Is it still correct to differentiate between early and very early onset psychosis?
Schizophr Res. 2016 Jan;170(1):211-6
Authors: Lin A, Wardenaar KJ, Pontillo M, De Crescenzo F, Mazzone L, Vicari S, Wood SJ, Beavan A, Armando M
OBJECTIVE: It remains unclear whether very early onset psychosis (VEOP; ?12years of age) and early onset psychosis (EOP; onset 13-17years of age) are homogeneous in their clinical presentation. We investigated the predictive value of age of psychosis onset for severity, functioning and demographic variation by: 1) comparing groups based on traditional cut-offs for age of psychosis onset, and 2) using receiver operating characteristic (ROC)-curve calculations, without a priori age of onset cut-offs.
METHOD: Participants were 88 (45 female, 43 male) children and adolescents with a recent onset of psychosis (age range=6.7-17.5years; M=13.74, SD=2.37).
RESULTS: The VEOP group had significantly shorter duration of untreated illness and untreated psychosis, and lower functioning than the EOP group. The VEOP and EOP groups did not differ significantly on gender proportion, urbanicity, psychotic diagnosis, family history of psychotic disorder, psychotic, depressive and anxiety symptoms or IQ. When applying ROC-curves to the lowest three quartiles of positive psychotic symptoms scores, the optimal age-cut-off was 14.0years (sensitivity=0.62; specificity=0.75). For the highest quartile of functioning scores, the optimal differentiating cut-off for age of psychosis onset was 14.7years (sensitivity=0.71; specificity=0.70).
CONCLUSIONS: Larger samples of patients, assessed at presentation and followed-up, are necessary to clearly examine clinical presentation and outcome as a function of social and neural development to better understand if the differentiation between VEOP and EOP is justified. This will aid the development of predictive diagnostic tools, more accurate prognosis prediction, and age-tailored therapeutic interventions.
PMID: 26639553 [PubMed - indexed for MEDLINE]
Associations between mood instability and emotional processing in a large cohort of bipolar patients.
Psychol Med. 2016 Nov;46(15):3151-3160
Authors: Bilderbeck AC, Reed ZE, McMahon HC, Atkinson LZ, Price J, Geddes JR, Goodwin GM, Harmer CJ
BACKGROUND: Aberrant emotional biases have been reported in bipolar disorder (BD), but results are inconsistent. Despite the clinical relevance of chronic mood variability in BD, there is no previous research investigating how the extent of symptom fluctuations in bipolar disorder might relate to emotional biases. This exploratory study investigated, in a large cohort of bipolar patients, whether instability in weekly mood episode symptoms and other clinical and demographic factors were related to emotional bias as measured in a simple laboratory task.
METHOD: Participants (N = 271, BDI = 206, BDII = 121) completed an 'emotional categorization and memory' task. Weekly self-reported symptoms of depression and mania were collected prospectively. In linear regression analyses, associations between cognitive bias and mood variability were explored together with the influence of demographic and clinical factors, including current medication.
RESULTS: Greater accuracy in the classification of negative words relative to positive words was associated with greater instability in depressive symptoms. Furthermore, greater negative bias in free recall was associated with higher instability in manic symptoms. Participants diagnosed with BDII, compared with BDI, showed overall better word recognition and recall. Current antipsychotic use was associated with reduced instability in manic symptoms but this did not impact on emotional processing performance.
CONCLUSIONS: Emotional processing biases in bipolar disorder are related to instability in mood. These findings prompt further investigation into the underpinnings as well as clinical significance of mood instability.
PMID: 27572660 [PubMed - in process]
Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.
Psychol Med. 2016 Nov;46(15):3187-3198
Authors: Schreiter S, Spengler S, Willert A, Mohnke S, Herold D, Erk S, Romanczuk-Seiferth N, Quinlivan E, Hindi-Attar C, Banzhaf C, Wackerhagen C, Romund L, Garbusow M, Stamm T, Heinz A, Walter H, Bermpohl F
BACKGROUND: Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses.
METHOD: During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately.
RESULTS: BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation.
CONCLUSIONS: This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.
PMID: 27573157 [PubMed - in process]
Reelin and Neuropsychiatric Disorders.
