Sarah Wooderson

Decision making and set shifting impairments are associated with distinct symptom dimensions in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The authors examined how specific OCD symptom dimensions were related to neuropsychological functions using multiple regression analyses. A total of 39 OCD patients and 40 controls completed the Iowa Gambling Task (IGT; A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994), which is a test of decision making, and the Wisconsin Card Sorting Test (R. K. Heaton, 1981), which is a test of set shifting. OCD patients and controls showed comparable decision making. However, patients with prominent hoarding symptoms showed impaired decision making on the IGT as well as reduced skin conductance responses. OCD patients had poorer set shifting abilities than controls, and symmetry/ordering symptoms were negatively associated with set shifting. These results help explain previous inconsistent findings in neuropsychological research in OCD and support recent neuroimaging data showing dissociable neural mechanisms involved in mediating the different OCD symptom dimensions.

What happens to patients with treatment-resistant depression? A systematic review of medium to long term outcome studies

BACKGROUND Treatment-resistant depression (TRD) is relatively common and accounts for a large proportion of the overall burden caused by depression. We conducted a systematic review of outcome studies of TRD in order to summarise findings on the longer term outcome of TRD and make recommendations. METHODS Studies were identified through MEDLINE (1960--June Week 1 2008), EMBASE (1974--June Week 1 2008) and PsycINFO (1967--June Week 1 2008) searches. We included studies that followed adults with highly probable TRD for a minimum of 6 months. Statistical analyses were conducted on selected outcome variables whenever possible. Methodological heterogeneity of studies prohibited formal meta-analysis. RESULTS We identified nine outcome studies with a total of 1279 participants and follow-up duration of between 1 and 10 years. In the short term, TRD was highly recurrent with as many as 80% of those requiring multiple treatments relapsing within a year of achieving remission. For those with a more protracted illness, the probability of recovery within 10 years was about 40%. TRD was also associated with poorer quality of life and increased mortality. LIMITATIONS Included primary studies were heterogeneous. CONCLUSIONS TRD is associated with poorer clinical outcome, particularly among those who require multiple antidepressant medications. The main limitations of the review arise from the variability in recruitment procedures, definitions and outcome assessments of the original studies. We recommend further follow-up studies of carefully identified samples in order to gain a more detailed understanding of this domain of depression and plan effective interventions.

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.

Abnormal amplitude low-frequency oscillations in medication-naive, first-episode patients with major depressive disorder: A resting-state fMRI study

BACKGROUND Recent resting-state fMRI studies on major depressive disorder (MDD) have found altered temporal correlation between low-frequency oscillations (LFOs). However, changes on the amplitudes of these LFOs remain largely unknown. METHODS Twenty-two medication-naive, first-episode patients with MDD and 19 age-, sex-, education-matched healthy controls were recruited. Resting-state fMRI was obtained by using an echo-planar imaging sequence and the fractional amplitude of low-frequency fluctuations (fALFF) was calculated to investigate the amplitude of LFOs in the resting state. RESULTS Compared with control subjects, patients with MDD showed significantly decreased fALFF in right cerebellum posterior lobe, left parahippocampal gyrus and right middle frontal gyrus and increased fALFF in left superior occipital gyrus/cuneus (p<0.05, corrected for multiple comparisons). Further receiver operating characteristic curves (ROC) analyses suggested that the alterations of fALFF in these regions might be used as markers to classify patients with MDD from healthy controls. CONCLUSIONS These findings indicated LFOs abnormalities in MDD and the fALFF analysis might be a potential approach in further exploration of this disorder.

Abnormal regional spontaneous neural activity in first-episode, treatment-naive patients with late-life depression: a resting-state fMRI study.

BACKGROUND The previous resting perfusion or task-based studies have provided evidence of functional changes in the brains of patients with late-life depression (LLD). Little is known, so far, about the changes in the spontaneous brain activity in LLD during the resting state. The aim of this study was to investigate the spontaneous neural activity in first-episode, treatment-naive patients with LLD by using resting-state functional magnetic resonance imaging (fMRI). METHODS A novel analytical method, coherence-based regional homogeneity (Cohe-ReHo), was used to assess regional spontaneous neural activity during the resting state in 15 first-episode, treatment-naive patients with LLD and 15 age- and gender-matched healthy controls. RESULTS Compared to the healthy controls, the LLD group showed significantly decreased Cohe-ReHo in left caudate nucleus, right anterior cingulate gyrus, left dorsolateral prefrontal cortex, right angular gyrus, bilateral medial prefrontal cortex, and right precuneus, while significantly increased Cohe-ReHo in left cerebellum posterior lobe, left superior temporal gyrus, bilateral supplementary motor area, and right postcentral gyrus (p<0.005, corrected for multiple comparisons). CONCLUSIONS These findings indicated abnormal spontaneous neural activity was distributed extensively in first-episode, treatment-naive patients with LLD during the resting state. Our results might supply a novel way to look into the underlying pathophysiology mechanisms of patients with LLD.

Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: A resting-state fMRI study

BACKGROUND Patients with treatment-resistant depression (TRD) and those with treatment-response depression (TSD) respond to antidepressants differently and previous studies have commonly reported different brain networks in resistant and nonresistant patients. Using the amplitude of low-frequency fluctuations (ALFF) approach, we explored ALFF values of the brain regions in TRD and TSD patients at resting state to test the hypothesis of the different brain networks in TRD and TSD patients. METHODS Eighteen TRD patients, 17 TSD patients and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. RESULTS There are widespread differences in ALFF values among TRD patients, TSD patients and healthy subjects throughout the cerebellum, the visual recognition circuit (middle temporal gyrus, middle/inferior occipital gyrus and fusiform), the hate circuit (putamen), the default circuit (ACC and medial frontal gyrus) and the risk/action circuit (inferior frontal gyrus). The differences in brain circuits between the TRD and TSD patients are mainly in the cerebellum, the visual recognition circuit and the default circuit. CONCLUSIONS The affected brain circuits of TRD patients might be partly different from those of TSD patients.

The impact of childhood adversity on suicidality and clinical course in treatment-resistant depression

BACKGROUND Childhood adversity is a risk factor for the development of depression and can also affect clinical course. We investigated this specifically in treatment-resistant depression (TRD). METHODS One hundred and thirty-seven patients with TRD previously admitted to an inpatient affective disorders unit were included. Clinical, demographic and childhood adversity (physical, sexual, emotional abuse; bullying victimization, traumatic events) data were obtained during admission. Associations between childhood adversity, depressive symptoms and clinical course were investigated. RESULTS Most patients had experienced childhood adversity (62%), with traumatic events (35%) and bullying victimization (29%) most commonly reported. Childhood adversity was associated with poorer clinical course, including earlier age of onset, episode persistence and recurrence. Logistic regression analyses revealed childhood adversity predicted lifetime suicide attempts (OR 2.79; 95% CI 1.14, 6.84) and childhood physical abuse predicted lifetime psychosis (OR 3.42; 95% CI 1.00, 11.70). LIMITATIONS The cross-sectional design and retrospective measurement of childhood adversity are limitations of the study. CONCLUSIONS Childhood adversity was common amongst these TRD patients and was associated with poor clinical course, psychosis and suicide attempts. Routine assessment of early adversity may help identify at risk individuals and inform clinical intervention.

The Maudsley Staging Method for Treatment-Resistant Depression: Prediction of Longer-Term Outcome and Persistence of Symptoms

