The association between lithium use and neurocognitive performance in patients with bipolar disorder

Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1–5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1–5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically.acceptedVersio

GnRH Irnmunocontraception of Male Cats

The develop~llenot f nonsurgical co~ltraceptivesf or cats may facilitate population control of the species. The purpose of this study was to investigate the utility of GI&H for iinillu~locontraceptioo~fl male cats. Male cats (11=12) were divided into groups of tlxee and were inunuilized once with 0 (sham), 50, 200, or 400 i g synthetic GI&H coupled to keyhole limpet hernocyanin and combined with a nlycobacterial adjuvant to e~lhance inullunogenicity. GI&H ailtibody titer, serunl testostero~lec oncentration, and scrota1 size were detenniiled monthly. At 6 1110, semen was collected by electroejaculation and testes were examined histologically. GnRH antibodies were detected in all cats receiving GuRH vaccine by 1 nlo post-treatment and persisted tl~oughouth e study. No dose effect of GnRH was observed as titers were not significantly different between cats treated with 50, 200, or 400 i g GnRH (P = 0.5). Six of ni11e treated cats were classified as responders based on high GIIRH ailtibody titers (\u3e32,000). By 3 mo post-treat~llent,r espo~lderc ats had undetectable testosteroile and testicular atrophy. Nonrespoilder cats had GnRH titers of 4,000 to 32,000 and testosterone conce~ltrationsin tei-nlediate between responder and sllailr treated cats. At 6 mo, total spenn counts were similar for shamtreated cats (3.1 i 1 S x lo6 sperm) and noixesponder cats (3.4 k 1.6 x lo6 sperm; P = 0.7). Only one of the six responder cats produced spei-111, none of which were motile. Co~llbinedte sticular weights of respoilder cats (1.3 k 0.1 g) were lower than sha~n-treatedc oiltrols (5.3 * 1.3 g; P = 0.02) and ilomesponder cats (2.9 k 0.3 g; P = 0.02). Histologic evaluatioil of the testes revealed that in responder cats, the interstitial cells that were present were pale and shruilltei~c onlpared to the pluillp, polyhedral eosinophilic cells in shan~treatedc ats. GnRH responder cats had marked tubular atrophy with vacuolated Sertoli cells and a paucity of germ cells. SingIe-dose GnRH treatment resulted in testosterone concelltrations and semen quality coilsistent with imrnunocastration in a majority of cats treated

GnRH immunocontraception of male cats

The development of non-surgical contraceptives for cats may facilitate population control of the species. The purpose of this study was to investigate the utility of GnRH for immunocontraception of male cats. Male cats (n ¼ 12) were divided into groups of three and were immunized once with 0 (sham), 50, 200, or 400 mg synthetic GnRH coupled to keyhole limpet hemocyanin and combined with a mycobacterial adjuvant to enhance immunogenicity. GnRH antibody titer, serum testosterone concentration, and scrotal size were determined monthly. At 6 months, semen was collected by electroejaculation and testes were examined histologically. GnRH antibodies were detected in all cats receiving GnRH vaccine by 1 month post-treatment and persisted throughout the study. No dose effect of GnRH was observed; titers were not different among cats treated with 50, 200, or 400 mg GnRH (P ¼ 0:5). Six of nine treated cats were classified as responders based on high GnRH antibody titers (\u3e32,000). By 3 months post-treatment, responder cats had undetectable testosterone concentrations and testicular atrophy. Non-responder cats had GnRH titers of 4000–32,000 and testosterone concentrations intermediate between responder and sham-treated cats. At 6 months, total sperm counts were similar for sham-treated cats (3:1 _ 1:8 _ 106 sperm) and non-responder cats (3:4 _ 1:6 _ 106 sperm; P ¼ 0:7). Only one of the six responder cats produced sperm, none of which were motile. Combined testicular weights of responder cats (1:3 _ 0:1 g) were lower than sham-treated controls (5:3 _ 1:3 g; P ¼ 0:02) and non-responder cats (2:9 _ 0:3 g; P ¼ 0:02). Histologic evaluation of the testes revealed that in responder cats, the interstitial cells that were present were pale and shrunken compared to the plump, polyhedral eosinophilic cells in sham-treated cats

Thalamic Volume Loss Is Greater in Children Than in Adults Following Middle Cerebral Artery Territory Arterial Ischemic Stroke

Background: Younger stroke patients may suffer worse outcomes than older patients; however, the extent to which age at stroke impacts remote areas of the brain remains unclear. The objective of this study was to determine thalamic volume changes ipsilateral to middle cerebral artery territory strokes based on age at acute ischemic stroke onset. Methods: Acute ischemic stroke patients 18 years old were retrospectively recruited from a large quaternary care system. Each subject underwent an acute (90 days) magnetic resonance imaging (MRI) scan. Manual thalamic segmentation was performed. Results: Younger and older children had significantly greater stroke-side thalamic volume loss compared to adults (48.2%, P = .022; 40.7%, P = .044, respectively). Conclusions: Stroke-side thalamic volumes decreased across the age spectrum but to a greater degree in pediatric patients. This observation can affect functional and cognitive outcomes post stroke and warrants further research

Supplemental Material, TVA-17-030.R1_2018_supplementary_material_final_ - Global Posttrauma Symptoms: A Systematic Review of Qualitative Literature

<p>Supplemental Material, TVA-17-030.R1_2018_supplementary_material_final_ for Global Posttrauma Symptoms: A Systematic Review of Qualitative Literature by Lynn Murphy Michalopoulos, Melissa Meinhart, Justina Yung, Samuel Monroe Barton, Xinyi Wang, Urmi Chakrabarti, Megan Ritchey, Emily Haroz, Nakita Joseph, Judith Bass, and Paul Bolton in Trauma, Violence, & Abuse</p

The association between lithium use and neurocognitive performance in patients with bipolar disorder

Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1–5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1–5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically

Clinical predictors of non-response to lithium treatment in the Pharmacogenomics of Bipolar Disorder (PGBD) study

Background Lithium is regarded as a first-line treatment for bipolar disorder (BD), but partial response and non-response commonly occurs. There exists a need to identify lithium non-responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response. Methods The PGBD Study was an eleven site prospective trial of lithium treatment in bipolar I disorder. Subjects were stabilized on lithium monotherapy over 4 months and gradually discontinued from all other psychotropic medications. After ensuring a sustained clinical remission (defined by a score of ≤3 on the CGI for 4 weeks) had been achieved, subjects were followed for up to 2 years to monitor clinical response. Cox proportional hazard models were used to examine the relationship between clinical measures and time until failure to remit or relapse. Results A total of 345 individuals were enrolled into the study and included in the analysis. Of these, 101 subjects failed to remit or relapsed, 88 achieved remission and continued to study completion, and 156 were terminated from the study for other reasons. Significant clinical predictors of treatment failure (p < 0.05) included baseline anxiety symptoms, functional impairments, negative life events and lifetime clinical features such as a history of migraine, suicidal ideation/attempts, and mixed episodes, as well as a chronic course of illness. Conclusions In this PGBD Study of lithium response, several clinical features were found to be associated with failure to respond to lithium. Future validation is needed to confirm these clinical predictors of treatment failure and their use clinically to distinguish who will do well on lithium before starting pharmacotherapy