Association of 5-HTTLPR With Post-Traumatic Stress Disorder in US Service Members.

Objective: Post-traumatic stress disorder (PTSD) is a mental disorder that manifests after exposure to a stressful traumatic event, such as combat experience. Accumulated evidence indicates an important genetic influence in the development of PTSD. The serotonin transporter (5-HTT) gene has been identified as a candidate for PTSD and a polymorphism of the serotonin transporter-linked promoter region (5-HTTLPR) is associated with the disorder in the general population. However, whether it is associated with PTSD in active military service members has not been investigated. This study aimed to investigate the relationship between 5-HTTLPR and PTSD in service members. Methods: Leucocyte genomic DNA was extracted from service members, including those with PTSD (n = 134) or without PTSD (n = 639). The 5-HTTLPR polymorphism was detected by means of 2 stages of TaqMan fluorescent PCR assay. PTSD symptoms and symptom severity were assessed using the PTSD Checklist (PCL), a 17-item, DSM-based, self-report questionnaire with well-established validity and reliability. PTSD was determined based on endorsement of DSM-IV criteria and a PCL total score ≥ 44. Results: Significant differences in biallele distribution were observed between PTSD and controls (χ2 = 7.497, P = .024). The frequency of SS, SL, and LL genotypes in the PTSD group was 0.17, 0.56, and 0.27 respectively, compared to the frequencies of 0.27, 0.43, and 0.29 in non-PTSD controls. Carriers of the L allele had higher scores for reexperiencing and arousal symptoms on the PCL, compared to SS homozygote carriers (P < .05). The triallele genotypes showed no significant differences in distribution between the PTSD and control groups (P > .05) and no relationship with PTSD symptom severity. The interaction of triallelic genotypes of 5-HTTLPR and traumatic life events was associated with re-experiencing, avoidance, and arousal (P < .05 for all). Multiple regression analysis revealed significant correlations between both biallelic and triallelic genotypes of 5-HTTLPR, the interaction of the number of stressful lifetime events, and 5-HTTLPR genotypes with PCL total score (P < .001). Conclusion: Our findings suggested that 5-HTT might play a minor role in PTSD, and the interaction between 5-HTTLPR and the environment had effects on PCL score, complementing and emphasizing 5-HTT for PTSD, especially in the military population.

Sex-related difference of association of mitochondrial DNA copy number with PTSD in U.S. service members.

Gender differences in the lifetime prevalence of post-traumatic stress disorder (PTSD) have been well described with rates reported as approximately 10%-12% in females and 5%-6% in males (Olff, 2017). This study examined whether the sex-related difference of mitochondrial DNA copy number (mtDNAcn), an emerging systemic index of mitochondrial biogenesis and function can serve as a potential biomarker for PTSD. Leukocyte mtDNAcn of service members with PTSD (male = 127, female = 24) or without PTSD (male = 621, female = 78) was assessed using a TaqMan assay. The results were validated by the absolute quantification of QX-200 droplet digital PCR (ddPCR). PTSD symptoms and symptom severity were assessed using the PTSD Checklist (PCL), a 17-item, DSM-based, self-report questionnaire with well-established validity and reliability. DSM-IV criteria and PTSD were determined by PCL total score. We found that mtDNAcn of female subjects with PTSD was significantly higher compared to either male or female non-PTSD controls or male subjects with PTSD (p < 0.05). There was no significant difference in mtDNAcn between males with PTSD and male/female controls without PTSD. Using in vitro cultured SH-SY5Y cells (human neuroblastoma), we demonstrated that estrogen (Estro) treatment significantly decreased mtDNAcn (P < 0.001) compared to the vehicle control. We also found that pre-treatment with either synthetic glucocorticoid dexamethasone (Dex) or Estro blocker tamoxifen (Tamox) attenuated the estrogen-induced decreases of mtDNAcn. Our data suggest that mtDNAcn may be gender-dependent in the Servicemembers with PTSD. Glucocorticoid and/or estrogen receptors may play a role in the regulation of mtDNAcn. The sex-related difference of mtDNAcn may serve as a PTSD biomarker for females.

