Stephan Arndt

Regional Brain Enlargement in Autism: A Magnetic Resonance Imaging Study

OBJECTIVE To determine whether increased brain volume in autism, suggested in previous studies, is the result of general or regional brain size differences and to study the effect of gender on brain size and pattern of enlargement. METHOD Total brain volume and cerebral cortical lobe volumes were examined in 35 autistic and 36 comparison subjects using magnetic resonance imaging and an automated method of brain volume measurement. RESULTS After controlling for height and nonverbal IQ, the authors detected a significant diagnosis x gender effect (F = 7.4; p = .009) for total brain volume. A repeated-measures analysis of variance indicated that the pattern of enlargement (brain region x diagnosis) in autistic subjects differed from that in controls (F = 4.88; p = .0004). Subsequent sex-specific analysis revealed significantly increased total brain volume in autistic males but not females. Analysis of lobe sizes showed significant enlargement in autistic subjects in temporal, parietal, and occipital, but not frontal lobes. CONCLUSIONS These results suggest that brain size is increased in autism and that differences are not generalized but appear to be the result of a pattern of enlargement with increases in the size of specific cortical lobes.

Escitalopram and Problem-Solving Therapy for Prevention of Poststroke Depression: A Randomized Controlled Trial

CONTEXT Depression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality. Prevention of depression thus represents a potentially important goal. OBJECTIVE To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication. DESIGN, SETTING, AND PARTICIPANTS A multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n = 59) with placebo (n = 58), and a nonblinded problem-solving therapy group (n = 59). MAIN OUTCOME MEASURES The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression (ie, research criteria). RESULTS Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 minor cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4-8.2; P < .001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4-3.5; P < .001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site, and severity of impairment in the model. Using an intention-to-treat conservative method of analyzing the data, which assumed that all 27 patients who did not start randomized treatment would have developed depression, and controlling for prior history of mood disorders, escitalopram was superior to placebo (23.1% vs 34.5%; adjusted HR, 2.2; 95% CI, 1.2-3.9; P = .007), while problem-solving therapy was not significantly better than placebo (30.5% vs 34.5%; adjusted HR, 1.1; 95% CI, 0.8-1.5; P = .51). Adverse events, including all-cause hospitalizations, nausea, and adverse effects associated with escitalopram were not significantly different between the 3 groups. CONCLUSIONS In this study of nondepressed patients with recent stroke, the use of escitalopram or problem-solving therapy resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo, but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00071643.

fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder

BACKGROUND Previous studies suggest that a neural circuit involving over-activation of cortical, paralimbic, limbic, and striatal structures may underlie OCD symptomatology, but results may have been limited by medication use in those studies. To address this, we examined the effects of symptom induction on fMRI neural activation in medication-free patients with OCD. METHODS Seven outpatients with OCD were exposed to individually tailored provocative and innocuous stimuli during fMRI scans. Self-ratings of OCD symptoms were performed prior to each scan and after exposure to stimuli. Images were analyzed as composite data sets and individually. RESULTS Stimulus presentation was associated with significant increases in OCD self-ratings. Significant activation was demonstrated in several regions of the frontal cortex (orbitofrontal, superior frontal, and the dorsolateral prefrontal); the anterior, medial and lateral temporal cortex; and the right anterior cingulate. Right superior frontal activation inversely correlated with baseline compulsion symptomatology and left orbitofrontal cortical activation was inversely associated with changes in OCD self-ratings following provocative stimuli. CONCLUSIONS These results in unmedicated patients are consistent with those from previous studies with medicated patients and suggest that OCD symptomatology is mediated by multiple brain regions including the anterior cingulate as well as frontal and temporal brain regions.

