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International Review of Psychosis & Bipolarity

Join us in Rome, Italy, 22-24 May 2016

Chair: Professor Paolo Girardi (IT)

Co-Chair: Dr Giulio Perugi (IT)

The ONLY speciality International Conference in Schizophrenia & Bipolar Disorders in Europe in 2016





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Most Recent Articles Published on Psychosis and Bipolarity:

Related Articles

Delirious mania of Charles VI of France in the fourteenth century.

Acta Psychiatr Scand. 2015 Dec;132(6):499-500

Authors: Appiani FJ

PMID: 26696385 [PubMed - indexed for MEDLINE]

Related Articles

Voice quality in patients suffering from bipolar disease.

Conf Proc IEEE Eng Med Biol Soc. 2015;2015:6106-9

Authors: Guidi A, Schoentgen J, Bertschy G, Gentili C, Landini L, Scilingo EP, Vanello N

People suffering from bipolar disease are more and more common. Such pathology can severely affect patients' lifestyle by wide, and sometimes extreme, mood swings. Biosignals can be very useful to understand this disease. Specifically, speech-related features have been seen to vary in depressed people with respect to healthy subjects. Usually prosodic, spectral and energy-related features are studied. Some further information, instead, can be provided studying voice quality. According to Laver's model, voice quality is sensitive and depends on both anatomic/physiologic issues and long-term muscular adjustments of the larynx or the supraglottal vocal tract. A pilot study on both bipolar patients and healthy control subjects, performed by means of the Long-Term Average Spectrum (LTAS) is presented. The effects on LTAS estimation of a F0-correction procedure are discussed. Pairwise statistical comparisons between subjects in euthymic and depressed states and euthymic and hypomanic states were performed. Significant differences were found in some frequency intervals in both cases. The F0-correction procedure modified the values of the significant frequency intervals in the euthymic/depressed comparison, that also was characterized by a change of F0. Noticeably, no statistically significant differences were found in control subjects acquired in the same mood state. Though the number of subjects is small, the results are encouraging given their coherence across patients and the lack of differences in the control group. Finally, this work suggests that particular vocal settings might be involved in different mood states.

PMID: 26737685 [PubMed - indexed for MEDLINE]

[How to characterize and treat sleep complaints in bipolar disorders?]

Encephale. 2016 Sep 23;

Authors: Geoffroy PA, Micoulaud Franchi JA, Lopez R, Poirot I, Brion A, Royant-Parola S, Etain B

OBJECTIVES: Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD.
METHODS: We examined the international scientific literature in June 2016 and performed a literature search with PubMed electronic database using the following headings: "bipolar disorder" and ("sleep" or "insomnia" or "hypersomnia" or "circadian" or "apnoea" or "apnea" or "restless legs").
RESULTS: Patients with BD suffer from sleep and circadian rhythm abnormalities during major depressive episodes (insomnia or hypersomnia, nightmares, nocturnal and/or early awakenings, non-restorative sleep) and manic episodes (insomnia, decreased need for sleep without fatigue), but also some of these abnormalities may persist during remission. These remission phases are characterized by a reduced quality and quantity of sleep, with a longer sleep duration, increased sleep latency, a lengthening of the wake time after sleep onset (WASO), a decrease of sleep efficiency, and greater variability in sleep/wake rhythms. Patients also present frequent sleep comorbidities: chronic insomnia, sleepiness, sleep phase delay syndrome, obstructive sleep apnea/hypopnea syndrome (OSAHS), and restless legs syndrome (RLS). These disorders are insufficiently diagnosed and treated whereas they are associated with mood relapses, treatment resistance, affect cognitive global functioning, reduce the quality of life, and contribute to weight gain or metabolic syndrome. Sleep and circadian rhythm abnormalities have been also associated with suicidal behaviors. Therefore, a clinical exploration with characterization of these abnormalities and disorders is essential. This exploration should be helped by questionnaires and documented on sleep diaries or even actimetric objective measures. Explorations such as ventilatory polygraphy, polysomnography or a more comprehensive assessment in a sleep laboratory may be required to complete the diagnostic assessment. Treatments obviously depend on the cause identified through assessment procedures. Treatment of chronic insomnia is primarily based on non-drug techniques (by restructuring behavior and sleep patterns), on psychotherapy (cognitive behavioral therapy for insomnia [CBT-I]; relaxation; interpersonal and social rhythm therapy [IPSRT]; etc.), and if necessary with hypnotics during less than four weeks. Specific treatments are needed in phase delay syndrome, OSAHS, or other more rare sleep disorders.
CONCLUSIONS: BD are defined by several sleep and circadian rhythm abnormalities during all phases of the disorder. These abnormalities and disorders, especially during remitted phases, should be characterized and diagnosed to reduce mood relapses, treatment resistance and improve BD outcomes.

