Functional and Structural Neural Network Characterization of Serotonin Transporter Knockout Rats.

Functional and structural neural network characterization of serotonin transporter knockout rats.

PLoS One. 2013; 8(2): e57780
van der Marel K, Homberg JR, Otte WM, Dijkhuizen RM

Brain serotonin homeostasis is crucially maintained by the serotonin transporter (5-HTT), and its down-regulation has been linked to increased vulnerability for anxiety- and depression-related behavior. Studies in 5-HTT knockout (5-HTT) rodents have associated inherited reduced functional expression of 5-HTT with increased sensitivity to adverse as well as rewarding environmental stimuli, and in particular cocaine hyperresponsivity. 5-HTT down-regulation may affect normal neuronal wiring of implicated corticolimbic cerebral structures. To further our understanding of its contribution to potential alterations in basal functional and structural properties of neural network configurations, we applied resting-state functional MRI (fMRI), pharmacological MRI of cocaine-induced activation, and diffusion tensor imaging (DTI) in 5-HTT rats and wild-type controls (5-HTT). We found that baseline functional connectivity values and cocaine-induced neural activity within the corticolimbic network was not significantly altered in 5-HTT versus 5-HTT rats. Similarly, DTI revealed mostly intact white matter structural integrity, except for a reduced fractional anisotropy in the genu of the corpus callosum of 5-HTT rats. At the macroscopic level, analyses of complex graphs constructed from either functional connectivity values or structural DTI-based tractography results revealed that key properties of brain network organization were essentially similar between 5-HTT and 5-HTT rats. The individual tests for differences between 5-HTT and 5-HTT rats were capable of detecting significant effects ranging from 5.8% (fractional anisotropy) to 26.1% (pharmacological MRI) and 29.3% (functional connectivity). Tentatively, lower fractional anisotropy in the genu of the corpus callosum could indicate a reduced capacity for information integration across hemispheres in 5-HTT rats. Overall, the comparison of 5-HTT and wild-type rats suggests mostly limited effects of 5-HTT genotype on MRI-based measures of brain morphology and function. HubMed – depression


The Effectiveness of Internet Cognitive Behavioural Therapy (iCBT) for Depression in Primary Care: A Quality Assurance Study.

PLoS One. 2013; 8(2): e57447
Williams AD, Andrews G

Depression is a common, recurrent, and debilitating problem and Internet delivered cognitive behaviour therapy (iCBT) could offer one solution. There are at least 25 controlled trials that demonstrate the of iCBT. The aim of the current paper was to evaluate the of an iCBT Program in primary care that had been demonstrated to be efficacious in two randomized controlled trials (RCTs).Quality assurance data from 359 patients prescribed the Sadness Program in Australia from October 2010 to November 2011 were included.Intent-to-treat marginal model analyses demonstrated significant reductions in depressive symptoms (PHQ9), distress (K10), and impairment (WHODAS-II) with medium-large effect sizes (Cohen’s ?=?.51-1.13.), even in severe and/or suicidal patients (Cohen’s ?=?.50-1.49.) Secondary analyses on patients who completed all 6 lessons showed levels of clinically significant change as indexed by established criteria for remission, recovery, and reliable change.The Sadness Program is effective when prescribed by primary care practitioners and is consistent with a cost-effective stepped-care framework. HubMed – depression


Liver-targeting of interferon-alpha with tissue-specific domain antibodies.

PLoS One. 2013; 8(2): e57263
Coulstock E, Sosabowski J, Ove?ka M, Prince R, Goodall L, Mudd C, Sepp A, Davies M, Foster J, Burnet J, Dunlevy G, Walker A

Interferon alpha (IFN?) is used for the treatment of hepatitis C infection and whilst efficacious it is associated with multiple adverse events including reduced leukocyte, erythrocyte, and platelet counts, fatigue, and depression. These events are most likely caused by systemic exposure to interferon. We therefore hypothesise that targeting the therapeutic directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFN? therapy. We genetically fused IFN to a domain antibody (dAb) specific to a hepatocyte restricted antigen, asialoglycoprotein receptor (ASGPR). Our results show that the murine IFN?2 homolog (mIFN?2) fused to an ASGPR specific dAb, termed DOM26h-196-61, could be expressed in mammalian tissue culture systems and retains the desirable biophysical properties and activity of both fusion partners when measured . Furthermore a clear increase in targeting of the liver by mIFN?2-ASGPR dAb fusion protein, compared to that observed with either unfused mIFN?2 or mIFN?2 fused to an isotype control dAb VD2 (which does not bind ASGPR) was demonstrated using microSPECT imaging. We suggest that these findings may be applicable in the development of a liver-targeted human IFN molecule with improved safety and patient compliance in comparison to the current standard of care, which could ultimately be used as a treatment for human hepatitis virus infections. HubMed – depression


The diagnosis and treatment of bipolar disorder: recommendations from the current s3 guideline.

Dtsch Arztebl Int. 2013 Feb; 110(6): 92-100
Pfennig A, Bschor T, Falkai P, Bauer M

Bipolar disorder is a serious mental illness, characterized by frequent recurrences and major comorbidities. Its consequences can include suicide.An S3 guideline for the treatment of bipolar disorder was developed on the basis of a systematic literature search, evaluation of the retrieved publications, and a formal consensus-finding procedure. Several thousand publications were screened, and 611 were included in the analysis, including 145 randomized controlled trials (RCT).Bipolar disorder should be diagnosed as early as possible. The most extensive evidence is available for pharmacological monotherapy; there is little evidence for combination therapy, which is nonetheless commonly given. The appropriate treatment may include long-term maintenance treatment, if indicated. The treatment of mania should begin with one of the recommended mood stabilizers or antipsychotic drugs; the number needed to treat (NNT) is 3 to 13 for three weeks of treatment with lithium or atypical antipsychotic drugs. The treatment of bipolar depression should begin with quetiapine (NNT = 5 to 7 for eight weeks of treatment), unless the patient is already under mood-stabilizing treatment that can be optimized. Further options in the treatment of bipolar depression are the recommended mood stabilizers, atypical antipsychotic drugs, and antidepressants. For maintenance treatment, lithium should be used preferentially (NNT = 14 for 12 months of treatment and 3 for 24 months of treatment), although other mood stabilizers or atypical antipsychotic drugs can be given as well. Psychotherapy (in addition to any pharmacological treatment) is recommended with the main goals of long-term stabilization, prevention of new episodes, and management of suicidality. In view of the current mental health care situation in Germany and the findings of studies from other countries, it is clear that there is a need for prompt access to need-based, complex and multimodal care structures. Patients and their families need to be adequately informed and should participate in psychiatric decision-making.Better patient care is needed to improve the course of the disease, resulting in better psychosocial function. There is a need for further high-quality clinical trials on topics relevant to routine clinical practice. HubMed – depression