Left Amygdala Functional Connectivity Decreased after Fear of Negative Events was Disregarded in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a chronic and debilitating mental disorder that affects patients throughout their lives, leading to a diminished quality of life for patients and families, reduced productivity, and higher health care costs. It is of clinical and theoretical importance to investigate a more efficacious therapeutic approach for OCD and the neurophysiological mechanism underlying the efficacy of treatment, potentially associated with the etiology of OCD. Recently, a novel psychotherapy designated cognitive-coping therapy (CCT) has been reported to have a large effect size in OCD treatment. CCT hypothesizes that fear of negative events plays a crucial role in OCD. The study entitled "Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder" attempted to investigate the potential neurophysiological mechanism underlying the efficacy of CCT for OCD. The study provides crystal evidence showing that 4-week pharmacotherapy plus CCT decreases the left amygdala seed-based functional connectivity (LA-FC) with the right anterior cingulate gyrus and the left paracentral lobule/the left superior parietal/left inferior parietal, and 4-week CCT decreases the LA-FC with the left middle occipital gyrus/the left superior parietal. The alteration of the LA-FC with the right anterior cingulate gyrus positively correlates to the reduction of the Yale-Brown obsessive-compulsive scale (Y-BOCS) score. Therefore, it provides new insights into understanding the neurophysiology and neuropsychology behind the onset and treatment of OCD.

Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder.

It is of great clinical importance to explore more efficacious treatments for OCD. Recently, cognitive-coping therapy (CCT), mainly focusing on recognizing and coping with a fear of negative events, has been reported as an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. This study of 79 OCD patients collected Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after four weeks of CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Amygdala seed-based functional connectivity (FC) analysis was performed. Compared post- to pretreatment, pCCT-treated patients showed decreased left amygdala (LA) FC with the right anterior cingulate gyrus (cluster 1) and with the left paracentral lobule/the parietal lobe (cluster 2), while CCT-treated patients showed decreased LA-FC with the left middle occipital gyrus/the left superior parietal/left inferior parietal (cluster 3). The z-values of LA-FC with the three clusters were significantly lower after pCCT or CCT than pretreatment in comparisons of covert vs. overt and of non-remission vs. remission patients, except the z-value of cluster 2 in covert OCD. CCT and pCCT significantly reduced the Y-BOCS score. The reduction in the Y-BOCS score was positively correlated with the z-value of cluster 1. Our findings demonstrate that both pCCT and CCT with large effect sizes lowered LA-FC, indicating that FCs were involved in OCD. Additionally, decreased LA-FC with the anterior cingulate cortex (ACC) or paracentral/parietal cortex may be a marker for pCCT response or a marker for distinguishing OCD subtypes. Decreased LA-FC with the parietal region may be a common pathway of pCCT and CCT. Trial registration: ChiCTR-IPC-15005969.

Effects of short-term cognitive-coping therapy on resting-state brain function in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) tends to be treatment refractory. Recently, cognitive-coping therapy (CCT) for OCD is reported to be an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. Here, the effects of CCT on OCD and the resting-state brain function were investigated. METHODS: Fifty-nine OCD patients underwent CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Before and after a 4-week treatment, Yale-Brown obsessive-compulsive scale (Y-BOCS) was evaluated and resting-state functional magnetic resonance imaging (rs-fMRI) was scanned. RESULTS: Compared with the baseline, significant reduction of Y-BOCS scores was found after four-week treatment (p < .001) in groups of CCT and pCCT, not in pharmacotherapy. Post-treatment Y-BOCS scores of CCT group and pCCT group were not different, but significantly lower than that of pharmacotherapy group (p < .001). Compared with pretreatment, two clusters of brain regions with significant change in amplitude of low-frequency fluctuation (ALFF) were obtained in those who treated with CCT and pCCT, but not in those who received pharmacotherapy. The ALFF in cluster 1 (insula, putamen, and postcentral gyrus in left cerebrum) was decreased, while the ALFF in cluster 2 (occipital medial gyrus, occipital inferior gyrus, and lingual gyrus in right hemisphere) was increased after treatment (corrected p < .05). The changes of ALFF were correlated with the reduction of Y-BOCS score and were greater in remission than in nonremission. The reduction of the fear of negative events was correlated to the changes of ALFF of clusters and the reduction of Y-BOCS score. CONCLUSIONS: The effectiveness of CCT for OCD was related to the alteration of resting-state brain function-the brain plasticity. TRIAL REGISTRATION: ChiCTR-IPC-15005969.

