Archives for April 2016

EPIGENETIC VARIATION AT SKA2 PREDICTS SUICIDE PHENOTYPES AND INTERNALIZING PSYCHOPATHOLOGY.

April 27, 2016 02:36

EPIGENETIC VARIATION AT SKA2 PREDICTS SUICIDE PHENOTYPES AND INTERNALIZING PSYCHOPATHOLOGY.

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EPIGENETIC VARIATION AT SKA2 PREDICTS SUICIDE PHENOTYPES AND INTERNALIZING PSYCHOPATHOLOGY.

Depress Anxiety. 2016 Apr;33(4):308-15

Authors: Sadeh N, Wolf EJ, Logue MW, Hayes JP, Stone A, Griffin LM, Schichman SA, Miller MW

Abstract

BACKGROUND: DNA methylation of the SKA2 gene has recently been implicated as a biomarker of suicide risk and posttraumatic stress disorder (PTSD). To examine the specificity and reliability of these findings, we examined associations between SKA2 DNA methylation, broad dimensions of psychiatric symptoms, and suicide phenotypes in adults with high levels of trauma exposure.

METHODS: A total of 466 White, non-Hispanic veterans and their intimate partners (65% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. DNA methylation of the CpG locus cg13989295 and genotype at the methylation-associated single-nucleotide polymorphism (SNP) rs7208505 were examined in relation to current and lifetime PTSD, internalizing and externalizing psychopathology, and suicide phenotypes (ideation, plans, and attempts).

RESULTS: DNA methylation at the previously implicated SKA2 CpG locus (cg13989295) was associated with current and lifetime symptoms of internalizing (but not externalizing) disorders. SKA2 methylation levels also predicted higher rates of current suicidal thoughts and behaviors, even after including well-established psychiatric risk factors for suicide in the model. Associations between PTSD and SKA2 were not significant, and genetic variation at the methylation-associated SNP (rs7208505) was not related to any of the phenotypes examined.

CONCLUSIONS: SKA2 methylation may index a general propensity to experience stress-related psychopathology, including internalizing disorders and suicidal thoughts and behaviors. This study demonstrates that SKA2 methylation levels explain unique variance in suicide risk not captured by clinical symptom interviews, providing further evidence of its potential utility as a biomarker of suicide risk and stress-related psychopathology.

PMID: 27038412 [PubMed – in process]

STRUCTURAL AND FUNCTIONAL CONNECTIVITY IN POSTTRAUMATIC STRESS DISORDER: ASSOCIATIONS WITH FKBP5.

April 27, 2016 02:36

STRUCTURAL AND FUNCTIONAL CONNECTIVITY IN POSTTRAUMATIC STRESS DISORDER: ASSOCIATIONS WITH FKBP5.

STRUCTURAL AND FUNCTIONAL CONNECTIVITY IN POSTTRAUMATIC STRESS DISORDER: ASSOCIATIONS WITH FKBP5.

Depress Anxiety. 2016 Apr;33(4):300-7

Authors: Fani N, King TZ, Shin J, Srivastava A, Brewster RC, Jovanovic T, Bradley B, Ressler KJ

Abstract

BACKGROUND: The integrity of connections between the hippocampus and the anterior cingulate cortex (ACC) is critical for adaptive cognitive and emotional processing; these connections may be compromised in posttraumatic stress disorder (PTSD). However, there is a lack of PTSD research that combines structural and functional connectivity data, and no studies have examined whether abnormal ACC-hippocampal connectivity is associated with genetic variability, particularly for polymorphisms of a gene that has been previously associated with PTSD, FKBP5. This was the goal of the present study.

METHODS: Fifty-four women with and without PTSD underwent diffusion tensor imaging and resting-state MRI. Probabilistic tractography was used to examine ACC-hippocampal structural connectivity; mean fractional anisotropy (FA) values were extracted from connectivity streamlines, which represent the cingulum bundle. Genotype data were collected for a single nucleotide polymorphism (SNP) of FKBP5, rs1360780.

RESULTS: Participants with PTSD demonstrated poorer structural connectivity (lower cingulum FA) compared to traumatized controls (F1, 50 = 6.77, P < .05). An interaction of FKBP5 genotype and diagnostic group was also observed (F1, 37 = 4.52, P = .04), indicating lower cingulum FA in carriers of two risk alleles for this SNP, compared to other diagnostic and genotype groups. Carriers of two FKBP5 risk alleles also demonstrated poorer hippocampus-ACC connectivity at rest (P < .05). When cingulum FA was used a regressor in a brain-wide, seed-based regression analysis, significant associations were found between the hippocampus and dorsal regions of the ACC (P < .05).

CONCLUSIONS: Individuals with PTSD demonstrated compromised structural connectivity of the hippocampus-ACC pathway. Altered hippocampus-ACC connectivity may represent a highly salient intermediate neural phenotype for PTSD.

