Different preprocessing strategies lead to different conclusions: A [11C]DASB-PET reproducibility study.

Positron emission tomography (PET) neuroimaging provides unique possibilities to study biological processes in vivo under basal and interventional conditions. For quantification of PET data, researchers commonly apply different arrays of sequential data analytic methods ("preprocessing pipeline"), but it is often unknown how the choice of preprocessing affects the final outcome. Here, we use an available data set from a double-blind, randomized, placebo-controlled [11C]DASB-PET study as a case to evaluate how the choice of preprocessing affects the outcome of the study. We tested the impact of 384 commonly used preprocessing strategies on a previously reported positive association between the change from baseline in neocortical serotonin transporter binding determined with [11C]DASB-PET, and change in depressive symptoms, following a pharmacological sex hormone manipulation intervention in 30 women. The two preprocessing steps that were most critical for the outcome were motion correction and kinetic modeling of the dynamic PET data. We found that 36% of the applied preprocessing strategies replicated the originally reported finding (p < 0.05). For preprocessing strategies with motion correction, the replication percentage was 72%, whereas it was 0% for strategies without motion correction. In conclusion, the choice of preprocessing strategy can have a major impact on a study outcome.

The neural correlates of Neuroticism differ by sex prospectively mediate depressive symptoms among older women.

BACKGROUND: Mood disorders in old age increase the risk of morbidity and mortality for individuals and healthcare costs for society. Trait Neuroticism, a strong risk factor for such disorders into old age, shares common genetic variance with depression, but the more proximal biological mechanisms that mediate this connection are not well understood. Further, whether sex differences in the neural correlates of Neuroticism mirror sex differences in behavioral measures is unknown. The present research identifies sex differences in the stable neural activity associated with Neuroticism and tests whether this activity prospectively mediates Neuroticism and subsequent depressive symptoms. METHODS: A total of 100 (46 female) older participants (>55years) underwent a resting-state PET scan twice, approximately two years apart, and completed measures of Neuroticism and depressive symptoms twice. RESULTS: Replicating at both time points, Neuroticism correlated positively with resting-state regional cerebral blood-flow activity in the hippocampus and midbrain in women and the middle temporal gyrus in men. For women, hippocampal activity mediated the association between Neuroticism at baseline and depressive symptoms at follow-up. The reverse mediational model was not significant. CONCLUSIONS: Neuroticism was associated with stable neural activity in regions implicated in emotional processing and regulation for women but not men. Among women, Neuroticism prospectively predicted depressive symptoms through greater activity in the right hippocampus, suggesting one neural mechanism between Neuroticism and depression for women. Identifying responsible mechanisms for the association between Neuroticism and psychiatric disorders may help guide research on pharmacological interventions for such disorders across the lifespan.

Resting brain metabolic correlates of neuroticism and extraversion in young men.

Neuroticism and extraversion are two core dimensions of personality and are considered to be associated with emotional disorders. We investigated resting state brain metabolic correlates of neuroticism and extraversion using a positron emission tomography. Twenty healthy young men completed an F-flurodeoxyglucose-PET scan at rest and the Korean version of the revised Eysenck Personality Questionnaire. Neuroticism was negatively correlated with regional glucose metabolism in prefrontal regions including the medial prefrontal cortex. Extraversion was positively correlated with metabolism in the right putamen. These results suggest close associations between resting state brain activity in the prefrontal and striatal regions and specific personality traits and thus contribute to the understanding of the neurobiological bases of predisposition to psychiatric disorders.

Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder.

BACKGROUND: Serotonergic dysfunction has been associated with affective disorders. High trait neuroticism, as measured on personality inventories, is a risk factor for major depression. In this study we investigated whether neuroticism is associated with serotonin 2A receptor binding in brain regions of relevance for affective disorders. METHODS: Eighty-three healthy volunteers completed the standardized personality questionnaire NEO-PI-R (Revised NEO Personality Inventory) and underwent [(18)F]altanserin positron emission tomography imaging for assessment of serotonin 2A receptor binding. The correlation between the neuroticism score and frontolimbic serotonin 2A receptor binding was evaluated by multiple linear regression analysis with adjustment for age and gender. RESULTS: Neuroticism correlated positively with frontolimbic serotonin 2A receptor binding [r(79) = .24, p = .028]. Post hoc analysis of the contributions from the six constituent traits of neuroticism showed that the correlation was primarily driven by two of them: vulnerability and anxiety. Indeed, vulnerability, defined as a person's difficulties in coping with stress, displayed the strongest positive correlation, which remained significant after correction for multiple comparisons (r = .35, p = .009). CONCLUSIONS: In healthy subjects the personality dimension neuroticism and particularly its constituent trait, vulnerability, are positively associated with frontolimbic serotonin 2A binding. Our findings point to a neurobiological link between personality risk factors for affective disorder and the serotonergic transmitter system and identify the serotonin 2A receptor as a biomarker for vulnerability to affective disorder.

