Fluorodeoxyglucose positron emission tomography scans in patients with alcohol use disorder.

BACKGROUND: Diminished uptake of fluorodeoxyglucose (FDG) has been observed in patients with alcohol use disorder (AUD) but little statistical contrast of the regional brain deficits has been undertaken. This study examined prefrontal cortex inter-regional Brodmann area differences to delineate patterns associated with behavioral, neurotransmitter, and general toxicity hypotheses of cerebral involvement in AUD. METHODS: We obtained data from FDG positron emission tomography (PET) and anatomical magnetic resonance imaging (MRI) for 87 patients with AUD and 41 age- and sex-matched healthy volunteers. Patients were alcohol dependent and had negative breathalyzer tests at the time of imaging. They were assessed with the Beck Depression Inventory, Alcohol Urge Questionnaire, Obsessive Compulsive Drinking Scale, Spielberger State/Trait Anxiety Scale, Buss-Durkee Hostility Inventory, and the Drinker Inventory of Consequences (DrInC). PET images were co-registered to MRI and both voxel × voxel statistical mapping and stereotaxic regions of interest were obtained. RESULTS: Compared with healthy volunteers, patients with AUD had lower relative metabolic rates in the frontal, temporal, and parietal lobes, localizable most prominently to the dorsolateral and nearly all orbital prefrontal cortex, superior temporal gyrus, and inferior parietal lobule. In contrast, metabolic rates in the medial orbitofrontal and anterior cingulate cortex, and the subcortical structures (thalamus, cerebellum, ventral striatum, and the dorsal raphe nucleus) in patients were significantly greater. The severity of alcohol-related consequences as assessed by the DrInC scale was most highly associated with lower metabolism in the caudate, dorsolateral prefrontal, frontopolar, and anteroposterior cingulate cortex. CONCLUSIONS: Despite widespread metabolic abnormalities, decreases in AUD were most marked in frontal executive areas, consistent with diminished impulse control, and increases were most prominent in the striatum and cingulate areas, consistent with a suppressed reward system.

Bimagrumab improves body composition and insulin sensitivity in insulin-resistant individuals.

AIM: To test the hypothesis that an improving body composition in insulin-resistant individuals could enhance insulin sensitivity. METHODS: A total of 16 people with a mean body mass index of 29.3 kg/m2 and insulin resistance, received a single dose of bimagrumab or placebo and were assessed at week 10 for insulin sensitivity, using a hyperinsulinaemic-euglycaemic clamp and an intravenous glucose tolerance test (IVGTT), and for body composition using dual energy X-ray absorptiometry and positron-emission tomography. RESULTS: Bimagrumab increased lean mass by 2.7% (P < .05) and reduced fat mass by 7.9% (P = .011) at week 10 compared with placebo, and had a neutral effect on body weight. Bimagrumab reduced glycated haemoglobin by 0.21% at week 18 (P < .001) and improved insulin sensitivity by ~20% (according to the clamp) to ~40% (according to the IVGTT). CONCLUSION: Taking the observed changes together, and given that these occurred without accompanying dietary intervention and without any prescribed regular physical exercise, bimagrumab may offer a novel approach for the treatment of the metabolic complications of obesity.

FDG-PET scans in patients with Kraepelinian and non-Kraepelinian schizophrenia.

We recruited 14 unmedicated patients with Kraepelinian schizophrenia (12 men and 2 women; mean age = 47 years old), 27 non-Kraepelinian patients (21 men and 6 women; mean age = 36.4 years old) and a group of 56 age- and sex-matched healthy volunteers. FDG positron emission tomography and MRI scans were coregistered for both voxel-by-voxel statistical mapping and stereotaxic regions of interest analysis. While both Kraepelinian and non-Kraepelinian patients showed equally lower uptake than healthy volunteers in the frontal lobe, the temporal lobes (Brodmann areas 20 and 21) showed significantly greater decreases in Kraepelinian than in non-Kraepelinian patients. Kraepelinian patients had lower FDG uptake in parietal regions 39 and 40, especially in the right hemisphere, while non-Kraepelinian patients had similar reductions in the left. Only non-Kraepelinian patients had lower caudate FDG uptake than healthy volunteers. While both patient groups had lower uptake than healthy volunteers in the medial dorsal nucleus of the thalamus, Kraepelinian patients alone had higher uptake in the ventral nuclei of the thalamus. Kraepelinian patients also showed higher metabolic rates in white matter. Our results are consistent with other studies indicating that Kraepelinian schizophrenia is a subgroup of schizophrenia, characterized by temporal and right parietal deficits and normal rather than reduced caudate uptake. It suggests that Kraepelinian schizophrenia may be more primarily characterized by FDG uptake decreased in both the frontal and temporal lobes, while non-Kraepelinian schizophrenia may have deficits more limited to the frontal lobe. This is consistent with some neuropsychological and prognosis reports of disordered sensory information processing in Kraepelinian schizophrenia in addition to deficits in frontal lobe executive functions shared with the non-Kraepelinian subtype.