Course of Behavioral Change in Autism: A Retrospective Study of High-IQ Adolescents and Adults

OBJECTIVE The course of behavioral change in autistic behaviors has received little attention in previous research but is a potentially important parameter for study in autism. METHOD Autistic behaviors were systematically examined in 38 high-IQ adolescent and adult autistic individuals at their current age (13 through 28 years) and retrospectively at age 5 years using a standardized interview for autism. RESULTS Significant change over time in autistic behaviors, generally in the direction of improvement, was detected. The proportion of subjects showing improvement in communication and social behaviors was found to be significantly higher than the proportion showing improvement in ritualistic/repetitive behaviors. Five of 38 subjects who met DSM-IV criteria for autistic disorder at age 5 years no longer met criteria at their current age, although all five continued to have substantial impairment. CONCLUSIONS The study of patterns of behavioral change over time in autism has practical implications for both diagnosis and prognosis as well as potential importance in defining biologically meaningful subgroups and clarifying fundamental mechanisms underlying this disorder.

Systems Training for Emotional Predictability and Problem Solving (STEPPS) for Outpatients With Borderline Personality Disorder: A Randomized Controlled Trial and 1-Year Follow-Up

OBJECTIVE Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a 20-week manual-based group treatment program for outpatients with borderline personality disorder that combines cognitive behavioral elements and skills training with a systems component. The authors compared STEPPS plus treatment as usual with treatment as usual alone in a randomized controlled trial. METHOD Subjects with borderline personality disorder were randomly assigned to STEPPS plus treatment as usual or treatment as usual alone. Total score on the Zanarini Rating Scale for Borderline Personality Disorder was the primary outcome measure. Secondary outcomes included measures of global functioning, depression, impulsivity, and social functioning; suicide attempts and self-harm acts; and crisis utilization. Subjects were followed 1 year posttreatment. A linear mixed-effects model was used in the analysis. RESULTS Data pertaining to 124 subjects (STEPPS plus treatment as usual [N=65]; treatment as usual alone [N=59]) were analyzed. Subjects assigned to STEPPS plus treatment as usual experienced greater improvement in the Zanarini Rating Scale for Borderline Personality Disorder total score and subscales assessing affective, cognitive, interpersonal, and impulsive domains. STEPPS plus treatment as usual also led to greater improvements in impulsivity, negative affectivity, mood, and global functioning. These differences yielded moderate to large effect sizes. There were no differences between groups for suicide attempts, self-harm acts, or hospitalizations. Most gains attributed to STEPPS were maintained during follow-up. Fewer STEPPS plus treatment as usual subjects had emergency department visits during treatment and follow-up. The discontinuation rate was high in both groups. CONCLUSIONS STEPPS, an adjunctive group treatment, can deliver clinically meaningful improvements in borderline personality disorder-related symptoms and behaviors, enhance global functioning, and relieve depression.

The impact of substance abuse on the course of bipolar disorder

BACKGROUND Substance abuse occurs at high rates in bipolar disorder. The reasons for this co-occurrence are unknown. Alcohol use disorders have been associated with both earlier and later age of onset of bipolar disorder, in part based on the temporal associations of the two conditions. Both drug and alcohol use disorders are associated with impaired outcome of bipolar illness. This influence may involve both direct effects of alcohol or drugs on the initiation of affective symptoms and indirect effects on treatment compliance. To extend these previous findings we examined the temporal associations of substance abuse and affective symptoms in patients with new onset bipolar disorder. METHODS Associations between affective symptoms and alcohol and cannabis use disorder symptoms were evaluated using regression and time-series correlative methods in 50 new-onset bipolar patients. RESULTS The duration of alcohol abuse during follow-up was associated with the time patients experienced depression. The duration of cannabis abuse was associated with the duration of mania. Several subgroups could be identified with different temporal relationships among these disorders. CONCLUSIONS Although the relationships among substance use and bipolar disorders are complex, systematic study of the courses of the disorders might clarify how these conditions interact longitudinally. As the numbers of subjects in specific subgroups are relatively small in this study, these results should be considered preliminary.

