Increased visual gamma power in schizoaffective bipolar disorder.

BACKGROUND: Electroencephalography and magnetoencephalography (MEG) studies have identified alterations in gamma-band (30-80 Hz) cortical activity in schizophrenia and mood disorders, consistent with neural models of disturbed glutamate (and GABA) neuron influence over cortical pyramidal cells. Genetic evidence suggests specific deficits in GABA-A receptor function in schizoaffective bipolar disorder (SABP), a clinical syndrome with features of both bipolar disorder and schizophrenia. This study investigated gamma oscillations in this under-researched disorder. METHOD: MEG was used to measure induced gamma and evoked responses to a visual grating stimulus, known to be a potent inducer of primary visual gamma oscillations, in 15 individuals with remitted SABP, defined using Research Diagnostic Criteria, and 22 age- and sex-matched healthy controls. RESULTS: Individuals with SABP demonstrated increased sustained visual cortical power in the gamma band (t 35 = -2.56, p = 0.015) compared to controls. There were no group differences in baseline gamma power, transient or sustained gamma frequency, alpha band responses or pattern onset visual-evoked responses. CONCLUSIONS: Gamma power is increased in remitted SABP, which reflects an abnormality in the cortical inhibitory-excitatory balance. Although an interaction between gamma power and medication can not be ruled out, there were no group differences in evoked responses or baseline measures. Further work is needed in other clinical populations and at-risk relatives. Pharmaco-magnetoencephalography studies will help to elucidate the specific GABA and glutamate pathways affected.

Hedonic tone is associated with left supero-lateral medial forebrain bundle microstructure.

BACKGROUND: The medial forebrain bundle (MFB) is an important pathway of the reward system. Two branches have been described using diffusion magnetic resonance imaging (MRI)-based tractography: the infero-medial MFB (imMFB) and the supero-lateral MFB (slMFB). Previous studies point to white-matter microstructural alterations of the slMFB in major depressive disorder (MDD) during acute episodes. To extend this finding, this study investigates whether white-matter microstructure is also altered in MDD patients that are in remission. Further, we explore associations between diffusion MRI-based metrics of white-matter microstructure of imMFB, slMFB and hedonic tone, the ability to derive pleasure. METHOD: Eighteen remitted depressed (RD) and 22 never depressed (ND) participants underwent high angular resolution diffusion-weighted imaging (HARDI) scans. To reconstruct the two pathways of the MFB (imMFB and slMFB) we used the damped Richardson-Lucy (dRL) algorithm. Mean fractional anisotropy (FA) was sampled along the tracts. RESULTS: Mean FA of imMFB, slMFB and a comparison tract (the middle cerebellar peduncle) did not differ between ND and RD participants. Hedonic capacity correlated negatively with mean FA of the left slMFB, explaining 21% of the variance. CONCLUSIONS: Diffusion MRI-based metrics of white-matter microstructure of the MFB in RD do not differ from ND. Hedonic capacity is associated with altered white-matter microstructure of the slMFB.

Are we really mapping psychosis risk? Neuroanatomical signature of affective disorders in subjects at ultra high risk.

BACKGROUND: The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown. METHOD: We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses. RESULTS: The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive-compulsive disorder symptoms. CONCLUSIONS: Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state.

Neural markers of symptomatic improvement during antidepressant therapy in severe depression: subgenual cingulate and visual cortical responses to sad, but not happy, facial stimuli are correlated with changes in symptom score.

Resting state activity in the ventral cingulate may be an important neural marker of symptomatic improvement in depression. The number of task related functional magnetic resonance imaging (fMRI) studies correlating blood oxygenation level dependent (BOLD) response with symptomatic improvement is limited and methodologies are still evolving. We measured BOLD responses to sad and happy facial stimuli in 12 severely depressed individuals in the early stages of antidepressant treatment (Time 1) and 12 weeks later (Time 2) using event-related fMRI. We calculated correlations between temporal changes in BOLD response and changes in symptom scores. Most subjects improved markedly by Time 2. At Time 1, depression severity correlated positively with responses to sad stimuli in the right visual cortex, subgenual cingulate, anterior temporal pole and hippocampus and correlated negatively with responses to happy stimuli in left visual cortex and right caudate. Decreases in individual effect sizes of right subgenual cingulate and right visual cortical responses to sad, but not happy, facial stimuli were correlated with decreases in symptom scores. There are contrasting cortical and subcortical responses to sad and happy stimuli in severe depression. Responses to sad stimuli show the strongest correlates of clinical improvement, particularly in the subgenual cingulate.

What do anxiety scales measure?

At present researchers appear to rely on instruments for the assessment of anxiety without due consideration of what it is that the instrument may be presumed to measure. A survey was undertaken of the presently most frequently used rating scales which purport to assess anxiety. The allocation of items of the scales to the major aspects of anxiety was examined. It was found that the scales tapped different areas of psychopathology. Furtherance of research requires closer attention to the nature of the scales and the assumption that they all measure much the same construct must be discarded.

Further analysis of the short-term inhibition of food intake in humans by the dipeptide L-aspartyl-L-phenylalanine methyl ester (aspartame).

It was reported previously that the dipeptide sweetener aspartame suppresses food intake in humans by a postingestive action. The present study examined the hypothesis that this is due to an effect of phenylalanine, one of the primary breakdown products of aspartame (phenylalanine is a potent releaser of the so-called satiety hormone cholecystokinin, CCK). Capsulated aspartame (400 mg) administered to human volunteers reduced food intake by 15% (253 kcal) in a lunchtime test meal begun 1 hour later. However, neither phenylalanine (200 mg) nor the other constituent amino acid of aspartame, aspartic acid (200 mg), altered intake compared with placebo. Despite the large effect on food intake there were no treatment differences in pre- or postmeal ratings of motivation to eat. This suggests that aspartame may act to intensify the satiating effects of ingested food. Although high doses of phenylalanine reduce food intake, an individual action of phenylalanine cannot account for the potent anorexic effect of aspartame. In discussing alternative mechanisms it is noted that the amino acid sequence of aspartame (Asp-Phe) is the same as the C-terminal dipeptide of CCK. A direct action of aspartame at CCK receptors appears to be unlikely; however, aspartame might act as CCK releaser. Further studies are required to elucidate the mechanism of aspartame's anorexic action and perhaps to evaluate its therapeutic potential as an antiobesity agent.