Relationship between neuroticism personality trait and serotonin transporter binding.

BACKGROUND: Personality trait is thought to be one of the important factors for vulnerability to depression. The relation between serotonin transporter (5-HTT) polymorphism and anxiety-related personality has been investigated in genetic research. In this study, we investigated the relation between in vivo regional 5-HTT binding in the brain and personality inventory measures in normal male volunteers. METHODS: Thirty-one healthy male volunteers underwent positron emission tomography scans with (11)C-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl) benzonitrile ([(11)C]DASB) to measure 5-HTT and completed revised NEO Personality Inventory. Correlation of [(11)C]DASB binding potentials (BP) with personality inventory measures was calculated using region-of-interest analysis and statistical parametric mapping based on the BP images. RESULTS: Neuroticism was positively correlated with 5-HTT binding in the thalamus (p = .004). No significant correlation was observed in any other brain region. Within the neuroticism dimension, the facet of depression was positively correlated with 5-HTT binding in the thalamus (p = .001). CONCLUSIONS: Subjects with higher thalamic 5-HTT binding are more likely to express higher levels of neuroticism and depressive feeling. Serotonin transporter binding in the thalamus might be a marker of vulnerability to depression.

Regional cerebral brain metabolism correlates of neuroticism and extraversion.

Factor-analytic approaches to human personality have consistently identified several core personality traits, such as Extraversion/Introversion, Neuroticism, Agreeableness, Consciousness, and Openness. There is an increasing recognition that certain personality traits may render individuals vulnerable to psychiatric disorders, including anxiety disorders and depression. Our purpose in this study was to explore correlates between the personality dimensions neuroticism and extraversion as assessed by the NEO Five-Factor Inventory (NEO-FFI) and resting regional cerebral glucose metabolism (rCMRglu) in healthy control subjects. Based on the anxiety and depression literatures, we predicted correlations with a network of brain structures, including ventral and medial prefrontal cortex (encompassing anterior cingulate cortex and orbitofrontal cortex), insular cortex, anterior temporal pole, ventral striatum, and the amygdala. Twenty healthy women completed an (18F)FDG (18F-fluorodeoxyglucose) positron emission tomography (PET) scan at rest and the NEO-FFI inventory. We investigated correlations between scores on NEO-FFI Neuroticism and Extraversion and rCMRglu using statistical parametric mapping (SPM99). Within a priori search territories, we found significant negative correlations between Neuroticism and rCMRglu in the insular cortex and positive correlations between Extraversion and rCMRglu in the orbitofrontal cortex. No significant correlations were found involving anterior cingulate, amygdala, or ventral striatum. Neuroticism and Extraversion are associated with activity in insular cortex and orbitofrontal cortex, respectively.

[Single photon emission computed tomography (SPECT) for the diagnosis of depressive disorders, neurotic and eating disorders]. / Tomografia emisyjna pojedynczego fotonu (SPECT) w diagnostyce zaburzen depresyjnych, nerwicowych oraz zaburzen odzywiania sie.

AIM: The aim of the study was to estimate usefulness of the single photon emission computed tomography (SPECT) for the diagnostics of the depressive disorders, neurotic and eating disorders, and detect the organic factors and correlation between cerebral hypoperfusion and results of Benton's and Bender's tests. MATERIAL AND METHOD: Study of 43 patients (33 women and 10 men) aged 16--59 years (SD+38, 65 +/- 11, 62) which were examined with single photon emission computed tomography (SPECT) and Benton's and Bender's tests during their treatment in the 1st Department of Psychiatry, Medical University in Gdansk in the years 2000 to 2003. 30 patients were diagnosed with depression (first depressive episodes--8, recurrent depressive disorders--9, organic depression--13), 8--neurotic disorders and 5--eating disorders. RESULTS AND CONCLUSIONS: SPECT in 38 (88,37%) cases showed hypoperfusion mostly on the left side and in the frontal region. Hypoperfusion in the recurrent depressive disorders was considerably greater (nearly significant) in comparison with the first depressive episodes. The correlation between hypoperfusion and CNS impairment examined with Benton's and Bender's tests was observed. The correlation coefficient of was 0.6845.

