Abstract Background Relatively few studies have focused on the validation of psychometric scales measuring depression during pregnancy. The aim of this review was to critically appraise and review ...antenatal validation studies of the Edinburgh Postnatal Depression Scale (EPDS). Methods A systematic search was performed in MEDLINE, EMBASE, ISI, CINAHL, SCIELO and PsyCINFO for the period 1987–2013. Results Eleven validation studies met the inclusion criteria. The study design varied between studies. Sensitivity and specificity estimates also varied between 64–100% and 73–100%, respectively. The confidence interval estimates also showed a high degree of variability. Our estimates suggest lower positive predictive values in the general population than those reported in the validation study samples. The sensitivity values in validation studies of the EPDS show fairly large variability, ranging from good to acceptable. Limitations Future studies should have larger sample sizes and include both representative and clinical samples and look at the psychometric performance of the EPDS in each trimester. Conclusions Due to differences in study design and variation in the cultural/linguistic adaptation, uncertainty remains regarding the comparability of the sensitivity and specificity estimates of different EPDS versions. Future studies should have larger sample sizes, include both representative and clinical samples, and look at the psychometric performance of the EPDS in each trimester. Reporting quality, especially as regards checks to ensure content validity, should be improved.
Both people with autism spectrum conditions (ASC) and borderline personality disorder (BPD) are significantly challenged in terms of understanding and responding to emotions and in interpersonal ...functioning.
To compare ASC, BPD, and comorbid patients in terms of autistic traits, empathy, and systemizing.
624 ASC, 23 BPD, and 16 comorbid (ASC+BPD) patients, and 2,081 neurotypical controls (NC) filled in the Autism Spectrum Quotient (AQ), the Empathy Quotient (EQ) and the Systemizing Quotient-Revised (SQ-R).
On the AQ, the comorbid group scored higher than the ASC group, who in turn scored higher than the BPD group, who scored higher than controls. On the EQ, we found the comorbid and ASC groups scored lower than the BPD group, who were not different from controls. Finally, on the SQ-R, we found the ASC and BPD group both scored higher than controls.
Similar to ASC, BPD patients have elevated autistic traits and a strong drive to systemize, suggesting an overlap between BPD and ASC.
Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, ...and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.
In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various ...neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.
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ABCG2/BCRP is an ABC transporter that plays an important role in tissue protection by exporting endogenous substrates and xenobiotics. ABCG2 is of major interest due to its ...involvement in multidrug resistance (MDR), and understanding its complex efflux mechanism is essential to preventing MDR and drug-drug interactions (DDI). ABCG2 export is characterized by two major conformational transitions between inward- and outward-facing states, the structures of which have been resolved. Yet, the entire transport cycle has not been characterized to date. Our study bridges the gap between the two extreme conformations by studying connecting pathways. We developed an innovative approach to enhance molecular dynamics simulations, ‘kinetically excited targeted molecular dynamics’, and successfully simulated the transitions between inward- and outward-facing states in both directions and the transport of the endogenous substrate estrone 3-sulfate. We discovered an additional pocket between the two substrate-binding cavities and found that the presence of the substrate in the first cavity is essential to couple the movements between the nucleotide-binding and transmembrane domains. Our study shed new light on the complex efflux mechanism, and we provided transition pathways that can help to identify novel substrates and inhibitors of ABCG2 and probe new drug candidates for MDR and DDI.
Borderline personality disorder (BPD) is a common psychiatric condition associated with self-harm. Self-harm is poorly understood and there is currently no treatment for acute presentations with ...self-harm urges.
By using a new task (Self-relevant Task; SRT), to explore emotions related to one's own person (PERSON task) and body (BODY task), to study the correlations of these emotions, specifically disgust, with self-harm urge level changes, and to test the task's potential to be developed into an experimental model of self-harming for treatment trials.
