J. Blanch

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.

Patient-rated emotional and physical functioning among hematologic cancer patients during hospitalization for stem-cell transplantation

Summary:In this 3-year prospective inpatient study, 220 patients received stem-cell transplantation (SCT) for hematologic cancer at a single institution. The objective of the study is to provide data on patient-rated emotional (depression and anxiety) and physical (overall physical status, energy level, and systemic symptomatology) functioning during hospitalization for SCT and to compare whether these differ between autologous and allogeneic SCT. Patients were assessed at hospital admission (T1), day of SCT (T2), and 7 days (T3) and 14 days (T4) after SCT, yielding a total of 852 evaluations. For the overall sample, anxiety was highest at T1 and decreased afterwards; a marked worsening in physical health status variables corresponded with a sharp increase in depression from T1 to T3, and was followed by an improvement in physical health and a reduction of depression. Compared to allogeneic SCT, a better physical outcome for autologous SCT was demonstrated by the significant group effect for systemic symptomatology and by the significant group × time interaction for overall physical status and energy level; there were no significant differences in depression or anxiety between SCT groups. These findings have implications for treatment decision making, coping with the transplantation process, and improving prevention and treatment strategies.

First-episode psychosis is characterized by failure of deactivation but not by hypo- or hyperfrontality.

BACKGROUND It is not known whether first-episode psychosis is characterized by the same prefrontal cortex functional imaging abnormalities as chronic schizophrenia. METHOD Thirty patients with a first episode of non-affective functional psychosis and 28 healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Voxel-based analyses of brain activations and deactivations were carried out and compared between groups. The connectivity of regions of significant difference between the patients and controls was also examined. RESULTS The first-episode patients did not show significant prefrontal hypo- or hyperactivation compared to controls. However, they showed failure of deactivation in the medial frontal cortex. This area showed high levels of connectivity with the posterior cingulate gyrus/precuneus and parts of the parietal cortex bilaterally. Failure of deactivation was significantly greater in first-episode patients who had or went on to acquire a DSM-IV diagnosis of schizophrenia than in those who did not, and in those who met RDC criteria for schizophrenia compared to those who did not. CONCLUSIONS First-episode psychosis is not characterized by hypo- or hyperfrontality but instead by a failure of deactivation in the medial frontal cortex. The location and connectivity of this area suggest that it is part of the default mode network. The failure of deactivation seems to be particularly marked in first-episode patients who have, or progress to, schizophrenia.

Structural brain changes associated with tardive dyskinesia in schizophrenia

BACKGROUND The pathological basis of tardive dyskinesia is unknown. Although its clinical features implicate the basal ganglia, imaging studies have not found clear evidence that it is associated with volume changes in these or other brain structures. AIMS To determine, using voxel-based structural imaging, whether there are regions of grey matter volume change in people with schizophrenia who also have tardive dyskinesia compared with those without tardive dyskinesia. METHOD A total of 81 people with chronic schizophrenia, 32 with tardive dyskinesia and 49 without, were examined using magnetic resonance imaging (MRI) and whole-brain, optimised voxel-based morphometry. A comparison group of 61 healthy controls was also examined. RESULTS Compared with those without tardive dyskinesia, patients with tardive dyskinesia showed a pattern of volume reductions in predominantly subcortical regions, including the basal ganglia and the thalamus. Within the basal ganglia, volume reductions were seen in the caudate nucleus, to a lesser extent in the putamen, and only marginally in the globus pallidus. The patients with tardive dyskinesia, but not those without, showed significant volume reductions in the basal ganglia compared with the healthy controls but both groups had smaller volumes than controls in other affected areas. CONCLUSIONS The pathological process or processes that underlie the development of tardive dyskinesia are not just neurochemical in nature, but affect brain structure.

Brain structural changes in schizoaffective disorder compared to schizophrenia and bipolar disorder.

Brain structural changes in schizoaffective disorder, and how far they resemble those seen in schizophrenia and bipolar disorder, have only been studied to a limited extent.

Brain functional changes across the different phases of bipolar disorder

BACKGROUND Little is known about how functional imaging changes in bipolar disorder relate to different phases of the illness. AIMS To compare cognitive task activation in participants with bipolar disorder examined in different phases of illness. METHOD Participants with bipolar disorder in mania (n = 38), depression (n = 38) and euthymia (n = 38), as well as healthy controls (n = 38), underwent functional magnetic resonance imaging during performance of the n-back working memory task. Activations and de-activations were compared between the bipolar subgroups and the controls, and among the bipolar subgroups. All participants were also entered into a linear mixed-effects model. RESULTS Compared with the controls, the mania and depression subgroups, but not the euthymia subgroup, showed reduced activation in the dorsolateral prefrontal cortex, the parietal cortex and other areas. Compared with the euthymia subgroup, the mania and depression subgroups showed hypoactivation in the parietal cortex. All three bipolar subgroups showed failure of de-activation in the ventromedial frontal cortex. Linear mixed-effects modelling revealed a further cluster of reduced activation in the left dorsolateral prefrontal cortex in the patients; this was significantly more marked in the mania than in the euthymia subgroup. CONCLUSIONS Bipolar disorder is characterised by mood state-dependent hypoactivation in the parietal cortex. Reduced dorsolateral prefrontal activation is a further feature of mania and depression, which may improve partially in euthymia. Failure of de-activation in the medial frontal cortex shows trait-like characteristics.