Effects of the COVID-19 Pandemic on Obsessive-Compulsive Symptoms Among University Students: Prospective Cohort Survey Study.

BACKGROUND: The COVID-19 pandemic is associated with common mental health problems. However, evidence for the association between fear of COVID-19 and obsessive-compulsive disorder (OCD) is limited. OBJECTIVE: This study aimed to examine if fear of negative events affects Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores in the context of a COVID-19-fear-invoking environment. METHODS: All participants were medical university students and voluntarily completed three surveys via smartphone or computer. Survey 1 was conducted on February 8, 2020, following a 2-week-long quarantine period without classes; survey 2 was conducted on March 25, 2020, when participants had been taking online courses for 2 weeks; and survey 3 was conducted on April 28, 2020, when no new cases had been reported for 2 weeks. The surveys comprised the Y-BOCS and the Zung Self-Rating Anxiety Scale (SAS); additional items included questions on demographics (age, gender, only child vs siblings, enrollment year, major), knowledge of COVID-19, and level of fear pertaining to COVID-19. RESULTS: In survey 1, 11.3% of participants (1519/13,478) scored ≥16 on the Y-BOCS (defined as possible OCD). In surveys 2 and 3, 3.6% (305/8162) and 3.5% (305/8511) of participants had scores indicative of possible OCD, respectively. The Y-BOCS score, anxiety level, quarantine level, and intensity of fear were significantly lower at surveys 2 and 3 than at survey 1 (P<.001 for all). Compared to those with a lower Y-BOCS score (<16), participants with possible OCD expressed greater intensity of fear and had higher SAS standard scores (P<.001). The regression linear analysis indicated that intensity of fear was positively correlated to the rate of possible OCD and the average total scores for the Y-BOCS in each survey (P<.001 for all). Multiple regressions showed that those with a higher intensity of fear, a higher anxiety level, of male gender, with sibling(s), and majoring in a nonmedicine discipline had a greater chance of having a higher Y-BOCS score in all surveys. These results were redemonstrated in the 5827 participants who completed both surveys 1 and 2 and in the 4006 participants who completed all three surveys. Furthermore, in matched participants, the Y-BOCS score was negatively correlated to changes in intensity of fear (r=0.74 for survey 2, P<.001; r=0.63 for survey 3, P=.006). CONCLUSIONS: Our findings indicate that fear of COVID-19 was associated with a greater Y-BOCS score, suggesting that an environment (COVID-19 pandemic) × psychology (fear and/or anxiety) interaction might be involved in OCD and that a fear of negative events might play a role in the etiology of OCD.

Potential chemokine biomarkers associated with PTSD onset, risk and resilience as well as stress responses in US military service members.

