Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes.

IMPORTANCE: The neuroinflammatory hypothesis of major depressive disorder is supported by several main findings. First, in humans and animals, activation of the immune system causes sickness behaviors that present during a major depressive episode (MDE), such as low mood, anhedonia, anorexia, and weight loss. Second, peripheral markers of inflammation are frequently reported in major depressive disorder. Third, neuroinflammatory illnesses are associated with high rates of MDEs. However, a fundamental limitation of the neuroinflammatory hypothesis is a paucity of evidence of brain inflammation during MDE. Translocator protein density measured by distribution volume (TSPO VT) is increased in activated microglia, an important aspect of neuroinflammation. OBJECTIVE: To determine whether TSPO VT is elevated in the prefrontal cortex, anterior cingulate cortex (ACC), and insula in patients with MDE secondary to major depressive disorder. DESIGN, SETTING, AND PARTICIPANTS: Case-control study in a tertiary care psychiatric hospital from May 1, 2010, through February 1, 2014. Twenty patients with MDE secondary to major depressive disorder and 20 healthy control participants underwent positron emission tomography with fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA). Patients with MDE were medication free for at least 6 weeks. All participants were otherwise healthy and nonsmokers. MAIN OUTCOMES AND MEASURES: Values of TSPO VT in the prefrontal cortex, ACC, and insula. RESULTS: In MDE, TSPO VT was significantly elevated in all brain regions examined (multivariate analysis of variance, F15,23 = 4.5 [P = .001]). The magnitude of TSPO VT elevation was 26% in the prefrontal cortex (mean [SD] TSPO VT, 12.5 [3.6] in patients with MDE and 10.0 [2.4] in controls), 32% in the ACC (mean [SD] TSPO VT, 12.3 [3.5] in patients with MDE and 9.3 [2.2] in controls), and 33% in the insula (mean [SD] TSPO VT, 12.9 [3.7] in patients with MDE and 9.7 [2.3] in controls). In MDE, greater TSPO VT in the ACC correlated with greater depression severity (r = 0.63 [P = .005]). CONCLUSIONS AND RELEVANCE: This finding provides the most compelling evidence to date of brain inflammation, and more specifically microglial activation, in MDE. This finding is important for improving treatment because it implies that therapeutics that reduce microglial activation should be promising for MDE. The correlation between higher ACC TSPO VT and the severity of MDE is consistent with the concept that neuroinflammation in specific regions may contribute to sickness behaviors that overlap with the symptoms of MDE.

Relationship of monoamine oxidase-A distribution volume to postpartum depression and postpartum crying.

Postpartum depression (PPD) has a prevalence rate of 13% and a similarly high proportion of women report a subclinical state of one or more major depressive episode symptoms. The aim was to investigate whether monoamine oxidase-A (MAO-A) VT, an index of MAO-A density, is increased in the prefrontal and anterior cingulate cortex (PFC and ACC), during PPD or when a PPD spectrum symptom, greater predisposition to crying, is present. MAO-A is an enzyme that increases in density after estrogen decline, and has several functions including creating oxidative stress, influencing apoptosis and monoamine metabolism. Fifty-seven women were recruited including 15 first-onset, antidepressant naive, PPD subjects, 12 postpartum healthy who cry due to sad mood, 15 asymptomatic postpartum healthy women, and 15 healthy women not recently pregnant. Each underwent [(11)C]-harmine positron emission tomography scanning to measure MAO-A VT. Both PPD and greater predisposition to crying were associated with greater MAO-A VT in the PFC and ACC (multivariate analysis of variance (MANOVA), group effect, F21,135=1.856; p=0.019; mean combined region elevation 21% and 14% in PPD and crying groups, respectively, relative to postpartum asymptomatic). Greater MAO-A VT in the PFC and ACC represents a new biomarker in PPD, and the PPD symptom of predisposition to crying. Novel strategies for preventing PPD (and some PPD symptoms) may be possible by avoiding environmental conditions that elevate MAO-A level and enhancing conditions that normalize MAO-A level. These findings also argue for clinical trials in PPD with the newer, well-tolerated MAO-A inhibitor antidepressants.

Limbic response to psychosocial stress in schizotypy: a functional magnetic resonance imaging study.

Psychological stress causes dopamine release in the striatum and is thought to play a role in susceptibility to psychotic illness. Previous work suggests that an elevated dopaminergic response to stress may index vulnerability to psychosis in certain individuals. With functional magnetic resonance imaging, we measured stress-induced changes in brain activity in healthy individuals at elevated risk of developing psychosis. Participants were 15 controls and 25 psychometric schizotypes: 12 with positive symptom schizotypy (perceptual aberrations) and 13 with negative symptom schizotypy (physical anhedonia), as determined by questionnaires (Chapman et al., 1976; Chapman and Chapman, 1978). In the scanner, participants performed the Montreal Imaging Stress Task and a matched sensory-motor control task. Measures of self-reported stress and salivary cortisol levels were taken throughout the experiment. All three groups showed significant increases in self-reported stress and significant fMRI signal change in the striatal, limbic and cortical regions. However, the Physical Anhedonia group showed greater stress-induced striatal and limbic deactivation than the other two groups. Deactivation in the striatum was significantly correlated with Physical Anhedonia score across all subjects. Our findings suggest the presence of abnormalities in striatal response to stress in negative symptom schizotypy.

Hemodynamic retrieval intensity in hippocampus is decreased by pre-exposure to autobiographic test items.