Serotonin transporter binding after recovery from bulimia nervosa.

OBJECTIVE: Physiological and pharmacological studies indicate that altered brain serotonin (5-HT) activity could contribute to a susceptibility to develop appetitive and behavioral alterations that are characteristic of bulimia nervosa (BN). METHOD: Eight individuals recovered from BN (REC BN) and eight healthy control women were scanned with [11C]DASB and positron emission tomography imaging of the 5-HT transporter (5-HTT). Logan graphical analysis was applied, and parametric binding potential (BP(nondisplaceable (ND)) ) images were generated. Voxel-by-voxel t-tests and a region of interest (ROI) analysis were conducted. RESULTS: REC BN had significantly lower [11C]DASB BP(ND) in midbrain, superior and inferior cingulate and significantly higher [11C]DASB BP(ND) in anterior cingulate and superior temporal gyrus in the voxel-based analysis. ROI analysis indicated lower [11C]DASB BP(ND) in midbrain (p = .07), containing the dorsal raphe, in REC BN, consistent with our earlier studies. DISCUSSION: These preliminary findings of a small-scale study confirm and extend previous data suggesting that ill and recovered BN have altered 5-HTT measures, which potentially contribute to BN symptomatology and/or differential responses to medication.

Neurocognitive profile of adolescents with early-onset schizophrenia and their unaffected siblings.

BACKGROUND: We investigated the neurocognitive profiles of Early-Onset Schizophrenia (EOS; onset before age 18) and paired unaffected siblings and the little-studied effect of age-of-onset and duration of illness on cognitive performance. METHODS: 31 EOS probands, and 31 of their siblings, had four cognitive domains assessed: (a) Memory: California Verbal Learning Test, and the Wechsler Memory Scale-Revised; (b) Working memory: Digit Span; (c) Attention: Degraded-Stimulus Continuous Performance Test, Span of Apprehension (SPAN), and Trail Making Test (TMT) part A; (d) Executive function: Wisconsin card sorting task, and TMT part B. Diagnosis was confirmed using the structured clinical interview for DSM-IV. RESULTS: While EOS showed a generalised neurocognitive deficit (0.25-0.50 effect size) compared with siblings, across all cognitive domains, significantly greater patient deficits were observed with, working memory, attention, and executive function and minimal differences for digit span forward, block design and false alarms on the SPAN-12 confirmed by repeated measures MANOVA. Patients with earlier onset (12-15) showed greater deficits on false alarm and digits backward scores. Siblings showed individual cognitive task profiles similar to patients, confirming familial effects. EOS showed much more variable scores than siblings with more individual tasks showing 2 SD deficits than siblings. Long duration patients had greater z-score variability across tasks. CONCLUSIONS: Duration of illness was a more important characteristic in patients with onset 16 and over than in younger onset patients with comparable durations. Both the similarity of sibling pair profiles and greater patient variability across task provide further support for neurobiological heterogeneity in schizophrenia.

Four-modality imaging of unmedicated subjects with schizophrenia: 18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, and MRI.