Cytokines, including chemokines, are small secreted proteins, which specifically effect on the interactions and communications between cells. Pro-inflammatory cytokines are produced predominantly by activated macrophages and are involved in the upregulation of inflammatory reactions. Dysregulation of cytokines is associated with post-traumatic stress disorder (PTSD). Here, we use both before-and-after and case-control studies to search for potential chemokine biomarkers associated with PTSD onset, risk, and resilience as well as stress responses in US military service members deployed to Iraq and Afghanistan. Blood samples and scores of the PTSD Checklist (PCL) were obtained from soldiers pre- and post deployment (pre, post). Forty chemokines were measured using the Bio-Plex Pro Human Chemokine Panel Assays. The before-and-after analysis showed potential markers (CCL2, CCL15, CCL22, CCL25, CXCL2, and CXCL12) are associated with PTSD onset, and CCL3, CXCL11, and CXCL16 are related to stress response. The case-control study demonstrated that CCL13, CCL20, and CXCL6 were possible PTSD risk markers, and CX3CL1 might be a resilience marker. In addition, CCL11, CCL13, CCL20, and CCL25 were correlated with the PCL scores, indicating their association with PTSD symptom severity. Our data, for the first time, suggest that these dysregulated chemokines may serve as biomarkers for PTSD onset, risk, and resilience as well as stress responses, and may benefit developing approaches not only for PTSD diagnosis but also for PTSD treatment.

Genetic association of FKBP5 with PTSD in US service members deployed to Iraq and Afghanistan.

Post-traumatic stress disorder (PTSD) is a debilitating mental disorder with a prevalence of more than 7% in the US population and 12% in the military. An interaction of childhood trauma with FKBP5 (a glucocorticoid-regulated immunophilin) has been reported to be associated with PTSD in the general population. However, there are few reports on the association of FKBP5 with PTSD, particularly in important high-risk population such as the military. Here, we examined the association between four single-nucleotide polymorphisms (SNPs; rs3800373, rs9296158, rs1360780, rs9470080) covering the FKBP5 gene and probable PTSD in US service members deployed to Iraq and Afghanistan, a high-risk military population (n = 3890) (Hines et al., 2014). We found that probable PTSD subjects were significantly more likely to carry the A-allele of rs3800373, G-allele of rs9296158, C-allele of rs1360780, and C-allele of rs9470080. Furthermore, the four SNPs were in one block of strong pairwise linkage disequilibrium (r = 0.91-0.96). Within the block there were two major haplotypes of CATT and AGCC (rs3800373-rs9296158-rs1360780-rs9470080) that account for 99% of haplotype diversity. The distribution of the AGCC haplotype was significantly higher in probable PTSD subjects compared to non-PTSD (p<.05). The diplotype-based analysis indicated that the AGCC carriers tended to be probable PTSD. In this study, we demonstrated the association between FKBP5 and probable PTSD in US service members deployed to Iraq and Afghanistan, indicating that FKBP5 might be a risk factor for PTSD.

Clinical remission of a treatment-refractory individual with severe repetitive rituals and rumination.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a severe chronic mental disorder and tends to be refractory to pharmacotherapy or psychotherapy. For treatment-refractory patients, neurosurgical interventions are options. 64 % of OCD patients who undergo neurosurgery still have greater than 16 in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) after a long-term follow-up. Here, we reported a patient living with long-term OCD (20 years) who was refractory to pharmacotherapy, mindfulness-based psychotherapy, and neurosurgery that injured his bilateral anterior cingulates (AC) and caudate nucleus. METHODS: The patient accepted a novel psychotherapy named cognitive-coping therapy (CCT) and completed Y-BOCS, Hamilton depression rating scale, the Hamilton anxiety rating scale, social and occupational function assessment, and resting-state function magnetic resonance imaging scans (rs-fMRI) before and after 4-week CCT. RESULTS: His Y-BOCS score was reduced from 25 to 4. His depression score and anxiety score were reduced from 19 to 3 and from 12 to 3, respectively. The global assessment of functioning score increased from 32 to 88. CONCLUSIONS: The remission of the patient suggested that CCT could be an alternative intervention for treatment-refractory OCD and those with severe OCD could be cured in short-term.

Updates in PTSD Animal Models Characterization.

