Antonio Bulbena

A validation study of the hospital anxiety and depression scale (HADS) in a Spanish population.

The present study aims to validate the Spanish version of the Hospital Anxiety and Depression Scale (HADS) and to determine the use of this tool for screening mood and anxiety disorders. Psychometric properties of the HADS were assessed in different groups of general medical outpatients attending the Hospital Clínic in Barcelona (N=385), and psychiatric diagnoses were made using DSM-IV criteria. A two-factor solution corresponding to the original two subscales of the HADS was found. The Spanish version of the HADS had good internal consistency and external validity, with favorable sensitivity and specificity in identifying cases of psychiatric disorder as defined by the Structured Clinical Interview for DSM-IV (SCID-I). The psychometric properties of the HADS and its brevity make it useful for screening for psychiatric disorders in the medically ill.

Evaluación psicométrica comparativa de las versiones en español de 6, 17 y 21 ítems de la Escala de valoración de Hamilton para la evaluación de la depresión

Fundamento y objetivo Los estudios espanoles previos de la Hamilton Depression Rating Scale(HDRS) se han centrado en su version de 17 items y se han realizado fundamentalmente enpoblaciones hospitalizadas. En el presente estudio se ha llevado a cabo una evaluacion psicometricacomparativa de las versiones en espanol de la HDRS de 6, 17 y 21 items en pacientescon depresion en tratamiento ambulatorio. Pacientes y metodo Estudio multicentrico, observacional y prospectivo en pacientes con depresion,clinicamente estables o inestables. Se evaluaron la validez discriminante, la fiabilidad(consistencia interna, estabilidad temporal y entre observadores) y la sensibilidad al cambio dela HDRS con 6, 17 y 21 items. Resultados Se incluyo a 168 pacientes de 15 centros de asistencia psiquiatrica. Las versionesde 6, 17 y 21 items de la HDRS presentaron una adecuada validez discriminante (HDRS-ImpresionClinica Global de Gravedad, p Conclusiones Las versiones en espanol de la HDRS con 6, 17 y 21 items presentan similarespropiedades psicometricas. El buen rendimiento de HDRS-6 justifica su utilizacion en mediosambulatorios y en atencion primaria.

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.

An independent components and functional connectivity analysis of resting state fMRI data points to neural network dysregulation in adult ADHD

Spontaneous fluctuations can be measured in the brain that reflect dissociable functional networks oscillating at synchronized frequencies, such as the default mode network (DMN). In contrast to its diametrically opposed task‐positive counterpart, the DMN predominantly signals during a state of rest, and inappropriate regulation of this network has been associated with inattention, a core characteristic of attention‐deficit/hyperactivity disorder (ADHD). To examine whether abnormalities can be identified in the DMN component of patients with ADHD, we applied an independent components analysis to resting state functional magnetic resonance imaging data acquired from 22 male medication‐naïve adults with ADHD and 23 neurotypical individuals. We observed a stronger coherence of the left dorsolateral prefrontal cortex (dlPFC) with the DMN component in patients with ADHD which correlated with measures of selective attention. The increased left dlPFC‐DMN coherence also surfaced in a whole‐brain replication analysis involving an independent sample of 9 medication‐naïve adult patients and 9 controls. In addition, a post hoc seed‐to‐voxel functional connectivity analysis using the dlPFC as a seed region to further examine this regions suggested connectivity differences uncovered a higher temporal coherence with various other neural networks and confirmed a reduced anticorrelation with the DMN. These results point to a more diffuse connectivity between functional networks in patients with ADHD. Moreover, our findings suggest that state‐inappropriate neural activity in ADHD is not confined to DMN intrusion during attention‐demanding contexts, but also surfaces as an insufficient suppression of dlPFC signaling in relation to DMN activity during rest. Together with previous findings, these results point to a general dysfunction in the orthogonality of functional networks. Hum Brain Mapp 35:1261–1272, 2014.

Response inhibition and reward anticipation in medication-naïve adults with attention-deficit/hyperactivity disorder: a within-subject case-control neuroimaging study.

Background: Previous research suggests that ADHD patients are characterized by both reduced activity in the inferior frontal gyrus (IFG) during response inhibition tasks (such as the Go‐NoGo task), and reduced activity in the ventral striatum during reward anticipation tasks (such as the Monetary‐Incentive‐Delay [MID] task). However, no prior research has applied either of these paradigms in medication‐naïve adults with ADHD, nor have these been implemented in an intrasubject manner. Methods: The sample consisted of 19 medication‐naïve adults with ADHD and 19 control subjects. Main group analyses were based on individually defined regions of interest: the IFG and the VStr for the Go‐NoGo and the MID task respectively. In addition, we analyzed the correlation between the two measures, as well as between these measures and the clinical symptoms of ADHD. Results: We observed reduced bilateral VStr activity in adults with ADHD during reward anticipation. No differences were detected in IFG activation on the Go‐NoGo paradigm. Correlation analyses suggest that the two tasks are independent at a neural level, but are related behaviorally in terms of the variability of the performance reaction time. Activity in the bilateral VStr but not in the IFG was associated negatively with symptoms of hyperactivity/impulsivity. Conclusions: Results underline the implication of the reward system in ADHD adult pathophysiology and suggest that frontal abnormalities during response inhibition performance may not be such a pivotal aspect of the phenotype in adulthood. In addition, our findings point toward response variability as a core feature of the disorder. Hum Brain Mapp 33:2350–2361, 2012.

