Marisol Picado

Ventro-Striatal Reductions Underpin Symptoms of Hyperactivity and Impulsivity in Attention-Deficit/Hyperactivity Disorder

BACKGROUND Models of attention-deficit/hyperactivity disorder (ADHD) classically emphasize the relevance of executive processes and, recently, reward circuits. The neural bases of reward processes have barely been explored in relation to this disorder, in contrast to extensive neuroimaging studies that examine executive functions in patients with ADHD. To our knowledge, no previous studies have analyzed the volume of the ventral striatum, a key region for reward processes in ADHD children. METHODS We used a manual region-of-interest approach to examine whether there were volumetric differences in the ventral striatum of ADHD children. Forty-two children/adolescents with ADHD (ages 6-18), and 42 healthy control subjects matched on age, gender, and handedness were selected for the study. RESULTS The ADHD children presented significant reductions in both right and left ventro-striatal volumes (t = 3.290, p = .001; and t = 3.486, p = .001, respectively). In addition, we found that the volume of the right ventral striatum negatively correlated with maternal ratings of hyperactivity/impulsivity (r = -.503, p = .003). CONCLUSIONS Our study provides neuroanatomical evidence of alterations in the ventral striatum of ADHD children. These findings coincide with previous explicative models as well as with recent reports in behavioral and functional neuroimaging studies. Furthermore, the negative correlations we observed strongly uphold the relation between the ventral striatum and symptoms of hyperactivity/impulsivity.

Laminar thickness alterations in the fronto-parietal cortical mantle of patients with attention-deficit/hyperactivity disorder.

Although Attention-Deficit/Hyperactivity Disorder (ADHD) was initially regarded as a disorder exclusive to childhood, nowadays its prevalence in adulthood is well established. The development of novel techniques for quantifying the thickness of the cerebral mantle allows the further exploration of the neuroanatomical profiles underlying the child and adult form of the disorder. To examine the cortical mantle in children and adults with ADHD, we applied a vertex-wise analysis of cortical thickness to anatomical brain MRI scans acquired from children with (n = 43) and without ADHD (n = 41), as well as a group of adult neurotypical individuals (n = 31), adult patients with a history of stimulant treatment (n = 31) and medication-naïve adults with ADHD (n = 24). We observed several clusters of reduced laminar cortical thickness in ADHD patients in comparison to neurotypical individuals. These differences were primarily located in the dorsal attention network, including the bilateral inferior and superior parietal cortex and a section of the frontal cortex (centered on the superior frontal and precentral gyrus bilaterally). Further laminar thickness deficits were observed in the bilateral orbitofrontal cortex and medial occipital cortex. The deficits in the cortical surface were especially pronounced in the child sample, while adult patients showed a more typical laminar thickness across the cerebral mantle. These findings show that the neuroanatomical profile of ADHD, especially the childhood form of the disorder, involves robust alterations in the cortical mantle, which are most prominent in brain regions subserving attentional processing.

Stimulant drugs trigger transient volumetric changes in the human ventral striatum

The ventral striatum (VStr) integrates mesolimbic dopaminergic and corticolimbic glutamatergic afferents and forms an essential component of the neural circuitry regulating impulsive behaviour. This structure represents a primary target of psychostimulant medication, the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), and is biochemically modified by these drugs in animals. However, the effects of stimulants on the human VStr remain to be determined. We acquired anatomical brain MRI scans from 23 never-medicated adult patients with ADHD, 31 adult patients with a history of stimulant treatment and 32 control subjects, and VStr volumes were determined using individual rater-blinded region of interest delineation on high-resolution neuroanatomical scans. Furthermore, we also extracted VStr volumes before and after methylphenidate treatment in a subsample of the medication-naïve adult patients as well as in 20 never-medicated children with ADHD. We observed smaller VStr volumes in adult patients with a history of stimulant treatment in comparison to never-medicated patients. Moreover, our longitudinal analyses uncovered a reduction of grey matter volume in the bilateral VStr in adult patients after exposure to methylphenidate, which was followed by volumetric recovery to control level. In children, the same pattern of VStr volume changes was observed after treatment with methylphenidate. These findings suggest that the altered VStr volumes previously observed in patients with ADHD may represent a transitory effect of stimulant exposure rather than an intrinsic feature of the disorder. More generally, these data show that stimulant drugs can render plastic volume changes in human VStr neuroanatomy.

