age 4-18, showed significant effects of age and gender on brain morphometry. Males had larger cerebral (9%) and cerebellar (8%) volumes (P < 0.0001 and P = 0.008, respectively), which remained significant even after correction for height and weight. After adjusting for cerebral size, the putamen and globus pallidus remained larger in males, while relative caudate size was larger in females. Neither cerebral nor cerebellar volume changed significantly across this age range. Lateral ventricular volume increased significantly in males (trend for females), with males showing an increase in slope after age 11. In males only, caudate and putamen decrease with age (P = 0.007 and 0.05, respectively). The left lateral ventricles and putamen were significantly greater than the right (P = 0.01 and 0.001, respectively). In contrast, the cerebral hemispheres and caudate showed a highly consistent right-greater-than-left asymmetry (P < 0.0001 for both). All volumes demonstrated a high degree of variability. These findings highlight gender-specific maturational changes of the developing brain and the need for large gender-matched samples in pediatric neuropsychiatric studies.

Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder.

BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. METHODS: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. RESULTS: Subjects with ADHD had a 4.7% smaller total cerebral volume (P = .02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right > left asymmetry in the caudate (P = .006), smaller right globus pallidus (P = .005), smaller right anterior frontal region (P = .02), smaller cerebellum (P = .05), and reversal of normal lateral ventricular asymmetry (P = .03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. CONCLUSION: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.

Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia.

BACKGROUND: Early-onset schizophrenia (first psychotic symptoms by age 12 years) has been the subject of a small number of studies, and its biological continuity with later-onset disorder has not been established. In this study quantitative anatomic brain magnetic resonance images of children and adolescents with early-onset schizophrenia were compared with those of matched controls. Brain abnormalities in childhood-onset schizophrenia were examined in relation to those reported for later-onset schizophrenics. METHODS: Anatomic brain magnetic resonance imaging scans were obtained for 21 patients (mean +/- SD age, 14.6 +/- 2.1 years; range, 10 to 18 years) with childhood-onset schizophrenia (13 males, eight females) and 33 age-, sex-, height-, and weight-matched normal controls. Quantitative measurements were obtained for the cerebrum, anterior frontal region, lateral ventricles, thalamus, caudate, putamen, and globus pallidus. RESULTS: Total cerebral volume and midsagittal thalamic area were smaller in the patients (analysis of variance, P = .002, and analysis of covariance, P = .03, respectively); the caudate, putamen, and globus pallidus were larger in the patients (analysis of covariance, P = .05, P = .007, and P < .001, respectively); and the lateral ventricles tended to be larger in the patients (analysis of covariance, P = .06). Globus pallidus enlargement correlated with neuroleptic exposure and with age of onset of psychosis. The magnitude of abnormalities compared with controls was similar to that reported in adult studies, although there was a trend toward relatively smaller cerebral volumes for the childhood-onset group compared with controls. CONCLUSION: Brain anatomic abnormalities in childhood-onset schizophrenia are similar to those reported for adult populations, indicating overall continuity between these rare childhood cases and the adult schizophrenia populations.

Childhood-onset schizophrenia: brain MRI rescan after 2 years of clozapine maintenance treatment.

OBJECTIVE: The effect of clozapine on striatal morphology was examined in adolescents with childhood-onset schizophrenia. METHOD: Eight adolescent patients with onset of psychosis before age 12 and eight matched comparison subjects had initial and 2-year follow-up brain magnetic resonance imaging scans. Basal ganglia and lateral ventricle volumes were measured. The patients were on a clozapine regimen during the 2-year interim. RESULTS: Caudate volume was larger in the patients at the initial scanning, decreased in the patients between scans, and did not differ significantly between the patients and the comparison subjects at the second scanning. CONCLUSIONS: Caudate enlargement in patients with childhood-onset schizophrenia who are taking typical neuroleptics appears to be secondary to medication exposure. Rescanning to examine basal ganglia morphology is indicated for these patients when they are taking an atypical neuroleptic.

Temporal lobe morphology in childhood-onset schizophrenia.

