The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants.
Proc Natl Acad Sci U S A. 2014 Oct 20;
Authors: Mergy MA, Gowrishankar R, Gresch PJ, Gantz SC, Williams J, Davis GL, Wheeler CA, Stanwood GD, Hahn MK, Blakely RD
Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.
PMID: 25331903 [PubMed - as supplied by publisher]
Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility.
Schizophr Bull. 2014 Oct 20;
Authors: Kimura H, Tsuboi D, Wang C, Kushima I, Koide T, Ikeda M, Iwayama Y, Toyota T, Yamamoto N, Kunimoto S, Nakamura Y, Yoshimi A, Banno M, Xing J, Takasaki Y, Yoshida M, Aleksic B, Uno Y, Okada T, Iidaka T, Inada T, Suzuki M, Ujike H, Kunugi H, Kato T, Yoshikawa T, Iwata N, Kaibuchi K, Ozaki N
Background: Nuclear distribution E homolog 1 (NDE1), located within chromosome 16p13.11, plays an essential role in microtubule organization, mitosis, and neuronal migration and has been suggested by several studies of rare copy number variants to be a promising schizophrenia (SCZ) candidate gene. Recently, increasing attention has been paid to rare single-nucleotide variants (SNVs) discovered by deep sequencing of candidate genes, because such SNVs may have large effect sizes and their functional analysis may clarify etiopathology. Methods and Results: We conducted mutation screening of NDE1 coding exons using 433 SCZ and 145 pervasive developmental disorders samples in order to identify rare single nucleotide variants with a minor allele frequency ?5%. We then performed genetic association analysis using a large number of unrelated individuals (3554 SCZ, 1041 bipolar disorder [BD], and 4746 controls). Among the discovered novel rare variants, we detected significant associations between SCZ and S214F (P = .039), and between BD and R234C (P = .032). Furthermore, functional assays showed that S214F affected axonal outgrowth and the interaction between NDE1 and YWHAE (14-3-3 epsilon; a neurodevelopmental regulator). Conclusions: This study strengthens the evidence for association between rare variants within NDE1 and SCZ, and may shed light into the molecular mechanisms underlying this severe psychiatric disorder.
PMID: 25332407 [PubMed - as supplied by publisher]
Naturally Occurring Peer Support through Social Media: The Experiences of Individuals with Severe Mental Illness Using YouTube.
PLoS One. 2014;9(10):e110171
Authors: Naslund JA, Grande SW, Aschbrenner KA, Elwyn G
Increasingly, people with diverse health conditions turn to social media to share their illness experiences or seek advice from others with similar health concerns. This unstructured medium may represent a platform on which individuals with severe mental illness naturally provide and receive peer support. Peer support includes a system of mutual giving and receiving where individuals with severe mental illness can offer hope, companionship, and encouragement to others facing similar challenges. In this study we explore the phenomenon of individuals with severe mental illness uploading videos to YouTube, and posting and responding to comments as a form of naturally occurring peer support. We also consider the potential risks and benefits of self-disclosure and interacting with others on YouTube. To address these questions, we used qualitative inquiry informed by emerging techniques in online ethnography. We analyzed n?=?3,044 comments posted to 19 videos uploaded by individuals who self-identified as having schizophrenia, schizoaffective disorder, or bipolar disorder. We found peer support across four themes: minimizing a sense of isolation and providing hope; finding support through peer exchange and reciprocity; sharing strategies for coping with day-to-day challenges of severe mental illness; and learning from shared experiences of medication use and seeking mental health care. These broad themes are consistent with accepted notions of peer support in severe mental illness as a voluntary process aimed at inclusion and mutual advancement through shared experience and developing a sense of community. Our data suggest that the lack of anonymity and associated risks of being identified as an individual with severe mental illness on YouTube seem to be overlooked by those who posted comments or uploaded videos. Whether or not this platform can provide benefits for a wider community of individuals with severe mental illness remains uncertain.
PMID: 25333470 [PubMed - as supplied by publisher]
Severe Rhabdomyolysis Induced Electrolyte Abnormalities Mimicking ST Elevation Myocardial Infarction.
Chest. 2014 Oct 1;146(4_MeetingAbstracts):115A
Authors: Patel R, Auraha N, Dyal H, Fernandez J, Nazneen W
SESSION TITLE: Cardiovascular Student/Resident Case Report Posters ISESSION TYPE: Medical Student/Resident Case ReportPRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PMINTRODUCTION: Rhabdomyolysis is characterized by expulsion of intracellular contents of striated muscle following direct insult to sarcoplasmic reticulum or exhaustion of myocyte ATP. This in turn causes electrolyte abnormalities including hypocalcemia and hyperkalemia which can produce EKG changes that rarely mimic an ST elevation myocardial infarction.CASE PRESENTATION: A 39 year old African-American male presented to the ED by EMS after being found down in his home for an unknown period of time. Prior to presentation, he had ingested 50 tablets of acetaminophen-hydrocodone in a suicide attempt. The gentleman had a history of bipolar disorder, schizoaffective disorder and previous suicide attempts by self-mutilation. On presentation, the patient was afebrile and hemodynamically stable, and orientated only to person and place. He did not complain of chest pain at any time during his hospitalization. Laboratory findings were significant for potassium of 7.0meq/L, calcium of 7.6mg/dL, aspartate aminotransferase of 13,347u/L, alanine aminotransferase of 5,309u/L, troponin of 1.4 ng/mL, CPK of 33,427u/L, INR of 1.94 and acetaminophen level of 37.9ug/mL. Troponin peaked at 15.93 and CPK peaked at 101,731 IU/L. Initial EKG showed left axis deviation, widened QRS interval, prolonged QTc of 540ms, flattened p waves, RBBB and ST segment elevation along V1-V3 and aVR (Figure 1). Stat transthoracic echocardiogram was performed which was negative for wall motion abnormalities or signs of ventricular dysfunction. Following immediate administration of N-acetyl cysteine, normal saline and calcium replacement, his hyperkalemia and hypocalcemia resolved. Subsequent EKGs taken following correction of electrolyte abnormalities showed resolution of EKG changes without q wave development (Figure 2).DISCUSSION: EKG changes due to electrolyte abnormalities are thought to be related to their effects on the cardiac myocyte action potential. Calcium primarily effects phase two of the action potential in cardiac contractile cells and phase one of pacemaker cells(1). Potassium will most commonly affect the repolarization phase of the SA node and cardiac contractile cell(1). Hypocalcemia may decrease the gradient to enter the cell resulting in prolongation of the plateau phase, leading to the potential for coronary vasospasm and elevated troponin(2). Hyperkalemia can result in prolonged periods of repolarization, manifested as a widened QRS interval as was seen in this patient's initial EKG(1).CONCLUSIONS: Anterior STEMI pattern by EKG and troponin elevation in this patient is most likely related to sequela of severe rhabdomyolysis.Reference #1: Grant, AO. Cardiac Ion Channels. Circ Arrhythm Electrophysiol.2009;2:185-194Reference #2: Lehmann, G, Deisenhofer, I, Ndrepepa, G, et al. ECG changes in a 25-year old woman with hypocalcemia due to hypoparathyroidism: hypocalcemia mimicking acute myocardial infarction. Chest. 2000;118:260-262DISCLOSURE: The following authors have nothing to disclose: Ruchir Patel, Nena Auraha, Herman Dyal, Juan Fernandez, Waheeda NazneenNo Product/Research Disclosure Information.