The purpose of this experiment was to assess the effects of probe familiarity, the consequences of having recently retrieved an autobiographic memory (AM), on subsequent recall. This was accomplished by replicating an earlier imaging experiment, using the same participants and memory probes. Subtractions between sessions showed significant pre-exposure effects (i.e., drop in BOLD signal intensity) in the prefrontal cortex, thalamus, cerebellum and other brain structures. Further, region of interest (ROI) analysis illustrated a significant decrease in neural activity in the hippocampus in both conditions. The results are discussed in terms of the pre-scan interview technique, a method applied in AM research to procure personal information. Although invaluable, we emphasize it must be used with caution as it can result in a loss of power. The widespread use of this method in AM research may explain why studies often fail to find evidence of significant responding in the hippocampus in response to memory probes. Alternatively, when activity in the hippocampus is reported, it often fails to differentiate between recent and remote memories. This point is of particular importance to the on-going consolidation debate, as it often centers on a failure to detect an effect in the hippocampus in one or both conditions.

Interference resolution in the elderly: evidence suggestive of differences in strategy on measures of prepotent inhibition and dual task processing.

The ability to effectively resolve interference was investigated in young and elderly participants using a test of inhibition and a dual task measure. The tasks stressed the ability to suppress prepotent responding, and balance primary and secondary task demands, respectively. Successful performance on both measures hinged on the ability to minimize the distraction generated between competing aspects of each task. Increasing demands resulted in performance decrements despite titration for individual differences in span size and generalized slowing. These were more pronounced on the hardest condition of each task, especially in older participants. Furthermore, the nature of the decrements suggested the use of different strategies between groups. It is argued that a fundamental source of the age-associated variability in cognition is due to compromised ability to effectively resolve interference, and cannot be sufficiently explained by memory span differences or generalized slowing.

'I find you to be very attractive... ' biases in compliance estimates to sexual offers / «Te encuentro muy atractivo/a » Disposición de aceptación ante ofertas sexuales

The classic experiments by Clark and Hatfield on sex differences in compliance to offers of dates, apartment visits, and casual sex, and the related informal project of Molzer served as the foundation for the present study. However, whereas individuals in these previous investigations directly approached opposite-sex participants, our research employed surveys to gauge compliance. A sample of 195 male and 179 female Austrian adults were provided with written forms of the Clark and Hatfield scenarios and asked to predict the rates of compliance on a thermometer scale ranging from 0% to 100%. Results indicated that compliance estimates are largely effected by the sex of the receiver to these offers, and to a lesser degree, participants’ age and relationship status. The sex of the participant did not significantly effect the results. Relative to the previous work, the compliance rate of males was overestimated, while that of females was underestimated. We offer explanations for the differences in findings between the original investigations and our research, discuss the importance of contextual factors as well as the generality of the Clark-Hatfield findings, especially with respect to females’ near-zero receptivity to explicit sexual offers, and point out the relevance of the current findings for health psychology

Los clasicos experimentos de Clark y Hatfield sobre las diferencias del sexo de acuerdo a las proposiciones de citas, visitas a departamentos, sexo casual, y la relación informal al proyecto de Molzer sirvió como base para el estudio presente, mas, sin embargo, las personas que en estas investigaciones previas tuvieron acceso directo con participantes del sexo opuesto, hemos empleado encuestas para medir niveles de aceptación. Un ejemplo de 195 varones y 179 mujeres austriacos adultos, les fueron entregados formas escritas con argumentos de Clark y Hatfield, a las cuales se les preguntó predecir los niveles de aceptación en una escala termométrica del 0 al 100%. Los resultados indicaron que, de acuerdo a las estimaciones, éstas son altamente causadas por el sexo del recipiente de estos ofrecimientos y a un menor grado por la edad de los participantes y su manera de relacionarse. El sexo de los participantes no tuvo causa significativa en el resultado en relación a la investigación anterior. La evaluación del consentimiento de los varones fue exagerado, mientras que aquella de las mujeres fue subestimado. Ofrecemos explicaciones por las diferencias de lo descubierto entre las investigaciones originales y nuestras propias investigaciones, discutir la importancia de los factores del contexto, así como la generalidad de los descubrimientos de Clark-Hatfield, especialmente con respecto a las mujeres con casi cero receptividad a los ofrecimientos explícitos de sexo, y subrayar la relevancia de los descubrimientos comunes para la salud psicológica

"I find you to be very attractive..." Biases in compliance estimates to sexual offers.

The classic experiments by Clark and Hatfield on sex differences in compliance to offers of dates, apartment visits, and casual sex, and the related informal project of Molzer served as the foundation for the present study. However, whereas individuals in these previous investigations directly approached opposite-sex participants, our research employed surveys to gauge compliance. A sample of 195 male and 179 female Austrian adults were provided with written forms of the Clark and Hatfield scenarios and asked to predict the rates of compliance on a thermometer scale ranging from 0% to 100%. Results indicated that compliance estimates are largely effected by the sex of the receiver to these offers, and to a lesser degree, participants' age and relationship status. The sex of the participant did not significantly effect the results. Relative to the previous work, the compliance rate of males was overestimated, while that of females was underestimated. We offer explanations for the differences in findings between the original investigations and our research, discuss the importance of contextual factors as well as the generality of the Clark-Hatfield findings, especially with respect to females' near-zero receptivity to explicit sexual offers, and point out the relevance of the current findings for health psychology.