Front Cell Neurosci. 2016;10:229
Authors: Ishii K, Kubo KI, Nakajima K
Proper neuronal migration and laminar formation during corticogenesis is essential for normal brain function. Disruption of these developmental processes is thought to be involved in the pathogenesis of some neuropsychiatric conditions. Especially, Reelin, a glycoprotein mainly secreted by the Cajal-Retzius cells and a subpopulation of GABAergic interneurons, has been shown to play a critical role, both during embryonic and postnatal periods. Indeed, animal studies have clearly revealed that Reelin is an essential molecule for proper migration of cortical neurons and finally regulates the cell positioning in the cortex during embryonic and early postnatal stages; by contrast, Reelin signaling is closely involved in synaptic function in adulthood. In humans, genetic studies have shown that the reelin gene (RELN) is associated with a number of psychiatric diseases, including Schizophrenia (SZ), bipolar disorder (BP) and autistic spectrum disorder. Indeed, Reln haploinsufficiency has been shown to cause cognitive impairment in rodents, suggesting the expression level of the Reelin protein is closely related to the higher brain functions. However, the molecular abnormalities in the Reelin pathway involved in the pathogenesis of psychiatric disorders are not yet fully understood. In this article, we review the current progress in the understanding of the Reelin functions that could be related to the pathogenesis of psychiatric disorders. Furthermore, we discuss the basis for selecting Reelin and molecules in its downstream signaling pathway as potential therapeutic targets for psychiatric illnesses.
PMID: 27803648 [PubMed - in process]
Non-Compliance and Related Factors in Patients With Bipolar I Disorder: A Six Month Follow-Up Study.
Iran J Psychiatry Behav Sci. 2016 Jun;10(2):e2448
Authors: Azadforouz S, Shabani A, Nohesara S, Ahmadzad-Asl M
BACKGROUND: Medication treatment compliance among bipolar patients is quite widespread.
OBJECTIVES: Treatment compliance depends on multiple factors. The aim of this study was to evaluate the predicting factors of noncompliance in patients with bipolar I disorder admitted to an Iranian hospital during a six-month follow up period.
MATERIALS AND METHODS: This cross-sectional study included 47 bipolar I disorder subjects who were admitted to the Iran psychiatric hospital and that were chosen using a non-randomized convenient sampling model. The patients were assessed at baseline, and at two and six months after admission. For evaluating the patients, we used the medication possession ratio (MPR), the drug attitude inventory (DIA-10), the young mania rating scale (Y-MRS) and the scale for the assessment of positive symptoms (SAPS). The data were analyzed using a general linear model by SPSS 16 software.
RESULTS: The repeated measures analysis revealed that medication compliance increased successively (P = 0.045), and age, gender and symptom severity did not alter the pattern.
CONCLUSIONS: There is an increasing pattern in treatment compliance in bipolar I disorder patients, regardless of the known predicting factors for nonadherence.
PMID: 27803718 [PubMed - in process]
A Magnetic Resonance Spectroscopy study of lovastatin for treating Bipolar Mood disorder, A-4 week Randomized Double Blind, Placebo- Controlled Clinical Trial.
Recent Pat Inflamm Allergy Drug Discov. 2016 Oct 28;
Authors: Lotfi M, Shafiee S, Ghanizadeh A, Sigaroudi MO, Rzeghian L
BACKGROUND: No trial have examined the effect of lovastatin on the brain metabolites in patients with bipolar mood disorder.
OBJECTIVES: Current medications for treating bipolar disorders cause metabolic syndrome. it is supposed that lovastatin not only decreases the rate of metabolic syndrome but also impacts some brain metabolitis and their ratio like common treatments that are measured by Magnetic Resonance Spectroscopy .
METHODS: 27 manic phase patients were randomly allocated into two groups,lovastatin and placebo as their adjuant medication.Clinical symptoms were assessed at baseline,weeks 2,4.The brain metabolites were measured at baseline and week 4.
RESULT: Regarding the change of clinical symptoms, no significant difference was found between two groups. However, lovastatin significantly increased the level of NAA in cingulate gyrus in comparison to the placebo group.Moreover, lovastatin more than placebo increased Creatine in left basal ganglia. Furthermore, choline/creatine showed a significant decrease in left basal ganglia in lovastatin group.
CONCLUSION: Using MRS after treating with Lovastatin showed lovastatin increases NAA in cingulate gyrus, indicating the possible effect of NAA for increasing the reduced viable neuron. Moreover, the increment of Cr by lovastatin in the left basal ganglia suggests the role of lovastatin for maintaining energy homeostasis, anti-apoptotic activity and ATP production in bipolar disorder.Some patents on the use of lovastatin as an adjuant therapy for treating bipolar patients and depression in MDD patients are also outlined. This trial was registered in the Iranian Clinical Trials Registry (http://www.irct.ir/)(IRCT201302203930N18) .
PMID: 27804862 [PubMed - as supplied by publisher]
Pros and cons of medical cannabis use by people with chronic brain disorders.