Post-traumatic stress disorder (PTSD) is a chronic, debilitating mental disorder afflicting more than 7% of the US population and 12% of military service members. Since the Afghanistan and Iraq wars, thousands of US service members have returned home with PTSD. Despite recent progress, the molecular mechanisms underlying the pathology of PTSD are poorly understood. To promote research on PTSD (especially its molecular mechanisms) and to set a molecular basis for discovering novel medications for this disorder, well-validated animal models are needed. However, to develop PTSD animal models is a challenging process, due to predisposing factors such as physiological, behavioral, emotional, and cognitive changes that emerge after trauma. Currently, there is no well-validated animal model of PTSD, although several stress paradigms mimic the behavioral symptoms and neurological alterations seen in PTSD. In this chapter, we will provide an overview of animal models of PTSD including learned helplessness, footshock, restraint stress, inescapable tail shock, single-prolonged stress, underwater trauma, social isolation, social defeat, early-life stress, and predator-based stress. We emphasize rodent models because they reproduce some of the behavioral and biotical phenotypes seen in PTSD. We will also present data showing that homologous biological measures are increasingly incorporated in studies to assess markers of risk and therapeutic response in these models. Therefore, PTSD animal models may be refined in hopes of capitalizing on the understanding of the molecular mechanisms and delivering tools in order to develop new and more efficacious treatments for PTSD.

Association between leukocyte telomere length and hostility in US army service members.

Hostility is a common form of emotionally charged anger which can lead to maladaptive and unhealthy behaviors. Significant association between shortened telomeres and greater levels of hostility has been observed in civilian populations, but has not yet been comprehensively studied in military populations. Our study investigates the relationship between hostility, post-traumatic stress disorder (PTSD), and leukocyte telomere length (LTL) in a sample of United States Army Special Operations personnel (n = 474) who deployed to Iraq and/or Afghanistan as part of combat operations. Hostility was measured with five items from the Brief Symptom Inventory (BSI). PTSD was determined using the PTSD Checklist (PCL) total score. The LTL was assessed using quantitative polymerase chain reaction methods and regression analyses were conducted to determine the association of hostility and telomere length. PTSD subjects reported higher hostility scores compared with those without PTSD. Among the participants with PTSD, those with medium or high level of hostility had shorter LTL than those with low level hostility (P < 0.01). Stepwise regression indicated that hostility level and age, but not gender and PTSD, were negatively correlated with LTL. Univariate regression showed that total hostility score was negatively associated with LTL (CI= -0.06 to -0.002, Beta= -0.095, p < 0.039) as well as a significant correlation between LTL and hostility impulses (HI) (CI= -0.108 to -0.009, Beta= -0.106, p < 0.021) and hostility controlling (HC) (CI= -0.071 to -0.002, Beta= -0.095, p < 0.004). Multiple regression analyses revealed that, while HC has no significant association with LTL, HI was still negatively correlated with LTL (p = 0.021). Our data indicates that LTL is associated with HI levels. Prevention and treatment efforts designed to reduce hostility may help mitigate risk for LTL shortening, a process of cellular aging, and thus slow accelerated aged-related health outcomes.

Genetic predictor of current suicidal ideation in US service members deployed to Iraq and Afghanistan.

OBJECTIVE: Suicide is one of the ten leading causes of death in United States and the suicide rate in the military population has increased since the start of the Iraq and Afghanistan wars. However, few biomarkers for current suicidal ideation (CSI) have been identified. The current study examined the association of four candidate genes with CSI in active duty US Army Special Operations Command and National Guard units (n = 3,889) who served in Iraq and Afghanistan between November 2009 and July 2014. METHODS: Current PTSD symptoms and CSI were assessed using the PTSD Checklist (PCL) and PHQ-9, respectively. Traumatic events were assessed using items from the Life Events Checklist (LEC) that met the DSM-IV PTSD criteria of a traumatic stressor. All genotypes of saliva DNA were discriminated using the TaqMan 5'-exonuclease assay. RESULTS: The associations between CSI and brain-derived neurotrophic factor (BDNF), FK506 binding protein (FKBP5), catechol-O-methyltransferase (COMT), or S100A10 (p11) were examined. We found CSI was associated with BDNF (OR = 1.5, 95% CI = 1.5-1.8, P = 0.0002), but not FKBP5, COMT and p11. Female soldiers reported CSI more often than males (χ2 = 7.403, p = 0.0065), although gender did not affect CSI severity. In addition, associations were found between CSI and depression, PTSD, and BDNF, but not traumatic events. The BDNF Val66Met contributed to the severity of CSI even after adjusting to PTSD, depression and LEC. CONCLUSIONS: The associations of BDNF with CSI and its severity suggest that BDNF may be a predictor of suicidal risk and present an opportunity to develop laboratory tools with clinical implications in suicide prevention and treatment.