Diminished prefrontal function, dopaminergic abnormalities in the striatum and thalamus, reductions in white matter integrity and frontotemporal gray matter deficits are the most replicated findings in schizophrenia. We used four imaging modalities (18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, structural MRI) in 19 healthy and 25 schizophrenia subjects to assess the relationship between functional (dopamine D2/D3 receptor binding potential, glucose metabolic rate) and structural (fractional anisotropy, MRI) correlates of schizophrenia and their additive diagnostic prediction potential. Multivariate ANOVA was used to compare structural and functional image sets for identification of schizophrenia. Integration of data from all four modalities yielded better predictive power than less inclusive combinations, specifically in the thalamus, left dorsolateral prefrontal and temporal regions. Among the modalities, fractional anisotropy showed highest discrimination in white matter whereas 18F-fallypride binding showed highest discrimination in gray matter. Structural and functional modalities displayed comparable discriminative power but different topography, with higher sensitivity of structural modalities in the left prefrontal region. Combination of functional and structural imaging modalities with inclusion of both gray and white matter appears most effective in diagnostic discrimination. The highest sensitivity of 18F-fallypride PET to gray matter changes in schizophrenia supports the primacy of dopaminergic abnormalities in its pathophysiology.

Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia.

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.

Neural Correlates of Autobiographical Memory: Evidence From a Positron Emission Tomography Study in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

Background: Autobiographical memory (AM) changes are the hallmark of Alzheimer's disease (AD) and mild cognitive impairment (MCI). In recent neuroimaging studies, AM changes have been associated with numerous cerebral sites, such as the frontal cortices, the mesial temporal lobe, or the posterior cingulum. Regional glucose uptake in these sites was investigated for underlying subdimensions using factor analysis. Subsequently, the factors were examined with respect to AM performance in a subgroup of patients. Methods: Data from 109 memory clinic referrals, who presented with MCI (n = 60), mild AD (n = 49), or were cognitively intact, were analyzed. The glucose metabolic rates determined by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in 34 cerebral sites important for AM were investigated for underlying subdimensions by calculating factor analysis with varimax rotation. Subsequently, the respective factor scores were correlated with the episodic and semantic AM performance of 22 patients, which was measured with a semi-structured interview assessing episodic memories (characterized by event-related emotional, sensory, contextual, and spatial-temporal details) and personal semantic knowledge from three periods of life (primary school, early adulthood, and recent years). Results: Factor analysis identified seven factors explaining 69% of the variance. While patients with MCI and AD showed lower values than controls on the factors frontal cortex, mesial temporal substructures, and occipital cortex, patients with MCI presented with increased values on the factors posterior cingulum and left temporo-prefrontal areas. The factors anterior cingulum and right temporal cortex showed only minor, non-significant group differences. Solely, the factor mesial temporal substructures was significantly correlated with both episodic memories (r = 0.424, p < 0.05) and personal semantic knowledge (r = 0.547, p < 0.01) in patients with MCI/AD. Conclusions: The factor structure identified corresponds by large to the morphological and functional interrelations of the respective sites. While reduced glucose uptake on the factors frontal cortex, mesial temporal substructures, and occipital cortex in the patient group may correspond to neurodegenerative changes, increased values on the factors posterior cingulum and left temporo-prefrontal areas in MCI may result from compensatory efforts. Interestingly, changes of the mesial temporal substructures were correlated with both semantic and episodic AM. Our findings suggest that AM deficits do not only reflect neurodegenerative changes but also refer to compensatory mechanisms as they involve both quantitative losses of specific memories and qualitative changes with a semantization of memories.

Reading abilities and dopamine D2/D3 receptor availability: An inverted U-shaped association in subjects with schizophrenia.

Reading impairments are prominent trait-like features of cognitive deficits in schizophrenia, predictive of overall cognitive functioning and presumably linked to dopaminergic abnormalities. To evaluate this, we used 18F-fallypride PET in 19 healthy and 21 antipsychotic-naïve schizophrenia subjects and correlated dopamine receptor binding potentials in relevant AFNI-derived regions and voxelwise with group performance on WRAT4 single-word reading subtest. Healthy subjects' scores were positively and linearly associated with D2/D3 receptor availability in the rectus, orbital and superior frontal gyri, fusiform and middle temporal gyri, as well as middle occipital gyrus and precuneus, all predominantly in the left hemisphere and previously implicated in reading, hence suggesting that higher dopamine receptor density is cognitively advantageous. This relationship was weakened in schizophrenia subjects and in contrast to healthy participants followed an inverted U-shaped curve both in the cortex and dorsal striatum, indicating restricted optimal range of dopamine D2/D3 receptor availability for cognitive performance in schizophrenia.