PMID: 25334111 [PubMed - as supplied by publisher]
Holy Moly! Severe Serotonin Syndrome Associated With a Recreational Agent.
Chest. 2014 Oct 1;146(4_MeetingAbstracts):248A
Authors: Rai S, Shrestha P, Katpally R, Adelman M
SESSION TITLE: Critical Care Case Report Posters ISESSION TYPE: Affiliate Case Report PosterPRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PMINTRODUCTION: Serotonin syndrome is a potentially life-threatening drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs . It is caused by drug induced excess of intrasynaptic 5-hydroxytryptamine (5-HT) . We report a case of severe serotonin syndrome caused by interaction between a serotonin-norepinephrine reuptake inhibitor (SNRI) and street drug- `Molly'.CASE PRESENTATION: A 41-year-old male with history of bipolar disorder was brought to ED for evaluation of extreme combativeness for one day. He was on risperidone and desvenlafaxine (an SNRI) and admitted to taking a "street drug -Molly". Vitals revealed temperature of 40?C, pulse of 108bpm and blood pressure of 155/122mmhg. The patient was extremely agitated, diaphoretic and tremulous. Despite multiple intravenous lorazepam boluses, he remained combative. He was subsequently intubated and placed on a mechanical ventilator. Laboratory workup was significant for sodium of 118 meq/L, creatinine kinase (CK) of 3543U/L and myoglobin of 16,261ng/ml. Based on his clinical presentation, severe serotonin syndrome was diagnosed and managed with aggressive fluid hydration, cessation of serotonergic agent, sedation and neuromuscular blockade with cisatracurium. He subsequently developed massive rhabdomyolysis followed by acute renal failure requiring initiation of hemodialysis. With supportive care, his renal and neurological function improved and he was successfully extubated on day 19. He was discharged to a subacute facility on day 35.DISCUSSION: "Molly" colloquially refers to MDMA(3,4-methylenedioxy-N-methylamphetamine) that is relatively free of adulterants. MDMA is a ring-substituted amphetamine derivative which indirectly stimulates the release and inhibits the reuptake of 5-HT . Its use especially in association with SSRIs or SNRIs has been associated with severe serotonin syndrome [1,3] requiring immediate and aggressive medical intervention.CONCLUSIONS: Clinicians should be aware about the dangerous interaction between serotonergic agents and recreational drugs which could result in potentially lethal serotonin syndrome.Reference #1: Boyer EW, Shannon M.The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20.Reference #2: Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999;13:100 - 9.Reference #3: Parrott AC. Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav. 2002 Apr;71(4):837-44.DISCLOSURE: The following authors have nothing to disclose: Srijana Rai, Pranabh Shrestha, Ram Katpally, Marc AdelmanNo Product/Research Disclosure Information.
PMID: 25334257 [PubMed - as supplied by publisher]
An Electrolyte Vortex.
Chest. 2014 Oct 1;146(4_MeetingAbstracts):264A
Authors: Hayward B, Smith R
SESSION TITLE: Critical Care Case Report Posters IIISESSION TYPE: Affiliate Case Report PosterPRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PMINTRODUCTION: We present an interesting case of medication-induced electrolyte disarray leading to a diagnostic challenge.CASE PRESENTATION: A patient presented with 1 month progressive lethargy, confusion, and polyuria. Past medical history included anal SCC in remission, bipolar disorder treated with lithium, and HIV controlled with HAART including tenofovir. Exam was notable for altered mental status, dry mucous membranes, abdominal tenderness, and copious dilute urine. Initial laboratory results in Table 1. 15 L of free water was repleted over 3 days without change in metabolic disarray. Hypernatremia was consistent with nephrogenic DI as no change occured in low urine osmolarity when given ddAVP. Hypercalcemia with inappropriately normal iPTH (and low PTHrp in setting of SCC) likely worsened free water loss. Lithium induced both of these disorders. Free water loss persisted. A concurrent metabolic acidosis was suspected from tenofovir-induced proximal RTA. Bicarbonate replacement was initiated with continued free water repletion with resultant improvement in mental status and hypercalcemia. Interestingly, once calcium was near normal level, iPTH was rechecked and found to be elevated (>200). By continuing this treatment, as well as discontinuing any offending agents, the patient had recovery from symptoms and near correction of metabolic disarray.DISCUSSION: Nephrogenic DI occurs in up to 20% of chronic lithium patients. It interferes with insertion of aquaporins into apical membranes and decreases density of ADH receptors, leading to free-water loss. It induces hypercalcemia by influencing kidney and parathyroid calcium-sensing receptors, altering the set-point of calcium-PTH axis. Hypercalcemia and elevated PTH result. Furthermore, hypercalcemia can worsen DI by interfering with vasopressin-stimulated water flow, downregulating aquaporins in the collecting ducts, and inhibiting NaCl reabsorption in the medullary thick ascending limb. Complicating matters, the high PTH could have led to bicarbonate loss in urine based on studies in animal models, worsening the tenofovir-induced RTA.CONCLUSIONS: A perpetual cycle of lithium-induced DI and hypercalcemia with tenofovir-induced proximal RTA existed in this patient. Close analysis and attempts to unify all metabolic derangements was needed to help diagnose and treat the persistent symptoms in this patient.Reference #1: Khairallah W et al. Hypercalcemia and diabetes insipidus in a patient previously treated with lithium. Nat Clin Pract Nephrol 2007;3:397-404.DISCLOSURE: The following authors have nothing to disclose: Bradley Hayward, Robert SmithNo Product/Research Disclosure Information.