Effect of the Interleukin-1β Gene on Dorsolateral Prefrontal Cortex Function in Schizophrenia: A Genetic Neuroimaging Study

BACKGROUND Genetic studies have found that the interleukin-1β gene (IL1B, 2q13) influences the risk for schizophrenia, but the underlying biological mechanisms of the association are still unclear. Investigation of the effects of genetic variability in this gene on brain function could provide more information about its role in the disorder. METHODS The present study examined the effects of a functional polymorphism at IL1B gene promoter (-511C/T; rs16944) on brain correlates of working memory performance in schizophrenia. Forty-eight schizophrenia patients and 46 control subjects underwent functional magnetic resonance imaging while performing the n-back task. RESULTS In the pooled sample, genetic variability at this locus was associated with differential brain activation in a bilateral frontal region including the dorsolateral prefrontal cortex. There was also a significant diagnosis × genotype interaction effect in an overlapping frontal region: the IL1B polymorphism did not affect activation in the control subjects in this area, but the schizophrenia patients who were T carriers showed significantly higher activation than the CC homozygotes. CONCLUSIONS The findings support a role for IL1B variability in the dorsolateral prefrontal cortex dysfunction classically associated with schizophrenia.

Failure of deactivation in the default mode network: a trait marker for schizophrenia?

BACKGROUND Functional imaging studies in relatives of schizophrenic patients have had inconsistent findings, particularly with respect to altered dorsolateral prefrontal cortex activation. Some recent studies have also suggested that failure of deactivation may be seen. METHOD A total of 28 patients with schizophrenia, 28 of their siblings and 56 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance was fitted to individual whole-brain maps from each set of patient-relative-matched pair of controls. Clusters of significant difference among the groups were then used as regions of interest to compare mean activations and deactivations among the groups. RESULTS In all, five clusters of significant differences were found. The schizophrenic patients, but not the relatives, showed reduced activation compared with the controls in the lateral frontal cortex bilaterally, the left basal ganglia and the cerebellum. In contrast, both the patients and the relatives showed significant failure of deactivation compared with the healthy controls in the medial frontal cortex, with the relatives also showing less failure than the patients. Failure of deactivation was not associated with schizotypy scores or presence of psychotic-like experiences in the relatives. CONCLUSIONS Both schizophrenic patients and their relatives show altered task-related deactivation in the medial frontal cortex. This in turn suggests that default mode network dysfunction may function as a trait marker for schizophrenia.

Brain abnormalities in adults with Attention Deficit Hyperactivity Disorder revealed by voxel-based morphometry.

UNLABELLED Attention Deficit Hyperactivity Disorder (ADHD) commonly affects children, although the symptoms persist into adulthood in approximately 50% of cases. Structural imaging studies in children have documented both cortical and subcortical changes in the brain. However, there have been only a few studies in adults and the results are inconclusive. METHOD Voxel-based morphometry (VBM) was applied to 44 adults with ADHD, Combined subtype, aged 18-54 years and 44 healthy controls matched for age, sex and IQ. RESULTS ADHD patients showed reduced gray matter (GM) volume in the right supplementary motor area (SMA). Using more lenient thresholds we also observed reductions in the subgenual anterior cingulate (ACC) and right dorsolateral prefrontal (DLPFC) cortices and increases in the basal ganglia, specifically in the left caudate nucleus and putamen. There was a positive correlation between the cumulative stimulant dose and volume in the right SMA and DLPFC clusters. CONCLUSIONS The findings suggest that adults with ADHD show brain structural changes in regions belonging to the so-called cool executive function network. Long-term stimulant medication may act to normalize these GM alterations.

Cortisol-binding globulin levels in bipolar disorder

Cortisol-binding globulin (CBG) is an alpha-1-glycoprotein with high affinity for cortiso that could be a potential biological marker of chronic stress, according to several previous studies. In order to examine CBG concentrations in bipolar disorder, we determined serum CBG levels by radioimmunoassay with monoclonal antibodies in a sample of 39 RDC bipolar I patients in remission and 21 healthy age-, sex- and weight-matched control subjects. Only lithium treatment was permitted. Plasma cortisol and serum lithium levels were also determined. Bipolar males showed statistically significant lower serum CBG levels than controls, whereas women showed very similar values. No correlation was found between CBG levels and cortisol or lithium concentrations. It is concluded that CBG levels are affected by chronic affective illness, even during remission periods, at least in bipolar males.