Curr Neuropharmacol. 2016 Oct 31;
Authors: Suryadevara U, Bruijnzeel DM, Nuthi M, Jagnarine DA, Tandon R, Bruijnzeel AW
BACKGROUND: Cannabis is the most widely used illicit drug in the world and there is growing concern about the mental health effects of cannabis use. These concerns are at least partly due to the strong increase in recreational and medical cannabis use and the rise in tetrahydrocannabinol (THC) levels. Cannabis is widely used to self-medicate by older people and people with brain disorders such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), bipolar disorder, and schizophrenia.
OBJECTIVE: This review provides an overview of the perceived benefits and adverse mental health effects of cannabis use in people with ALS, MS, AD, PD, bipolar disorder, and schizophrenia.
RESULTS: The reviewed studies indicate that cannabis use diminishes some symptoms associated with these disorders. Cannabis use decreases pain and spasticity in people with MS, decreases tremor, rigidity, and pain in people with PD, and improves the quality of life of ALS patients by improving appetite, and decreasing pain and spasticity. Cannabis use is more common among people with schizophrenia than healthy controls. Cannabis use is a risk factor for schizophrenia and increases positive symptoms in schizophrenia patients but diminishes negative symptoms. Cannabis use worsens bipolar disorder and there is no evidence that bipolar patients derive any benefit from cannabis. In late stage Alzheimer's patients, cannabis products may improve food intake, sleep quality, and diminish agitation.
CONCLUSION: Cannabis use diminishes some of the adverse effects of neurological and psychiatric disorders. However, chronic cannabis use may lead to cognitive impairments and dependence.
PMID: 27804883 [PubMed - as supplied by publisher]
Can subsyndromal manifestations of major depression be identified in children at risk?
Acta Psychiatr Scand. 2016 Nov 2;:
Authors: Uchida M, Fitzgerald M, Lin K, Carrellas N, Woodworth H, Biederman J
OBJECTIVE: Children of parents with major depression are at significantly increased risk for developing major depression themselves; however, not all children at genetic risk will develop major depressive disorder (MDD). We investigated the utility of subsyndromal scores on the Child Behavior Checklist (CBCL) Anxiety/Depression scale in identifying children at the highest risk for pediatric MDD from among the pool of children of parents with MDD or bipolar disorder.
METHOD: The sample was derived from two previously conducted longitudinal case-control family studies of psychiatrically and pediatrically referred youth and their families. For this study, probands were stratified based on the presence or absence of a parental mood disorder.
RESULTS: Subsyndromal scores on the CBCL Anxiety/Depression scale significantly separated the children at high risk for pediatric MDD from those at low risk in a variety of functional areas, including social and academic functioning. Additionally, children at genetic risk without elevated CBCL Anxiety/Depression scale scores were largely indistinguishable from controls.
CONCLUSION: These results suggest that the CBCL Anxiety/Depression scale can help identify children at highest risk for pediatric MDD. If implemented clinically, this scale would cost-effectively screen children and identify those most in need of early intervention resources to impede the progression of depression.
PMID: 27805260 [PubMed - as supplied by publisher]
Rethinking the Use of Neutral Faces as a Baseline in fMRI Neuroimaging Studies of Axis-I Psychiatric Disorders.
J Neuroimaging. 2016 Nov 2;:
Authors: Filkowski MM, Haas BW
Major Axis-I disorders including major depressive disorder (MDD), bipolar disorder (BD), anxiety disorder, and schizophrenia are associated with a host of aberrations in the way social stimuli are processed. Face perception tasks are often used in neuroimaging research of emotion processing in both healthy and patient populations, and to date, there exists a mounting body of evidence, both behavioral and within the brain, indicating that emotional faces compared to neutral faces are processed abnormally by those with Axis-I disorders relative to healthy control (HC) groups. The use of neutral faces as a "baseline control condition" is predicated on the assumption that neutral faces are processed in the same way HCs and individuals with major Axis-I disorders. In this paper, existing fMRI studies examining the way neutral faces are processed in groups with Axis-I disorders involving socioaffective perception are reviewed. In reviewing available studies, a consistent pattern of results demonstrated that these disorders are associated with abnormal frontolimbic activity in response to neutral faces and in particular within the amygdala and prefrontal regions such as the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) compared to HC groups. Specifically, increased amygdala activation was consistently reported in response to neutral faces in anxiety disorders and schizophrenia. Abnormal medial PFC activity was reported in patients with MDD, and patients with BD exhibit decreased activity in the DLPFC and ACC relative to HCs. In addition, specific suggestions to overcome these obstacles with new research and additional analyses are discussed.
PMID: 27805291 [PubMed - as supplied by publisher]
Step-wise loss of antidepressant effectiveness with repeated antidepressant trials in bipolar II depression.
Bipolar Disord. 2016 Nov 2;:
Authors: Amsterdam JD, Lorenzo-Luaces L, DeRubeis RJ
OBJECTIVE: This study examined the relationship between the number of prior antidepressant treatment trials and step-wise increase in pharmacodynamic tolerance (or progressive loss of effectiveness) in subjects with bipolar II depression.