PMID: 27038411 [PubMed – in process]

ALTERED DEFAULT MODE NETWORK (DMN) RESTING STATE FUNCTIONAL CONNECTIVITY FOLLOWING A MINDFULNESS-BASED EXPOSURE THERAPY FOR POSTTRAUMATIC STRESS DISORDER (PTSD) IN COMBAT VETERANS OF AFGHANISTAN AND IRAQ.

April 27, 2016 02:36

ALTERED DEFAULT MODE NETWORK (DMN) RESTING STATE FUNCTIONAL CONNECTIVITY FOLLOWING A MINDFULNESS-BASED EXPOSURE THERAPY FOR POSTTRAUMATIC STRESS DISORDER (PTSD) IN COMBAT VETERANS OF AFGHANISTAN AND IRAQ.

Depress Anxiety. 2016 Apr;33(4):289-99

Authors: King AP, Block SR, Sripada RK, Rauch S, Giardino N, Favorite T, Angstadt M, Kessler D, Welsh R, Liberzon I

Abstract

BACKGROUND: Recent studies suggest that mindfulness may be an effective component for posttraumatic stress disorder (PTSD) treatment. Mindfulness involves practice in volitional shifting of attention from “mind wandering” to present-moment attention to sensations, and cultivating acceptance. We examined potential neural correlates of mindfulness training using a novel group therapy (mindfulness-based exposure therapy (MBET)) in combat veterans with PTSD deployed to Afghanistan (OEF) and/or Iraq (OIF).

METHODS: Twenty-three male OEF/OIF combat veterans with PTSD were treated with a mindfulness-based intervention (N = 14) or an active control group therapy (present-centered group therapy (PCGT), N = 9). Pre-post therapy functional magnetic resonance imaging (fMRI, 3 T) examined resting-state functional connectivity (rsFC) in default mode network (DMN) using posterior cingulate cortex (PCC) and ventral medial prefrontal cortex (vmPFC) seeds, and salience network (SN) with anatomical amygdala seeds. PTSD symptoms were assessed at pre- and posttherapy with Clinician Administered PTSD Scale (CAPS).

RESULTS: Patients treated with MBET had reduced PTSD symptoms (effect size d = 0.92) but effect was not significantly different from PCGT (d = 0.46). Increased DMN rsFC (PCC seed) with dorsolateral dorsolateral prefrontal cortex (DLPFC) regions and dorsal anterior cingulate cortex (ACC) regions associated with executive control was seen following MBET. A group × time interaction found MBET showed increased connectivity with DLPFC and dorsal ACC following therapy; PCC-DLPFC connectivity was correlated with improvement in PTSD avoidant and hyperarousal symptoms.

CONCLUSIONS: Increased connectivity between DMN and executive control regions following mindfulness training could underlie increased capacity for volitional shifting of attention. The increased PCC-DLPFC rsFC following MBET was related to PTSD symptom improvement, pointing to a potential therapeutic mechanism of mindfulness-based therapies.

PMID: 27038410 [PubMed – in process]

Neurology in the Vietnam War.

April 27, 2016 02:36

Neurology in the Vietnam War.

Neurology in the Vietnam War.

Front Neurol Neurosci. 2016 Apr 1;38:201-213

Authors: Gunderson CH, Daroff RB

Abstract

Between December 1965 and December 1971, the United States maintained armed forces in Vietnam never less than 180,000 men and women in support of the war. At one time, this commitment exceeded half a million soldiers, sailors, and airmen from both the United States and its allies. Such forces required an extensive medical presence, including 19 neurologists. All but two of the neurologists had been drafted for a 2-year tour of duty after deferment for residency training. They were assigned to Vietnam for one of those 2 years in two Army Medical Units and one Air Force facility providing neurological care for American and allied forces, as well as many civilians. Their practice included exposure to unfamiliar disorders including cerebral malaria, Japanese B encephalitis, sleep deprivation seizures, and toxic encephalitis caused by injection or inhalation of C-4 explosive. They and neurologists at facilities in the United States published studies on all of these entities both during and after the war. These publications spawned the Defense and Veterans Head Injury Study, which was conceived during the Korean War and continues today as the Defense and Veterans Head Injury Center. It initially focused on post-traumatic epilepsy and later on all effects of brain injury. The Agent Orange controversy arose after the war; during the war, it was not perceived as a threat by medical personnel. Although soldiers in previous wars had developed serious psychological impairments, post-traumatic stress disorder was formally recognized in the servicemen returning from Vietnam.

PMID: 27035455 [PubMed – as supplied by publisher]

Observational evidence for buprenorphine’s impact on posttraumatic stress symptoms in veterans with chronic pain and opioid use disorder.

April 27, 2016 02:36

Observational evidence for buprenorphine’s impact on posttraumatic stress symptoms in veterans with chronic pain and opioid use disorder.

Observational evidence for buprenorphine’s impact on posttraumatic stress symptoms in veterans with chronic pain and opioid use disorder.