PMID: 25334275 [PubMed - as supplied by publisher]
Dextromethorphan-Induced Serotonin Syndrome.
Chest. 2014 Oct 1;146(4_MeetingAbstracts):320A
Authors: Madisi N, Roopnarinesingh N, Berkeley J
SESSION TITLE: Critical Care Student/Resident CasesSESSION TYPE: Medical Student/Resident Case ReportPRESENTED ON: Tuesday, October 28, 2014 at 04:30 PM - 05:30 PMINTRODUCTION: Approximately one million patients misuse over the counter(OTC) dextromethorphan(DXM)-containing medications each year. Abuse has increased over the years as DXM is easily available and has dose-dependent hallucinogenic properties. Here we present a case of DXM-overdose resulting in serotonin syndrome (SS), a life-threatening condition.CASE PRESENTATION: A 52 year old man with a history of bipolar disorder and prior abuse of DXM, was brought to the ED after being found stiff in a chair and poorly responsive. Exam was significant for diaphoresis, tremors, agitation, hyperreflexia and altered mental status(AMS) requiring ICU admission for hypotension and hypoxemia. Significant laboratory data included a CPK of 18,000 units/L and myoglobin of 16,000 mcg/ml,consistent with rhabdomyolysis. He developed oliguric renal failure. Urine toxicology was positive for phencyclidine(PCP), though the serum toxicology screen was negative. All other toxicology screens were negative. History revealed that the patient had ingested 3 bottles of DXM earlier that day. Given his rigidity, AMS and diaphoresis, he was diagnosed with SS. He was treated with cyproheptadine and supportive therapy, including pressors, intubation and continous renal replacement therapy. His symptoms improved and he was discharged home.DISCUSSION: SS due to DXM is an under-recognized complication of abuse of this easily accessible OTC medication. DXM enhances serotonin activity by inhibiting its reuptake in the central nervous system1. SS is often difficult to recognize and the clinical diagnosis is made on the basis of the Hunter Criteria1. While several fatal cases of SS have been reported following overdose of DXM combined with co-ingestants, there are few case reports of acute respiratory and renal failure. Treatment involves supportive care. Cyproheptadine, an H1 antagonist, may also be used as it binds to 85-90% of serotonin receptors. Other treatments may include benzodiazepines, atypical antipsychotics and nondepolarizing muscle relaxants. Because SS can be fatal if not recognized and treated in a timely manner, it is especially important to consider all substances a patient may have ingested with the potential to cause SS. In this case, the positive toxicology screen for PCP was misleading, however, several reports have shown that DXM causes a false positive test result for PCP. Thus, in patients who present symptoms of SS, DXM overdose should be considered.CONCLUSIONS: Serotonin syndrome may be the dangerous result of medication abuse, misuse or most commonly, unintended drug interactions. Once SS is recognized, consultation with a toxicologist, clinical pharmacologist, or poison-control center can identify serotonergic agents and drug interactions, assist clinicians in anticipating adverse effects, and provide valuable clinical support.Reference #1: Boyer EW et al.The serotonin syndrome.N Engl J Med.2009 Oct 22;361(17):1714DISCLOSURE: The following authors have nothing to disclose: Nagendra Madisi, Nira Roopnarinesingh, Jennifer BerkeleyNo Product/Research Disclosure Information.
PMID: 25334337 [PubMed - as supplied by publisher]
Neck Swelling and Prostate Cancer...Can They Be Related?