METHODS: Subjects ?18 years old with bipolar II depression (n=129) were randomized to double-blind venlafaxine or lithium carbonate monotherapy for 12 weeks. Responders (n=59) received continuation monotherapy for six additional months.
RESULTS: After controlling for baseline covariates of prior medications, there was a 25% reduction in the likelihood of response to treatment with each increase in the number of prior antidepressant trials (odds ratio [OR]=0.75, unstandardized coefficient [B]=-0.29, standard error (SE)=0.12; ?(2) =5.70, P<.02], as well as a 32% reduction in the likelihood of remission with each prior antidepressant trial (OR=0.68, B=-0.39, SE=0.13; ?(2) =9.71, P=.002). This step-wise increase in pharmacodynamic tolerance occurred in both treatment conditions. Prior selective serotonin reuptake inhibitor (SSRI) therapy was specifically associated with a step-wise increase in tolerance, whereas other prior antidepressants or mood stabilizers were not associated with pharmacodynamic tolerance. Neither the number of prior antidepressants, nor the number of prior SSRIs, or mood stabilizers, were associated with an increase in relapse during continuation therapy.
CONCLUSIONS: The odds of responding or remitting during venlafaxine or lithium monotherapy were reduced by 25% and 32%, respectively, with each increase in the number of prior antidepressant treatment trials. There was no relationship between prior antidepressant exposure and depressive relapse during continuation therapy of bipolar II disorder.
PMID: 27805299 [PubMed - as supplied by publisher]
Validity of the Associated Symptom Criteria for Generalized Anxiety Disorder: Observations From the Singapore Mental Health Study.
J Nerv Ment Dis. 2016 Oct 31;
Authors: Lee SP, Ong C, Vaingankar JA, Chong SA, Subramaniam M
Previous findings on the diagnostic validity and reliability of generalized anxiety disorder (GAD)-associated symptom criteria suggest need for further evaluation. The current study examined convergent validity and specificity of GAD-associated symptoms in a representative Singapore community sample. The Singapore of Mental Health Study a cross-sectional epidemiological survey conducted among 6166 Singapore residents aged 18 and older. The Composite International Diagnostic Interview version 3.0 was used to diagnose mental disorders. Associated symptoms in the GAD criteria and autonomic hyperactivity symptoms showed convergent validity with a GAD diagnosis. However, associated symptoms of GAD were also linked to major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder, suggesting lack of adequate specificity. The inability of the diagnostic criteria to differentiate GAD from symptoms of other conditions highlights the need to better define its associated symptoms criteria. The relationship of overlapping symptoms between GAD and MDD is also discussed.
PMID: 27805985 [PubMed - as supplied by publisher]
Postmortem human brain genomics in neuropsychiatric disorders--how far can we go?
Curr Opin Neurobiol. 2016 Feb;36:107-11
Authors: Jaffe AE
Large-scale collection of postmortem human brain tissue and subsequent genomic data generation has become a useful approach for better identifying etiological factors contributing to neuropsychiatric disorders. In particular, studying genetic risk variants in non-psychiatric controls can identify biological mechanisms of risk free from confounding factors related to epiphenomena of illness. While the field has begun moving towards cell type-specific analyses, homogenate brain tissue with accompanying cellular profiles, can still identify useful hypotheses for more focused experiments, particularly when the dysregulated cell types are unknown. Technological advances, larger sample sizes, and focused research questions can continue to further leverage postmortem human brain research to better identify and understand the molecular etiology of neuropsychiatric disorders.
PMID: 26685806 [PubMed - indexed for MEDLINE]
Positive Attributes Buffer the Negative Associations Between Low Intelligence and High Psychopathology With Educational Outcomes.
J Am Acad Child Adolesc Psychiatry. 2016 Jan;55(1):47-53
Authors: Hoffmann MS, Leibenluft E, Stringaris A, Laporte PP, Pan PM, Gadelha A, Manfro GG, Miguel EC, Rohde LA, Salum GA
OBJECTIVE: This study examines the extent to which children's positive attributes are distinct from psychopathology. We also investigate whether positive attributes change or "buffer" the impact of low intelligence and high psychopathology on negative educational outcomes.
METHOD: In a community sample of 2,240 children (6-14 years of age), we investigated associations among positive attributes, psychopathology, intelligence, and negative educational outcomes. Negative educational outcomes were operationalized as learning problems and poor academic performance. We tested the discriminant validity of psychopathology versus positive attributes using confirmatory factor analysis (CFA) and propensity score matching analysis (PSM), and used generalized estimating equations (GEE) models to test main effects and interactions among predictors of educational outcomes.
RESULTS: According to both CFA and PSM, positive attributes and psychiatric symptoms were distinct constructs. Positive attributes were associated with lower levels of negative educational outcomes, independent of intelligence and psychopathology. Positive attributes buffer the negative effects of lower intelligence on learning problems, and higher psychopathology on poor academic performance.
CONCLUSION: Children's positive attributes are associated with lower levels of negative school outcomes. Positive attributes act both independently and by modifying the negative effects of low intelligence and high psychiatric symptoms on educational outcomes. Subsequent research should test interventions designed to foster the development of positive attributes in children at high risk for educational problems.
PMID: 26703909 [PubMed - indexed for MEDLINE]
Modeling psychiatric disorders with patient-derived iPSCs.
Curr Opin Neurobiol. 2016 Feb;36:118-27
Authors: Wen Z, Christian KM, Song H, Ming GL
Psychiatric disorders are heterogeneous disorders characterized by complex genetics, variable symptomatology, and anatomically distributed pathology, all of which present challenges for effective treatment. Current treatments are often blunt tools used to ameliorate the most severe symptoms, often at the risk of disrupting functional neural systems, thus there is a pressing need to develop rational therapeutics. Induced pluripotent stem cells (iPSCs) reprogrammed from patient somatic cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue and organ development, and provides new approaches for understanding disease mechanisms and for drug discovery with higher predictability of their effects in humans. Here we review recent progress and challenges in using human iPSCs for modeling neuropsychiatric disorders and developing novel therapeutic strategies.
PMID: 26705693 [PubMed - indexed for MEDLINE]
Psychotherapeutic Treatment of Bipolar Depression.
Psychiatr Clin North Am. 2016 Mar;39(1):35-56
Authors: McMahon K, Herr NR, Zerubavel N, Hoertel N, Neacsiu AD
The gold standard for treating bipolar depression is based on the combination of mood stabilizers and psychotherapy. Therefore, the authors present evidence-based models and promising approaches for psychotherapy for bipolar depression. Cognitive-behavioral therapy, family focused therapy, interpersonal and social rhythm therapy, mindfulness-based cognitive therapy, and dialectical behavior therapy are discussed. Behavioral activation, the cognitive behavioral analysis system of psychotherapy, and the unified protocol as promising future directions are presented. This review informs medical providers of the most appropriate referral guidelines for psychotherapy for bipolar depression. The authors conclude with a decision tree delineating optimal referrals to each psychotherapy approach.
PMID: 26876317 [PubMed - indexed for MEDLINE]
Bipolar Depression: Pregnancy, Postpartum, and Lactation.
Psychiatr Clin North Am. 2016 Mar;39(1):57-74
Authors: Wald MF, Muzyk AJ, Clark D
Medication management of bipolar depression in pregnancy and lactation is best done by assessing each patient's and family's needs in detail. Keeping pregnant patients as psychiatrically stable as possible is the most important principle for clinicians. Unfortunately, there is no risk-free situation for patients with psychiatric illness. This is often the most difficult and hard to accept reality for these patients, families, and clinicians. Clinicians serve these patients best by being as transparent as possible about the risk/benefit analysis of each patient's situation with the realization that ultimately the decisions are made by the patient and family.
PMID: 26876318 [PubMed - indexed for MEDLINE]
The Challenge of Bipolar Depression in the 21st Century.
Psychiatr Clin North Am. 2016 Mar;39(1):xi-xii
Authors: Beyer JL
PMID: 26876325 [PubMed - indexed for MEDLINE]
Biological hypotheses and biomarkers of bipolar disorder.
Psychiatry Clin Neurosci. 2016 Oct 31;:
Authors: Sigitova E, Fi?ar Z, Hroudová J, Cikánková T, Raboch J
The most common mood disorders are major depressive disorders and bipolar disorders. The pathophysiology of bipolar disorder is complex, multifactorial, and not fully understood. Creation of new hypotheses in the field gives impetus for studies and searching new biomarkers of the bipolar disorder. Conversely, new biomarkers facilitate not only diagnosis of a disorder and monitoring of biological effects of treatment, but also formulation of new hypotheses of the causes and pathophysiology of the bipolar disorder. Bipolar disorder is characterized by multiple associations between disturbed brain development, neuroplasticity, and chronobiology, caused by genetic and environmental factors, and defects in apoptotic, immune-inflammatory, neurotransmitter, neurotrophin, and calcium signaling pathways, oxidative and nitrosative stress, cellular bioenergetics, and membrane or vesicular transport. Current biological hypotheses of bipolar disorder are summarized, including related pathophysiological processes and key biomarkers, which have been associated with changes in genetics, systems of neurotransmitter and neurotrophic factors, neuroinflammation, autoimmunity, cytokines, stress axis activity, chronobiology, oxidative stress, and mitochondrial dysfunctions. Therapeutic hypotheses and mechanisms of the switch between depressive and manic state are discussed.
