Subcortical volumetric abnormalities in bipolar disorder.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

CACNA1C risk variant is associated with increased amygdala volume.

Genome-wide association studies suggest that genetic variation within L-type calcium channel subunits confer risk to psychosis. The single nucleotide polymorphism at rs1006737 in CACNA1C has been associated with both schizophrenia and bipolar disorder and with several intermediate phenotypes that may serve as neurobiological antecedents, linking psychosis to genetic aetiology. Amongst others, it has been implicated in alterations in amygdala structure and function. In the present study, we show that the risk allele (A) is associated with increased amygdala volume in healthy individuals (n = 258). This observation reinforces a hypothesis that genetic variation may confer risk to psychosis via alterations in limbic structures. Further study of CACNA1C using intermediate phenotypes for psychosis will determine the mechanisms by which variation in this gene confers risk.

Association between genetic risk scoring for schizophrenia and bipolar disorder with regional subcortical volumes.

Previous research has shown coincident abnormal regional brain volume in patients with schizophrenia (SCZ) and bipolar disorder (BD) compared with controls. Whether these abnormalities are genetically driven or explained by secondary effects of the disorder or environmental factors is unknown. We aimed to investigate the association between genetic risk scoring (GRS) for SCZ and BD with volume of brain areas previously shown to be different between these clinical groups and healthy controls. We obtained subcortical brain volume measures and GRS for SCZ and BD from a sample of 274 healthy volunteers (71.4% females, mean age 24.7 (s.d. 6.9)). Volume of the globus pallidus was associated with the shared GRS between SCZ and BD, and also with the independent GRS for each of these disorders. Volume of the amygdala was associated with the non-shared GRS between SCZ and BD, and with the independent GRS for BD. Our results for volume of the globus pallidus support the idea of SCZ and BD sharing a common underlying neurobiological abnormality associated with a common genetic risk for both these disorders. Results for volume of the amygdala, though, would suggest the existence of a distinct mechanism only associated with genetic risk for BD. Finally, the lack of association between genetic risk and volume of most subcortical structures suggests that the volumetric differences reported in patient-control comparisons may not be genetically driven, but a consequence of the disorder or co-occurring environmental factors.

Predicting response to cognitive behavioral therapy in contamination-based obsessive-compulsive disorder from functional magnetic resonance imaging.

BACKGROUND: Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), few reliable predictors of treatment outcome have been identified. The present study examined the neural correlates of symptom improvement with CBT among OCD patients with predominantly contamination obsessions and washing compulsions, the most common OCD symptom dimension. METHOD: Participants consisted of 12 OCD patients who underwent symptom provocation with contamination-related images during functional magnetic resonance imaging (fMRI) scanning prior to 12 weeks of CBT. RESULTS: Patterns of brain activity during symptom provocation were correlated with a decrease on the Yale-Brown Obsessive Compulsive Scale (YBOCS) after treatment, even when controlling for baseline scores on the YBOCS and the Beck Depression Inventory (BDI) and improvement on the BDI during treatment. Specifically, activation in brain regions involved in emotional processing, such as the anterior temporal pole and amygdala, was most strongly associated with better treatment response. By contrast, activity in areas involved in emotion regulation, such as the dorsolateral prefrontal cortex, correlated negatively with treatment response mainly in the later stages within each block of exposure during symptom provocation. CONCLUSIONS: Successful recruitment of limbic regions during exposure to threat cues in patients with contamination-based OCD may facilitate a better response to CBT, whereas excessive activation of dorsolateral prefrontal regions involved in cognitive control may hinder response to treatment. The theoretical implications of the findings and their potential relevance to personalized care approaches are discussed.

Understanding the contribution of neural and physiological signal variation to the low repeatability of emotion-induced BOLD responses.

Previous studies have reported low repeatability of BOLD activation measures during emotion processing tasks. It is not clear, however, whether low repeatability is a result of changes in the underlying neural signal over time, or due to insufficient reliability of the acquired BOLD signal caused by noise contamination. The aim of this study was to investigate the influence of "cleaning" the BOLD signal, by correcting for physiological noise and for differences in BOLD responsiveness, on measures of repeatability. Fifteen healthy volunteers were scanned on two different occasions, performing an emotion provocation task with faces (neutral, 50% fearful, 100% fearful) followed by a breath-hold paradigm to provide a marker of BOLD responsiveness. Repeatability of signal distribution (spatial repeatability) and repeatability of signal amplitude within two regions of interest (amygdala and fusiform gyrus) were estimated by calculating the intraclass correlation coefficient (ICC). Significant repeatability of signal amplitude was only found within the right amygdala during the perception of 50% fearful faces, but disappeared when physiological noise correction was performed. Spatial repeatability was higher within the fusiform gyrus than within the amygdala, and better at the group level than at the participant level. Neither physiological noise correction, nor consideration of BOLD responsiveness, assessed through the breath-holding, increased repeatability. The findings lead to the conclusion that low repeatability of BOLD response amplitude to emotional faces is more likely to be explained by the lack of stability in the underlying neural signal than by physiological noise contamination. Furthermore, reported repeatability might be a result of repeatability of task-correlated physiological variation rather than neural activity. This means that the emotion paradigm used in this study might not be useful for studies that require the BOLD response to be a stable measure of emotional processing, for example in the context of biomarkers.

The functional neuroanatomy of blood-injection-injury phobia: a comparison with spider phobics and healthy controls.

BACKGROUND: Most neuroimaging studies of specific phobia have investigated the animal subtype. The blood-injection-injury (BII) subtype is characterized by a unique biphasic psychophysiological response, which could suggest a distinct neural substrate, but direct comparisons between phobia types are lacking. METHOD: This study compared the neural responses during the presentation of phobia-specific stimuli in 12 BII phobics, 14 spider (SP) phobics and 14 healthy controls using functional magnetic resonance imaging (fMRI). RESULTS: Subjective ratings showed that the experimental paradigm produced the desired symptom-specific effects. As in many previous studies, when viewing spider-related stimuli, SP phobics showed increased activation in dorsal anterior cingulate and anterior insula, compared to BII phobics and healthy controls. However, when viewing images of blood-injection-injuries, participants with BII phobia mainly showed increased activation in the thalamus and visual/attention areas (occipito-temporo-parietal cortex), compared with the other two groups. The degree of provoked anxiety and disgust by phobia-relevant images was strongly associated with activation in several common regions across the two phobia groups (thalamus, cerebellum, occipito-temporal regions) but only correlated with activation in the dorsal anterior cingulate gyrus and the anterior insula in the SP phobics. CONCLUSIONS: These results suggest partially distinct neurobiological substrates of animal and BII phobias and support their current classification as two distinct subtypes in the DSM-IV-TR. Further research is needed to better understand the precise neurobiological mechanisms in BII phobia and particularly the fainting response.

The neural correlates of fatigue: an exploratory imaginal fatigue provocation study in chronic fatigue syndrome.

BACKGROUND: Fatigue is the central symptom in chronic fatigue syndrome (CFS) and yet very little is known about its neural correlates. The aim of this study was to explore the functional brain response, using functional magnetic resonance imaging (fMRI), to the imaginal experience of fatigue in CFS patients and controls. METHOD: We compared the blood oxygen level dependent (BOLD) responses of 12 CFS patients and 11 healthy controls to a novel fatigue provocation procedure designed to mimic real-life situations. A non-fatiguing anxiety-provoking condition was also included to control for the non-specific effects of negative affect. RESULTS: During the provocation of fatigue, CFS patients reported feelings of both fatigue and anxiety and, compared to controls, they showed increased activation in the occipito-parietal cortex, posterior cingulate gyrus and parahippocampal gyrus, and decreased activation in dorsolateral and dorsomedial prefrontal cortices. The reverse pattern of findings was observed during the anxiety-provoking scenarios. CONCLUSIONS: The results may suggest that, in CFS patients, the provocation of fatigue is associated with exaggerated emotional responses that patients may have difficulty suppressing. These findings are discussed in relation to the cognitive-behavioural model of CFS.

Postherpetic neuralgia: a descriptive analysis of patients seen in pain clinics.

BACKGROUND AND OBJECTIVE: Postherpetic neuralgia (PHN) is a common ailment that pain specialists must often cope with. The goal of the present survey is to investigate the pain characteristics of 119 PHN patients with persistent pain seen at different pain clinics. Methods information on demographic features, pain characteristics (MPQ-SV, VAS, VRS), and treatment was recorded by means of a standard case report form. RESULTS: Gender, age, location, and treatment were consistent with previous reports. Antidepressant, antiepileptic, and analgesic drugs were the most commonly used by patients. The patients seen in pain clinics are probably a subset of severe cases of PHN, where delayed referral to these units plays an important role. The most frequent qualitative features of the disease were the McGill Pain Questionnaire-Spanish Version (MPQ-SV). These features may change in relation to illness evolution; electric shocklike pain and emotional distress were significantly higher after 6 months of evolution and age (those younger than 70 were more able to locate painful areas and to feel pain as pricking or sharp), and gender (men selected spatial pressure and traction pressure more frequently). None of the explored variables was relevant to predicting pain intensity. CONCLUSIONS: This study reveals a subset of patients, mostly suffering from long-term PHN, where pain persists. The most frequent qualitative traits of PHN patients are described. Some variables were involved in modulation of pain characteristics in these patients. The effect of study design in interpretation of results is discussed.

[Measurement of postoperative pain: analysis of the sensitivity of various self-evaluation instruments]. / Medida del dolor postoperatorio: análisis de la sensibilidad de diversos instrumentos de autovaloración.

OBJECTIVES: This study compared the sensitivity of two one-dimensional scales (a visual analog scale [VAS] and a verbal scale of pain intensity [VSPI]) and one multidimensional scale (McGill Pain Questionnaire-Spanish Version [MPQ-SV]) for detecting changes in pain after a variety of surgical procedures with postoperative analgesia provided by one of two methods. PATIENTS AND METHODS: Forty-two patients who underwent abdominal surgery, hysterectomy, cesarean, inguinal herniorrhaphy, subcostal or medial laparoscopic cholecystectomy were studied. Postoperative analgesia consisted of 1 mg/Kg of intravenous pethidine every 4 h in group one (n = 20) and intramuscular diclofenac every 12 h in group two. Assessment was at 24 h and/or at 48 and 72 h using the VAS, the VSPI and the MPQ-SV. RESULTS: All the scales were useful for assessing postoperative pain, giving estimates that were sensitive to variations in pain on days after the operation. The MPQ-SV was able to detect different pain-producing capacities for the surgical procedures more effectively than were the one-dimensional scales. The MPQ-SV was also able to discriminate the qualitative and quantitative differences among the mechanisms of action of opioid and nonsteroidal anti-inflammatory drugs, whereas the one-dimensional scales were unable to distinguish therapeutic approach. CONCLUSIONS: All the scales were sensitive to changes in postoperative pain, but the MPQ-SV gave more precise information of differences between analgesic treatments and among operations.

Medida del dolor postoperatorio: análisis de la sensibilidad de diversos instrumentos de autovaloración / Measurement of postoperative pain: an analysis of the sensitivity of several self assessment instruments

OBJETIVOS: El presente estudio comparó la sensibilidad de las escalas unidimensionales (escala visual analógica o EVA, Escala verbal de intensidad del dolor o EVID) y multidimensionales (McGill Pain Questionnaire-Spanish Versión o MPQ-SV), para detectar los cambios del dolor postoperatorio tras diferentes procedimientos quirúrgicos y analgesia postoperatoria. PACIENTES Y MÉTODOS: Se estudiaron 42 pacientes intervenidos de cirugía abdominal, histerectomía, cesárea, herniorrafia inguinal, colecistectomía subcostal o laparotomía media. La analgesia postoperatoria consistió en el primer grupo (n=22) en 1 mg/kg de petidina iv cada 4 h, mientras que en el segundo (n=20) se administró diclofenaco a dosis de 10 mg im cada 12 h. La evaluación se realizó a las 24 h y/o a las 48-72 h utilizando los instrumentos EVA, EVID y MPQ-SV. RESULTADOS: Todas las escalas fueron útiles para valorar el dolor postoperatorio, produciendo estimaciones de dolor sensibles a las variaciones que se producen durante los días subsiguientes a la intervención. El MPQ-SV fue capaz de determinar la distinta capacidad algógena de los procedimientos quirúrgicos empleados, con más eficacia que las escalas unidimensionales. Del mismo modo, el MPQ-SV fue capaz de discriminar las diferencias cualitativas y cuantitativas que existen entre los mecanismos de acción entre fármacos opioides y AINE, sin que las escalas unidimensionales pudieran establecer diferencias dependientes del abordaje terapéutico empleado. CONCLUSIONES: Todos los instrumentos mostraron su sensibilidad para detectar las diferencias en el dolor postoperatorio, pero el MPQ-SV permite obtener información más precisa sobre las diferencias entre tratamientos y entre intervenciones quirúrgicas (AU)

Psychometric properties of a Spanish version of the McGill Pain Questionnaire in several Spanish-speaking countries.

OBJECTIVE: Versions of the McGill Pain Questionnaire are available in a several languages and are used in clinical studies and sociocultural or ethnic comparisons of pain issues. However, there is a lack of studies that compare the validity and reliability of the instrument in the countries where it is used. The current study investigates the psychometric properties of a Spanish version of the McGill Pain Questionnaire in five Spanish-speaking countries. DESIGN: The authors conducted a multicenter and transnational study with one investigator in each center. Patients were evaluated once with a Spanish version of the McGill Pain Questionnaire, a visual analog scale, and a verbal rating scale. SETTING: The study was performed in pain clinics and acute pain units of four Latin American countries (Argentina, Costa Rica, Mexico, and Panama) and Spain. PATIENTS: The study included 205 patients (84 with acute pain, 121 with chronic pain) from Latin America. Their data were compared with those of 282 Spanish patients. INTERVENTIONS: The McGill Pain Questionnaire, visual analog scale, and verbal rating scale were administered once to all patients. The McGill Pain Questionnaire was administered again to patients from Latin America countries to ascertain descriptor comprehension. OUTCOME MEASURES: Demographic data, McGill Pain Questionnaire parameters, and visual analog scale and a verbal rating scale scores were obtained from patients with chronic and acute pain. Psychometric properties of the Spanish version of the McGill Pain Questionnaire were established for each country by calculating the ordinal consistency by means of rank-scale correlation (Spearman test), intercategory correlation, and interparameter correlation (Pearson test). Concurrent validity was also calculated by comparing scores from the visual analog scale (Pearson test) and verbal rating scale (Spearman test) with questionnaire parameters (qualitative-to-quantitative comparisons). RESULTS: The Spanish version of the McGill Pain Questionnaire maintained a high internal validity when tested in different countries. Ordinal consistency, intercategory, interparameter, and qualitative-to-quantitative parameter correlations were similar in all countries. Few descriptors were considered to be inappropriate or difficult to understand. CONCLUSIONS: The psychometric properties of the Spanish version of the McGill Pain Questionnaire assessed in different Latin-American countries suggest that the questionnaire may be used to evaluate Spanish-speaking patients. The validity of this test should be extended with reliability studies to further establish its usefulness in the evaluation of pain.