Chest. 2014 Oct 1;146(4_MeetingAbstracts):654A
Authors: Khawar M, Phan M, Ali T
SESSION TITLE: Cancer Student/Resident Case Report Posters IISESSION TYPE: Medical Student/Resident Case ReportPRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PMINTRODUCTION: Prostate adenocarcinoma commonly metastasizes to the axial skeleton, lungs, and liver. Isolated metastasis to the thyroid gland is rare. We describe a patient with a sudden onset of neck swelling accompanied by clinical features of Superior Vena Cava Syndrome (SVCS), who later was found to have thyroid metastasis from prostate adenocarcinoma.CASE PRESENTATION: A 73-year-old male with a past medical history significant for hypertension and bipolar disorder, presented with the complaint of neck swelling, shortness of breath and hoarseness of voice. His symptoms started suddenly a few weeks back and accompanied by dysphagia to solid foods. The patient did not report any fever, chills, cough, hemoptysis, nausea/vomiting, change in appetite, weight loss, altered bowel movements, or dysuria. He had a 50 pack-year smoking history and a recovered alcoholic. Initial vital signs were stable and on physical examination, he had a moderate to large size swelling in the anterior part of the neck, palpable cervical and supraclavicular lymphadenopathy with telangiectasia and visible veins on the anterior neck. The Ultrasound of thyroid and soft tissue neck showed enlarged thyroid gland with no discrete nodules and multiple soft tissue masses/lymph nodes in the neck. Chest computed tomography (CT) showed small bilateral pleural effusion, cervical, supraclavicular and mediastinal lymphadenopathy, non-specific thyromegaly, and early side-to-side narrowing of the airways. Next, an Ultrasound guided fine needle aspiration & biopsy of thyroid gland and lymph nodes was done. The pathology came back positive for immunostaining with PSA and prostatic acid phosphatase; this was consistent with metastatic poorly differentiated adenocarcinoma of the prostate.DISCUSSION: Prostate Cancer is the most common malignancy in men and the second leading cause of cancer-related deaths. Prostate cancer with solitary metastasis to the thyroid gland and causing SVCS is very rare, to date there have been only six documented cases in the published literature. Patients presenting with a neck mass are commonly presumed to have a thyroid malignancy, less often is metastatic prostate cancer included in the differential diagnosis. Approximately 10-15% of patients with prostate cancer present with metastatic disease at the time of diagnosis.
CONCLUSIONS: Our case demonstrates that prostate cancer has the ability to uncommonly metastasize to the thyroid gland with neck swelling and SVCS being the sole clinical manifestation.Reference #1: Albsoul N, Obeidat F, Azmy H, et al. Isolated Multiple Bilateral Thyroid Metastases from Prostatic Adenocarcinoma: Case Report and Literature Review. Endocr Pathol (2013) 24:36-39DISCLOSURE: The following authors have nothing to disclose: Muhammad Khawar, Minh Phan, Tauseef AliNo Product/Research Disclosure Information.
PMID: 25334706 [PubMed - as supplied by publisher]
Asenapine in the treatment of older adults with bipolar disorder.
Int J Geriatr Psychiatry. 2014 Oct 21;
Authors: Sajatovic M, Dines P, Fuentes-Casiano E, Athey M, Cassidy KA, Sams J, Clegg K, Locala J, Stagno S, Tatsuoka C
OBJECTIVE: In spite of growing numbers of older people, there are few treatment studies on late-life bipolar disorder (BD). This was a 12-week prospective, open-label trial to assess efficacy and tolerability of adjunct asenapine in non-demented older adults (?60?years) with sub-optimal previous response to BD treatments.
METHODS: Asenapine was initiated at 5?mg/day and titrated as tolerated. Effects on global psychopathology were measured with Clinical Global Impression, bipolar version (CGI-BP), and the Brief Psychiatric Rating Scale (BPRS). Mood polarity severity was measured with the Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, and Young Mania Rating Scale. Other outcomes included the World Health Organization Disability Assessment Schedule II.
RESULTS: Fifteen individuals were enrolled (mean age 68.6, SD 6.12; 53% female; 73% Caucasian, 13% African American, and 7% Asian). There were 4/15 (27%) individuals who prematurely terminated the study, whereas 11/15 (73%) completed the study. There were significant improvements from baseline on the BPRS (p?<?0.05), on CGI-BP overall (p?<?0.01), and on CGI-BP mania (p?<?0.05) and depression (p?<?0.01) subscales. The mean dose of asenapine was 11.2 (SD 6.2)?mg/day. The most common reported side effects were gastrointestinal discomfort (n?=?5, 33%), restlessness (n?=?2, 13%), tremors (n?=?2, 13%), cognitive difficulties (n?=?2, 13%), and sluggishness (n?=?2, 13%).
CONCLUSIONS: Older people with BD had global improvements on asenapine. Most reported adverse effects were mild and transient, but adverse effects prompted drug discontinuation in just over one quarter of patients. Although risks versus benefits in older people must always be carefully considered, asenapine may be a treatment consideration for some non-demented geriatric BD patients. Copyright © 2014 John Wiley & Sons, Ltd.
PMID: 25335125 [PubMed - as supplied by publisher]
Antidepressants increase risk of behavioural symptoms in children and adolescents with depression or anxiety.
Evid Based Ment Health. 2014 Feb;17(1):4
Authors: Brent DA, Birmaher B
PMID: 24196004 [PubMed - indexed for MEDLINE]
Immunohistochemical mapping of neuropeptide Y in the tree shrew brain.
J Comp Neurol. 2014 Oct 17;
Authors: Ni RJ, Shu YM, Luo PH, Fang H, Wang Y, Yao L, Zhou JN
Day-active tree shrews are promising animals as research models for a variety of human disorders. Neuropeptide Y (NPY) modulates many behaviors in vertebrates. Here, we examined the distribution of NPY in the brain of tree shrews (Tupaia belangeri chinensis) using immunohistochemical techniques. The differential distribution of NPY-immunoreactive (-ir) cells and fibers were observed in the rhinencephalon, telencephalon, diencephalon, mesencephalon, metencephalon and myelencephalon of tree shrews. Most NPY-ir cells were multipolar or bipolar in shape with triangular, fusiform and/or globular perikarya. The densest cluster of NPY-ir cells were found in the mitral cell layer of the main olfactory bulb (MOB), arcuate nucleus of the hypothalamus and pretectal nucleus of the thalamus. The MOB presented a unique pattern of NPY immunoreactivity. Laminar distribution of NPY-ir cells was observed in the MOB, neocortex and hippocampus. Compared to rats, the tree shrews exhibited a particularly robust and widespread distribution of NPY-ir cells in the MOB, bed nucleus of the stria terminalis and amygdala as well as the ventral lateral geniculate nucleus and pretectal nucleus of the thalamus. By contrast, a low density of neurons were scattered in the striatum, neocortex, polymorph cell layer of the dentate gyrus, superior colliculus, inferior colliculus and dorsal tegmental nucleus. These findings provide the first detailed mapping of NPY immunoreactivity in the tree shrew brain and demonstrate species differences in the distribution of this neuropeptide, providing an anatomical basis for the participation of the NPY system in the regulation of numerous physiological and behavioral processes. J. Comp. Neurol., 2014. © 2014 Wiley Periodicals, Inc.