OBJECTIVE A recently proposed multidimensional method of staging treatment resistance in depression, the Maudsley Staging Method (MSM), has been shown to predict short-term outcome of treatment. This study tested whether the MSM predicts longer-term clinical outcome. We hypothesized that patients with higher scores on the MSM would experience a worse longer-term outcome in terms of time spent in a depressive episode and level of functional impairment. METHOD From May through July of 2008, we followed up patients with treatment-resistant depression discharged from an inpatient unit of an affective disorders service; all had MSM scores previously calculated from preadmission clinical data. We used the Longitudinal Interval Follow-up Evaluation (LIFE) chart to determine the monthly symptomatic course of depression blind to initial MSM scores. We employed a regression model to adjust for various confounding factors, including variable duration of follow-up, to determine the independent association of MSM scores with persistence of depressive disorder. RESULTS We assessed 62 of 80 eligible patients (78%) in a median follow-up duration (interquartile range) of 29.5 (19.0-52.5) months. The MSM independently predicted (1) being in an episode for 50% or longer of the follow-up duration (OR = 2.11, 95% CI = 1.25 to 3.57), (2) being in an episode at the time of follow-up assessment (OR = 1.89, 95% CI = 1.17 to 3.05), (3) being persistently in an episode throughout the follow-up period (OR = 2.01, 95% CI = 1.14 to 3.54), and (4) total months spent in a depressive episode (OR = 1.22, 95% CI = 1.06 to 1.40). The MSM also predicted functional impairment. Antidepressant count and the Thase and Rush model did not independently predict persistence of depression or functional impairment. CONCLUSION The MSM appears to have reasonable predictive validity regarding the longer-term course of illness, particularly persistence of depressive episodes. The MSM may be a useful, and possibly an improved, alternative to existing models of staging of treatment-resistant depression.

Decreased resting-state interhemispheric coordination in first-episode, drug-naive paranoid schizophrenia

BACKGROUND Dysconnectivity hypothesis posits that schizophrenia relates to abnormalities in neuronal connectivity. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in patients with paranoid schizophrenia. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric FC of the whole brain in patients with paranoid schizophrenia at rest. METHODS Forty-nine first-episode, drug-naive patients with paranoid schizophrenia and 50 age-, gender-, and education-matched healthy subjects underwent a resting-state functional magnetic resonance imaging (fMRI) scans. An automated VMHC approach was used to analyze the data. RESULTS Patients exhibited lower VMHC than healthy subjects in the precuneus (PCu), the precentral gyrus, the superior temporal gyrus (STG), the middle occipital gyrus (MOG), and the fusiform gyrus/cerebellum lobule VI. No region showed greater VMHC in the patient group than in the control group. Significantly negative correlation was observed between VMHC in the precentral gyrus and the PANSS positive/total scores, and between VMHC in the STG and the PANSS positive/negative/total scores. CONCLUSIONS Our results suggest that interhemispheric resting-state FC of VMHC is reduced in paranoid schizophrenia with clinical implications for psychiatric symptomatology thus further contribute to the dysconnectivity hypothesis of schizophrenia.

Early and late onset, first-episode, treatment-naive depression: same clinical symptoms, different regional neural activities

BACKGROUND Patients with early onset depression (EOD) and late onset depression (LOD) have distinctive risk factors and clinical pictures. Using regional homogeneity (ReHo) approach, we were to test the hypothesis of the different abnormal neural activity between patients with EOD or LOD. METHODS Fifteen patients with EOD, 15 patients with LOD, 15 young healthy subjects (HS) and 15 old HS participated in the study. ReHo approach was employed to analyze the scans. RESULTS ANOVA analysis revealed widespread differences in ReHo values among the four groups throughout frontal, parietal, temporal, occipital cortex, cerebellum and limbic regions. Compared to LOD group, EOD group had higher ReHo in right precuneus (PCu) and bilateral superior frontal gyrus, and lower ReHo in left superior temporal gyrus. Compared to young HS, lower ReHo in left parahippocampal gyrus and higher ReHo in left fusiform gyrus and bilateral superior frontal gyrus were seen in EOD group; in contrast, in LOD group, lower ReHo in right PCu and higher ReHo in left superior temporal gyrus and left Crus I of the cerebellum were observed. Further ROC analysis suggested that the mean ReHo values in right PCu and bilateral superior frontal gyrus could serve as markers to identify patients with EOD from individuals with LOD. LIMITATION The large age gap may limit the translational value of our findings. CONCLUSIONS Patients with EOD and those with LOD have abnormal neural activities in different brain regions, although the two groups share the same symptoms.