PMID: 27800654 [PubMed - as supplied by publisher]
Experimental drugs for bipolar psychosis.
Expert Opin Investig Drugs. 2016 Nov 1;
Authors: Fornaro M, Nardi A, De Berardis D, Carta MG
INTRODUCTION: Psychotic features are common in bipolar disorder (BD), especially during acute mania. Even when early detected, their long-term management is difficult, essentially due to the unsatisfactory efficacy/tolerability profile of currently available treatments, thus soliciting the development of novel experimental drugs. Areas covered: Potential drug targets towards the development of experimental drugs in the treatment of bipolar psychosis are yet to be systematically characterized. Among other potential avenues, the kynurenic acid pathway may represent an intriguing opportunity. Safer lithium alternatives should also be investigated in bipolar psychosis models. Expert Opinion: Regardless of the neurobiological pathways potentially worthy of investigation towards the development of experimental drugs in the treatment of bipolar psychosis, a number of unmet needs should be addressed. Primary goals of novel experimental drugs should be a better metabolic and cognitive tolerability profile, ultimately aiming to reduce the burden of acute psychotic mania and BD overall.
PMID: 27802062 [PubMed - as supplied by publisher]
Bipolar Disorder and Frontotemporal Dementia: An Intriguing Association.
J Alzheimers Dis. 2016 Oct 11;
Authors: Papazacharias A, Lozupone M, Barulli MR, Capozzo R, Imbimbo BP, Veneziani F, De Blasi R, Nardini M, Seripa D, Panza F, Logroscino G
Bipolar disorder (BD) could represent a prodromal state of frontotemporal dementia (FTD). Two patients affected by lifelong BD with a progressive decline of cognitive functions, behavioral, and neurological signs, reached the early diagnosis of FTD before the age of 60. They were diagnosed as affected by primary progressive aphasia and FTD with parkinsonism, respectively. A diagnosis of FTD should therefore be taken into account, in case of unexpected cognitive and behavioral decline in patients with a long history of BD. Follow-up studies with genetic, neuropsychological, and neuroimaging markers of these BD/FTD patients could further explore some of the underlying association, opening new viable therapeutic options.
PMID: 27802240 [PubMed - as supplied by publisher]
Here/In this issue and there/abstract thinking: trials in child psychiatry: and now ? be more pragmatic, please!
J Am Acad Child Adolesc Psychiatry. 2015 Feb;54(2):79-80
Authors: Cortese S
PMID: 25617246 [PubMed - indexed for MEDLINE]
Retrospective comparison of effectiveness of right unilateral ultra-brief pulse with brief pulse ECT in older adults (over 65) with depression.
Int Psychogeriatr. 2016 Mar;28(3):469-75
Authors: Ramalingam J, Elias A, George K, Thangapandian S, Bhat R
BACKGROUND: To compare response, remission and switch (to other pulse width and/or electrode placement) rates and number of treatments between groups receiving right unilateral ultra-brief (RUL-UB), Bitemporal brief (BT), Bifrontal Brief (BF) and Right unilateral brief (RUL-B).
METHOD: Data was collected from case notes in three centers. There were 133 in total, grouped as RUL-UB (50), BT (43), BF (23), RUL-B (17). Two of the three centers had a preferred electrode placement and pulse width.
RESULTS: Apart from age, the groups did not differ significantly on sex distribution, proportion of bipolar depression and psychotic symptoms. 56% of patients in RUL-UB switched compared to 12.5% in RUL-B, 4.9% in BT and none in BF (p value < 0.0001). When we considered patients who switched as treatment failures, remission rates were significantly different (p value < 0.0001) 40% in RUL-UB, 81.3% in RUL-B, 73.9% in BF and 78.0% in BT. Mean number of treatments in each group was significantly different (p value < 0.0001); 12.02 in RUL-UB, 10.2 in RUL-B, 7 in BF and 7.5 in BT. Post-hoc analysis indicated that RUL-UB differed significantly from BT and BF. Final response and remission rates including patients who switched were 98% and 82% in RUL-UB, 100% and 93.8% in RUL-B, 100% and 73.9% in BF and 97.7% and 83.7% in BT.
CONCLUSION: Majority commencing RUL-UB switched and received 4-5 more treatments compared to bilateral placements. RUL-UB ECT appears less effective and might not be appropriate as first line for all older adults as some patients at higher anaesthetic risk would benefit from having reduced number of treatments.
PMID: 26344656 [PubMed - indexed for MEDLINE]
In This Issue. Randomized Controlled Trials in the Era of Big Data.
