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Side effects to antidepressant medications are common and can impact the prognosis of successful treatment outcome in people with major depressive disorder (MDD). However, few studies have investigated the severity of side effects over the course of treatment and their association with treatment outcome. Here we assessed the severity of side effects and the impact of treatment type and anxiety symptoms over the course of treatment, as well as whether side effects were associated with treatment outcome. Participants were N = 1008 adults with a current diagnosis of single-episode or recurrent, nonpsychotic MDD. Participants were randomised to receive escitalopram, sertraline, or venlafaxine-extended release with equal probability and reassessed at 8 weeks regarding Hamilton Rating Scale Depression (HRSD17) and Quick Inventory of Depressive Symptomatology (QIDS-SR16) remission and response. Severity of side effects were assessed using the Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale and assessed at day 4 and weeks 2, 4, 6, and 8. Frequency, intensity, and burden of side effects were greatest at week 2, then only frequency and intensity of side effects gradually decreased up to week 6. Treatment type and anxiety symptoms did not impact the severity of side effects. A greater burden—but not frequency or intensity—of side effects was associated with poorer treatment outcome and as early as 4 days post-treatment. Together, this work provides an informative mapping of the progression of side effects throughout the treatment course and their association with treatment outcome. Importantly, the burden of side effects that are present as early as 4 days post-treatment predicts poorer treatment outcome and should be monitored closely. iSPOT-D: Registry name: ClinicalTrials.gov. Registration number: NCT00693849.

This study tested the extent to which coached participants can simulate the neural responses of participants with posttraumatic stress disorder (PTSD) when they are presented with signals of fear. Functional magnetic resonance imaging (fMRI) was used to study blood oxygenation level-dependent signal during the presentations of fearful and neutral faces under both conscious and nonconscious (masked) conditions. Participants comprised 12 patients with PTSD and 12 trauma-exposed controls who were instructed to simulate PTSD. During conscious fear processing, simulators showed greater activation in the left amygdala and medial prefrontal cortex (MPFC) than PTSD participants. By contrast, during nonconscious processing, PTSD participants had greater MPFC activation than simulators. These findings suggest that coached simulators produce a profile of ‘over-responding’ to fear when controlled conscious processing is possible, but are not able to simulate the exaggerated medial prefrontal responses observed in PTSD participants under conditions of nonconscious processing.

Previous studies have shown that exposure to early life stress (ELS) is associated with reduced volume of brain regions critical for information processing, memory and emotional function. Further, recent studies from our lab utilizing diffusion tensor imaging (DTI) have found alterations in the microstructural integrity of white matter pathways among adults exposed to ELS. However, it is not clear if these relationships extend to children and adolescents, and it is also unclear if these DTI abnormalities are associated with cognitive performance. The present study examined the relationship between ELS and the microstructural integrity of the corpus callosum among a sample of otherwise healthy controls between the ages of 8 and 73. The participants were subdivided into four age groups (8–12, 13–18, 19–50, 51–73). Individuals with three or more ELS events were compared to individuals with fewer than 3 ELS events on fractional anisotropy (FA) in the genu of the corpus callosum. Separate analyses examined the two groups on tests of verbal memory, information processing speed, psychomotor speed and cognitive flexibility. Results revealed that the youngest group and the oldest group of individuals with ELS exhibited significantly lower FA in the genu compared to individuals without ELS. However, there were no group differences on any of the cognitive tasks. Our results indicate that ELS is related to subtle alterations in brain structure, but not function. The effects found with regard to DTI occurred during periods of critical age-related developmental windows.

Assessment of neurocognitive functioning is a critical task in many clinical, educational, service, and industrial settings. We report on descriptive and validation data of a new, World-Wide-Web-based, comprehensive battery of neurocognitive functioning, WebNeuro, that can be used in both applied and research contexts. Fifty healthy control participants completed both WebNeuro, and an established non-Internet-based computerized cognitive assessment battery, IntegNeuro, that uses a touchscreen platform. Results indicated comparability across the two batteries, in terms of critical single test scores, factor analysis derived indices, overall performance scores, and sex differences. These results support the validity of WebNeuro as a neurocognitive assessment measure. Advantages of its use in applied and research settings are discussed.

A recently developed fragmentary decomposition method is employed to analyse single-trial event-related potentials (ERPs), thereby extending the traditional method of averaging. Using a conventional auditory oddball paradigm with 40 target stimuli, single-trial ERPs in 40 normal subjects were analysed for midline scalp (Fz, Cz and Pz) recording sites. The normalization effect, reported in our previous study of eye blink EMGs and proposed to be a characteristic property of a wide class of non-stationary physiological processes, was found to apply to these single-trial ERPs. Fragmentary decomposition of single-trial ERPs may be regarded as re-statement of the normalization effect. This allows both pre-stimulus EEGs and post-stimulus ERPs to be regarded as overlapping generic mass potentials (GMPs), with a characteristic Gaussian amplitude spectrum. On theoretical and empirical grounds we uniquely deduce a model GMP using an introduced “bud” function, and physically support it by the resting and transient conditions. The model takes into account the shape of the component, which suggests a simple relationship between the peak latency and the time of the component onset. Given that GMPs may be manipulated and sorted out, we present principles of the fragmentary synthesis, i.e. probabilistic ERP reconstructions on the basis of individual and ensemble properties of its identified components. Summarizing the component quantification in the form of the dynamic model provides for the first time the opportunity to quantify all significant components in single-trial ERPs. This method of single-trial analysis opens up new possibilities of exploring the dynamical ERP changes within a recording trial, particularly in late component “cognitive” paradigms.