An MRI study of autism: The cerebellum revisited

We addressed the controversies surrounding the size of the neocerebellar vermis in autism and examined cerebellar size in light of recent reports of enlarged brain size in this disorder. In this study we use detailed MRI (1.5 mm) to examine the area of cerebellar lobules I through V and VI and VII and the volume of the total cerebellum in 35 autistic subjects and 36 controls. No abnormalities in the size of cerebellar lobules VI and VII in autistic individuals were detected, but the volume of the total cerebellum was significantly increased. We conclude that selective neocerebellar size abnormalities are not present in autistic individuals. Enlarged total cerebellar volume detected in this study is consistent with previous reports of regional brain enlargement in autism and also consistent with theories hypothesizing that the primary defect in autism is the result of abnormal development of a distributed neural network involving a number of regions of the brain.

Depression following traumatic brain injury: a 1 year longitudinal study

A group of 66 patients hospitalized for the treatment of closed head injury, were assessed for the presence of mood disorders during their hospital admission and at 3, 6 and 12 months follow-up. A total 28 patients met DSM-III-R diagnostic criteria for major depression at some time during the study (17 in the acute stage, 11 during follow-up). The mean duration of major depression was 4.7 months. However, there appeared to be a group of transiently depressed patients (41%) who where depressed inhospital but were no longer depressed at 3 months follow-up. Throughout the follow-up period, major depression showed a strong relationship with poor social functioning. There was not, however, a consistent relationship between depression and quantitative measures of either physical or cognitive impairment. Location of the brain lesion was associated with the development of major depression only in the acute stage. Transient depressive syndromes were associated with left dorsolateral frontal and/or left basal ganglia lesions.

Comorbidity of substance abuse and schizophrenia: the role of pre-morbid adjustment

Co-morbid substance use and abuse is common in schizophrenic patients, and the role of substance abuse in initiating and maintaining psychosis has important definitional and aetiological implications. We investigated the issue in a cohort of 131 schizophrenic patients. We found non-users (N = 67) were similar to pathological users (N = 64) in current symptomatology and clinical history. The pathological users did, however, have better pre-morbid adjustment levels. Only alcohol use and to some extent cannabis use contributed to this effect; use of stimulants or hallucinogens did not. These results indicate the importance of evaluating the various types of substance used when attempting to explore the significance of co-morbidity. The results also suggest that co-morbidity of substance abuse and schizophrenia may be explained by a common factor antecedent to both: better pre-morbid adjustment. A two-stage model is proposed to explain these findings: increased sociability increases exposure to opportunities of substance use in a subset of patients; subsequent onset of psychotic illness accelerates the use to a pathological level as the individual attempts to cope with the stress of the developing mental illness.

Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome.

OBJECTIVE To evaluate the efficacy and tolerability of risperidone in comparison with clonidine in the treatment of children and adolescents with Tourettes syndrome (TS). METHOD Following a 7- to 14-day single-blind, placebo lead-in, 21 subjects aged 7 to 17 years were randomly assigned to 8 weeks of double-blind treatment with clonidine or risperidone. Research scales evaluated tics and comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms. RESULTS Risperidone and clonidine appeared equally effective in the treatment of tics in an intent-to-treat analysis, as rated by the Yale Global Tic Severity Scale (YGTSS). Risperidone produced a mean reduction in the YGTSS of 21%; clonidine produced a 26% reduction. Among subjects with comorbid obsessive-compulsive symptoms, 63% of the risperidone group and 33% of the clonidine group responded to treatment (not significant). The most common adverse event seen with both treatments was sedation, which was mild to moderate in severity. Sedation subsequently resolved with continued administration of the medication or with a dose reduction. No clinically significant extrapyramidal symptoms were observed. CONCLUSIONS In this pilot study, risperidone demonstrated efficacy equivalent to clonidine in the treatment of tic symptoms in children and adolescents with TS. Further research is needed to clarify the role of atypical antipsychotics in TS and to delineate potential benefits for comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms.