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.

Neurological soft signs in obsessive-compulsive disorder: two empirical studies and meta-analysis.

BACKGROUND: Neurological soft signs (NSS) have been inconsistently reported in obsessive-compulsive disorder (OCD) but may make an impact on treatment response. Method The current study examined the presence of NSS in two independent European samples of OCD patients (combined 85 patients and 88 matched healthy controls) using a standardized instrument and conducted a meta-analysis of all published studies identified in the literature with the aim to provide a more definitive answer to the question of whether OCD patients are characterized by increased NSS. RESULTS: Both empirical studies found elevated NSS scores in patients compared with matched controls. The results of the meta-analysis, which included 15 studies (combined 498 patients and 520 controls) showed large effect sizes (Hedges' g=1.27, 95% confidence interval 0.80-1.75), indicating that OCD patients have significantly higher rates of NSS than matched controls on both sides of the body and in multiple domains (motor coordination, sensory integration and primitive reflexes). The results were robust and remained largely unchanged in our reliability analyses, which controlled for possible outliers. Meta-regression was employed to examine the role of potential variables of interest including sociodemographic variables, symptom severity, medication effects and the use of different instruments, but none of these variables was clearly associated with NSS. CONCLUSIONS: As a group, OCD patients are characterized by increased rates of NSS, compared with healthy controls. However, their origins and potential clinical importance remain to be clarified. Future directions for research are discussed.

Psychological and physiological effects of caring for patients with treatment-resistant depression.

BACKGROUND: Carers of patients with psychiatric disorders show high levels of anxiety and depression, possibly mediated through disruption of the hypothalamo-pituitary-adrenal (HPA) axis. Among carers of patients with treatment-resistant depression (TRD), we set out to determine the psychological and physiological (HPA axis) consequences of caring, and the association of these consequences with long-term outcome in patients. METHOD: Thirty-five informal carers of patients with severe TRD requiring in-patient treatment were recruited and compared with 23 controls. HPA-axis activity was assessed by measuring post-awaking salivary cortisol. The Involvement Evaluation Questionnaire (IEQ) and the General Health Questionnaire-12 (GHQ-12) were administered to measure carer burden and psychiatric caseness respectively. Independent t tests were used to compare differences between carers and controls and a linear regression model was used to determine the association of post-awakening cortisol with carer status while controlling for confounding variables. Data on long-term patient outcome (12 to 83 months), measured using the Hamilton Depression Rating Scale (HAMD), were also obtained and linear regression was used to determine the association between cortisol output in carers and remission status in patients. RESULTS: Carers experienced high carer burden and high psychiatric caseness. Carers showed reduced cortisol output after awakening, calculated as the area under the curve with respect to ground (AUCg), which remained significant after controlling for potential confounders. In a linear regression model, non-remission in patients was associated with reduced cortisol output in carers. CONCLUSIONS: Caring for patients with TRD is associated with adverse psychological and physiological changes suggesting hypocortisolism post-awakening. These changes are associated with poor patient outcome.

Discrepancy between subjective and objective severity in treatment-resistant depression: prediction of treatment outcome.

OBJECTIVE: Identifying predictors of outcome among patients with treatment-resistant depression (TRD) is challenging. We hypothesised that discrepancy between self-rated and observer-rated scales may be a simple way of making such a prediction. METHOD: 102 patients were admitted to a unit specialising in the treatment of resistant depression and underwent fortnightly assessment with clinician-rated (Hamilton Depression Rating Scale-21, HAM-D) and self-rated (Beck Depression Inventory, BDI) measures. All patients had significant depressive symptoms that were treatment resistant, 70% as part of a major depressive disorder and the remainder as part of a bipolar or other disorder. A discrepancy score between the HAM-D and BDI was calculated on admission and its association with patient clinico-demographic factors was determined. A subset of 67 patients remained as inpatients for 40 weeks or until clinical response and were entered into a responder analysis, in which response was defined as ≥50% reduction in admission HAM-D score. The association of the admission BDI-HAM-D discrepancy score with subsequent patient response, was determined. RESULTS: The magnitude of BDI-HAM-D discrepancy was higher in those with co-morbid personality disorder, lower in those with psychosis and positively correlated with anxiety. High BDI-HAM-D discrepancy score predicted delayed treatment response (odds ratio 5.40, p = 0.005). CONCLUSION: Within TRD, higher discrepancy predicts slower response to treatment independent of objective illness severity; this may be mediated by underlying personality traits and co-morbid anxiety.

To discard or not to discard: the neural basis of hoarding symptoms in obsessive-compulsive disorder.

Preliminary neuroimaging studies suggest that patients with the 'compulsive hoarding syndrome' may be a neurobiologically distinct variant of obsessive-compulsive disorder (OCD) but further research is needed. A total of 29 OCD patients (13 with and 16 without prominent hoarding symptoms) and 21 healthy controls of both sexes participated in two functional magnetic resonance imaging experiments consisting of the provocation of hoarding-related and symptom-unrelated (aversive control) anxiety. In response to the hoarding-related (but not symptom-unrelated) anxiety provocation, OCD patients with prominent hoarding symptoms showed greater activation in bilateral anterior ventromedial prefrontal cortex (VMPFC) than patients without hoarding symptoms and healthy controls. In the entire patient group (n=29), provoked anxiety was positively correlated with activation in a frontolimbic network that included the anterior VMPFC, medial temporal structures, thalamus and sensorimotor cortex. Negative correlations were observed in the left dorsal anterior cingulate gyrus, bilateral temporal cortex, bilateral dorsolateral/medial prefrontal regions, basal ganglia and parieto-occipital regions. These results were independent from the effects of age, sex, level of education, state anxiety, depression, comorbidity and use of medication. The findings are consistent with the animal and lesion literature and several landmark clinical features of compulsive hoarding, particularly decision-making difficulties. Whether the results are generalizable to hoarders who do not meet criteria for OCD remains to be investigated.

Predischarge screening of very low birthweight infants by click evoked otoacoustic emissions.

OBJECTIVE: To evaluate the role of transient evoked otoacoustic emission (TEOAE) in screening very low birthweight (VLBW) neonatal intensive care unit (NICU) graduates for hearing loss in comparison with visual reinforcement orientation audiology (VROA) at 10 months. METHODOLOGY: The study population was all VLBW neonatal survivors discharged from a single regional NICU at John Hunter Childrens Hospital (JHCH), Newcastle, New South Wales, Australia, between April 1994 and March 1996. A TEOAE screen was performed prior to discharge and repeated if necessary until a pass was obtained in at least one ear. Infants were further screened by VROA at their local Australian Hearing Services (AHS) office at 10 months corrected age. Repeated TEOAE failures were referred directly for an ENT opinion. RESULTS: A total of 193 infants were eligible for enrolment during the study period. One hundred and forty-four (75%) received TEOAE testing. The median age of first screen was 36 weeks gestational age. Ninety-five (66%) of infants tested passed on a single screen. Of the remaining 49 infants, 26 passed on retesting (overall pass rate 84%). Twenty-three (16%) were deemed to have failed the TEOAE screen. Of the 121 infants who passed TEOAE, only 67 (55%) completed VROA. Two of these infants have a high frequency sensorineural loss and one of them has been aided. In the 23 who failed TEOAE, nine have subsequently had normal VROA, another, though not tested is clinically normal. three have hearing loss with middle ear disease and eight have confirmed sensorineural deafness, all aided. One infant has died and an infant with Down's syndrome has been adopted out of the area. It is of interest to note that the eight aided infants are all of less than 28 weeks gestation. If we restrict analysis to infants with completed VROA testing, the TEOAE has a 97% negative predictive value for sensorineural deafness and a 38% positive predictive value. CONCLUSIONS: This study has highlighted both the prevalence of hearing impairment in the very premature survivors and difficulties in compliance with a VROA based hearing screen. We see an advantage in directing resources towards an early screening test, such as TEOAE, that can be applied while the target population is still captive.

Neurological outcome of severe cystic periventricular leukomalacia.

OBJECTIVE: To determine the neurological outcome of a cohort of premature babies having ultrasound diagnoses of severe cystic periventricular leukomalacia. METHODOLOGY: All neonatal intensive care unit admissions born at less than 35 weeks gestation or weighing less than 1500 g underwent serial cranial ultrasounds. Those developing severe bilateral cystic periventricular leukomalacia (12 patients) were then followed clinically to a mean age of 27.3 months. RESULTS: Ten of the 12 patients fulfilling strict ultrasound criteria survived. All had a major neurological handicap, all having spastic quadriparesis and visual impairments, with most suffering global developmental delay and epilepsy. CONCLUSIONS: Severe bilateral cystic periventricular leukomalacia results in major permanent handicap. It is currently impossible to identify most patients with this condition while they are being ventilated. Non-ultrasound techniques are needed to diagnose the condition earlier, and to give guidance to management.