Pietro De Rossi

Trajectories of Cerebral Cortical Development in Childhood and Adolescence and Adult Attention-Deficit/Hyperactivity Disorder

BACKGROUNDnChildhood attention-deficit/hyperactivity disorder (ADHD) persists into adulthood in around half of those affected, constituting a major public health challenge. No known demographic, clinical, or neuropsychological factors robustly explain the clinical course, directing our focus to the brain. Herein, we link the trajectories of cerebral cortical development during childhood and adolescence with the severity of adult ADHD.nnnMETHODSnUsing a longitudinal study design, 92 participants with ADHD had childhood (mean 10.7 years, SD 3.3) and adult clinical assessments (mean 23.8 years, SD 4.3) with repeated neuroanatomic magnetic resonance imaging. Contrast was made against 184 matched typically developing volunteers.nnnRESULTSnAttention-deficit/hyperactivity disorder persisted in 37 (40%) subjects and adult symptom severity was linked to cortical trajectories. Specifically, as the number of adult symptoms increased, particularly inattentive symptoms, so did the rate of cortical thinning in the medial and dorsolateral prefrontal cortex. For each increase of one symptom of adult ADHD, the rate of cortical thinning increased by .0018 mm (SE = .0004, t = 4.2, p < .0001), representing a 5.6% change over the mean rate of thinning for the entire group. These differing trajectories resulted in a convergence toward typical dimensions among those who remitted and a fixed, nonprogressive deficit in persistent ADHD. Notably, cortical thickening or minimal thinning (greater than -.007 mm/year) was found exclusively among individuals who remitted.nnnCONCLUSIONSnAdult ADHD status is linked with the developmental trajectories of cortical components of networks supporting attention, cognitive control, and the default mode network. This informs our understanding of the developmental pathways to adult ADHD.

Mapping the Development of the Basal Ganglia in Children With Attention-Deficit/ Hyperactivity Disorder

OBJECTIVEnThe basal ganglia are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), but little is known of their development in the disorder. Here, we mapped basal ganglia development from childhood into late adolescence using methods that define surface morphology with an exquisite level of spatial resolution.nnnMETHODnSurface morphology of the basal ganglia was defined from neuroanatomic magnetic resonance images acquired in 270 youth with DSM-IV-defined ADHD and 270 age- and sex-matched typically developing controls; 220 individuals were scanned at least twice. Using linear mixed model regression, we mapped developmental trajectories from age 4 through 19 years at approximately 7,500 surface vertices in the striatum and globus pallidus.nnnRESULTSnIn the ventral striatal surfaces, there was a diagnostic difference in developmental trajectories (t = 5.6, p < .0001). Here, the typically developing group showed surface area expansion with age (estimated rate of increase of 0.54 mm(2) per year, standard error [SE] 0.29 mm(2) per year), whereas the ADHD group showed progressive contraction (decrease of 1.75 mm(2) per year, SE 0.28 mm(2) per year). The ADHD group also showed significant, fixed surface area reductions in dorsal striatal regions, which were detected in childhood at study entry and persisted into adolescence. There was no significant association between history of psychostimulant treatment and developmental trajectories.nnnCONCLUSIONSnProgressive, atypical contraction of the ventral striatal surfaces characterizes ADHD, localizing to regions pivotal in reward processing. This contrasts with fixed, nonprogressive contraction of dorsal striatal surfaces in regions that support executive function and motor planning.

Predominant polarity and temperament in bipolar and unipolar affective disorders

INTRODUCTIONnRecently, the concept of predominant polarity (two-thirds of episodes belonging to a single pole of the illness) has been introduced to further characterise subtypes of bipolar disorders. This concept has been proven to have diagnostic and therapeutic implications, but little is known on the underlying psychopathology and temperaments. With this study, we aimed to further validate the concept and explore its relationships with temperament.nnnMETHODSnThis study enrolled 143 patients with bipolar or unipolar disorder. We analysed predominant polarity in the sample of bipolar I patients (N=124), focussing on those who showed a clear predominance for one or the other polarity, and distinguishing manic/hypomanic (MP) from depressive polarity (DP), and a unipolar major depression (UP) group (N=19),. We also assessed temperament by means of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A).nnnRESULTSnOver 55% of the bipolar I sample fulfilled predominant polarity criteria, with two-thirds of those meeting criteria for MP and one third for DP. MP and DP were similar in scoring higher than UP on the hyperthymic/cyclothymic scales of the TEMPS-A; the UP group scored higher on the anxious/depressive scales.nnnDISCUSSIONnOur results show that both bipolar I MP and DP subgroups are temperamentally similar and different from UP. Depression in DP bipolar I patients should be viewed as the overlap of depression on a hyperthymic/cyclothymic temperament. These findings confirm the value of the predominant polarity concept as well as the importance of temperaments to separate bipolar from unipolar disorders.