PMID: 25327585 [PubMed - as supplied by publisher]
Molecular study of weight gain related to atypical antipsychotics: clinical implications of the CYP2D6 genotype.
Rom J Morphol Embryol. 2014;55(3):877-884
Authors: Nussbaum LA, Dumitra?cu V, Tudor A, Gr?dinaru R, Andreescu N, Puiu M
Atypical antipsychotics, especially some of them, influence cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of atypical antipsychotics in children and adolescents, their metabolic and endocrine adverse effects are of particular concern especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on atypical antipsychotics adverse effects include CYP2D6 polymorphisms. Our study, performed in 2009-2014, with a two-year enrolment period during which we recruited children and adolescents with a diagnosis of schizophrenia or bipolar disorder on treatment with the antipsychotics (Risperidone, Aripiprazole or Olanzapine), included 81 patients, aged between 9 and 20 years, median age being 15.74 years. The gender percentage was 54% girls÷46% boys. The CYP2D6 genotyping was performed after enrolment of the last patient. Based on the CYP2D6 genotype, three activity groups were identified and compared and we found that the patients with wt÷*4 genotype, intermediary metabolizer (carrier of one functional and one non-functional allele) have significantly higher weight gain values than the patients who did not exhibit allele *4. The CYP2D6 genotype in children and adolescents with schizophrenia and bipolar disorder, proved to be a good predictor for the response to atypical antipsychotics and the side effects registered. The significant correlations between the CYP2D6 polymorphisms and the weight gain÷BMI (body mass index) increase, as major side effects induced by antipsychotics proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk individuals.
PMID: 25329115 [PubMed - as supplied by publisher]
International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder.
Bipolar Disord. 2014 Oct 20;
Authors: Schaffer A, Isometsä ET, Tondo L, H Moreno D, Turecki G, Reis C, Cassidy F, Sinyor M, Azorin JM, Kessing LV, Ha K, Goldstein T, Weizman A, Beautrais A, Chou YH, Diazgranados N, Levitt AJ, Zarate CA, Rihmer Z, Yatham LN
OBJECTIVES: Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder.
METHODS: Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which ? 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies.
RESULTS: Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide.
CONCLUSIONS: This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder.
PMID: 25329791 [PubMed - as supplied by publisher]
Quantitative EEG and Current Source Density Analysis of Combined Antiepileptic Drugs and Dopaminergic Agents in Genetic Epilepsy: Two Case Studies.
Clin EEG Neurosci. 2014 Oct 17;
Authors: Emory H, Wells C, Mizrahi N
Two adolescent females with absence epilepsy were classified, one as attention deficit and the other as bipolar disorder. Physical and cognitive exams identified hypotension, bradycardia, and cognitive dysfunction. Their initial electroencephalograms (EEGs) were considered slightly slow, but within normal limits. Quantitative EEG (QEEG) data included relative theta excess and low alpha mean frequencies. A combined treatment of antiepileptic drugs with a catecholamine agonist/reuptake inhibitor was sequentially used. Both patients' physical and cognitive functions improved and they have remained seizure free. The clinical outcomes were correlated with statistically significant changes in QEEG measures toward normal Z-scores in both anterior and posterior regions. In addition, low resolution electromagnetic tomography (LORETA) Z-scored source correlation analyses of the initial and treated QEEG data showed normalized patterns, supporting a neuroanatomic resolution. This study presents preliminary evidence for a neurophysiologic approach to patients with absence epilepsy and comorbid disorders and may provide a method for further research.
PMID: 25326290 [PubMed - as supplied by publisher]
Creative cognition and systems biology on the edge of chaos.
Front Psychol. 2014;5:1104
Authors: Bilder RM, Knudsen KS
PMID: 25324809 [PubMed]
Gender and the relative importance of mental health satisfaction domains.
Eval Program Plann. 2014 Apr;43:9-15
Authors: Robillos E, Lale R, Wooldridge J, Heller R, Sarkin A
Consumer-reported satisfaction data is a tool used for measuring and targeting areas for quality improvement in mental healthcare. In this study, we investigated the relationship between gender and the relative importance of mental health service satisfaction domains to overall satisfaction, in addition to gender differences in satisfaction across domains. People receiving mental health services (1765 males and 1950 females) completed questionnaires regarding their overall service satisfaction and satisfaction along six domains: Access to Services, Quality and Appropriateness, Participation in Treatment Planning, Outcome of Services, Social Connectedness, and Functioning. While all were important to overall satisfaction across genders, women reported slightly higher overall satisfaction. Linear regression analyses were used to determine the relative importance of these subscales to overall satisfaction for each gender. While the correlations between each subscale and overall satisfaction were significant for both, gender was found to moderate the relationship between some subscales and overall satisfaction. Although predictive of overall service satisfaction across the sample, we found Functioning, Outcome of Services, Social Connectedness, and Access to Services were relatively more important to overall satisfaction for men than women. Consistent feedback of results and improved access to services may be particularly effective for engaging both men and women in treatment.
PMID: 24246160 [PubMed - indexed for MEDLINE]
Characteristics of men accompanying their partners to a specialist antenatal clinic for women with severe mental illness.
Asian J Psychiatr. 2014 Feb;7(1):46-51
Authors: Frayne J, Brooks J, Nguyen TN, Allen S, Maclean M, Fisher J
PURPOSE: Partners are often enlisted in the care and management of pregnant women with severe mental illness (SMI); however their needs and capacity to provide support is not yet well understood. We aim to describe the psychosocial characteristics, health behaviours and appraisals of parenthood of men accompanying their partners with SMI to a specialist antenatal clinic.
