Neuronal response to high negative affective stimuli in major depressive disorder: An fMRI study.

BACKGROUND: Disturbed emotion processing underlies depression. We examined the neuronal underpinnings of emotional processing in patients (PAT) with major depressive disorder (MDD) compared to healthy volunteers (HV) using functional magnetic resonance (fMRI) scan. METHODS: Thirty-six MDD patients and 30 HV underwent T2-weighted fMRI assessments during the presentation of an implicit affective processing task in three conditions. They differed regarding their affective quality (=valence, high negative, low negative and neutral stimuli) and regarding the arousal based on stimuli from the International Affective Picture System. RESULTS: Group contrasts showed lower left-sided activation in dorsolateral prefrontal cortex (DLPFC), anterior PFC, precentral and premotor cortex in PAT compared with HV (Cluster-level threshold, 5000 iterations, p<0.01). We found a significant interaction effect of valence and group, a significant effect of emotional valence and a significant effect of group. All effects were shown in brain regions within the emotional network (Cluster-level threshold, 5000 iterations, p<0.01). Higher arousal (rho=-0.33, p<0.01) and higher valence (rho=-0.33, p<0.01) during high negative stimuli presentation as well as more severe depression (Beck Depression Inventory II [BDI II]; r = 0.39, p = 0.01) were significantly negatively associated with left DLFPC activity in patients. LIMITATIONS: Potential influence of psychopharmacological drugs on functional activation is one of the most discussed source of bias in studies with medicated psychiatric patients. CONCLUSIONS: The results highlight the importance of left DLPFC during the processing of negative emotional stimuli in MDD. The integration of a neurophysiological model of emotional processing in MDD may help to clarify and improve therapeutic options.

Abnormal functional and structural asymmetry as biomarker for schizophrenia.

The hemispheres of the human brain are anatomically and functionally asymmetric. Many cognitive and motor functions such as language and handedness are lateralized. In this review, we discuss the principles of laterality and brain asymmetry in relation to schizophrenia. Schizophrenia is one of the most disabling forms of mental illness. One important challenge is to develop and set up biological markers, which can accurately identify at-risk individuals in preclinical stages and thus improve the effects of early intervention strategies. The concept of hemispheric laterality plays a central role in current neuropsychological and pathophysiological models of schizophrenia. Recent research reflects an increasing interest in the molecular and population genetics of laterality and its potential use as biological marker for the illness. The review is an overview of literature from the 1990's on cerebral asymmetry in schizophrenia. We critically discuss the use of cerebral asymmetry for biomarker research, regarding diagnosis improvements, the improvement of psychopharmacology and the prediction of conversion in at-risk individuals. We propose that abnormal cerebral asymmetry is an attractive biomarker candidate for schizophrenia that could index changes in a range of pathophysiological pathways.

Cortical-basal ganglia imbalance in schizophrenia patients and unaffected first-degree relatives.

Structural brain changes are amongst the most robust biological alterations in schizophrenia, and their investigation in unaffected relatives is important for an assessment of the contribution of genetic factors. In this cross-sectional morphometry study we investigated whether volume changes in SZ are linked with genetic vulnerability and whether these effects are separated from secondary illness effects. We compared density of grey and white matter using high-resolution 3D-anatomical MRI imaging data in 31 SZ patients, 29 first-degree relatives and 38 matched healthy controls, using Voxel-Based Morphometry (VBM) with SPM8. Volume of basal ganglia was also compared by manual segmentation. We found increased grey matter in the striatum, globus pallidus internus and thalamus and decreased grey matter in the parahippocampal and cingulate gyri both in SZ patients and relatives. Additionally, SZ patients had decreased volume of temporal, frontal and limbic grey and white matter in comparison with relatives and controls. Relatives showed intermediate values in many of these areas. Increased volume in the thalamus and parts of the basal ganglia and decreased volume of cortical areas and underlying white matter were thus associated with schizophrenia and its genetic vulnerability. These results suggest that brain morphological changes associated with SZ are in part determined by genetic risk factors and are not entirely explained by effects of medication or changes secondary to illness.