Personality influences limbic-cortical interactions during sad mood induction.

The current study examined limbic-cortical activation under transient emotional stress as a function of personality style. A ventral cingulate (Cg25)-centred limbic-cortical network was identified using positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) during a sad mood challenge that demonstrated differences for individuals selected for specific patterns of Negative and Positive emotional traits, indexed by the NEO Personality Inventory-Revised. Healthy subjects scoring both low on the dispositional Depression facet of Neuroticism (N3) and high on the Positive Emotions facet of Extraversion (E6) were compared to those scoring high on the Depression facet (N3) and low on Positive Emotions (E6), a combination of traits previously linked to normal variations in mood reactivity. Scan analyses were designed to further characterize known variations in Cg25 activity previously reported in studies of negative mood in both healthy subjects and depressed patients. A multivariate technique, partial least squares (PLS) demonstrated a divergent Cg25-mediated network that differentiated temperamentally negative (NAS) from temperamentally positive (PAS) subjects providing a potential neural link between these specific combinations of trait affective styles and vulnerability to depression.

[Prevalence and clinical significance of computerized tomography verified idiopathic calcinosis of the basal ganglia]. / Prävalenz und klinische Bedeutung computertomographisch gesicherter idiopathischer Stammganglienverkalkungen.

With increasing CT examinations of the cerebrum, the discovery of basal ganglia calcification becomes more frequent. In order to correlate these calcifications to the symptoms believed to be accompanied with Fahr's disease 2318 cranial CT scans were examined. There was an overall incidence of basal ganglia calcification of 12.5%. The most frequent location was the globus pallidus (96.4%). In the examined population there was no correlation found between the calcifications and symptoms having been described with striopallidentate calcifications.

Single photon emission tomography with 99mTc-exametazime in major depression and the pattern of brain activity underlying the psychotic/neurotic continuum.

Forty patients with a major depressive episode were investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, an intravenous ligand taken into brain in proportion to regional cerebral blood flow, thereby providing an estimate of regional metabolism. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. They also completed a range of neuropsychological tests. They were compared with 20 control subjects matched for age, gender, premorbid intelligence and education. The uptake of 99mTc-exametazime was expressed for a range of anatomically defined regions of interest relative to calcarine/occipital cortex. The depressed group showed reduced uptake in the majority of cortical and sub-cortical regions examined, most significantly in temporal, inferior frontal and parietal areas. Unexpectedly, there was a strong positive association between uptake and scores on the Newcastle scale, especially in cingulate areas and frontal cortex. After removing the variance attributable to the Newcastle ratings, however, there emerged the expected negative association between Hamilton scores and anterior tracer uptake. The associations between neuropsychological impairment and regional brain uptake of tracer in part reflected the pattern seen with the Newcastle scale: for example, impairment of memory function correlated with higher uptake into posterior cingulate areas. We propose that depressive illness may be characterised by two processes. One leads to an overall reduction in anterior neocortical function, perhaps related to symptom severity. The other mechanism is manifest as relatively increased function, most notably within cingulate and frontal areas of the cerebral cortex in association with psychotic symptoms. The findings offer new understanding of the brain states underlying depressive illness and a potential focus to subsequent neuropharmacological analysis.

[Study of the morphological characteristics of the brain in patients with schizophrenia by the method of computerized tomography]. / Izuchenie morfologicheskikh osobennostei golovnogo mozga bo'lnykh shizofreniei metodom kom'piuternoi tomografii.

The article presents the data on 57 schizophrenic and 26 neurotic patients investigated by computerized tomography (CT). Only 4 of the neurosis patients (15.4%) displayed minor CT changes. In 45 schizophrenic patients (78.9%) CT changes were detected varying in their markedness. Most frequent were enlargement of cortical sulci (39 patients). Brain ventricles were dilated in 18 patients, cistern, retropineal and retrosellar spaces dilated in 13. Deficit disorders prevailed clinically in patients whose CT scans showed distinct signs of cortical and subcortical atrophy. These patients also had signs of organic pathology accumulated in the early childhood anamnesis. The authors suggest that this was a factor increasing the brain system' susceptibility to destructive impact of endogenous events.