Diffusion tensor anisotropy in the cingulate gyrus in schizophrenia.

It has been proposed that schizophrenia results partly from altered brain connectivity. The anterior cingulate cortex in particular has been demonstrated to be affected in schizophrenia, with studies reporting reduced volume, altered neuronal arrangement, decreased anisotropy in diffusion tensor images, and hypometabolism. We used a 3T Siemens scanner to acquire structural and diffusion tensor imaging in age-and sex-matched groups of 41 adults with chronic schizophrenia, 6 adults with recent-onset schizophrenia, and 38 healthy control subjects. We manually traced the anterior and posterior cingulate gyri on all subjects and then compared the volume and anisotropy across groups for the left and right anterior and posterior cingulate gyri. The anterior cingulate gyrus was divided axially into six equal segments, and the posterior cingulate gyrus into two segments. Volume was calculated for the anterior and posterior gyri, and average anisotropy was then calculated for each individual segment, looking separately at gray and white matter. We found decreased overall relative left and right gray matter volume in the anterior cingulate gyrus in persons with schizophrenia compared with healthy controls. Additionally, in both gray and white matter of the cingulate, we found that recent-onset patients had the highest anisotropy, chronic patients had the lowest, and controls were intermediate. These results provide additional evidence for the presence of both white and gray matter abnormalities in the cingulate gyrus, which has been implicated in schizophrenia.

Basal Ganglia activity in pathological gambling: a fluorodeoxyglucose-positron emission tomography study.

BACKGROUND: Pathological gambling (PG) is a disorder classified as an impulse control disorder (DSM-IV) bridging impulsive, compulsive and addictive behaviors. The striatum and thalamus are supposed to be involved in the pathophysiological substrate of these behaviors. An increased relative glucose metabolic rate (rGMR) in patients with a diagnosis of PG had previously been reported in the medial and orbitofrontal cortex. We extended our studies to include functional alterations of the striatum and thalamus in a cohort of patients with PG before and after treatment with lithium. METHODS: Twenty-one patients with PG who met lifetime comorbid bipolar spectrum diagnoses and a comparison group of 21 age- and sex-matched controls underwent a baseline positron emission tomography (PET) scan. Sixteen of these patients entered a randomized double-blind placebo-controlled parallel-group-design trial of lithium and underwent a follow-up PET scan at week 10. Anatomical MRI were obtained and the structures outlined on consecutive axial slices. These individual hand-drawn templates were used to identify structures on the PET scan of each patient, and the rGMR was measured. RESULTS: The PG patients had a decrement of the rGMR in the ventral parts of the striatum and thalamus, and an increment of the rGMR in the dorsal parts as compared with the controls. Lithium treatment increased the ventral caudate rGMR to a trend level in the patients, but had no effect on the metabolism of either the putamen or the thalamus. CONCLUSION: Because of their extensive connectivity to the frontal cortex, striatal and thalamic functional alteration may contribute to faulty decision making processes in PG patients. By increasing the ventral rGMR of the caudate nucleus, lithium treatment may reduce cognitive dysfunction and symptoms in PG patients.

Progressive ventricular expansion in chronic poor-outcome schizophrenia.

OBJECTIVE: To compare progressive changes in lateral ventricular size in chronic schizophrenia patients with good and poor outcomes. BACKGROUND: Several longitudinal studies associated excessive ventricular enlargement with poor outcome early in the course of schizophrenia. Changes in its chronic phase have not been as well ascertained. METHODS: We used MRI to evaluate progression of the lateral ventricular size in 49 chronic schizophrenia patients (26 with poor outcome, 23 with good outcome) and 16 healthy comparison participants, scanned twice 4 years apart. RESULTS: In comparison with healthy participants, schizophrenia patients displayed significantly enlarged body, and anterior and posterior horns of the lateral ventricles at baseline and follow-up, but no between-group differences in their longitudinal expansion were observed. Progressive enlargement of the posterior horn in the poor-outcome (Kraepelinian) group, however, was more pronounced than in schizophrenia patients with good outcome. CONCLUSIONS: Excessive ventricular enlargement in the chronic phase of schizophrenia may be specifically associated with poor functional outcome of the illness.