Serum levels of risperidone and its metabolite, 9-hydroxyrisperidone: Correlation between drug concentration and clinical response

The aim of this study was to assess a method able to analyze serum levels of risperidone (RIS) and its metabolite, 9-hydroxyrisperidone (9-OH-RIS), and to investigate possible relationships between changes in serum concentrations of these drugs and clinical measures, so to identify early markers of treatment response. The authors developed a sensitive and specific liquid chromatography-tandem mass spectrometry method to measure RIS and its metabolite in serum. Fifteen RIS-naive patients were admitted to an acute psychiatric care unit and treated with 4-6 mg/d oral RIS. At days 7 and 21 of hospital stay, serum levels were measured; clinical scales and serum prolactin were assessed. RIS and its metabolite were analyzed by a Q-Trap 2000 triple quadrupole/ion trap mass spectrometer in the multiple reaction-monitoring mode. Chromatographic separation was accomplished using a cyano column with an analytical run of 9 minutes. The calibration curve exhibited consistent linearity and reproducibility in the range 0-100 ng/mL for both analytes. Lower limit of quantification was 0.2 ng/mL; limit of detection, for a signal to noise ratio of 3, was 0.05 ng/mL for both analytes. Serum RIS and 9-OH-RIS levels increased at day 7, reaching a steady state, and remaining constant up to day 21. Scores on psychopathology rating scales decreased; serum prolactin and neurological rating scale for extrapyramidal effects rose at day 7 and remained stable thereafter. No correlation was found between serum concentration values, including sum and ratio of RIS and 9-OH-RIS, and any of the other clinical values (serum prolactin and clinical scales). These data indicate that clinical changes are related to the achievement of steady state levels of RIS and its metabolite and are maintained, but not continued, with continued RIS treatment. Therapeutic drug monitoring of RIS and its metabolites is not recommended as a routine procedure in patients with psychotic disorders.

Deep Transcranial Magnetic Stimulation for treatment-resistant bipolar depression: A case report of acute and maintenance efficacy

Deep Transcranial Magnetic Stimulation (dTMS) is currently being evaluated as a possible treatment for several neuropsychiatric disorders and has been demonstrated as a safe and effective procedure. This case presents a patient with bipolar depression that has been treated with 20 daily consecutive dTMS sessions and with one dTMS session every 2 weeks for the following 3 months. Depressive symptoms improved rapidly and response was maintained during the next 6 months; cognitive performances also improved. This report suggests that add-on dTMS may help overcoming drug-resistance in bipolar depression and protect from subsequent bipolar episodes of any polarity.

Brain white matter microstructure in deficit and non-deficit subtypes of schizophrenia

Dividing schizophrenia into its deficit (SZD) and nondeficit (SZND) subtypes may help to identify specific and more homogeneous pathophysiological characteristics. Our aim was to define a whole brain voxelwise map specifically characterizing white matter tracts of schizophrenia patients with and without the deficit syndrome. We compared microstructural diffusion-related parameters as measured by diffusion tensor imaging in 21 SZD patients, 21 SZND patients, and 21 healthy controls, age- and gender-matched. Results showed that fractional anisotropy was reduced in the right precentral area in SZND patients, and in the left corona radiata of the schizophrenia group as a whole. Axial diffusivity was reduced in the left postcentral area of SZD patients and in the left cerebellum of the whole schizophrenia group. Radial diffusivity was increased in the left forceps minor of SZD patients, in the left internal capsule of SZND patients, and in the right inferior fronto-occipital fasciculus in the whole schizophrenia group. Mean diffusivity was increased from healthy controls to SZD patients to SZND patients in the right occipital lobe. In conclusion, SZD patients are not simply at the extreme end of a severity continuum of white matter disruption. Rather, the SZD and SZND subtypes are associated with distinct and specific brain microstructural anomalies that are consistent with their peculiar psychopathological dimensions.

