Antoni Bulbena

A Polymorphic Genomic Duplication on Human Chromosome 15 Is a Susceptibility Factor for Panic and Phobic Disorders

Anxiety disorders are complex and common psychiatric illnesses associated with considerable morbidity and social cost. We have studied the molecular basis of the cooccurrence of panic and phobic disorders with joint laxity. We have identified an interstitial duplication of human chromosome 15q24-26 (named DUP25), which is significantly associated with panic/agoraphobia/social phobia/joint laxity in families, and with panic disorder in nonfamilial cases. Mosaicism, different forms of DUP25 within the same family, and absence of segregation of 15q24-26 markers with DUP25 and the psychiatric phenotypes suggest a non-Mendelian mechanism of disease-causing mutation. We propose that DUP25, which is present in 7% control subjects, is a susceptibility factor for a clinical phenotype that includes panic and phobic disorders and joint laxity.

Global and regional gray matter reductions in ADHD: A voxel-based morphometric study

Attention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by inattentiveness, motor hyperactivity and impulsivity. According to neuroimaging data, the neural substrate underlying ADHD seems to involve fronto-striatal circuits and the cerebellum. However, there are important discrepancies between various studies, probably due to the use of different techniques. The aim of this study is to examine cerebral gray (GM) and white (WM) matter abnormalities in a group of ADHD children using a voxel-based morphometry protocol. The sample consisted of 25 children/adolescents with DSM-IV TR diagnosis of ADHD (medicated, aged 6-16 years) who were compared with 25 healthy volunteer children/adolescents. ADHD brains on an average showed a global volume decrease of 5.4% as compared to controls. Additionally, there were regionally specific effects in the left fronto-parietal areas (left motor, premotor and somatosensory cortex), left cingulate cortex (anterior/middle/posterior cingulate), parietal lobe (precuneus bilaterally), temporal cortices (right middle temporal gyrus, left parahippocampal gyrus), and the cerebellum (bilateral posterior). There were no differences in WM volume between ADHD children and control subjects. The results are consistent with previous studies that used different techniques, and may represent a possible neural basis for some of the motor and attentional deficits commonly found in ADHD.

Anxiety disorders in the joint hypermobility syndrome

A case-control study was designed to test the association between joint hypermobility syndrome (JHS), an inherited disorder of collagen synthesis, and anxiety and phobic disorders. One hundred fourteen cases of JHS diagnosed at the rheumatology outpatient clinic of the Hospital del Mar (Barcelona) were compared to 59 control subjects randomly selected from patients seen at the same clinic. Both cases and controls were examined by a psychologist who used the Structured Clinical Interview for DSM-III-R and who was unaware of their medical diagnoses. DSM-III-R diagnoses of panic disorder, agoraphobia, and simple phobia, but not generalized anxiety disorder, dysthymic disorder, or major depression were found to be highly associated with JHS (age- and sex-adjusted odds ratio = 10.7). Mitral valve prolapse (MVP) was present only among JHS cases. Among cases of JHS, subjects with MVP were almost three times more likely to suffer from anxiety than subjects without MVP (odds ratio = 2.95), although the association was not statistically significant. The strong association between panic anxiety and JHS appears to occur at a higher level than the association between panic and MVP, and provides a new basis for further studies on the genetic background of panic-anxiety.

Pediatric OCD structural brain deficits in conflict monitoring circuits : A voxel-based morphometry study

The aim of this study is to use a voxel-based morphometry protocol to compare the brains of 18 children with obsessive-compulsive disorder (OCD) with those of a healthy group matched for gender and handedness. Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with an optimized voxel-based morphometry protocol. OCD children presented a 5.93% reduction of gray matter (GM) total volume in comparison with control brains. We identified OCD brain volume reductions in regions that have been extensively related to action monitoring and error signaling processes. Specifically, we found decreased bilateral GM in frontal (significant after Family Wise Error (FEW), multiple comparisons correction) and cingulate regions as well as decreased white matter (WM) in bilateral frontal and right parietal (p<0.001 uncorrected). Additionally, we found a negative correlation between symptom severity and bilateral hippocampal GM-volume (p<0.001uncorrected) as well as a positive correlation between age and GM left caudate volume (p=0.037 FWE small volume corrected) in the OCD group. As a conclusion, our results point to conflict monitoring structural brain regions as primary deficits in pediatric OCD, and to striatal abnormalities as age-related deficits.

Clinical and prognostic implications of seasonal pattern in bipolar disorder: a 10-year follow-up of 302 patients.