Dopamine receptor density and white mater integrity: 18F-fallypride positron emission tomography and diffusion tensor imaging study in healthy and schizophrenia subjects.

Dopaminergic dysfunction and changes in white matter integrity are among the most replicated findings in schizophrenia. A modulating role of dopamine in myelin formation has been proposed in animal models and healthy human brain, but has not yet been systematically explored in schizophrenia. We used diffusion tensor imaging and 18F-fallypride positron emission tomography in 19 healthy and 25 schizophrenia subjects to assess the relationship between gray matter dopamine D2/D3 receptor density and white matter fractional anisotropy in each diagnostic group. AFNI regions of interest were acquired for 42 cortical Brodmann areas and subcortical gray matter structures as well as stereotaxically placed in representative white matter areas implicated in schizophrenia neuroimaging literature. Welch's t-test with permutation-based p value adjustment was used to compare means of z-transformed correlations between fractional anisotropy and 18F-fallypride binding potentials in hypothesis-driven regions of interest in the diagnostic groups. Healthy subjects displayed an extensive pattern of predominantly negative correlations between 18F-fallypride binding across a range of cortical and subcortical gray matter regions and fractional anisotropy in rostral white matter regions (internal capsule, frontal lobe, anterior corpus callosum). These patterns were disrupted in subjects with schizophrenia, who displayed significantly weaker overall correlations as well as comparatively scant numbers of significant correlations with the internal capsule and frontal (but not temporal) white matter, especially for dopamine receptor density in thalamic nuclei. Dopamine D2/D3 receptor density and white matter integrity appear to be interrelated, and their decreases in schizophrenia may stem from hyperdopaminergia with dysregulation of dopaminergic impact on axonal myelination.

Positive association between cerebral grey matter metabolism and dopamine D2/D3 receptor availability in healthy and schizophrenia subjects: An 18F-fluorodeoxyglucose and 18F-fallypride positron emission tomography study.

Objectives: Overlapping decreases in extrastriatal dopamine D2/D3-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental.Methods: To ascertain this, we used two consecutive 18F-fluorodeoxyglucose and 18F-fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects. Matrices of correlations between 18F-fluorodeoxyglucose uptake and 18F-fallypride binding in voxels at the same xyz location and AFNI-generated regions of interest were evaluated in both diagnostic groups.Results:18F-fluorodeoxyglucose uptake and 18F-fallypride binding potential were predominantly positively correlated across the striatal and extrastriatal grey matter in both healthy and schizophrenia subjects. In comparison to healthy subjects, significantly weaker correlations in subjects with schizophrenia were confirmed in the right cingulate gyrus and thalamus, including the mediodorsal, lateral dorsal, anterior, and midline nuclei. Schizophrenia subjects showed decreased D2/D3-receptor availability in the hypothalamus, mamillary bodies, thalamus and several thalamic nuclei, and increased glucose uptake in three lobules of the cerebellar vermis.Conclusions: Dopaminergic system may be involved in modulation of grey matter metabolism and neurometabolic coupling in both healthy human brain and psychopathology. Hyperdopaminergic state in untreated schizophrenia may at least partly account for the corresponding decreases in grey matter metabolism.

Relationship between white matter glucose metabolism and fractional anisotropy in healthy and schizophrenia subjects.

Decreased fractional anisotropy and increased glucose utilization in the white matter have been reported in schizophrenia. These findings may be indicative of an inverse relationship between these measures of white matter integrity and metabolism. We used 18F-fluorodeoxyglucose positron emission tomography and diffusion-tensor imaging in 19 healthy and 25 schizophrenia subjects to assess and compare coterritorial correlation patterns between glucose utilization and fractional anisotropy on a voxel-by-voxel basis and across a range of automatically placed representative white matter regions of interest. We found a pattern of predominantly negative correlations between white matter metabolism and fractional anisotropy in both healthy and schizophrenia subjects. The overall strength of the relationship was attenuated in subjects with schizophrenia, who displayed significantly fewer and weaker correlations in all regions assessed with the exception of the corpus callosum. This attenuation was most prominent in the left prefrontal white matter and this region also best predicted the diagnosis of schizophrenia. There exists an inverse relationship between the measures of white matter integrity and metabolism, which may therefore be physiologically linked. In subjects with schizophrenia, hypermetabolism in the white matter may be a function of lower white matter integrity, with lower efficiency and increased energetic cost of task-related computations.