Enhanced neural activity in frontal and cerebellar circuits after cognitive training in children with attention-deficit/hyperactivity disorder.

The brain is a plastic entity that can undergo dynamic changes throughout the lifespan as a result of training. Attention‐deficit/hyperactivity disorder (ADHD) is commonly treated with psychostimulant medication, and the prevalence of ADHD medication prescription is a topic of heated scientific debate. In addition, cognitive training is frequently provided to patients with ADHD. Although psychostimulant effects have been thoroughly investigated, no previous studies have assessed the neural effects of cognitive training in ADHD. We applied fMRI‐paradigms of response inhibition and selective attention to chart the effects of a 10‐day cognitive training program in 19 unmedicated ADHD children receiving either cognitive or control training. The two resulting longitudinal datasets were analyzed using whole‐brain random‐effects general linear models. Although we observed no increases of activity in the control group, both fMRI‐datasets revealed enhanced activity after cognitive training in neural structures closely related to ADHD pathophysiology. On the inhibition paradigm, our results indicated increases in orbitofrontal, superior frontal, middle temporal, and inferior frontal cortex. The attentional task was characterized by increased activity in the cerebellum, which correlated with improvement on in‐scanner measures of attention. Our findings provide preliminary evidence that cognitive training enhances activity in neural structures typically affected by the disorder. Similar results have been obtained following methylphenidate administration, suggesting that training of cognitive functions may mimic the effects of psychostimulant medication on the brain. These findings postulate a neural account for the potency of cognitive training in ADHD, and hold clinical implications, supporting the inclusion of training programs in standard ADHD‐treatment. Hum Brain Mapp, 2010.

Tardive dyskinesia associated with higher mortality in psychiatric patients: results of a meta-analysis of seven independent studies.

This article reports a meta-analysis of seven independent studies on the association of tardive dyskinesia with all-cause mortality in psychiatric patients. Most of the studies included provide either small sample sizes or follow-up periods too short to reach a substantive conclusion on their own. In the meta-analysis, the overall odds ratio (OR) was significant when calculated either by the fixed-effects model (OR = 1.4, 95% confidence interval [CI] = 1.2-1.7, p < 0.005) or the random-effects model (OR = 1.4, 95% CI = 1.1-1.8, p < 0.005). There was no overall heterogeneity (Q test = 8.1, df = 7,p = 0.32). The overall estimate changed within study designs (OR = 1.4,p = 0.002 in three prospective controlled studies; OR = 2.2, p = 0.02 in two prospective uncontrolled studies; and OR = 0.9, p = 0.80 in two retrospective controlled studies). It was modified upward when the two most influential studies (one prospective and one retrospective) were removed from the overview (OR = 2.2, 95% CI = 1.4-3.5,p = 0.001; Q test = 0.81, df = 4,p = 0.94). The conclusion of the meta-analysis was that tardive dyskinesia must be considered a weak risk factor in terms of mortality. It remains to be elucidated whether it is a risk factor on its own or just a surrogate for any unknown organic liability.

Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility

Objective: Anxiety is associated with increased physiological reactivity and also increased “interoceptive” sensitivity to such changes in internal bodily arousal. Joint hypermobility, an expression of a common variation in the connective tissue protein collagen, is increasingly recognized as a risk factor to anxiety and related disorders. This study explored the link between anxiety, interoceptive sensitivity and hypermobility in a sub-clinical population using neuroimaging and psychophysiological evaluation. Methods: Thirty-six healthy volunteers undertook interoceptive sensitivity tests, a clinical examination for hypermobility and completed validated questionnaire measures of state anxiety and body awareness tendency. Nineteen participants also performed an emotional processing paradigm during functional neuroimaging. Results: We confirmed a significant relationship between state anxiety score and joint hypermobility. Interoceptive sensitivity mediated the relationship between state anxiety and hypermobility. Hypermobile, compared to non-hypermobile, participants displayed heightened neural reactivity to sad and angry scenes within brain regions implicated in anxious feeling states, notably insular cortex. Conclusions: Our findings highlight the dependence of anxiety state on bodily context, and increase our understanding of the mechanisms through which vulnerability to anxiety disorders arises in people bearing a common variant of collagen.

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.

Brain regions related to fear extinction in obsessive-compulsive disorder and its relation to exposure therapy outcome: a morphometric study

BACKGROUND The size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD. METHOD A total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed. RESULTS Compared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r - 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results. CONCLUSIONS OCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.