MRS Shows Regionally Increased Glutamate Levels among Patients with Exhaustion Syndrome Due to Occupational Stress.

Despite the rapid increase of reports of exhaustion syndrome (ES) due to daily occupational stress, the mechanisms underlying ES are unknown. We used voxel-based 1H-MR spectroscopy to examine the potential role of glutamate in this condition. The levels of glutamate were found to be elevated among ES patients (n = 30, 16 females) compared with controls (n = 31, 15 females). Notably, this increase was detected only in the anterior cingulate and mesial prefrontal cortex (ACC/mPFC), and the glutamate levels were linearly correlated with the degree of perceived stress. Furthermore, there was a sex by group interaction, as the glutamate elevation was present only in female patients. Female but not male ES patients also showed an increase in N-acetyl aspartate (NAA) levels in the amygdala. No group differences were detected in glutamine concentration (also measured). These data show the key role of glutamate in stress-related neuronal signaling and the specific roles of the amygdala and ACC/mPFC. The data extend previous reports about the neurochemical basis of stress and identify a potential neural marker and mediator of ES due to occupational stress. The observation of specific sex differences provides a tentative explanation to the well-known female predominance in stress-related psychopathology.

Abnormal regional homogeneity and functional connectivity in adjustment disorder of new recruits: a resting-state fMRI study.

PURPOSE: To explore the regional spontaneous neural activity and functional connectivity alterations of adjustment disorder (AD) in new recruits with in vivo resting-state functional MR (rs-fMRI). MATERIALS AND METHODS: Resting-state fMRI was performed in 31 recruits with AD and in 31 control recruits. Regional homogeneity (ReHo) was used to detect the regional synchronizing features of neuronal activations. Correlative analysis was performed to investigate the relationship between the Symptom Check List-90 (SCL-90) score and ReHo in regions with significant group differences. Regions with significant correlation were then defined as regions of interest (ROIs), and seed-ROI based whole-brain functional connectivity was performed. RESULTS: Compared with the controls, patients with AD had significantly lower ReHo in the left posterior cerebellar lobe, bilateral medial orbitofrontal cortex, bilateral caudate and left middle temporal gyrus, whereas regions with enhanced ReHo were confined to bilateral posterior cingulate gyrus/precuneus. Only the left posterior cerebellar lobe showed significant correlation between ReHo and the SCL-90 score, and was defined as the seed ROI. Decreased functional connectivity was found between the ROI and bilateral supplementary motor area. CONCLUSION: This study reveals abnormalities in recruits with AD in baseline brain function activities, which could further improve our understanding of the neural substrates of cognitive impairment in AD.

Chronic stress is linked to 5-HT(1A) receptor changes and functional disintegration of the limbic networks.

There are increasing reports about stress related cognitive and psychic declines in subjects who have no psychiatric premorbidity, depression, or major life trauma. Yet, little is known about the underlying neurobiology. Based on the typical symptomatology, fMRI data suggesting that stress activates the limbic circuits, and animal data showing a major involvement of the 5-HT(1A) receptor in stress regulation, we hypothesized that enduring daily stress causes widespread limbic dysfunctions, and specific changes of the 5-HT(1A) receptor. To test these hypotheses combined PET studies were carried out in 16 chronically stressed, and 16 non-stressed subjects. Limbic function was tested by measuring cerebral blood flow during rest, and when using an odor activation paradigm. 5-HT(1A) receptor binding potential (BP) was assessed with [(11)C]WAY100635. All subjects went through a battery of neuropsychological tests. Stressed subjects showed a functional disconnection between the amygdala and ACC/medial prefrontal cortex (mPFC), and an impaired odor activation of the ACC. They also displayed a reduced 5-HT(1A) receptor BP in the anterior cingulate (ACC), the insular-cortex, and the hippocampus. Their performance in attention-, odor discrimination-, and semantic memory tasks was impaired, and correlated with the BP-values in the respective region. The degree of reported stress was inversely correlated with activation of ACC, and the 5-HT(1A) receptor BP in the amygdala and hippocampus. Enduring every day psychosocial stress seems to be associated with a limbic reduction of 5-HT(1A) receptor binding and functional disintegration of ACC/mPFC. These changes support the notion of an impaired top-down regulation of stress stimuli, and identify potential targets for early treatment.