PMID: 27669996 [PubMed - as supplied by publisher]

Paediatric bipolar disorder: What are the dangers of treating a hypothetical disorder as a real disease?

Aust N Z J Psychiatry. 2016 Sep 26;

Authors: Allison S, Parry P, Roeger L, Bastiampillai T

PMID: 27670831 [PubMed - as supplied by publisher]

Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis.

Psychiatry Clin Neurosci. 2016 Sep 27;

Authors: Kageyama Y, Kasahara T, Morishita H, Mataga N, Deguchi Y, Tani M, Kuroda K, Hattori K, Yoshida S, Inoue K, Kato T

AIMS: There is an urgent need for diagnostic biomarkers of bipolar disorder (BD) and schizophrenia (SZ); however, confounding effects of medication on hamper biomarker discovery. In this study, we conducted metabolome analyses to identify novel plasma biomarkers in drug-free patients with BD and SZ.
METHODS: We comprehensively analyzed plasma metabolites using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) in patients with SZ (n = 17), BD (n = 6), and major depressive disorder (n = 9), who had not received psychotropics for at least two weeks, and in matched healthy controls (n = 19). The results were compared with previous reports, or verified in an independent sample set using alternative analytical approach.
RESULTS: Lower creatine level and higher 2-hydroxybutyric acid level were observed in SZ than in controls (uncorrected P = 0.016 and 0.043, respectively), whereas they were unaltered in a previously reported dataset. Citrulline was nominally significantly decreased in BD compared to controls (uncorrected P = 0.043); however, this finding was not replicated in an independent sample set of medicated patients with BD. N-methyl-norsalsolinol, a metabolite of dopamine, was suggested as a candidate biomarker of BD; however, it was not detected by the other analytical-method. Betaine, a previously reported candidate biomarker of schizophrenia, were unchanged in the current dataset.
CONCLUSION: Our preliminary findings they suggest that the effect of confounding factors, such as duration of illness and medication, should be carefully controlled when searching for plasma biomarkers. Further studies are required to establish robust biomarkers for these disorders.

PMID: 27676126 [PubMed - as supplied by publisher]

A 52-Week Study of Olanzapine with a Randomized Behavioral Weight Counseling Intervention in Adolescents with Schizophrenia or Bipolar I Disorder.

J Child Adolesc Psychopharmacol. 2016 Sep 27;

Authors: Detke HC, DelBello MP, Landry J, Hoffmann VP, Heinloth A, Dittmann RW

OBJECTIVES: To evaluate the 52-week safety/tolerability of oral olanzapine for adolescents with schizophrenia or bipolar mania and compare effectiveness of a standard versus intense behavioral weight intervention in mitigating risk of weight gain.
METHODS: Patients 13-17 years old with schizophrenia (Brief Psychiatric Rating Scale for Children [BPRS-C] total score >30; item score ?3 for hallucinations, delusions, or peculiar fantasies) or bipolar I disorder (manic or mixed episode; Young Mania Rating Scale [YMRS] total score ?15) received open-label olanzapine (2.5-20?mg/day) and were randomized to standard (n?=?102; a single weight counseling session) or intense (n?=?101; weight counseling at each study visit) weight intervention. The primary outcome measure was mean change in body mass index (BMI) from baseline to 52 weeks using mixed-model repeated measures. Symptomatology was also assessed.
RESULTS: No statistically significant differences between groups were observed in mean baseline-to-52-week change in BMI (standard: +3.6?kg/m(2); intense: +2.8?kg/m(2); p?=?0.150) or weight (standard: +12.1?kg; intense: +9.6?kg; p?=?0.148). Percentage of patients at endpoint who had gained ?15% of their baseline weight was 40% for the standard group and 31% for the intense group (p?=?0.187). Safety/tolerability results were generally consistent with those of previous olanzapine studies in adolescents, with the most notable exception being the finding of a mean decrease in prolactin. On symptomatology measures, patients with schizophrenia had a mean baseline-to-52-week change in BPRS-C of -32.5 (standard deviation [SD]?=?10.8), and patients with bipolar disorder had a mean change in YMRS of -16.7 (SD?=?8.9), with clinically and statistically significant improvement starting at 3-4 days for each.
CONCLUSIONS: Long-term weight gain was high in both groups, with no statistically significant differences between the standard or intense behavioral weight interventions in BMI or weight. Safety, tolerability, and effectiveness findings were generally consistent with the known profile of olanzapine in adolescents.

