Noam Soreni

Stop Signal and Conners' Continuous Performance Tasks: Test-Retest Reliability of Two Inhibition Measures in ADHD Children.

Objective: To measure test -retest reliability of the Stop-Signal Task (SST) and the Conners’ Continuous Performance Test (CPT) in children with ADHD. Methods: 12 children with ADHD (age 11.46 ±1.66) participated in the study. Primary outcome measures were stop-signal reaction time (SSRT) for the SST and CPT’s commission errors (%FP). For each participant, we acquired three morning (8:00am) measurements and behavioral observations, separated by two 7-day intervals. Reliability of cognitive measures and behavioral observations was measured using the Intraclass-correlation coefficient (ICC). Results: ICC values for SSRT and %FP were 0.72. Consistency of behavioral observations was much lower (ICC =0.41). Conclusion: Both the SST and the CPT yielded reliable measurements in ADHD children. Our findings lend further support to using these measures in the study of ADHD. (J. of Att. Dis. 2009; 13(2) 137-143)

Evidence for the involvement of the hippocampus in the pathophysiology of schizophrenia

The hippocampus, a medial temporal lobe structure, is often considered to play an important role in the pathophysiology of schizophrenia. Recent developments of neuroimaging and molecular postmortem techniques have significantly increased our ability to study the role of discrete brain regions in the pathophysiology of schizophrenia. This article describes animal models, structural, histological, molecular biology, and neuropsychological evidence for the involvement of the hippocampus in the pathophysiology of schizophrenia. The major findings in schizophrenic patients are decreased volumes, hypometabolism, and cytoarchitectural abnormalities which are more robust on the left hippocampus, as well as verbal memory impairment. It is yet to be determined whether these changes are neurodevelopmental or neurodegenerative in nature. Overall, these findings indicate that there are subtle changes in the hippocampus of schizophrenic patients. More comprehensive and focused hippocampal research in schizophrenia is required to elucidate the contribution of this intriguing brain structure to the pathophysiology of schizophrenia.

Hippocampal metabolic abnormalities at first onset and with recurrent episodes of a major depressive disorder: A proton magnetic resonance spectroscopy study☆

The neural underpinnings of major depressive disorder (MDD) are unknown but there is evidence for structural alteration in the hippocampus that may become more pronounced over the course of illness. The aim of the present study was to examine metabolite levels of N-acetyl-aspartate (NAA), Myo-inositol (MI), Glutamate-glutamine (Glx) and choline-containing compounds (GPC and GPC+PCh) in patients presenting for first treatment of a depressive episode compared to those with multiple past episodes and age and sex matched controls. We used single voxel proton magnetic resonance spectroscopy ((1)H-MRS) centered on the hippocampus. Choline-containing compounds were significantly increased in patients with a high past illness burden relative to controls after controlling for hippocampal volume. The group presenting for first treatment had only increases in MI levels compared with matched controls. These results suggest that abnormal membrane turnover in the hippocampus is greater in patients with highly recurrent illness, and provide support for the hypothesis that there are neuronal changes in this region over the course of illness.

Depression and suicidal behavior in adolescent inpatients with obsessive compulsive disorder

BACKGROUND To investigate the prevalence and correlations of suicidal behavior in obsessive compulsive disorder (OCD) among adolescent psychiatric inpatients. METHODS A total of 348 adolescents, representing consecutive admissions to an adolescent inpatient unit, were assessed. Of these, 40 patients had OCD, 118 had schizophrenia, 59 had an affective disorder, 81 had a conduct disorder and 50 had an eating disorder. In addition, 87 normal community controls were assessed. All subjects were assessed for suicidal behavior by the Childhood Suicide Potential Scale (CSPS), for depression by the Beck Depression Inventory, for impulsiveness by the Impulse Control Scale, for anxiety by the State-Trait Anxiety Scale and for aggression by the Yudowsky Overt Aggression Scale. RESULTS All the psychiatrically ill subjects, including those with OCD, had high levels of depression, anxiety and impulsiveness, which were far higher than those of the controls. The rate of attempted suicide was, however, much lower in the OCD subjects. In addition, there was a significant inverse correlation between suicidal behavior levels on the CSPS and depression in the OCD subjects, while all other subjects showed the expected significant positive correlation between level of suicidal behavior and depression. LIMITATIONS This study looked at a referred population and generalization to outpatient and community samples cannot be made. Distinguishing between the primary and the comorbid diagnosis is difficult and some findings are based on small sample size and therefore may be vulnerable to type I error. CONCLUSIONS Although suicidal ideation and depressive symptoms are common in OCD adolescent inpatients, they seem to be protected against suicide attempts. The inverse relationship between suicidal behavior and depression may mean that suicidal behavior is, in some ways, qualitatively different from that seen in other psychiatrically ill adolescents.

Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis.

OBJECTIVE Structural brain imaging studies in obsessive-compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta- and mega-analyses of data from OCD sites worldwide. METHOD T1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta-analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. RESULTS The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohens d=-0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results. CONCLUSIONS The results indicate different patterns of subcortical abnormalities in pediatric and adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful.

Decreased platelet peripheral-type benzodiazepine receptors in adolescent inpatients with repeated suicide attempts

BACKGROUND Peripheral-type benzodiazepine receptors (PBR) are responsible for mitochondrial cholesterol uptake, the rate limiting step of steroidiogenesis. They have been shown to be increased after acute stress, and decreased during exposure to chronic stressful conditions, and in patients with generalized anxiety disorder and post-traumatic stress disorder. In view of the proven connection between adolescent suicidal behavior and stress, we hypothesized that PBR may be decreased in the suicidal adolescent population. METHODS We measured [3H] PK 11195 binding to platelet membrane in nine adolescent (age 13-20 years) inpatients with a history of at least three suicidal attempts and ten age-matched psychiatric inpatients with no history of suicide attempts. Suicidality was assessed with the Suicide Risk Scale (SRS), and symptom severity with the Beck Depression Inventory, State-Trait Anxiety Inventory (STAI), Overt Aggression Scale (OAS), and Impulsivity Scale (IS). RESULTS Suicide Risk Scale scores were significantly higher in the suicidal group. The suicidal group showed a significant decrease in platelet PBR density (-35%) compared to the controls (p < 0.005). CONCLUSIONS Our results of PBR depletion in adolescent suicide are in accordance with the findings in patients with generalized anxiety disorder and posttraumatic stress disorder and lend further support to the role of PBR in human response to chronic stress in adolescent suicide.

Examining and Comparing Social Perception Abilities Across Childhood-Onset Neurodevelopmental Disorders

OBJECTIVE Several neurodevelopmental disorders are associated with social processing deficits. The objective of this study was to compare patterns of social perception abilities across obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and control participants. METHOD A total of 265 children completed the Reading the Mind in the Eyes Test-Child Version (RMET). Parents or caregivers completed established trait/symptom scales. The predicted percentage of accuracy on the RMET was compared across disorders and by item difficulty and item valence (i.e., positive/negative/neutral mental states), then analyzed for associations with trait/symptom scores. RESULTS The percentage of correct RMET scores varied significantly between diagnostic groups (p < .0001). On pairwise group comparisons controlling for age and sex, children with ADHD and ASD scored lower than the other groups (p < .0001). When IQ was also controlled for in the model, participants with OCD performed better than controls (p < .001), although differences between other groups were less pronounced. Participants with ASD scored lowest on easy items. Those with ASD and ADHD scored significantly lower than other groups on items with positive valence (p < .01). Greater social communication impairment and hyperactivity/impulsivity, but not OCD traits/symptoms, were associated with lower scores on the RMET, irrespective of diagnosis. CONCLUSION Social perception abilities in neurodevelopmental disorders exist along a continuum. Children with ASD have the greatest deficits, whereas children with OCD may be hypersensitive to social information. Social communication deficits and hyperactive/impulsive traits are associated with impaired social perception abilities; these findings highlight overlapping cognitive and behavioral manifestations across disorders.