J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):967-8
Authors: Kieling C
PMID: 26598468 [PubMed - indexed for MEDLINE]
Editorial: Mood Disorders and General Medical Comorbidities: Shared Biology and Novel Therapeutic Targets.
Curr Mol Med. 2016;16(2):104-5
Authors: McIntyre RS, Carvalho AF
PMID: 26812953 [PubMed - indexed for MEDLINE]
An 18th-century view of demonomania. I: Classification--psychiatry in history.
Br J Psychiatry. 2016 Feb;208(2):174
Authors: Subotsky F
PMID: 26834170 [PubMed - indexed for MEDLINE]
Three-year mortality in relation to early hospitalization and number of outpatient clinic visits in people with newly diagnosed bipolar disorder.
Gen Hosp Psychiatry. 2016 Nov - Dec;43:32-37
Authors: Pan YJ, Yeh LL, Chen YC, Chan HY
OBJECTIVE: Whether the early treatment pattern in people with bipolar disorder (BD) could influence later mortality remains to be determined. We aimed to explore the potential effects of early hospitalization and number of outpatient clinic visits on the 3-year mortality in patients with newly diagnosed BD.
METHOD: Adult participants with newly diagnosed BD were identified in Taiwan's National Health Insurance Research Database in 2008. Survival analyses were performed with this national cohort to examine the associations between the first-year treatment pattern (hospitalization and number of outpatient clinic visits) and mortality over a follow-up period of 3 years (2008-2011).
RESULTS: A total of 15,254 participants were included. The mean age was 44.9 (S.D.=16.7) years and around 39.9% were male. The average follow-up time was 1055 days. Compared to BD patients with ?7 times outpatient clinic visits within the first year, the risk of mortality was found elevated [hazard ratio=1.74; 95% confidence interval (CI), 1.40-2.15] for those who needed inpatient treatment. Number of outpatient clinic visits within the first year was found to be negatively associated with later mortality. Besides cancer (hazard ratio=2.14; 95% CI, 1.74-2.63), diabetes mellitus (hazard ratio=1.61; 95% CI, 1.38-1.89) and renal disease (hazard ratio=1.65; 95% CI, 1.36-2.00) were associated with the highest risk of mortality among the physical comorbidities. Substance use disorder stood out as the single comorbid mental illness associated with the highest mortality risk (hazard ratio=1.74; 95% CI, 1.37-2.21).
CONCLUSIONS: Early treatment pattern, including hospitalization and number of outpatient clinic visits, was associated with later mortality in BD patients. Special care should be given to enhance treatment adherence and to give psychoeducation to those with certain comorbid mental/physical illnesses to reduce health harming behavior and to improve health outcome.
PMID: 27796255 [PubMed - in process]
Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease.
Rev Bras Psiquiatr. 2016 Oct 17;:0
Authors: Barbé-Tuana FM, Parisi MM, Panizzutti BS, Fries GR, Grun LK, Guma FT, Kapczinski F, Berk M, Gama CS, Rosa AR
Objective:: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls.
Methods:: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction.
Results:: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle.
Conclusion:: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD.
PMID: 27798713 [PubMed - as supplied by publisher]
Time-varying associations of suicide with deployments, mental health conditions, and stressful life events among current and former US military personnel: a retrospective multivariate analysis.
Lancet Psychiatry. 2016 Nov;3(11):1039-1048
Authors: Shen YC, Cunha JM, Williams TV
BACKGROUND: US military suicides have increased substantially over the past decade and currently account for almost 20% of all military deaths. We investigated the associations of a comprehensive set of time-varying risk factors with suicides among current and former military service members.
METHODS: We did a retrospective multivariate analysis of all US military personnel between 2001 and 2011 (n=110?035?573 person-quarter-years, representing 3?795?823 service members). Outcome was death by suicide, either during service or post-separation. We used Cox proportional hazard models at the person-quarter level to examine associations of deployment, mental disorders, history of unlawful activity, stressful life events, and other demographic and service factors with death by suicide.
FINDINGS: The strongest predictors of death by suicide were current and past diagnoses of self-inflicted injuries, major depression, bipolar disorder, substance use disorder, and other mental health conditions (compared with service members with no history of diagnoses, the hazard ratio [HR] ranged from 1·4 [95% CI 1·14-1·72] to 8·34 [6·71-10·37]). Compared with service members who were never deployed, hazard rates of suicide (which represent the probability of death by suicide in a specific quarter given that the individual was alive in the previous quarter) were lower among the currently deployed (HR 0·50, 95% CI 0·40-0·61) but significantly higher in the quarters following first deployment (HR 1·51 [1·17-1·96] if deployed in the previous three quarters; 1·14 [1·06-1·23] if deployed four or more quarters ago). The hazard rate of suicide increased within the first year of separation from the military (HR 2·49, 95% CI 2·12-2·91), and remained high for those who had separated from the military 6 or more years ago (HR 1·63, 1·45-1·82).