PMID: 27676420 [PubMed - as supplied by publisher]

Endocannabinoid signaling in social functioning: an RDoC perspective.

Transl Psychiatry. 2016;6(9):e905

Authors: Karhson DS, Hardan AY, Parker KJ

Core deficits in social functioning are associated with various neuropsychiatric and neurodevelopmental disorders, yet biomarker identification and the development of effective pharmacological interventions has been limited. Recent data suggest the intriguing possibility that endogenous cannabinoids, a class of lipid neuromodulators generally implicated in the regulation of neurotransmitter release, may contribute to species-typical social functioning. Systematic study of the endogenous cannabinoid signaling could, therefore, yield novel approaches to understand the neurobiological underpinnings of atypical social functioning. This article provides a critical review of the major components of the endogenous cannabinoid system (for example, primary receptors and effectors-?9-tetrahydrocannabinol, cannabidiol, anandamide and 2-arachidonoylglycerol) and the contributions of cannabinoid signaling to social functioning. Data are evaluated in the context of Research Domain Criteria constructs (for example, anxiety, chronic stress, reward learning, motivation, declarative and working memory, affiliation and attachment, and social communication) to enable interrogation of endogenous cannabinoid signaling in social functioning across diagnostic categories. The empirical evidence reviewed strongly supports the role for dysregulated cannabinoid signaling in the pathophysiology of social functioning deficits observed in brain disorders, such as autism spectrum disorder, schizophrenia, major depressive disorder, posttraumatic stress disorder and bipolar disorder. Moreover, these findings indicate that the endogenous cannabinoid system holds exceptional promise as a biological marker of, and potential treatment target for, neuropsychiatric and neurodevelopmental disorders characterized by impairments in social functioning.

PMID: 27676446 [PubMed - as supplied by publisher]

Related Articles

On the validity of within-nuclear-family genetic association analysis in samples of extended families.

Stat Appl Genet Mol Biol. 2015 Dec;14(6):533-49

Authors: Bureau A, Duchesne T

Splitting extended families into their component nuclear families to apply a genetic association method designed for nuclear families is a widespread practice in familial genetic studies. Dependence among genotypes and phenotypes of nuclear families from the same extended family arises because of genetic linkage of the tested marker with a risk variant or because of familial specificity of genetic effects due to gene-environment interaction. This raises concerns about the validity of inference conducted under the assumption of independence of the nuclear families. We indeed prove theoretically that, in a conditional logistic regression analysis applicable to disease cases and their genotyped parents, the naive model-based estimator of the variance of the coefficient estimates underestimates the true variance. However, simulations with realistic effect sizes of risk variants and variation of this effect from family to family reveal that the underestimation is negligible. The simulations also show the greater efficiency of the model-based variance estimator compared to a robust empirical estimator. Our recommendation is therefore, to use the model-based estimator of variance for inference on effects of genetic variants.

PMID: 26544107 [PubMed - indexed for MEDLINE]

Related Articles

DMDD in DSM-5.1: Do we need to be more lenient?

Asian J Psychiatr. 2015 Dec;18:102-3

Authors: Kavoor AR, Mitra S

PMID: 26602030 [PubMed - indexed for MEDLINE]

Related Articles

Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone.