Duration of untreated psychosis (DUP) and outcome of people with schizophrenia in rural China: 14-year follow-up study.

This study aims to examine the relationship between the duration of untreated psychosis (DUP) and 14-year outcomes of schizophrenia in a Chinese rural area. Participants with schizophrenia (n = 510) were identified in an epidemiological investigation of 123 572 people aged 15 years and older in 1994 and followed up in 2008 in Xinjin, Chengdu, China. Longer DUP (>6 months) was common in participants (27.3%). In 1994, participants with DUP ≤ 6 months were more likely to have a significantly lower rate of suicide attempts, shorter duration of illness and higher rate of full remission compared with those with DUP > 6 months. No significant differences were found regarding the rates of survival, suicide, death due to other causes and homelessness between individuals with shorter and longer DUP in 2008. Nevertheless, longer DUP (>6 months) of participants in 2008 was significantly associated with higher mean of PANSS total negative and general mental scores, longer duration of illness and higher rate of live alone in the logistic regression model. Earlier identification, treatment and rehabilitation, and family intervention should be addressed when developing mental health policies and delivering community mental health services.

Effectiveness of cognitive-coping therapy and alteration of resting-state brain function in obsessive-compulsive disorder.

BACKGROUND: Cognitive-coping therapy (CCT), integrating cognitive theory with stress-coping theory, is an efficacious therapy for obsessive-compulsive disorder (OCD). However, the potential brain mediation for the effectiveness remains unclear. We sought to investigate differences of resting-state brain function between OCD and healthy controls and if such differences would be changed by a four-week CCT. PATIENTS AND METHODS: Thirty-one OCD patients were recruited and randomized into CCT (n=15) and pharmacotherapy plus CCT (pCCT, n=16) groups, together with 25 age-, gender- and education-matched healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was scored to evaluate the severity in symptoms. Resting-state functional magnetic resonance imaging was scanned pre- and post-treatment. RESULTS: For patients, Y-BOCS scores were reduced during four-week treatment for CCT and pCCT (P<0.001), but no group difference was observed. No differences in amplitude of low-frequency fluctuation (ALFF) values were found between CCT and pCCT either pre- or post-treatment. Compared to controls, ALFF in OCD patients was higher in the left hippocampus, parahippocampus, and temporal lobes, but lower in the right orbitofrontal cortex, rectus, bilateral calcarine, cuneus, lingual, occipital, left parietal, postcentral, precentral, and parietal (corrected P<0.05). The ALFF in those regions was not significantly correlated to the severity of OCD symptoms. After a 4-week treatment, the ALFF differences between OCD patients and controls disappeared. LIMITATIONS: The pharmacotherapy group was not included since OCD patients generally do not respond to pharmacotherapy in four weeks. CONCLUSIONS: Our data indicated that resting-state brain function was different between OCD and controls; such differences disappeared after OCD symptoms were relieved.

Post-traumatic stress disorder risk and brain-derived neurotrophic factor Val66Met.