Association between neurological soft signs, temperament and character in patients with schizophrenia and non-psychotic relatives

The heritability of schizophrenia and most personality traits has been well established, but the role of personality in susceptibility to schizophrenia remains uncertain. The aim of this study was to test for an association between personality traits and Neurological Soft Signs (NSS), a well-known biological marker of schizophrenia, in non-psychotic relatives of patients with schizophrenia. For this purpose, we evaluated the NSS scale and personality measured by the Temperament and Character inventory (TCI-R) in three groups of subjects: 29 patients with schizophrenia, 24 unaffected relatives and 37 controls. The results showed that patients with schizophrenia were more asocial (higher harm avoidance and lower reward dependence), more perseverative (higher persistence), and more schizotypal (lower self-directedness and cooperativeness, higher self-transcendence). The unaffected relatives showed higher harm avoidance, lower self-directedness and cooperativeness than the healthy controls. Higher NSS scores and sub-scores were found in patients and non-psychotic relatives compared with the controls. Among all the patients, total NSS scores were positively correlated with harm avoidance but negatively correlated with novelty seeking and persistence. Total NSS were also correlated with low scores on self-directedness and cooperativeness, which are indicators of personality disorder. Our results show that susceptibility to NSS and to schizophrenia are both related to individual differences in the temperament and character features in non-psychotic relatives of patients with schizophrenia. High harm avoidance, low persistence, low self-directedness and low cooperativeness contribute to both the risk of NSS and schizophrenia. These findings highlight the value of using both assessments to study high risk populations.

Presence of Distractor Improves Time Estimation Performance in an Adult ADHD Sample

Objective: It is widely accepted that patients with ADHD exhibit greater susceptibility to distractors, especially during tasks with higher working memory load demands. However, no study to date has specifically measured the impact of distractors on timing functions, although these have consistently shown alterations in ADHD. In this investigation, we aimed to elucidate the neural mechanisms mediating distractor effects on timing functions. Method: We employed a time estimation functional magnetic resonance imaging (fMRI) paradigm including a distracting element in half of the trials in a sample of 21 patients with ADHD and 24 healthy controls. Results: As expected, the effect of the distractor was greater in ADHD patients, where it was associated with increased orbitofrontal activity compared with controls. Behaviorally, time estimation performance benefited from the presence of distractors in both groups. In turn, such improvement correlated with medial frontal and insular activity in the brain. Conclusion: These results suggest that distractors could be stimulating recruitment of frontal resources in ADHD, thus contributing to increase focus on the task.

Time and psychostimulants: Opposing long-term structural effects in the adult ADHD brain. A longitudinal MR study

Long-term effects of psychostimulants such as methylphenidate on ADHD patients have been proved to be difficult to capture in cross-sectional studies comparing medicated and non-medicated samples and in longitudinal studies with children, with age-related maturational processes possibly confounding independent effects of medication. However, chronic psychostimulant administration at therapeutic doses has been proven to yield profound neuroadaptive changes in rodent models. Here, we present for the first time the effect of psychostimulant treatment on brain volumes in a sample of medication-naïve adult ADHD patients. We investigated grey matter volume changes in a sample of 41 medication-naïve adult ADHD patients before and after three years of psychostimulant treatment (N = 25) or no treatment (N = 16) compared to healthy adults (N = 25). We found a significant group x time interaction effect on left putamen grey matter volumes, with a decrease in left putamen volumes in the non-medicated group compared to both the medicated group and controls, and no differences between the medicated group and controls. Our results suggest a normalizing effect of psychostimulant treatment on the left putamen volume loss detected in non-medicated ADHD patients.

The neuroanatomical basis of panic disorder and social phobia in schizophrenia: a voxel based morphometric study.

Objective It is known that there is a high prevalence of certain anxiety disorders among schizophrenic patients, especially panic disorder and social phobia. However, the neural underpinnings of the comorbidity of such anxiety disorders and schizophrenia remain unclear. Our study aims to determine the neuroanatomical basis of the co-occurrence of schizophrenia with panic disorder and social phobia. Methods Voxel-based morphometry was used in order to examine brain structure and to measure between-group differences, comparing magnetic resonance images of 20 anxious patients, 20 schizophrenic patients, 20 schizophrenic patients with comorbid anxiety, and 20 healthy control subjects. Results Compared to the schizophrenic patients, we observed smaller grey-matter volume (GMV) decreases in the dorsolateral prefrontal cortex and precentral gyrus in the schizophrenic-anxiety group. Additionally, the schizophrenic group showed significantly reduced GMV in the dorsolateral prefrontal cortex, precentral gyrus, orbitofrontal cortex, temporal gyrus and angular/inferior parietal gyrus when compared to the control group. Conclusions Our findings suggest that the comorbidity of schizophrenia with panic disorder and social phobia might be characterized by specific neuroanatomical and clinical alterations that may be related to maladaptive emotion regulation related to anxiety. Even thought our findings need to be replicated, our study suggests that the identification of neural abnormalities involved in anxiety, schizophrenia and schizophrenia-anxiety may lead to an improved diagnosis and management of these conditions.

Just-in-time response to reward as a function of ADHD symptom severity: An fMRI study on motivational context

Attention‐deficit hyperactivity disorder (ADHD) neuroimaging studies have identified substantial differences in reward‐related circuits on a trial‐by‐trial basis. However, no research to date has evaluated the effect of motivational context on neural activity in settings with intermittent reward in ADHD. The present study was designed to identify neural processes underlying both immediate effects of reward and sustained effects of reward associated with motivational context in adult ADHD patients.