J Affect Disord. 2016 Mar 15;193:381-90

Authors: Fu DJ, Turkoz I, Bossie CA, Patel H, Alphs L

BACKGROUND: Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended-release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains.
METHODS: In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score ?16), or manic (Young Mania Rating Scale score ?16) symptoms at baseline.
RESULTS: Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies.
LIMITATIONS: This post hoc analysis of two phase 3 trials requires confirmation in prospective studies.
CONCLUSION: This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA.

PMID: 26802315 [PubMed - indexed for MEDLINE]

Concomitant Anticonvulsants With Bitemporal Electroconvulsive Therapy: A Randomized Controlled Trial With Clinical and Neurobiological Application.

J ECT. 2016 Sep 23;

Authors: Rakesh G, Thirthalli J, Kumar CN, Muralidharan K, Phutane VH, Gangadhar BN

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for major affective disorders. The combined use of ECT and anticonvulsant mood stabilizers is a common clinical scenario. There is dearth of systematic studies on the use of this combination with regard to clinical or cognitive outcomes.
OBJECTIVE/HYPOTHESIS: We aimed to compare clinical improvement and cognitive adverse effects between patients who received only ECT versus those who received ECT and anticonvulsants. We hypothesized that improvement would be fastest in patients who received only ECT.
METHODS: We conducted a randomized controlled trial in which patients prescribed ECT while being treated with anticonvulsants were randomized into 3 groups: full-dose (FD), half-dose (HD), and stop anticonvulsant. A blind rater assessed clinical improvement in patients using rating scales [Young's Mania Rating Scale (YMRS) and Clinical Global Impression] for clinical improvement and cognitive adverse effects (Postgraduate Institute memory scale). Analysis was done using mixed-effects modeling to delineate differences in clinical and cognitive outcomes across the 3 arms of the study over the course of ECT.
RESULTS: Of the 54 patients recruited, 36 patients went into treatment allocation arms per the initial randomization plan. The main anticonvulsants prescribed were sodium valproate and carbamazepine. Patients in the 3 groups were comparable on clinical features. The most common diagnosis was bipolar affective disorder-with current episode of mania. Overall, there was no difference across the 3 groups in final clinical outcome scores (YMRS and Clinical Global Impression) when analyzed as intention to treat (ITT) or "as treated." In both analyses, group × time interaction was significant when comparing trend of YMRS scores between the FD anticonvulsant group and the HD group from baseline to last ECT (P = 0.0435 in ITT and P = 0.0055 in as treated). Patients in the FD group improved faster than those in the HD group. There were no differences across the 3 groups with regard to their cognitive adverse effects in the ITT analysis; "as-treated analysis" showed the HD patients to have performed poorly on some domains. Seizure parameters showed no significant difference across the 3 groups.
CONCLUSION: This is a preliminary prospective study examining whether coprescription of anticonvulsants with ECT affected clinical or cognitive outcomes. The most important takeaway point from this study is the significant reduction in YMRS scores when ECT was given with FD anticonvulsant compared with halving the dose (HD) of anticonvulsant. This difference was shown in both ITT and as-treated analysis. There is a need for more prospective studies to examine this clinical question.

PMID: 27668943 [PubMed - as supplied by publisher]

The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder.

Eur Neuropsychopharmacol. 2016 Sep 21;

Authors: Abramovic L, Boks MP, Vreeker A, Bouter DC, Kruiper C, Verkooijen S, van Bergen AH, Ophoff RA, Kahn RS, van Haren NE

There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ?normalise? global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium.

PMID: 27665062 [PubMed - as supplied by publisher]

Impulsivity is associated with blood pressure and waist circumference among adolescents with bipolar disorder.