J Clin Psychiatry. 2016 Mar 1;

Authors: Seal KH, Maguen S, Bertenthal D, Batki SL, Striebel J, Stein MB, Madden E, Neylan TC

Abstract

OBJECTIVE: Posttraumatic stress disorder (PTSD), chronic pain, and substance use disorders are prevalent co-occurring conditions that are challenging to treat individually, and there is no evidence-based treatment for all 3. Buprenorphine, used to treat opioid use disorder and chronic pain, is a partial nociceptin opioid receptor agonist. In preclinical studies, a nociceptin opioid receptor agonist was shown to mitigate PTSD symptoms in acute trauma. We compared buprenorphine to other opioid medications in its impact on PTSD symptoms in patients with chronic pain and opioid and/or other substance use disorders.

METHOD: We assembled a retrospective cohort of 382 Iraq and Afghanistan veterans in US Department of Veterans Affairs health care from October 1, 2007, to July 29, 2013, with ICD-9-CM diagnoses of PTSD, chronic pain, and substance use disorders. We used time-varying general estimating equation models to assess the primary outcome, which was change in PTSD symptoms (measured using the PTSD Checklist and the Primary Care PTSD Screen) among veterans initiated on sublingual buprenorphine versus those maintained on moderately high-dose opioid therapy.

RESULTS: Twice as many veterans in the buprenorphine group (23.7%) compared to those in the opioid therapy group (11.7%) experienced improvement in PTSD symptoms (P = .001). Compared to veterans in the opioid therapy group, veterans receiving buprenorphine showed significant improvement in PTSD symptoms after 8 months, with increasing improvement up to 24 months (incidence rate ratio = 1.79; 95% CI, 1.16-2.77; P = .009). There were no differences in the longitudinal course of pain ratings between groups.

CONCLUSIONS: This observational study is the first to report an incidental effect of buprenorphine compared to opioid therapy in improving PTSD symptoms in veterans.

PMID: 27035058 [PubMed – as supplied by publisher]

Validity testing and neuropsychology practice in the VA healthcare system: results from recent practitioner survey.

April 27, 2016 02:36

Validity testing and neuropsychology practice in the VA healthcare system: results from recent practitioner survey.

Validity testing and neuropsychology practice in the VA healthcare system: results from recent practitioner survey.

Clin Neuropsychol. 2016 Apr 1;:1-18

Authors: Young JC, Roper BL, Arentsen TJ

Abstract

OBJECTIVE: A survey of neuropsychologists in the Veterans Health Administration examined symptom/performance validity test (SPVT) practices and estimated base rates for patient response bias.

METHOD: Invitations were emailed to 387 psychologists employed within the Veterans Affairs (VA), identified as likely practicing neuropsychologists, resulting in 172 respondents (44.4% response rate). Practice areas varied, with 72% at least partially practicing in general neuropsychology clinics and 43% conducting VA disability exams.

RESULTS: Mean estimated failure rates were 23.0% for clinical outpatient, 12.9% for inpatient, and 39.4% for disability exams. Failure rates were the highest for mTBI and PTSD referrals. Failure rates were positively correlated with the number of cases seen and frequency and number of SPVT use. Respondents disagreed regarding whether one (45%) or two (47%) failures are required to establish patient response bias, with those administering more measures employing the more stringent criterion. Frequency of the use of specific SPVTs is reported.

CONCLUSIONS: Base rate estimates for SPVT failure in VA disability exams are comparable to those in other medicolegal settings. However, failure in routine clinical exams is much higher in the VA than in other settings, possibly reflecting the hybrid nature of the VA’s role in both healthcare and disability determination. Generally speaking, VA neuropsychologists use SPVTs frequently and eschew pejorative terms to describe their failure. Practitioners who require only one SPVT failure to establish response bias may overclassify patients. Those who use few or no SPVTs may fail to identify response bias. Additional clinical and theoretical implications are discussed.

PMID: 27032437 [PubMed – as supplied by publisher]

Medication for post traumatic stress disorder

April 27, 2016 02:30

Medication for post traumatic stress disorder Post traumatic stress disorder (PTSD) occurs after exposure to significant trauma and results in enormous personal and societal costs. Although traditionally treated with psychotherapy, there is increasing recognition of a theoretical basis for medication treatments. This was a systematic review of 35 short‐term randomised controlled trials of pharmacotherapy for PTSD (4597 participants). A significantly larger proportion of patients responded to medication (59.1%) than to placebo (38.5%) (13 trials, 1272 participants). Symptom severity was significantly reduced in 17 trials (2507 participants). The largest trials showing efficacy were of the selective serotonin reuptake inhibitors, with long‐term efficacy also observed for these medications.

Psychological therapies for chronic post‐traumatic stress disorder (PTSD) in adults

April 27, 2016 02:30

Psychological therapies for chronic post‐traumatic stress disorder (PTSD) in adults Background: Post‐traumatic stress disorder (PTSD) can occur following a traumatic event. It is characterised by symptoms of re‐experiencing the trauma (in the form of nightmares, flashbacks and distressing thoughts), avoiding reminders of the traumatic event, negative alterations in thoughts and mood, and symptoms of hyper‐arousal (feeling on edge, being easily startled, feeling angry, having difficulties sleeping, and problems concentrating).