Brain-derived neurotrophic factor (BDNF), which regulates neuronal survival, growth differentiation, and synapse formation, is known to be associated with depression and post-traumatic stress disorder (PTSD). However, the molecular mechanism for those mental disorders remains unknown. Studies have shown that BDNF is associated with PTSD risk and exaggerated startle reaction (a major arousal manifestation of PTSD) in United States military service members who were deployed during the wars in Iraq and Afghanistan. The frequency of the Met/Met in BDNF gene was greater among those with PTSD than those without PTSD. Among individuals who experienced fewer lifetime stressful events, the Met carriers have significantly higher total and startle scores on the PTSD Checklist than the Val/Val carriers. In addition, subjects with PTSD showed higher levels of BDNF in their peripheral blood plasma than the non-probable-PTSD controls. Increased BDNF levels and startle response were observed in both blood plasma and brain hippocampus by inescapable tail shock in rats. In this paper, we reviewed these data to discuss BDNF as a potential biomarker for PTSD risk and its possible roles in the onset of PTSD.

Highly efficacious cognitive-coping therapy for overt or covert compulsions.

Pharmacotherapy and cognitive-behavioral therapy (CBT) present limitations when they are used to treat obsessive-compulsive disorder (OCD), a severe and debilitating psychiatric disorder. To search for more efficacious treatment, we investigated the effects of pharmacotherapy plus cognitive-coping therapy (pCCT) on adult OCD patients with overt or covert compulsions. Two hundred and fifteen OCD patients were randomized into pharmacotherapy plus psychological support (PPS, n=107) and pCCT (n=108). The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to measure severity of symptoms in the OCD patients. The Y-BOCS scores were significantly lower in pCCT than in PPS in both acute term (<3 months) and long-term follow-up. In pCCT, severity of symptoms was not different between those with covert compulsions and those with overt compulsions, but was significantly reduced at any post-treatment time-point. Y-BOCS scores in the two subtype compulsions were significantly lower in pCCT than in PPS at any post-treatpost-treatment time-point. Compared with PPS, effect size, response rate and remission rate were significantly higher in pCCT. Our findings corroborated with the hypothesis that pCCT could efficaciously treat OCD with overt compulsions or covert compulsion, suggesting that pCCT might be a potential option for adult OCD.

Telomere length - a cellular aging marker for depression and Post-traumatic Stress Disorder.

Telomeres play a central role in cell fate and aging by adjusting the cellular response to both biological and psychological stress. Human telomeres are regions of tandem TTAGGG repeats at chromosomal ends that protect chromosomes from degradation, fusion, and recombination. They are made up of approximately 1000-2500 copies of the repeated DNA sequence. Over time, at each cell division, the telomere ends become shorter. Thus, telomere length (TL) has been considered a cellular marker for age-related diseases. In addition to biochemical stressors such as oxidation and inflammation, psychosocial traumatic stress has also been linked to shorter telomeres. TL is significantly inversely correlated with long-term depression, even after controlling for age. Average TL in depressed subjects, who were above the median of lifetime depression, was 281 base pairs shorter than that in controls, corresponding to approximately 7years of accelerated cell aging. Several recent studies have also demonstrated an inverse relationship between leukocyte telomere length (LTL) and the risk of PTSD. TL was inversely correlated with the duration of caregiving and PTSD. Here, we focus on the discussion of findings in studies of the relationships between stress-related disorders (e.g., depression and PTSD) and telomeres. We also present direct evidence that TL is associated with traumatic stress, depression, and PTSD, and hypothesize that traumatic stress affects not only mental disorders but also cellular aging. The nature of this relationship between stress and TL warrants further evaluation in psychiatry.

Cognitive-coping therapy for obsessive-compulsive disorder: a randomized controlled trial.