Substantia nigra hyperechogenicity in depressive subjects relates to motor asymmetry and impaired word fluency.

BACKGROUND: Substantia nigra hyperechogenicity (SNH) is a characteristic transcranial sonography (TCS) finding in Parkinson's disease (PD). SNH, found also in about 10% of healthy adults, was related to a subclinical malfunction of the nigrostriatal dopaminergic system on positron emission tomography studies. Both, liability for developing PD and frequency of SNH were found to be increased in depressed subjects. Here, we investigated whether SNH in depression is related to motor or cognitive abnormalities resembling early PD. METHODS: Fourty-one patients with major depressive disorder and 15 with adjustment disorder with depressed mood were studied clinically and with TCS. RESULTS: Frequency of SNH was similar in both groups (39, 33%; Chi-square test, P = 0.70). Larger SN echogenic size correlated with larger right-to-left asymmetry of finger tapping (Spearman test, r = 0.37, P = 0.009) and lower verbal fluency (r = -0.35, P = 0.038). These correlations were stronger in patients at ages >/= 50 years (r = 0.52, P = 0.007; r = -0.50, P = 0.020), and, independently from age, in patients with reduced echogenicity of brainstem raphe suggested to reflect alteration of the serotonergic system (r = 0.40, P = 0.045; r = -0.51, P = 0.044). Whereas bilateral sum score of finger tapping was negatively correlated with severity of depression on the beck depression inventory (r = -0.50, P = 0.001) and the Hamilton depression rating scale (r = -0.34, P = 0.019), no correlation was found between depression severity and tapping asymmetry, or between depression severity and verbal fluency. CONCLUSION: Data suggest that TCS detects a subgroup of patients with depression characterized by symptoms of early parkinsonism who are possibly at an elevated risk of later developing definite PD.

Brain metabolic changes associated with predispotion to onset of major depressive disorder and adjustment disorder in cancer patients--a preliminary PET study.

OBJECTIVES: To explore neurobiological risk factors for major depressive disorder (MDD) and adjustment disorder in cancer patients by examining regional brain metabolism before psychiatric manifestation using positron emission tomography and by prospectively observing depressive and anxiety symptoms. METHOD: Cancer patients who showed no psychiatric symptoms when they underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) were followed up for one year using the Hospital Anxiety and Depression Scale (HADS). Fourteen patients who showed high HADS scores and 14 patients who showed low HADS scores were assessed by a psychiatrist 2 years after the PET scan and grouped into the deterioration group (n=10) and the no-change group (n=9). 18F-FDG PET images were analyzed to examine the difference in local brain glucose metabolism between the two groups. RESULTS: The deterioration group showed a decreased glucose metabolism in the right medial frontal gyrus (BA6) and an increased glucose metabolism in the right posterior cingulate (BA29), right anterior cingulate (BA25), left subcallosal gyrus (BA25), and left caudate compared with the no-change group. CONCLUSION: Cancer patients who later developed MDD or adjustment disorder showed regional brain metabolic changes. These regions may be associated with vulnerability to the onset of MDD or adjustment disorder in cancer patients.

Regional brain serotonin and dopamine transporter binding capacity in suicide attempters relate to impulsiveness and mental energy.

To study different aspects of regional pre-synaptic brain (123)I-beta-CIT uptake on serotonin and dopamine re-uptake sites in drug-free suicide attempters in comparison with age- and sex matched control subjects, single photon emission computed tomography (SPECT) measurements were analysed for regional serotonin re-uptake (5HTT) and dopamine re-uptake (DAT) capacity (binding potential, BP()) after i.v. (123)I-beta-CIT administration. All suicide attempters were examined concerning seriousness of the attempt, and DSM-IV diagnosis. Both suicide attempters and control subjects were tested for psychotropic drugs, and completed the Marke-Nyman Temperament (MNT) test, including solidity (level of impulsiveness/initiative) and validity (level of mental energy). We found no significant difference between suicide attempters and control subjects concerning the regional levels of 5HTT BP() or DAT BP(). However, in suicide attempters, but not controls, we found significant regional correlations between MNT variables and SPECT results. We interpret the discrepant findings in suicide attempters and control subjects to be due to a disability of the suicide attempters to regulate their serotonin and dopamine levels, e.g. in response to external stress.