Age and diffusion tensor anisotropy in adolescent and adult patients with schizophrenia.

Findings of white matter pathology as indicated by diffusion tensor anisotropy values in schizophrenia are well established, but the differences in this measure between the onset of the disease and the chronic state are not well known. To investigate the differences between these states in the progression of the disease of schizophrenia we acquired 1.5 T diffusion tensor anisotropy images on 35 adult patients with schizophrenia and schizoaffective disorder, 23 adolescents having their first psychotic episode, and age and sex matched controls (33 adults and 15 adolescents). Regions of interest in major cortical white matter tracts chosen as salient to the prefrontal executive deficit in schizophrenia were assessed using stereotaxic coordinates from the Talairach and Tournoux atlas. Regions of each tract along anterior-posterior and/or inferior-superior directions in both hemispheres were evaluated in multiway ANOVA. Tracts between the frontal lobe and other brain regions, but not temporal, occipital and interhemispheric tracts, showed a differential aging pattern in normals and patients indicating that the white matter pathology in these regions is not stable between the onset and the chronic state in schizophrenia. This suggests that tracts involved in the connectivity of the temporal lobe white matter deficits were already well in place in adolescent patients, while frontal lobe pathology continues to develop from adolescence to adulthood.

The thalamus and schizophrenia: current status of research.

The thalamus provides a nodal link for multiple functional circuits that are impaired in schizophrenia (SZ). Despite inconsistencies in the literature, a meta analysis suggests that the volume of the thalamus relative to that of the brain is decreased in SZ. Morphometric neuroimaging studies employing deformation, voxel-based and region of interest methodologies suggest that the volume deficit preferentially affects the thalamic regions containing the anterior and mediodorsal nuclei, and the pulvinar. Postmortem design-based stereological studies have produced mixed results regarding volume and neuronal deficits in these nuclei. This review examines those aspects of thalamic circuitry and function that suggest salience to SZ. Evidence for anomalies of thalamic structure and function obtained from postmortem and neuroimaging studies is then examined and directions for further research proposed.

Changes in relative glucose metabolic rate following cortisol administration in aging veterans with posttraumatic stress disorder: an FDG-PET neuroimaging study.

The authors aimed to examine central glucocorticoids effects by measuring relative glucose metabolic rate (rGMR) in the hippocampus, amygdala, and anterior cingulate cortex (ACC) and the relationship between amygdala and ACC activity. The participants were male combat veterans with and without PTSD, 52 to 81 years old. The authors utilized randomized, double-blind, placebo-controlled examinations of the rGMR response to 17.5 mg hydrocortisone (HCORT) using 2-Deoxy-2-[(18)F]fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) neuroimaging. Group differences in hemispheric laterality of rGMR were observed following placebo administration, reflecting lower rGMR in the right hippocampus and ventral amygdala, and higher rGMR in the left ventral amygdala in the PTSD+ group compared to the PTSD- group. HCORT reduced these group differences in laterality. The net effect of HCORT was to restore a normal inverse association between the ACC and amygdala in the PTSD+ group, but disrupt this neural network in the PTSD- group. The magnitude of improvement in working memory correlated with greater hemispheric laterality in the dorsal amygdala following HCORT in both groups. The restorative effects of HCORT on metabolism and working memory provide a rationale for examining the therapeutic benefits of glucocorticoid manipulation in aging PTSD patients.

Forty years of editorship of psychiatry research.

The astonishing 20 fold growth of the yearly published psychiatric research literature over the past four decades has been paralleled and facilitated by the internet application of electronic publishing. This personal history highlights the decade by decade 1978-2018 augmentation and erosion of this interelationship from the founding of Psychiatry Research to the present day.