Executive functions in obsessive–compulsive disorder: An activation likelihood estimate meta-analysis of fMRI studies

Abstract Objectives: To identify activation changes assessed in functional magnetic resonance imaging (fMRI) studies of obsessive–compulsive disorder (OCD) through Activation Likelihood Estimate meta-analysis. Methods: We included 28 peer-reviewed standard stereotactic space studies assessing adult OCD patients (OCDpts) vs. healthy controls (HCs) with fMRI during executive task performance. Results: In within-group analyses, HCs showed task-related activations in bilateral inferior frontal gyri, right middle frontal gyrus, right inferior parietal lobule, right claustrum, bilateral cingulate gyri, and left caudate body. OCDpts showed task-related left-sided activations in the superior, medial, and inferior frontal gyri, and thalamus, and bilateral activations in the middle frontal gyri, inferior parietal lobule, and insular cortices. Subtraction analysis showed increased left middle frontal gyrus activation in OCDpts. In between-groups analyses, OCDpts hypoactivated the right caudate body, left putamen, left ACC, and right medial and middle frontal gyri. Right caudate hypoactivation persisted also after applying Family‐wise error algorithms. Conclusions: This meta-analysis confirms that during executive functioning OCDpts show a functional deficit of the right caudate body, which could represent a major neural functional correlate of their illness.

Hippocampal subfield volumes in short- and long-term lithium-treated patients with bipolar I disorder.

Patients diagnosed with bipolar disorder (BP) may experience hippocampal atrophy. Lithium exposure has been associated with increased hippocampal volumes. However, its effects on hippocampal subfields remain to be clarified.

Schizophrenia and bipolar disorder: The road from similarities and clinical heterogeneity to neurobiological types

Although diagnosis is a central issue in medical care, in psychiatry its value is still controversial. The function of diagnosis is to indicate treatments and to help clinicians take better care of patients. The fundamental role of diagnosis is to predict outcome and prognosis. To date serious concern persists regarding the clinical utility and predictive validity of the diagnosis system in psychiatry, which is at the most syndromal. Schizophrenia and bipolar disorder, which nosologists consider two distinct disorders, are the most discussed psychiatric illnesses. Recent findings in different fields of psychiatric research, such as neuroimaging, neuropathology, neuroimmunology, neuropsychology and genetics, have led to other conceptualizations. Individuals with schizophrenia or bipolar disorder vary greatly with regard to symptoms, illness course, treatment response, cognitive and functional impairment and biological correlates. In fact, it is possible to find heterogeneous correlates even within the same syndrome, i.e., from one stage of the disorder to another. Thus, it is possible to identify different subsyndromes, which share some clinical and neurobiological characteristics. The main goal of modern psychiatry is to ovethrow these barriers and to obtain a better understanding of the biological profiles underlying heterogeneous clinical features and thus reduce the variance and lead to a homogeneous definition. The translational research model, which connects the basic neuroscience research field with clinical experience in psychiatry, aims to investigate different neurobiological features of syndromes and of the shared neurobiological features between two syndromes. In fact, this approach should help us to better understand the neurobiological pathways underlying clinical entities, and even to distinguish different, more homogeneous, diagnostic subtypes.

Brain Functional Effects of Psychopharmacological Treatments in Schizophrenia: A Network-based Functional Perspective Beyond Neurotransmitter Systems.

Psychopharmacological treatments for schizophrenia have always been a matter of debate and a very important issue in public health given the chronic, relapsing and disabling nature of the disorder. A thorough understanding of the pros and cons of currently available pharmacological treatments for schizophrenia is critical to better capture the features of treatment-refractory clinical pictures and plan the developing of new treatment strategies. This review focuses on brain functional changes induced by antipsychotic drugs as assessed by modern functional neuroimaging techniques (i.e. fMRI, PET, SPECT, MRI spectroscopy). The most important papers on this topic are reviewed in order to draw an ideal map of the main functional changes occurring in the brain during antipsychotic treatment. This supports the hypothesis that a network-based perspective and a functional connectivity approach are needed to fill the currently existing gap of knowledge in the field of psychotropic drugs and their mechanisms of action beyond neurotransmitter systems.