144 research outputs found
Lurasidone for the treatment of bipolar depression: an evidence-based review
Get PDFBipolar disorder (BD) is a debilitating and difficult-to-treat psychiatric disease that presents a serious burden to patients’ lives as well as health care systems around the world. The essential diagnostic criterion for BD is episodes of mania or hypomania; however, the patients report that the majority of their time is spent in a depressive phase. Current treatment options for this component of BD have yet to achieve satisfactory remission rates. Lurasidone is a drug in the benzisothiazole class approved by the US Food and Drug Administration in June 2013 for the acute treatment of bipolar depression. Its pharmacological profile features high-affinity antagonism at D[subscript 2], 5-HT[subscript 2A], and 5-HT[subscript 7] receptors; moderate-affinity antagonism at α[subscript 2C]-adrenergic receptors; low- to very low-affinity antagonism at α[subscript 1A]-adrenergic, α[subscript 2A]-adrenergic, H[subscript 1], M[subscript 1], and 5-HT[subscript 2C] receptors; and high-affinity partial agonism at 5-HT1A. Preliminary findings from two recent double-blinded clinical trials suggest that lurasidone is efficacious in treating bipolar I depression, with clinical effects manifesting as early as the first 2–3 weeks of treatment (as measured by the Montgomery–Åsberg Depression Rating Scale and Clinical Global Impressions Scale for use in bipolar illness). Its therapeutic benefit appears to be comparable to the current US Food and Drug Administration-indicated treatments: quetiapine and olanzapine–fluoxetine, according to a measure of effect size known as number needed to treat. These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea. Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels. Lurasidone holds clinical potential as a novel, efficacious pharmacological treatment for bipolar depression. However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed
Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive disorder (OCD)
Get PDFDeep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region
Estimating a dynamic state to relate neural spiking activity to behavioral signals during cognitive tasks
No full textElectronic health records and stratified psychiatry: bridge to precision treatment?
Get PDFThe use of a stratified psychiatry approach that combines electronic health records (EHR) data with machine learning (ML) is one potentially fruitful path toward rapidly improving precision treatment in clinical practice. This strategy, however, requires confronting pervasive methodological flaws as well as deficiencies in transparency and reporting in the current conduct of ML-based studies for treatment prediction. EHR data shares many of the same data quality issues as other types of data used in ML prediction, plus some unique challenges. To fully leverage EHR datas power for patient stratification, increased attention to data quality and collection of patient-reported outcome data is needed
Caspian sea-level changes during the last millennium: Historical and geological evidence from the south Caspian Sea
Get PDFThis article is made available through the Brunel Open Access Publishing Fund. Copyright @ Author(s) 2013. This work is distributed
under the Creative Commons Attribution 3.0 License.Historical literature may constitute a valuable
source of information to reconstruct sea-level changes. Here,
historical documents and geological records have been combined
to reconstruct Caspian sea-level (CSL) changes during
the last millennium. In addition to a comprehensive literature
review, new data from two short sediment cores were
obtained from the south-eastern Caspian coast to identify
coastal change driven by water-level changes and to compare
the results with other geological and historical findings.
The overall results indicate a high-stand during the Little Ice
Age, up to −21m (and extra rises due to manmade river
avulsion), with a −28m low-stand during the Medieval Climate
Anomaly, while presently the CSL stands at −26.5 m.
A comparison of the CSL curve with other lake systems and
proxy records suggests that the main sea-level oscillations
are essentially paced by solar irradiance. Although the major
controller of the long-term CSL changes is driven by climatological
factors, the seismicity of the basin creates local
changes in base level. These local base-level changes should be considered in any CSL reconstruction
Closing the Loop in Deep Brain Stimulation for Psychiatric Disorders: Lessons from Motor Neural Prosthetics
No full textCharacterization of fear conditioning and fear extinction by analysis of electrodermal activity
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Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression
No full textMajor depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care
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