SOURCE: DocGuide
May 2015

AIM 
Previous studies have shown an association between childhood attention deficit hyperactivity disorder (ADHD) and a down-regulated hypothalamus-pituitary-adrenal axis (HPA-axis) with low diurnal cortisol levels. Given the role of the FK506 binding protein 5 (FKBP5) as an important regulator of the negative feedback system of the HPA-axis, we set out to investigate possible associations between single nucleotide polymorphisms (SNPs) in FKBP5 in relation to ADHD and diurnal cortisol levels.

METHODS 
Children with ADHD (n=81) and healthy comparisons (n=88) collected saliva four times during a regular school day for radioimmunoassay analysis of cortisol and for genotyping of five SNPs in FKBP5 (rs9296158, rs1360780, rs9470080, rs7748266 and rs9394309).

RESULTS 
We found associations between SNP genotypes and ADHD as well as between genotypes and diurnal cortisol levels. One of these SNPs, rs9470080, was significantly associated with both ADHD and lower cortisol levels.

CONCLUSION 
This study contributes to previous findings on a down-regulated HPA-axis in children with ADHD by demonstrating an association between ADHD, lower cortisol levels and SNPs of the FKBP5-gene. The relevance of these findings for the development and shaping of ADHD symptoms need to be approached in larger samples, preferably also taking stress reactivity into consideration. This article is protected by copyright. All rights reserved.

SOURCE: MPR

Aromatic-turmerone, a major bioactive compound of turmeric (Curcuma longa) and a common ingredient in curry, could help in treating neurodegenerative disease by regenerating endogenous neural stem cells (NSCs). 

A recent study injected rats with a single intracerebroventricular injection of aromatic-turmerone and endogenous NSCs activity was traced with noninvasive positron emission tomography (PET) imaging and the tracer [18F]-fluoro-L-thymidine ([18F]FLT). The data suggests that aromatic-turmerone promoted neuronal differentiation of NSCs; the NSCs were seen to be mobilized from the subventricular zone (SVZ) and the hippocampus of the adult rats. However, it is not known if these results can be replicated in human trials or if the increased NSC activity could help patients with neurodegenerative diseases such as Alzheimer’s.

SOURCE: HealthDay News

Key connections between brain networks seem to mature more slowly in young people with attention deficit hyperactivity disorder (ADHD), according to a new study.

These connections within and between certain brain networks control internally directed thought, such as daydreaming, and influence the ability to focus on external tasks. This slower development of these important connections could shed light on why those with ADHD are easily distracted or have trouble staying focused, the researchers said.

"It is particularly noteworthy that the networks we found to have lagging maturation in ADHD are linked to the very behaviors that are the symptoms of ADHD," said the study's lead author, Dr. Chandra Sripada, an assistant professor and psychiatrist at the University of Michigan in Ann Arbor.

The researchers said their findings might one day help doctors use brain scans to diagnose ADHD and track how well patients respond to treatment.

"We and others are interested in understanding the neural mechanisms of ADHD in hopes that we can contribute to better diagnosis and treatment," Sripada said in a university news release. "The results of this study set the stage for the next phase of this research, which is to examine individual components of the networks that have the maturational lag."

The goal is "to examine this phenomenon in a more fine-grained way that might lead us to a true biological marker, or neuromarker, for ADHD," she added.

ADHD, which affects 3 to 5 percent of American children, is more common in boys than girls, according to the U.S. Institutes of Health. Kids with the disorder are unusually restless and have difficulty controlling their behavior, making it hard to succeed academically and socially.

Using brain imaging technology called functional MRI, the researchers scanned the brains of 275 children and teens with ADHD and 481 young people without the neurobehavioral disorder. They identified key connections between brain networks that took longer to mature in the brains of the kids with ADHD.

The study, published Sept. 15 in the Proceedings of the National Academy of Sciences, found slower development of connections within the internally focused network, called the default mode network. A lag was also identified in the development of connections between the default mode network and two networks that process externally focused tasks, also known as task-positive networks.

The study authors said the methods used in this study could also be used to investigate other disorders involving problems with brain connectivity, such as autism and schizophrenia.