17 BPD patients, 27 major depressive disorder (MDD) patients, and 25 healthy volunteers performed the SRT. Emotion labels were extracted from task narratives and disgust and self-harm urge level changes measured by visual analogue scales. We used validated rating scales to measure symptom severity.
The SRT was effective at inducing negative emotions and self-harm urge changes. Self-harm urge changes correlated with borderline symptom severity. Post-task disgust levels on the visual analogue scales were higher in BPD patients than in healthy controls in the PERSON task, and higher than in both control groups in the BODY task. Changes in disgust levels during the task were significantly greater in the patient groups. Post-task disgust levels or changes in disgust were not associated with self-harm urge changes (except the latter in MDD in the PERSON task), but self-harm urge changes and disgust (but no other emotion) narrative labels were on a whole sample level.
Although associations with the analogue scale measures were not significant, self-disgust reported in the narrative of patients may be associated with a higher probability of self-harm urges. Further research with larger sample sizes is needed to confirm this relationship and to examine whether reducing self-disgust could reduce self-harm urges. The SRT was effective and safe, and could be standardized for experimental studies.
Highlights • The majority of the GHRH perikarya received contacting somatostatinergic axonal varicosities in the human hypothalamus. • These juxtapositions may represent the morphological substrate ...of the somatostatin-influenced GHRH secretion in humans. • In contrast, GHRH fibers commonly avoided the close vicinity of the somatostatinergic perikarya. • This phenomenon indicates that GHRH does not have significant direct influence on the hypothalamic somatostatin secretion. • GHRH may regulate somatostatin release by either hormonal route or indirectly, via other neurotransmitter systems.
Impairments in mismatch negativity (MMN) generation have been consistently reported in patients with schizophrenia. However, underlying oscillatory activity of MMN deficits in schizophrenia and the ...relationship with cognitive impairments have not been investigated in detail. Time-frequency power and phase analyses can provide more detailed measures of brain dynamics of MMN deficits in schizophrenia.
21 patients with schizophrenia and 21 healthy controls were tested with a roving frequency paradigm to generate MMN. Time-frequency domain power and phase-locking (PL) analysis was performed on all trials using short-time Fourier transforms with Hanning window tapering. A comprehensive battery (CANTAB) was used to assess neurocognitive functioning.
Mean MMN amplitude was significantly lower in patients with schizophrenia (95% CI 0.18 - 0.77). Patients showed significantly lower EEG power (95% CI -1.02 - -0.014) in the ~4-7 Hz frequency range (theta band) between 170 and 210 ms. Patients with schizophrenia showed cognitive impairment in multiple domains of CANTAB. However, MMN impairments in amplitude and power were not correlated with clinical measures, medication dose, social functioning or neurocognitive performance.
The findings from this study suggested that while MMN may be a useful marker to probe NMDA receptor mediated mechanisms and associated impairments in gain control and perceptual changes, it may not be a useful marker in association with clinical or cognitive changes. Trial-by-trial EEG power analysis can be used as a measure of brain dynamics underlying MMN deficits which also can have implications for the use of MMN as a biomarker for drug discovery.
Little is known about episodic and semantic memory in the early predementia stage of Alzheimer's disease (AD), which is referred to as mild cognitive impairment (MCI). To explore person knowledge, ...item recognition and spatial associative memory, we designed the Face Place Test (FPT). A total of 75 subjects participated: 22 patients with early AD, 24 with MCI and 29 matched controls.
As predicted, AD patients showed significant deficits in person naming, item recognition and recall of spatial location (placing). Surprisingly, subjects with MCI were also impaired on all components. There was no significant difference between AD and MCI except on the placing component. Analysis of the relationship between semantic (naming) and episodic (recognition and placing) components of the FPT revealed a significant association between the two episodic tasks, but not between episodic and semantic performance.
Patients with MCI show deficits of episodic and semantic memory. The extent of impairment suggests dysfunction beyond the medial temporal lobe. The FPT might form the basis of a sensitive early indicator of AD.
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