Pharmacotherapy and cognitive-behavioral therapy (CBT) are widely used to treat obsessive-compulsive disorder (OCD). These treatments have helped many patients with OCD, but there still is room for improvement. Recently, a promising psychotherapy for OCD, cognitive-coping therapy (CCT), has been developed. Pharmacotherapy plus CCT (PCCT) demonstrates higher efficacy in a shorter period of time and lower relapses than pharmacotherapy or pharmacotherapy plus CBT. In this randomized controlled trial, we investigated the efficacy of CCT for OCD treatment. One hundred and forty-five OCD patients were randomly assigned into two groups: pharmacotherapy (N = 72) and PCCT (N = 73). In each group, drug-resistant (DR) and non-drug-resistant (NDR) OCD were further analyzed to examine the efficacy of CCT. Some clinical features and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) were blindly assessed pre-treatment and post-treatment at week 1, 2, 3, 4, and 12. The Y-BOCS scores were significantly lower in PCCT than in the pharmacotherapy group at any post-treatment time-point (P < 0.001). Compared with pre-treatment, the Y-BOCS scores were significantly reduced at any time-point (P < 0.001) in PCCT group, but only at week 12 (P < 0.001) in the pharmacotherapy group. In the PCCT group, there were no differences between DR and NDR groups' Y-BOCS scores at any post-treatment time-point. The response rates and remission rates were higher in PCCT than in the pharmacotherapy group. Three variables, the number of weeks of treatment, insight, and disregarding of obsessions, were significantly correlated with the Y-BOCS score. Therefore, CCT might be a potential treatment for OCD.

A promising randomized trial of a new therapy for obsessive-compulsive disorder.

Pharmacotherapy and cognitive-behavioral therapy (CBT) are currently the most effective interventions for treating obsessive-compulsive disorder (OCD). These treatments, however, are time consuming and in some cases the patients do not show significant improvement. In all, 30%-60% of OCD patients do not respond adequately to pharmacotherapy and 20%-40% of OCD patients who complete CBT do not improve significantly, suggesting a more efficacious approach is needed. The objectives of this study are to demonstrate an efficacious pharmacotherapy plus psychotherapy, named cognitive-coping therapy (CCT), for OCD and to investigate the efficacy of this approach in a larger sample size. Therefore, a total of 108 patients with OCD were randomly allocated into three groups: pharmacotherapy (N = 38), pharmacotherapy plus CBT (PCBT, N = 34), and pharmacotherapy plus CCT (PCCT, N = 36). The severity of symptoms and the patients' functioning were assessed pretreatment and after 7, 14, 21 days, and 1-, 3-, 6-, and 12-month treatment using the Yale-Brown Obsessive Compulsive Scale and Global Assessment of Functioning (GAF). Compared with the pharmacotherapy and PCBT groups, the severity of OCD symptoms was significantly reduced (P < 0.001), the rates of response (100%) and remission (85.0%) were significantly higher (P < 0.001), and relapse rate was lower (P = 0.017) in PCCT group during the 1-year follow-up. In addition, the GAF score was significantly higher in the PCCT group than in the other two groups (P < 0.001). Our preliminary data suggest that PCCT is a more efficacious psychotherapy for OCD patients than pharmacotherapy or PCBT.

Alpha-linolenic acid is a potent neuroprotective agent against soman-induced neuropathology.

Nerve agents are deadly threats to military and civilian populations around the world. Nerve agents cause toxicity to peripheral and central sites through the irreversible inhibition of acetylcholinesterase, the enzyme that metabolizes acetylcholine. Excessive acetylcholine accumulation in synapses results in status epilepticus in the central nervous system. Prolonged status epilepticus leads to brain damage, neurological dysfunction and poor outcome. Anticonvulsants are effective but must be given rapidly following exposure. Because these agents cause mass casualties, effective neuroprotective agents are needed to reduce brain damage and improve cognitive outcome. α-Linolenic acid is an omega-3 fatty acid that is found in vegetable products and has no known side effects. α-Linolenic acid is neuroprotective against kainic acid-induced brain damage in vivo, but its neuroprotective efficacy against nerve agents is unknown. α-Linolenic acid also exerts anti-depressant and anti-inflammatory activities and enhances synaptic plasticity in vivo. These properties make this polyunsaturated fatty acid (PUFA) a potential candidate against nerve agent-induced neuropathology. Here we show that α-linolenic acid is neuroprotective against soman-induced neuropathology in either a pretreatment or post-treatment paradigm. We also show that subcutaneous injection of α-linolenic acid shows greater neuroprotective efficacy compared with intravenous injection in a brain region-specific manner.