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Biomedical subjects

Nic J A van der Wee

Publications and source records attributed to Nic J A van der Wee.

5 recordsLinked to original sources

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. METHODS: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). RESULTS: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected  = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected  = .001). CONCLUSIONS: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Humans↗

Spatial working memory in obsessive-compulsive disorder improves with clinical response: A functional MRI study.

To date, only a few studies have examined whether executive dysfunctions in obsessive-compulsive disorder (OCD) are state or trait dependent and almost none of these studies have used functional neuroimaging techniques. We conducted a functional MRI study before and after 12 weeks of pharmacological treatment in 14 psychotropic-free patients with OCD without comorbidity. Subjects performed a spatial variant of a working memory task with four increasing levels of difficulty (n-back task). Responders and non-responders did not differ in clinical and demographical characteristics or brain activation patterns before treatment. Performance improved only in responders and was associated with a change in the overall pattern of brain activity during the task. We found no correlations between (changes in) scores on symptom scales, brain activity and performance. Our preliminary findings suggests that spatial working memory deficits in OCD and their functional anatomical correlates, as assessed with a spatial n-back task, are, at least to some extent, state dependent.

Adult↗

Behavioural effects of rapid intravenous administration of meta-chlorophenylpiperazine in patients with panic disorder and controls.

Oral and intravenous challenge paradigms with the direct 5-HT agonist meta-chlorophenylpiperazine (m-CPP) in panic disorder (PD) have shown only moderate sensitivity or selectivity of the panicogenic effects in PD. However, the results of a study examining the effects of rapid intravenous administration of 0.1 mg/kg of m-CPP in healthy volunteers suggested that this approach may be a more selective and sensitive panicogenic paradigm in PD. We therefore compared the behavioural, neuroendocrine and physiological effects of rapid intravenous administration of 0.1 mg/kg of m-CPP in 10 patients with PD and 10 healthy controls. Panic attacks were significantly more provoked in patients with PD (90%) compared to healthy controls (0%). Effects on the behavioural, but not on the neuroendocrine and physiological parameters, were significantly greater in patients. Our data suggests that the behavioural effects of rapid intravenous administration of 0.1 mg/kg of m-CPP in patients with PD indeed show a unique combination of high sensitivity and selectivity.

Adult↗

Spatial working memory deficits in obsessive compulsive disorder are associated with excessive engagement of the medial frontal cortex.

Recent studies have shown that obsessive compulsive disorder (OCD) is associated with a specific deficit in spatial working memory, especially when task difficulty (i.e., working memory load) is high. It is not clear whether this deficit is associated with dysfunction of the brain system that subserves spatial working memory, or whether it is associated with a more generalized effect on executive functions. In contrast to studies in healthy volunteers and schizophrenia, spatial working memory in OCD has not been investigated before using functional neuroimaging techniques. We conducted a functional MRI study in 11 treatment-free female patients with OCD and 11 for sex-, age-, education-, and handedness pairwise-matched healthy controls in order to assess performance on a parametric spatial n-back task as well as the underlying neuronal substrate and its dynamics. Patients with OCD performed poorly at the highest level of task difficulty and engaged the same set of brain regions as the matched healthy controls. In this set, the effect of difficulty on magnitude of brain activity was the same in patients and in controls except for a region covering the anterior cingulate cortex. In this region activity was significantly elevated in patients with OCD at all levels of the parametric task. These findings do not provide evidence for a deficit of the spatial working memory system proper, but suggest that the abnormal performance pattern may be secondary to another aspect of executive dysfunctioning in OCD.

Adult↗

Release from proactive inhibition in schizophrenia and its potential as a genotypic marker.

Release from proactive inhibition (RPI) in first-episode (FE) schizophrenic patients and the potential of RPI as a genotypic marker of schizophrenia was investigated in two studies. The first study showed that FE patients ( n=35) exhibited weaker RPI than matched obsessive compulsive disorder (OCD) patients (n=20) as well as healthy controls (n=34). OCD patients and controls showed similar RPI. The second study showed that RPI is similar in both parents of patients (n=64) and matched controls (n=52). Results were explained in terms of additional evidence for impairment in the inhibition of irrelevant information in schizophrenia. Combination of our data and literature review suggests that diminished RPI can be attributed to a combination of dorsolateral-prefrontal and dorsomedial-thalamic impairment. RPI may not be a genotypic marker for schizophrenia but rather related to the illness or its treatment. An alternative explanation in terms of insufficient power of the parent-sample, due to unilineal inheritance of schizophrenia is, however, possible.

Adult↗