Source: Neurocase 
​June 2015

Patients with frontotemporal lobar degeneration (FTLD) can show superimposed amyloid pathology, though the impact of amyloid on the clinical presentation of FTLD is not well characterized. This cross-sectional case-control study compared clinical features, fluorodeoxyglucose-positron emission tomography metabolism and gray matter volume loss in 30 patients with familial FTLD in whom amyloid status was confirmed with autopsy or Pittsburgh compound B-PET. Compared to the amyloid-negative patients, the amyloid-positive patients performed significantly worse on several cognitive tests and showed hypometabolism and volume loss in more temporoparietal regions. Our results suggest that in FTLD amyloid positivity is associated with a more Alzheimer's disease-like pattern of neurodegeneration.

REFERENCES
Amyloid in dementia associated with familial FTLD: not an innocent bystander; Naasan G, Rabinovici G, Ghosh P, Elofson J, Miller B, Coppola G, Karydas A, Fong J, Perry D, Lee S, Yokoyama J, Seeley W, Kramer J, Weiner M, Schuff N, Jagust W, Grinberg L, Pribadi M, Yang Z, Sears R, Klein E, Wojta K, Rosen H; Neurocase 1-8 (Jun 2015)

Source: DGNews 
June 16, 2015

A magnetic resonance imaging (MRI) study has found distinct injury patterns in the brains of people with concussion-related depression and anxiety.

The findings, published online in the journal Radiology, may lead the way to improved treatment and understanding of these common disorders.

Post-concussion psychiatric disorders can be extremely disabling. The mechanisms underlying these changes after a mild traumatic brain injury (TBI) are not sufficiently understood, and conventional MRI results in most of these patients are normal.

Lea M. Alhilali, MD, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, and colleagues used diffusion tensor imaging (DTI) to see if injuries to the nerves may be the root cause of these post-traumatic depression and anxiety symptoms.

The researchers obtained DTI and neurocognitive testing results for 45 patients with TBI, including 38 with irritability, 32 with depression, and 18 with anxiety, and compared the results with those of 29 patients with TBI who had no neuropsychiatric symptoms.

“Using other concussion patients as our controls was a big advantage of our study,” said Dr. Alhilali. “When you are able to study a similar population with similar risk factors, you get much more reliable results.”

The researchers saw unique white matter injury patterns in the patients who had depression or anxiety. Compared with controls, patients with depression had decreased fractional anisotropy (FA), a measure of the structural integrity of white matter connections, around an area near the deep gray matter of the brain that is strongly associated with the brain's reward circuit.

“The regions injured in concussion patients with depression were very similar to those of people with non-traumatic major depression disorder,” said Dr. Alhilali. “This suggests there may be similar mechanisms to non-trauma and trauma-dependent depression that may help guide treatment.”

Patients with anxiety had diminished FA in the vermis. Since the vermis has not been associated with dysfunction in non-traumatic anxiety disorders, this finding may indicate that different treatment targets are required for patients with anxiety after trauma, the researchers said.

No regions of significantly decreased FA were seen in patients with irritability relative to the control subjects.

“There are two major implications for this study,” said Dr. Alhilali. “First, it gives us insight into how abnormalities in the brain occur after trauma, and second, it shows that treatments for non-trauma patients with neuropsychological symptoms may be applicable to some concussion patients.”

The study ​also raises the possibility that some people diagnosed with non-traumatic depression may actually have experienced a subclinical traumatic event at some point earlier in their lives that may have contributed to the development of depression, she noted.

In the future, the researchers hope to compare DTI findings in concussion patients with depression with those of people who have non-trauma-related depressive disorders.

SOURCE: Radiological Society of North America
​

BACKGROUND
Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have been shown to have a negative impact in terms of quality of life, compliance with anti-cancer treatment, suicide risk and likely even the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy and tolerability of antidepressants in this population group are few and often report conflicting results.

OBJECTIVES
To assess the effects and acceptability of antidepressants for treating depressive symptoms in adults (18 years or older) with cancer (any site and stage).

SEARCH METHODS
We searched the following electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 3), MEDLINE Ovid (1946 to April week 3, 2014), EMBASE Ovid (1980 to 2014 week 17) and PsycINFO Ovid (1987 to April week 4, 2014). We additionally handsearched the trial databases of the most relevant national, international and pharmaceutical company trial registers and drug-approving agencies for published, unpublished and ongoing controlled trials.