METHODS: A 36-question, study-specific cross sectional survey was completed by men whose partners with SMI were receiving antenatal care at a specialist multidisciplinary clinic over a 12-month period.
RESULTS: A high percentage of eligible participants (40/41, 97.5%) completed the survey. Overall 25% depended for income on social security benefits; 60% reported smoking, alcohol and drug using behaviours that carried high health risks; 18% had a history of domestic violence order (DVO) being taken out against them, and 12.5% a documented history of bipolar or schizophrenic illnesses. Despite these risk factors they reported high satisfaction with their intimate partner relationships, and all anticipated the birth of the baby and impending fatherhood with enthusiasm, optimism and perhaps idealisation.
CONCLUSIONS: Men who are the pregnancy partners of women with SMI, appear to be an especially vulnerable population, who report high rates of psychosocial difficulties, which are likely to have an adverse impact on their capacity for realistic planning and support of their partners in this critical period of adjustment to parenthood. We recommend enhanced models of clinical care in which assessment and provision of support for partners is incorporated in comprehensive care of the pregnant woman with SMI.
PMID: 24524709 [PubMed - indexed for MEDLINE]
Insulin resistance and outcome in bipolar disorder.
Br J Psychiatry. 2014 Oct 16;
Authors: Calkin CV, Ruzickova M, Uher R, Hajek T, Slaney CM, Garnham JS, O'Donovan MC, Alda M
Background Little is known about the impact of insulin resistance on bipolar disorder. Aims To examine the relationships between insulin resistance, type 2 diabetes and clinical course and treatment outcomes in bipolar disorder. Method We measured fasting glucose and insulin in 121 adults with bipolar disorder. We diagnosed type 2 diabetes and determined insulin resistance. The National Institute of Mental Health Life Chart was used to record the course of bipolar disorder and the Alda scale to establish response to prophylactic lithium treatment. Results Patients with bipolar disorder and type 2 diabetes or insulin resistance had three times higher odds of a chronic course of bipolar disorder compared with euglycaemic patients (50% and 48.7% respectively v. 27.3%, odds ratio (OR) = 3.07, P = 0.007), three times higher odds of rapid cycling (38.5% and 39.5% respectively v. 18.2%, OR = 3.13, P = 0.012) and were more likely to be refractory to lithium treatment (36.8% and 36.7% respectively v. 3.2%, OR = 8.40, P<0.0001). All associations remained significant after controlling for antipsychotic exposure and body mass index in sensitivity analyses. Conclusions Comorbid insulin resistance may be an important factor in resistance to treatment in bipolar disorder.
PMID: 25323142 [PubMed - as supplied by publisher]
Psychological problems and clinical outcomes of children with psychogenic non-epileptic seizures.
Yonsei Med J. 2014 Nov 1;55(6):1556-61
Authors: Yi YY, Kim HD, Lee JS, Cheon KA, Kang HC
PURPOSE: Our purpose was to investigate psychological problems and clinical outcomes in children with psychogenic non-epileptic seizures (PNES).
MATERIALS AND METHODS: We retrospectively reviewed the data of 25 patients who were diagnosed with PNES between 2006 and 2012.
RESULTS: Twenty-five children with PNES, aged 8 to 19 years (mean 13.82), were referred to psychiatrists for psychiatric assessment. On their initial visit, 72% of patients had comorbid psychological problems, including depression, anxiety, conduct disorder, adjustment disorder, Attention Deficit Hyperactivity Disorder, schizophrenia, and bipolar disorder. Among these, depression was the most frequent (36%). Predisposing and triggering factors included familial distress (40%), social distress (24%), and specific events (20%). The following treatment was advised based on the results of the initial psychological assessment: 3 patients regularly visited psychiatric clinic to assess their clinical status without treatment, nine underwent psychotherapy, and 13 received a combination of psychotherapy and psychopharmacological therapy. At the mean follow-up of 31.5 months after diagnosis, 20 patients (80%) were event-free at follow-up, three (12%) showed reduced frequency, and two (8%) experienced persistent symptoms.
CONCLUSION: The outcomes of PNES in children are much better than those in adults, despite a high rate of psychological comorbidities.
PMID: 25323891 [PubMed - in process]
Factors affecting disruption in families of adults with mental illness.
Perspect Psychiatr Care. 2014 Oct;50(4):235-42
Authors: Suresky MJ, Zauszniewski JA, Bekhet AK
PURPOSE: This study examined relationships between vulnerability/risk and protective factors, and family functioning in women family members of adults with serious mental illness.
DESIGN AND METHODS: Using a descriptive, correlational design, this secondary analysis examined characteristics of the family member with mental illness (e.g., diagnosis, level of care) and measures of caregiver stigma and strain, client dependence, family disruption, sense of coherence, and resourcefulness.
FINDINGS: Family disruption was greatest in women who provided direct care and whose family member had major depression, followed by bipolar disorder, schizophrenia, and panic disorder. Sense of coherence and resourcefulness were associated with lower family disruption, but did not mediate the effects of caregiver strain.
PRACTICE IMPLICATIONS: Interventions restricted to one family member may be insufficient for improving the family functioning.
PMID: 25324027 [PubMed - in process]
Training Mental Health Nurses to Assess the Physical Health Needs of Mental Health Service Users: A Pre- and Post-test Analysis.
Perspect Psychiatr Care. 2014 Oct;50(4):243-50
Authors: White J, Hemingway S, Stephenson J
PURPOSE: The aim of this project was to develop, deliver, and evaluate a brief evidenced-based education package to enhance physical health literacy in mental health nurses.
DESIGN AND METHODS: Pre- and post-test survey of knowledge of physical health in serious mental illness, satisfaction with the workshop, and applicability to practice.
