N. van der Wee

Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10−3) or a 2.87% smaller volume compared with controls (Cohen’s d=−0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28–0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

Childhood maltreatment modifies the relationship of depression with hippocampal volume.

BACKGROUNDnChildhood maltreatment (CM) may modify the relationship between major depressive disorder (MDD) and hippocampal volume reduction. To disentangle the impact of MDD and CM on hippocampal volume we investigated the association between MDD and hippocampal volume in persons with and without a history of CM in two independent cohorts.nnnMETHODnWe used data of 262 participants from the Netherlands Study of Depression and Anxiety (NESDA) (mean age 37 years, 32% male) and 636 participants from the SMART-Medea study (mean age 61 years, 81% male). In both studies a 12-month diagnosis of MDD and CM were assessed using a diagnostic interview. Hippocampal volume was measured in NESDA using FreeSurfer software on 3-T magnetic resonance (MR) images and in SMART it was manually outlined on 1.5-T MR images. With analysis of covariance adjusted for intracranial volume, age, gender and lifestyle factors we estimated the effects of MDD and CM on hippocampal volume.nnnRESULTSnIn both cohorts CM was not significantly associated with hippocampal volume. After pooling the data MDD was associated with smaller hippocampal volume (B = -138.90 mm(3), p = 0.05) and the interaction between MDD and CM reached significance (p = 0.04); in participants with CM, MDD was related to smaller hippocampal volume (NESDA: B = -316.8 mm(3), p = 0.02; SMART: B = -407.6, p = 0.046), but not in participants without CM (p > 0.05).nnnCONCLUSIONSnOur study shows that in two independent cohorts, particularly in individuals with CM, a diagnosis of MDD is related to smaller hippocampal volume. Prospective studies are needed to further determine through which mechanism CM may amplify the relationship between MDD and hippocampal volume.

AB0705 Psychopathologic Involvement in Systemic Sclerosis: A Pilot Study

Background Involvement of the brain in systemic sclerosis (SSc) could be suspected given the presence of disturbances on cerebrovascular imaging or mental dysfunction, including disorders of cognition or mood. It is important to confirm this since the intervention of first choice for cognitive disorders is highly depending on the pathophysiology. Objectives To investigate whether mental complaints in patients with SSc are related to organic brain dysfunction. Methods Twenty SSc patients with self-reported mental complaints, including concentration problems, fatigue, memory loss, or depression, were cross-sectionally assessed by neuropsychological testing, psychiatric evaluation and magnetic resonance imaging (MRI) of the brain. All patients completed the Hospital Anxiety and Depression Scale, Dissociation Experience Scale, a screenings tool for fatigue (MFI-20), Short Form-36 and Neuropsychiatric Inventory. Patients were compared with 20 age and sex matched healthy controls. Results Patients and healthy controls did not differ with respect to sociodemographic characteristics. In 5 SSc patients cognitive dysfunction was considered questionable by the neuropsychologist. Patients performed slightly worse on cognition tasks as compared to healthy controls, but all test results were within the normal range. The MRI showed small white matter hyperintensities (WMH) in 18 patients and in 15 healthy controls. The neuropsychological tests were completely normal within those 15 healthy controls. Thirteen SSc patients with WMH on MRI, had normal neuropsychological tests and no mood disorder. Four patients with WMH had a mood disorder. Conclusions Based on this pilot study, SSc patients show slight disturbances of mental functioning as compared to healthy controls, but their performance is within the normal range. No clear association between mental dysfunction and organic brain abnormalities could be detected. In case of mental dysfunctioning in SSc patients, we propose psychological intervention, starting with psychoeducation and in some cases cognitive-behavioural therapy, is the best treatment. Disclosure of Interest J. Meijs Grant/research support from: Jessica Meijs was supported by an unrestricted educational grant of Actelion Pharmaceuticals Nederland BV (Woerden, The Netherlands)., E. Ercan: None declared, E. Baptist: None declared, N. van der Wee: None declared, O. Tritanon: None declared, M. van Buchem: None declared, T. Huizinga: None declared, A. Schouffoer: None declared, H. Middelkoop: None declared, J. de Vries-Bouwstra: None declared