INTERPRETATION: The increased hazard rate of death by suicide for military personnel varies by time since exposure to deployment, mental health diagnoses, and other stressful life events. Continued monitoring is especially needed for these high-risk individuals. Additional information should be gathered to address the persistently raised risk of suicide among service members after separation.
FUNDING: Partly funded by the Naval Research Program.
PMID: 27697514 [PubMed - in process]
Test for association of common variants in GRM7 with alcohol consumption.
Alcohol. 2016 Sep;55:43-50
Authors: Melroy-Greif WE, Vadasz C, Kamens HM, McQueen MB, Corley RP, Stallings MC, Hopfer CJ, Krauter KS, Brown SA, Hewitt JK, Ehringer MA
Recent work using a mouse model has identified the glutamate metabotropic receptor 7 (Grm7) gene as a strong candidate gene for alcohol consumption. Although there has been some work examining the effect of human glutamate metabotropic receptor 7 (GRM7) polymorphisms on human substance use disorders, the majority of the work has focused on other psychiatric disorders such as ADHD, major depressive disorder, schizophrenia, bipolar disorder, panic disorder, and autism spectrum disorders. The current study aimed to evaluate evidence for association between GRM7 and alcohol behaviors in humans using a single nucleotide polymorphism (SNP) approach, as well as a gene-based approach. Using 1803 non-Hispanic European Americans (EAs) (source: the Colorado Center on Antisocial Drug Dependence [CADD]) and 1049 EA subjects from an independent replication sample (source: the Genetics of Antisocial Drug Dependence [GADD]), two SNPs in GRM7 were examined for possible association with alcohol consumption using two family-based association tests implemented in FBAT and QTDT. Rs3749380 was suggestively associated with alcohol consumption in the CADD sample (p = 0.010) with the minor T allele conferring risk. There was no evidence for association in the GADD sample. A gene-based test using four Genome-Wide Association Studies (GWAS) revealed no association between variation in GRM7 and alcohol consumption. This study had several limitations: the SNPs chosen likely do not tag expression quantitative trait loci; a human alcohol consumption phenotype was used, complicating the interpretation with respect to rodent studies that found evidence for a cis-regulatory link between alcohol preference and Grm7; and only common SNPs imputed in all four datasets were included in the gene-based test. These limitations highlight the fact that rare variants, some potentially important common signals in the gene, and regions farther upstream were not examined.
PMID: 27788777 [PubMed - in process]
Novel gene-brain structure relationships in psychotic disorder revealed using parallel independent component analyses.
Schizophr Res. 2016 Oct 24;:
Authors: Tandon N, Nanda P, Padmanabhan JL, Mathew IT, Eack SM, Narayanan B, Meda SA, Bergen SE, Ruaño G, Windemuth A, Kocherla M, Petryshen TL, Clementz B, Sweeney J, Tamminga C, Pearlson G, Keshavan MS
BACKGROUND: Schizophrenia, schizoaffective disorder, and psychotic bipolar disorder overlap with regard to symptoms, structural and functional brain abnormalities, and genetic risk factors. Neurobiological pathways connecting genes to clinical phenotypes across the spectrum from schizophrenia to psychotic bipolar disorder remain largely unknown.
METHODS: We examined the relationship between structural brain changes and risk alleles across the psychosis spectrum in the multi-site Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) cohort. Regional MRI brain volumes were examined in 389 subjects with a psychotic disorder (139 schizophrenia, 90 schizoaffective disorder, and 160 psychotic bipolar disorder) and 123 healthy controls. 451,701 single-nucleotide polymorphisms were screened and processed using parallel independent component analysis (para-ICA) to assess associations between genes and structural brain abnormalities in probands.
RESULTS: 482 subjects were included after quality control (364 individuals with psychotic disorder and 118 healthy controls). Para-ICA identified four genetic components including several risk genes already known to contribute to schizophrenia and bipolar disorder and revealed three structural components that showed overlapping relationships with the disease risk genes across the three psychotic disorders. Functional ontologies representing these gene clusters included physiological pathways involved in brain development, synaptic transmission, and ion channel activity.
CONCLUSIONS: Heritable brain structural findings such as reduced cortical thickness and surface area in probands across the psychosis spectrum were associated with somewhat distinct genes related to putative disease pathways implicated in psychotic disorders. This suggests that brain structural alterations might represent discrete psychosis intermediate phenotypes along common neurobiological pathways underlying disease expression across the psychosis spectrum.
PMID: 27789186 [PubMed - as supplied by publisher]