Proton magnetic resonance spectroscopy of prefrontal white matter in psychotropic naïve children and adolescents with obsessive–compulsive disorder

Obsessive-compulsive disorder (OCD) has a typical onset during childhood or adolescence. Although recent in-vivo proton magnetic resonance spectroscopy ((1)H-MRS) studies report gray matter metabolite abnormalities in children and adolescents with OCD, there are no existing (1)H-MRS studies that measure white matter (WM) metabolite levels in this population. In the present study, we measured metabolite levels in the left and right prefrontal WM (LPFWM and RPFWM, respectively) of psychotropic-naïve children and adolescents with OCD (LPFWM: N=15, mean age 13.3±2.4 years; right RPFWM: N=14, mean age 13.0±2.3 years) and healthy controls (LPFWM: N=17, mean age 11.8±2.7 years; RPFWM: N=18, mean age 12.2±2.8 years). Spectra were acquired using a 3T single voxel PRESS sequence (1.5×2.0×2.0cm(3)). When age and sex effects were controlled, OCD patients had higher levels of RPFWM choline and N-acetyl-aspartate (NAA). In addition, RPFWM levels of NAA, creatine and myo-inositol were positively and significantly correlated with severity of OCD symptoms. In summary, this is the first published study of WM metabolite levels in children and adolescents with OCD. Our preliminary findings lend further support to the previous findings of WM abnormalities in OCD.

The cost and impact of compulsivity: A research perspective

Compulsivity is the defining feature of various psychiatric disorders including Obsessive Compulsive Related Disorders (OCRDs), and other compulsive, impulsive, and addictive disorders. These disorders are disabling, chronic conditions with an early onset and high rates of comorbidity, misdiagnoses, and delay in treatment onset. Disorders of compulsivity are responsible for considerable socioeconomic burden to society. We review the costs and impacts of compulsivity. In order to facilitate earlier diagnosis and targeted treatments, we examine the overlapping mechanisms that underlie compulsivity. We reconceptualize psychiatric disorders based on core features of compulsivity, highlight challenges in harmonizing research in children and adults, describe newer research methodologies, and point to future directions that can impact the costs and impact of disorders of compulsivity.

Metabolite measurements in the caudate nucleus, anterior cingulate cortex and hippocampus among patients with mitochondrial disorders: a case–control study using proton magnetic resonance spectroscopy

BACKGROUND Mitochondrial disorders are clinical syndromes associated with mutations in the mitochondrial or nuclear genome that result in impaired oxidative phosphorylation and deficient energy production. Metabolic abnormalities in brain areas associated with cognitive functions could give rise to neuropsychiatric symptomatology. The aim of this study was to use single-voxel proton magnetic resonance spectroscopy to identify metabolic abnormalities in regions implicated in neuropsychiatric symptoms in patients with mitochondrial disorders. METHODS N-acetyl-aspartate and creatine levels were measured in the caudate nucleus, anterior cingulate cortex and hippocampus in 15 patients with mitochondrial disorders compared with 15 healthy controls matched for age and sex. RESULTS N-acetyl-aspartate levels were significantly lower in the caudate nucleus among patients with mitochondrial disorders (mean 7.04 ± 1.19 standard deviation [SD] institutional units) compared with healthy controls (mean 8.19 ± 1.18 SD institutional units; p = 0.02). Creatine levels were lower in the caudate nucleus among patients compared with controls (patients: mean 6.84 ± 1.42 SD institutional units; controls: mean 7.52 ± 0.76 SD institutional units; p = 0.03), but the results were no longer significant after correction for multiple comparisons. There were no significant differences in metabolite measurements between patients and controls in the anterior cingulate cortex and the hippocampus. INTERPRETATION Metabolic abnormalities were identified exclusively in the caudate nucleus, with significantly lower N-acetyl-aspartate levels among patients compared with controls. These results suggest that the corpus striatum may be highly susceptible to mitochondrial oxidative phosphorylation defects and resultant cell loss. Given the role of the caudate nucleus in cognitive and executive functions, our findings raise the possibility that metabolic abnormalities in the caudate nucleus may contribute to cognitive impairment and neuropsychiatric symptoms in patients with mitochondrial disorders, which could be investigated in future studies.