SAT0218 Clinical phenotypes in NPSLE; data from the leiden NPSLE clinic

Background Therapeutic decisions in NPSLE are made on a patient-by-patient basis guided by the severity of symptoms and the suspected underlying pathogenetic mechanism. Evidence for therapeutic decisions is scanty as is data on clinical phenotypes in NPSLE. Objectives To describe clinical phenotypes per suspected pathogenetic mechanism in NPSLE. Methods The Leiden NPSLE clinic is a tertiary referral centre that evaluates patients suspected of NPSLE and leads to a prospectively collected database. Standardized evaluation including serological, imaging, clinical and neuropsychological testing is followed by a multidisciplinary consensus meeting. Diagnosis and therapeutic decisions based on the suspected pathogenetic mechanism are made by consensus of all participating medical specialists. We describe clinical phenotypes with sociodemographic and clinical characteristics per pathogenetic mechanism. Results One hundred consecutive patients were evaluated in the Leiden NPSLE clinic. Three clinical phenotypes could be differentiated in primary NPSLE; 55% inflammatory NPSLE in patients who were advised immunosuppressive therapy, 32% ischemic NPSLE in patients who were advised anticoagulant therapy and 13% undefined NPSLE in patients who were advised symptomatic treatment. Age and disease duration in each group were 42 and 8, 47 and 9, 45 and 2 years, respectively. MRI abnormalities were present in 72%, 100% and 80% of respective phenotypes and SLEDAI scores were 10, 7 and 6. IgG anticardiolipin antibodies and lupus anticoagulans were present in respectively 33% and 48% of inflammatory and in 58% and 67% of ischemic NPSLE and were absent in undefined NPSLE patients. Twenty-five percent of ischemic NPSLE-patients reported transient ischemic attacks oppose to none in other groups. Cognitive dysfunction was present in 62% of inflammatory, 50% of ischemic and 20% of undefined NPSLE patients. As a fourth group secondary NPSLE was recognized in 11% of patients, in this group 75% of patients had a renal disorder and 88% of patients used steroids. Conclusions To the best of our kowledge this is the first prospective evaluation of a standardized multidisciplinary assessment of neuropsychiatric symptoms in SLE-patients. A remarkable feature of inflammatory NPSLE is a high SLEDAI and high prevalence of cognitive dysfunction. Whereas in ischemic NPSLE IgG anticardiolipin antibodies and lupus anticoagulans are highly prevalent and patients are distinguished by the report of TIA’s, also in this group all patients had abnormalities on MRI of the brain. Disclosure of Interest None Declared

Compensatory prefrontal activation during planning in major depressive disorder; an event related fMRI study

Introduction: Neuropsychological studies in Major Depression Disorder (MDD) have revealed decreased performance in executive functioning, like planning. A frequently used test to probe planning processes is the Tower of London task (ToL). In MDD a reduced performance and abnormal brain activation pattern during the TOL was found. (Elliot et al., 1996, 1997). Recently, a parametric self-paced pseudorandomized event-related version of the ToL, suitable for fMRI was developed and used in studies of healthy volunteers and patients with obsessive–compulsive disorder (van den Heuvel et al., 2003).We employed this novel fMRI version of the TOL in patients with MDD and matched controls. Methods: 21 matched healthy control subjects (HC) and 15 medication-free subjects with a primary diagnosis of MDD as current diagnosis or diagnosis in the past six months and no other axis I or II disorder participated (mean MADRS-score 13.29; SD 9.52). The present pilot study is part of the larger neuroimaging-study within the The Netherlands Study on Depression and Anxiety (NESDA), involving 320 subjects. All subjects performed a 17-minute parametric version of the TOL-task which consisted of five levels of difficulty and baseline items (3). Items were presented in a pseudo-randomized order. Scanning was performed on a Philips Intera 3T scanner. Data were analyzed with SPM5 in the context of the General LinearModel. Results: MDD-subjects and HC did not show any difference in performance and reaction times. However, MDD subjects showed an increase in activation in the left limbic anterior cingulate gyrus, right MTL and right medial frontal gyrus with increasing difficulty. Conclusion: Our data suggest that MDD-subjects needed more active control of attention than controls while performing this executive task. MDD-subjects might compensate with cingulate and bilateral activation of the DLPFC in order to obtain the same level of performance as the control subjects.