OBJECTIVE: Neurodevelopmental models of schizophrenia imply that a more severe early brain lesion may produce earlier onset of psychotic symptoms. The medial temporal lobes have been proposed as possible locations for such a lesion. The authors tested this hypothesis in a group of children and adolescents with childhood-onset schizophrenia who had severe, chronic symptoms and who were refractory to treatment with typical neuroleptics. METHOD: Anatomic brain magnetic resonance imaging scans were acquired with a 1.5-T scanner for 21 patients (mean age=14.6 years, SD=2.1) who had onset of schizophrenia by age 12 (mean age at onset=10.2, SD=1.5) and 41 normal children. Volumes of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus were measured by manually outlining these structures on contiguous 2-mm thick coronal slices. RESULTS: Patients with childhood-onset schizophrenia had significantly smaller cerebral volumes. With no adjustment for brain volume, no diagnostic differences were observed for any temporal lobe structure. Unexpectedly, with adjustment for total cerebral volume, larger volumes of the superior temporal gyrus and its posterior segment and a trend toward larger temporal lobe volume emerged for the patients with schizophrenia. These patients lacked the normal (right-greater-than-left) hippocampal asymmetry. CONCLUSIONS: These findings do not indicate a more severe medial temporal lobe lesion as the basis of very early onset schizophrenia.

Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: ages 4-18 years.

The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4-18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders.

A quantitative MRI study of the corpus callosum in children and adolescents.

Total midsagittal area and seven subdivisions of the corpus callosum were measured on magnetic resonance images of 114 healthy boys and girls, aged 4 to 18. Striking variability of size was noted for all measures. Total midsagittal corpus callosum area increased in a robust and linear fashion from ages 4 to 18 (slope = 13.1 mm2/year, P = 0.0001 and slope = 11.1 mm2/year, P = 0.0001 for females and males, respectively). Posterior and mid regions demonstrated greater age-related changes than anterior regions with the rostrum and genu (anterior regions) having reached adult sizes in the youngest of our subjects. There were no significant effects of sex for any measures. These findings support anatomical studies indicating ongoing myelination of higher association areas throughout adolescence, but raise intriguing questions about anterior-posterior gradients of interhemispheric myelination.

Sensorimotor gating in boys with Tourette's syndrome and ADHD: preliminary results.

Deficits in sensorimotor gating, defined by prepulse inhibition (PPI), have been associated with subcortical dopaminergic overactivity in animal and clinical studies. Utilizing supraorbital nerve electrical stimulation, we produced adequate blink responses and measured decreases in amplitude resulting from electric prestimuli just above sensory threshold. Seven boys comorbid for attention-deficit hyperactivity disorder (ADHD) and a tic disorder had significantly reduced PPI, compared to 14 screened controls and seven boys with ADHD alone. If independently replicated, these results may reflect greater neurologic immaturity in these comorbid subjects. Alternatively, these findings, together with other converging lines of evidence, suggest that deficient pallidal inhibition may be etiologically related to tic and movement disorders.

Sydenham's chorea: magnetic resonance imaging of the basal ganglia.

Analysis of cerebral magnetic resonance images of 24 subjects with Sydenham's chorea and 48 age-, height-, weight-, gender-, and handedness-matched controls demonstrated increased sizes of the caudate, putamen, and globus pallidus in the Sydenham's chorea group. In contrast, neither total cerebral, prefrontal, or midfrontal volumes or thalamic area were increased. These results indicate the selective involvement of the basal ganglia in Sydenham's chorea.

Activation of prefrontal cortex in children during a nonspatial working memory task with functional MRI.

Functional magnetic resonance imaging (fMRI) was used to examine the pattern of activity of prefrontal cortex in prepubertal children during performance of a nonspatial working memory task. The children observed sequences of letters and responded whenever a letter repeated with exactly one nonidentical letter intervening. In a comparison task, subjects monitored similar sequences of letters for any occurrence of a single, prespecified target letter. Location of activation closely approximated that observed in a recent fMRI study with adults using exactly the same task. Activation of the inferior and middle frontal gyri was reliably observed within individual subjects during performance of the working memory task relative to the comparison task. Activation increased and decreased with a time course that was highly consistent with the task manipulations and correlated with behavioral performance. To our knowledge, this study is one of the first to demonstrate the applicability of fMRI to a normative developmental population. Issues of age dependence of the hemodynamic responses of fMRI are discussed.

Reliability of cerebral measures in repeated examinations with magnetic resonance imaging.

This study examined the reliability of quantitative measures of cerebral magnetic resonance images (MRI) in repeated scans. Ten subjects were scanned twice, at 2- to 4-week intervals. Volumetric data from 14 regions of the cerebrum, the caudate nucleus, and the lateral ventricles and area measures of the corpus callosum were acquired. Intrarater and scan-rescan reliabilities, including the relative percent error from each of these two sources, were determined for each structure. Intraclass correlations ranged from 0.88 for the head of the caudate nucleus to 0.99 for the ventricular volume. Quantitative cerebral MRI measures of these structures are stable over time intervals of 2-4 weeks.

Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder.

OBJECTIVE: Because the caudate nuclei receive inputs from cortical regions implicated in executive functioning and attentional tasks, caudate and total brain volumes were examined in boys with attention deficit hyperactivity disorder (ADHD) and normal comparison subjects. To gain developmental perspective, a wide age range was sampled for both groups. METHOD: The brains of 50 male ADHD patients (aged 6-19) and 48 matched comparison subjects were scanned by magnetic resonance imaging (MRI). Volumetric measures of the head and body of the caudate nucleus were obtained from T1-weighted coronal images. Interrater reliabilities (intraclass correlations) were 0.89 or greater. RESULTS: The normal pattern of slight but significantly greater right caudate volume across all ages was not seen in ADHD. Mean right caudate volume was slightly but significantly smaller in the ADHD patients than in the comparison subjects, while there was no significant difference for the left. Together these facts accounted for the highly significant lack of normal asymmetry in caudate volume in the ADHD boys. Total brain volume was 5% smaller in the ADHD boys, and this was not accounted for by age, height, weight, or IQ. Smaller brain volume in ADHD did not account for the caudate volume or symmetry differences. For the normal boys, caudate volume decreased substantially (13%) and significantly with age, while in ADHD there was no age-related change. CONCLUSIONS: Along with previous MRI findings of low volumes in corpus callosum regions, these results support developmental abnormalities of frontal-striatal circuits in ADHD.

Looking for childhood-onset schizophrenia: the first 71 cases screened.

OBJECTIVE: To review psychiatric referrals to a study of childhood-onset schizophrenia. METHOD: Children and adolescents (N = 71) and their parents selected from a total of 260 patients referred to the National Institute of Mental Health between 1990 and 1993, with onset of psychosis at or before age 12 years, were screened in person, using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version, portions of the Diagnostic Interview for Children and Adolescents-Parent Version, and clinical interview. Best-estimate diagnoses using all sources of information were determined. Thought disorder was rated on a subset of subjects using standardized videotaped speech samples. RESULTS: Interrater reliability (kappa) between two child psychiatrists for best-estimate primary diagnoses ranged from .65 to .81. Schizophrenia was diagnosed for 19 children who by history had had onset at or before age 12, but all were in puberty when interviewed. Affect disorders (N = 14) and Asperger's syndrome and pervasive developmental disorder not otherwise specified (N = 6) were also diagnosed. A large group of reliably identifiable children not completely described by any DSM-III-R category and provisionally called "multidimensionally impaired" (N = 21) with multiple language or learning disorders, mood lability, and transient psychotic symptoms was seen. CONCLUSIONS: Childhood-onset schizophrenia is often misdiagnosed, perhaps is often misdiagnosed, perhaps because of the rarity of the disorder and the ambiguity in applying primary criteria. An array of developmental disturbances are seen with less pervasive childhood-onset psychotic symptoms.

Childhood-onset schizophrenia: an NIMH study in progress.

An ongoing study of the phenomenology, genetics, neuropsychology, physiology (eye tracking, autonomic responsivity), neuroimaging, biochemistry, and pharmacology of childhood-onset schizophrenia is described, and pilot data are presented for the first 22 subjects. Differentiation from autism "spectrum" disorders and other poorly defined, severe neurodevelopmental disorders is needed. Eye tracking and autonomic results are similar to patterns seen in later-onset schizophrenia and possibly more striking. Magnetic resonance imaging showed larger left frontal ventricular horn area for the schizophrenia subjects, larger left caudate, and lack of normal caudate asymmetry. Fluorodeoxyglucose positron emission tomography during an auditory continuous performance task revealed decreased right parietal/occipital glucose metabolic rate in the schizophrenia subjects, which may be secondary to poor attentional performance, and increased glucose metabolic rate in three left frontal regions, a left parietal region, and the right putamen. Clozapine has been effective and well tolerated in an open trial with 12 adolescents who responded poorly to typical neuroleptics; 16 subjects have been enrolled in a double-blind comparison of haloperidol and clozapine. Longitudinal study of this narrowly defined and possibly more homogeneous group of very early-onset schizophrenia subjects will be relevant to current neurodevelopmental theories addressing the role of puberty, progression of pathology, and continuity or discontinuity with later-onset schizophrenia.