BACKGROUND More than 20% of bipolar patients may present with seasonal pattern (SP). Seasonality can alter the course of bipolar disorder. However, to date, long-term follow-up studies of bipolar patients presenting with SP are scarce. We present a 10-year follow-up study comparing clinical and demographic features of bipolar patients with and without SP. METHOD Three hundred and twenty-five bipolar I and II patients were followed up for at least 10 years. SP was defined according to DSM-IV criteria. Clinical variables were obtained from structured interviews with the patients and their relatives. Patients with and without SP were compared regarding clinical and sociodemographic variables and a stepwise logistic regression was performed. RESULTS Seventy-seven patients (25.5%) were classified as presenting with SP, while 225 (74.5%) were considered as presenting with no significant seasonal variation. Twenty-three patients (7%) were excluded from the study because it was unclear whether they had seasonality or not. There were no differences between groups regarding demographic variables. Patients with SP predominantly presented with bipolar II disorder, depressive onset, and depressive predominant polarity. The greater burden of depression did not correlate with indirect indicators of severity, such as suicidality, hospitalizations or psychotic symptoms. CONCLUSIONS Our study links the presence of SP with both bipolar II disorder and predominant depressive component. However, we could not find any difference regarding functionality or hospitalization rates. Modifications in the criteria to define SP are suggested for a better understanding of bipolar disorder.

Joint hypermobility syndrome is a risk factor trait for anxiety disorders: a 15-year follow-up cohort study

OBJECTIVE The objective of the study was to assess whether joint hypermobility syndrome (JHS) is a risk factor for developing anxiety disorders using a 15-year prospective cohort study. METHOD The initial cohort recruited 158 subjects aged 16 to 20 years from the general population in a Spanish rural town. The cohort was studied at baseline and at a 15-year follow-up. Joint hypermobility syndrome was assessed using Beightons criteria, and the psychiatric disorders were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Disorders. Subjects with anxiety disorders at baseline were excluded from the follow-up. RESULTS Joint hypermobility syndrome at baseline was found in 29 of 158 subjects (21.1%). Cumulative incidence of panic/agoraphobia disorder at follow-up, as main diagnosis, was significantly higher for the JHS group (41.4%) than for the control group (1.9%), with a relative risk of 22.3 [95% confidence interval (CI) 4.6-108.7, P<.0001] (Number Needed to Treat [NNT] 3, 95% CI 2.9-2.3). Incidence of social phobia and simple phobia was also significantly higher for the JHS group [relative risk (RR)=6.52, 95% CI 1.7-24.2, P<.001 and RR=3.31, 95% CI 1.1-9.6, P=.02, respectively]. Moreover, anxiolytic drug use was nearly fourfold higher among JHS compared to non-JHS subjects. CONCLUSION Joint hypermobility syndrome was associated with higher risk of developing anxiety disorders. If replicated, these findings may give enhanced value to JHS assessment in clinical and general population studies.

Gray matter volume deficits and correlation with insight and negative symptoms in first-psychotic-episode subjects

Bergé D, Carmona S, Rovira M, Bulbena A, Salgado P, Vilarroya O. Gray matter volume deficits and correlation with insight and negative symptoms in first‐psychotic‐episode subjects.

Neural correlates of impaired emotional discrimination in borderline personality disorder: An fMRI study

A common approach to study neuronal aspects of emotional reactivity of borderline personality disorder (BPD) is to study the brain response to emotional faces with functional magnetic resonance imaging (fMRI). 10 BPD patients and 10 matched controls were submitted to an emotional discrimination task in which subjects had to identify an emotional face from a neutral face while fMRI data was acquired. BPD patients made more mistakes than controls in the discrimination task when negative faces were involved. The emotional discrimination task activated brain areas that are known to participate in processing of emotional faces (fusiform gyrus, insula and amygdala) regardless of the psychiatric condition. Additionally, BPD showed higher activation than controls in the middle and inferior temporal cortical areas, brain areas that participate in the processing of face features that carry emotional value. Furthermore, activity at this site correlated with impulsivity score in the Zuckerman-Kuhlman Personality Questionnaire. Our findings may be related to cognitive impairment that may be characteristic of the disorder.

Predictors of antidepressant treatment outcome in melancholia: Psychosocial, clinical and biological indicators.

Predictive variables of response to imipramine and to phenelzine at 6 weeks and 6 months were studied in 116 patients suffering from major depression with melancholia (DSM-III). Several sociodemographic, clinical, and biological variables were studied. For imipramine-treated patients, high social support predicted a better response at 6 weeks, while development of hypomania during follow-up was associated with a better response at 6 weeks; absence of life events during the 6-month follow-up and initial non-suppression of dexamethasone predicted a better outcome at 6 months. For phenelzine-treated patients, development of hypomania during follow-up was associated with a better outcome at 6 months and absence of life events prior to the onset of the episode was associated with a worse outcome at 6 months.

Psychiatric Co-Morbidity and Substance Use Disorders: Treatment in Parallel Systems or in One Integrated System?

Psychiatric co-morbidity among substance users refers to the simultaneous presence of at least another psychiatric disorder in a person diagnosed with a substance use disorder. Co-morbid patients represent a substantial number of people in treatment and present greater disorder severity from both the clinical and social perspectives than those people diagnosed with only one type of disorder. We present an overview of the current state of the art concerning the choice of site of treatment, the kind of intervention, the length of such treatment, and future goals, aiming to establish a more effective intervention, and finally so as to further improve clinical outcomes.