SELECTION CRITERIA
We included RCTs allocating adults (18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis) comparing antidepressants versus placebo, or antidepressants versus other antidepressants.

DATA COLLECTION AND ANALYSIS
Two review authors independently checked eligibility and extracted data using a form specifically designed for the aims of this review. The two authors compared the data extracted and then entered data into RevMan 5 with a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by The Cochrane Collaboration.

MAIN RESULTS
We retrieved a total of nine studies (861 participants), with seven studies contributing to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants and one-three armed study compared two antidepressants and a placebo arm. For the acute phase treatment response (6 to 12 weeks), we found very low quality evidence for the effect of antidepressants as a class on symptoms of depression compared with placebo when measured as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants) or as a proportion of people who had depression (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants). No trials reported data on the follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, providing very low quality evidence for the difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants). No clear evidence of an effect of antidepressants versus either placebo or other antidepressants emerged from the analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low quality evidence). We found very low quality evidence for the effect of antidepressants as a class in terms of dropouts due to any cause compared with placebo (RR 0.87, 95% CI 0.49 to 1.53, six RCTs, 455 participants), as well as between SSRIs and tricyclic antidepressants (RR 0.83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the quality of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity.

AUTHORS' CONCLUSIONS
Despite the impact of depression on people with cancer, available studies were very few and of low quality. This review found very low quality evidence for the effects of these drugs compared with placebo. On the basis of these results clear implications for practice cannot be made. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent should be prescribed may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. Large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer with depressive symptoms, with or without a formal diagnosis of a depressive disorder, are urgently needed to better inform clinical practice.

REFERENCES
​Antidepressants for the treatment of depression in people with cancer; Ostuzzi G, Matcham F, Dauchy S, Barbui C, Hotopf M; The Cochrane Database of Systematic Reviews 6 CD011006 (Jun 2015)

Here's a link to this handy tool to help provider's convert from one dose of a stimulant to another. 

SOURCE: Medscape | SNMMI 2015 Annual Meeting
June 8th 2015

The heavy, long-term use of cannabis is associated with negative changes in parts of the brain not previously implicated, and is linked to deficits in learning and memory, new research suggests.

"In light of a current trend toward legalizing marijuana, with potentially increased exposure of adolescents, we believe our findings are important to consider," said investigator Jodi Weinstein, MD, from the Columbia University Medical Center and the New York State Psychiatric Institute in New York City.

If used daily, cannabis "can be as bad as other drugs in terms of consequences," said senior investigator Anissa Abi-Dargham, MD, also from the Columbia University Medical Center and the New York State Psychiatric Institute.

"People often think of cannabis as a lighter, harmless drug. This study shows that it is not and that it has negative consequences," she told Medscape Medical News.

The study results were presented here at the Society of Nuclear Medicine and Molecular Imaging 2015 Annual Meeting.

The team used the highly specific carbon 11-labeled (+)-4-propyl-9-hydroxynaphthoxazine radiotracer — known as [11C]PHNO — to image the impact of cannabis on the brain. The radiotracer binds preferentially to dopamine D₃ receptors. Because it is a different class of compound than most other D₂ and D₃ radiotracers — an agonist rather than an antagonist — it is sensitive to dopamine release.

People often think of cannabis as a lighter, harmless drug. This study shows that it is not and that it has negative consequences. 
With [11C]PHNO, the investigators showed that heavy chronic cannabis use is associated with lower dopamine release in the associative striatum and the sensory motor striatum, regions involved in cognition.

In contrast, previous reports have suggested that other drugs affect the limbic striatum, which processes reward information, Dr Weinstein explained

"Cannabis shares a negative impact on dopaminergic transmission with other drugs, only with a different regional profile," explained Dr Abi-Dargham.

An exploratory analysis showed a significant association between lower dopamine release capacity in the associative striatum and decreased cognitive measures in probabilistic category learning and working memory tasks, Dr Weinstein reported.

Additional reading:

• Structural MRI findings in long-term cannabis users: what do we know?

• Telling true from false: cannabis users show increased susceptibility to false memories
• Cannabis linked to brain differences in the young