FINDINGS: Participants were motivated to attend and complete the questions. There was statistically significant knowledge gain immediately post workshop and participants described satisfaction with the content and a willingness to apply learning from the session to their practice.
PRACTICE IMPLICATIONS: If such workshops are provided as a collaborative and relatively inexpensive way of education, they can contribute to building the capacity of mental health nurses to be literate in physical health interventions.
PMID: 25324028 [PubMed - in process]
Clinical Evaluation of Youth with Pediatric Acute Onset Neuropsychiatric Syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference.
J Child Adolesc Psychopharmacol. 2014 Oct 17;
Authors: Chang K, Frankovich J, Cooperstock M, Cunningham M, Latimer ME, Murphy TK, Pasternack M, Thienemann M, Williams K, Walter J, Swedo SE
Abstract On May 23 and 24, 2013, the First PANS Consensus Conference was convened at Stanford University, calling together a geographically diverse group of clinicians and researchers from complementary fields of pediatrics: General and developmental pediatrics, infectious diseases, immunology, rheumatology, neurology, and child psychiatry. Participants were academicians with clinical and research interests in pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS) in youth, and the larger category of pediatric acute-onset neuropsychiatric syndrome (PANS). The goals were to clarify the diagnostic boundaries of PANS, to develop systematic strategies for evaluation of suspected PANS cases, and to set forth the most urgently needed studies in this field. Presented here is a consensus statement proposing recommendations for the diagnostic evaluation of youth presenting with PANS.
PMID: 25325534 [PubMed - as supplied by publisher]
Gaze Maintenance and Autism Spectrum Disorder.
J Dev Behav Pediatr. 2014 Oct 16;
Authors: Kaye L, Kurtz M, Tierney C, Soni A, Augustyn M
CASE: Chase is a 5½-year-old boy whom you have followed in your primary care practice since age 26 months. He was born full-term vaginal delivery weighing 6 pounds 15 ounces. His biological mother used heroin, tobacco, and cocaine during pregnancy. From 8 weeks to 18 months, he spent time in a foster home where he was provided limited attention and nurturing. At age 18 months, he entered a loving foster home; at 26 months, he was adopted. There is maternal history of attention-deficit hyperactivity disorder, learning disability, depression, bipolar disorder, and substance abuse but no history of autism or cognitive disability.Chase received early intervention before adoption. Specific concerns are unknown. At the time of his adoption, he had delays in gross motor and fine motor skills, nonverbal communication, and speech production. Familiar listeners find Chase to be 100% intelligible but unfamiliar listeners understand about 70% of what Chase says. He enjoys being with his adopted mother and imitating her. He has demonstrated significant anxiety during his play therapy. He has difficulty in paying attention to multistep directions. Chase can point and wave but has difficulty following someone's eyes to see where another person is looking.Chase enjoys a variety of interests but has a special fixation on Toy Story characters. Chase does initiate social interactions but can be aggressive toward his siblings and oppositional toward his parents. He is not aggressive at school. Teachers note hyperactivity and impulsivity. Chase is bothered by bright lights and by others making loud noises but has no difficulty with crowds. Chase is reported to have difficulty in transitioning between activities.At his 5-year-old visit, you as well as his mother and therapists note that he has trouble following with his eyes so he is referred to a neuro-ophthalmologist. Evaluation showed Chase was able to fix on and follow objects and light, his peripheral vision was normal, his pupils were equal and reactive without afferent pupillary defect, and normal visual tracking as assessed through pursuit and saccades. There were some head jerking motions observed which were not thought to be part of Chase's attempts to view objects. Gaze impersistence was noted, although it was not clear if this was due to a lack of attention or a true inability to maintain a gaze in the direction instructed.On review of the school's speech and language report, they state that he is >90% intelligible. He has occasional lip trills. Testing with the Clinical Evaluation of Language Fundamentals shows mild delays in receptive language, especially those that require visual attention. Verbal Motor Production Assessment for Children reveals focal oromotor control and sequencing skills that are below average, with groping when asked to imitate single oromotor nonspeech movements and sequenced double oromotor nonspeech movements.At 5½ years, he returns for follow-up, and he is outgoing and imaginative, eager to play and socialize. He makes eye contact but does not always maintain it. He asks and responds to questions appropriately, and he is able to follow verbal directions and verbal redirection. He is very interested in Toy Story characters but willing to share them and plays with other toys. Chase's speech has predictable, easy to decode sound substitutions.On interview with him, you feel that he has borderline cognitive abilities. He also demonstrates good eye contact but lack of visual gaze maintenance; this is the opposite of the pattern you are accustomed to in-patients with autism spectrum disorder. What do you do next?
PMID: 25325757 [PubMed - as supplied by publisher]
Successful use of right unilateral ECT for catatonia: a case series.
J ECT. 2014 Mar;30(1):69-72
Authors: Cristancho P, Jewkes D, Mon T, Conway C
Catatonia is a neuropsychiatric syndrome involving motor signs in association with disorders of mood, behavior, or thought. Bitemporal electrode placement electroconvulsive therapy (ECT) is a proven effective treatment for catatonia, and this mode of ECT delivery is the preferred method of treatment in this condition. Studies in major depressive disorder have demonstrated that suprathreshold, nondominant (right) hemisphere, unilateral electrode placement ECT has fewer adverse effects, especially cognitive adverse effects, than bitemporal ECT. This case series describes the use of right unilateral (RUL) ECT in 5 patients with catatonia. Before ECT, all 5 patients in this series initially failed therapy with benzodiazepines and psychotropic medications. Each catatonic patient received a series of 8 to 12 RUL ECT in an every-other-day series. After ECT, 4 of the 5 patients had a full recovery from catatonia. One patient achieved only partial response to RUL ECT, and no additional benefit was obtained with bitemporal ECT. All patients in this case series tolerated RUL ECT without major adverse effects. This case series illustrates successful use of RUL ECT in patients with catatonia and adds to the early literature demonstrating its effective use in treating this complex condition.
PMID: 23859978 [PubMed - indexed for MEDLINE]
The role of ECT in suicide prevention.
J ECT. 2014 Mar;30(1):5-9
Authors: Fink M, Kellner CH, McCall WV
Suicide is a leading cause of death among psychiatric patients, and a leading cause of death from all causes in people younger than 30 years. The rapid relief of severe depression, mania, and psychosis by electroconvulsive therapy (ECT) is accompanied by the rapid reduction in suicide drive. Electroconvulsive therapy use is, however, inhibited by fear of electricity, unreasoned prejudice, legislative restrictions, and the limited availability of trained professionals and adequate facilities. This review assesses the experience with ECT in persons with suicide risk and recommends the consideration of ECT in treatment algorithms to reduce suicide rates.
PMID: 24091903 [PubMed - indexed for MEDLINE]
Mixed depression in the postpartum period: diagnostic and treatment issues.
J Psychiatry Neurosci. 2013 Nov;38(6):E30-1
Authors: Sharma V
PMID: 24148848 [PubMed - indexed for MEDLINE]
Symptoms and observations: differences in time course during electroconvulsive therapy in geriatric depressed patients.
J ECT. 2014 Mar;30(1):e7-8
Authors: Mahgoub N, Lerner M, Kalayam B, Young RC
Electroconvulsive therapy is used for the management of severe and refractory depression across the age spectrum. Treatment is guided by clinical response. However, there may be differences between the time course of improvement in clinical observations and patients' self-report of improvements. We report 4 cases of depression in late life that illustrate this issue. We discuss the potential significance of such differences and the need for research.
PMID: 24487646 [PubMed - indexed for MEDLINE]
Increased ICAM, VCAM, and E-selectin levels in first manic episode.
Bipolar Disord. 2014 Oct 16;
Authors: Kesebir S, Turan C, Süner O, Yaylac? ET
OBJECTIVES: In patients with bipolar disorder, the rate of mortality from cardiovascular disease is twofold higher than that in other psychiatric disorders. The risk of cardiovascular disease has been found to be associated with intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and E-selectin. The aim of the present study was to compare ICAM, VCAM, and E-selectin levels in patients with bipolar disorder at first manic episode and in healthy controls, and to investigate the presence of a relationship between adhesion molecule levels and clinical properties.
METHODS: Fifty patients with bipolar disorder diagnosed with mania according to DSM-IV-TR criteria, who were experiencing their first episode, were evaluated consecutively. The control group consisted of 50 healthy individuals with no history of psychiatric treatment, matched with the manic patients in terms of age, gender, and smoking status. The Young Mania Rating Scale was used for confirmation of severity of mania. Plasma ICAM, VCAM, and E-selectin levels were measured and compared between the two groups.
RESULTS: ICAM and VCAM levels were found to be higher in first-manic episode patients than in healthy individuals. A weak correlation was found between ICAM levels and YMRS scores in manic patients.
CONCLUSIONS: In the present study, which is the first to look at the proinflammatory and prothrombotic state in bipolar disorder, ICAM and VCAM levels were found to be higher in first-episode mania patients than in healthy individuals. As the study group included first-episode mania cases, there was no effect seen from the long-term use of psychotropic agents. Risk of cardiovascular disease, reflected by increased ICAM and VCAM levels, is generally present in patients with bipolar disorder at the onset of the disease.
PMID: 25318825 [PubMed - as supplied by publisher]
Intensive ketamine use for multiple years: A case report.
Am J Addict. 2014 Oct 15;
Authors: Liu JX, Zerbo E, Ross S
Ketamine is known within the medical field for its anesthetic properties, yet its unique psychedelic and antidepressant properties are being increasingly recognized. We document the case of a patient with bipolar I disorder and an extensive history of substance dependence who used large doses of ketamine (1-3?g) on a daily basis over a period of 5 years, and described acute antidepressant effects as well as diminished cravings for alcohol. While his use was untenable and ultimately led to an inpatient admission, it is notable that he did not experience a withdrawal syndrome nor did he have any observable cognitive deficits upon cessation of use. Such a unique drug profile suggests that further exploration of its risks and therapeutic potential in treating mood and addiction disorders is warranted. (Am J Addict 2014;XX:1-3).
PMID: 25318850 [PubMed - as supplied by publisher]
Whole Genome/Exome Sequencing in Mood and Psychotic Disorders.
Psychiatry Clin Neurosci. 2014 Oct 16;
Authors: Kato T
Recent developments in DNA sequencing technologies have allowed for genetic studies using whole genome or exome analysis, and these have been applied in the study of mood and psychotic disorders, including bipolar disorder, depression, schizophrenia, and schizoaffective disorder. In this review, current situation, recent findings, methodological problems, and future directions of whole genome/exome analysis studies of these disorders are summarized. Whole genome/exome studies of bipolar disorder have included pedigree analysis and case control studies, demonstrating the role of previously implicated pathways, such as calcium signaling, CREB signaling, and potassium channels. Extensive analysis of trio families and case control studies showed that de novo mutations play a role in the genetic architecture of schizophrenia and indicated that mutations in several molecular pathways including chromatin regulation, activity-regulated cytoskeleton, post synaptic density, NMDA (N-methyl-D-aspartate) receptor, and targets of FMRP (fragile X mental retardation protein), are associated with this disorder. Depression is a heterogeneous group of diseases and studies using exome analysis have been conducted to identify rare mutations causing Mendelian diseases that accompany depression. In the near future, clarification of the genetic architecture of bipolar disorder and schizophrenia is expected. Identification of causative mutations using these new technologies will facilitate neurobiological studies of these disorders.
PMID: 25319632 [PubMed - as supplied by publisher]