J Psychiatr Res. 2016 Aug 28;83:230-239

Authors: Naiberg MR, Newton DF, Collins JE, Bowie CR, Goldstein BI

OBJECTIVE: Cardiovascular risk factors (CVRFs) and impulsivity are common in bipolar disorder (BD), and CVRFs are also linked with impulsivity through a number of mechanisms, both behavioral and biological. This study examines the association between CVRFs and impulsivity in adolescents with BD.
METHODS: Subjects were 34 adolescents with BD and 35 healthy control (HC) adolescents. CVRFs were based on International Diabetes Federation metabolic syndrome criteria (triglycerides, high-density lipoprotein cholesterol, waist circumference, blood pressure (BP) and glucose). Impulsivity was measured using the computerized Cambridge Gambling Task (CGT). Analyses controlled for age, IQ, lifetime attention deficit hyperactivity disorder, and current antipsychotic use.
RESULTS: Adolescents with BD had higher diastolic BP (73.36 ± 9.57 mmHg vs. 67.91 ± 8.74 mmHg, U = 401.0, p = 0.03), higher triglycerides (1.13 ± 0.60 mmol/L vs. 0.78 ± 0.38 mmol/L, U = 373.5, p = 0.008), and were more likely to meet high-risk criteria for waist circumference (17.6% vs. 2.9%, p = 0.04) vs. HC. Within the BD group, CGT sub-scores were correlated with CVRFs. For example, overall proportion bet was positively correlated with systolic (r = 0.387, p = 0.026) and diastolic (? = 0.404, p = 0.020) BP. Quality of decision-making was negatively correlated with systolic BP (? = -0.401, p = 0.021) and waist circumference (? = -0.534, p = 0.003). Significant interactions were observed, such that BD diagnosis moderates the relationship between both waist circumference and BP with CGT sub-scores.
CONCLUSION: BP and waist circumference are associated with impulsivity in BD adolescents, but not in HC adolescents. Future studies are warranted to determine temporality and to evaluate whether optimizing CVRFs improves impulsivity among BD adolescents.

PMID: 27665535 [PubMed - as supplied by publisher]

[Metabolic syndrome and bipolar disorder: Is sleep the missing link?]

Encephale. 2016 Sep 20;

Authors: Brochard H, Boudebesse C, Henry C, Godin O, Leboyer M, Étain B

OBJECTIVE: To examine the pathophysiologic mechanisms that may link circadian disorder and metabolic syndrome in bipolar disorder (BP).
METHOD: A systematic review of the literature was conducted from January 2013 to January 2015, using the Medline and Cochrane databases, using the keywords "metabolic syndrome", "obesity", "leptin" and "circadian disorders", "sleeping disorders" and cross-referencing them with "bipolar disorder". The following types of publications were candidates for review: (i) clinical trials; (ii) studies involving patients diagnosed with bipolar disorder; (iii) studies involving patients with sleeping disorder; or (iv) data about metabolic syndrome.
RESULTS: Forty articles were selected. The prevalence of metabolic syndrome in BP was significantly higher compared to the general population (from 36 to 49% in the USA [Vancampfort, 2013]), and could be explained by several factors including reduced exercise and poor diet, genetic vulnerability, frequent depressive episodes, psychiatric comorbidity and psychotropic treatment. This high frequency of metabolic syndrome worsens the prognosis of these patients, increasing morbidity and mortality. Secondly, patients with BP experienced circadian and sleep disturbance, including modification in melatonin secretion. These perturbations are known to persist in periods of mood stabilization and are found in patients' relatives. Circadian disturbances are factors of relapse in bipolar patients, and they may also have a role in the metabolic comorbidities of these patients. Recent studies show that in populations of patients with bipolar disorder, a correlation between circadian disturbance and metabolic parameters are found. To identify the pathophysiological pathway connecting both could lead to a better comprehension of the disease and new therapeutics. In the overall population, mechanisms have been identified linking circadian and metabolic disorder involving hormones like leptin and ghrelin. These hormones are keys to regulation of energy balance in the organism, via their action on the hypothalamus, and are also regulated by sleep. We have hypothesized that these pathways could be implicated in the vulnerability of bipolar patients to metabolic syndrome. This hypothesis is supported by several studies showing dysregulation in leptin and ghrelin secretion in multiple psychiatric disorders, including bipolar disorder, as well as genetic variations of leptin and ghrelin genes in these diseases. We also assume that other mechanisms may be at stake to explain this link, such as melatonin dysregulation and inflammation.
CONCLUSIONS: Circadian and sleeping disorder may have a role in the prevalence of metabolic syndrome in BP. Hormones like leptin and ghrelin could be the link between these perturbations. Prevention and treatment of circadian disorder in BP may greatly reduce the occurrence of MetS in these patients. Being aware of this statement and taking care of these troubles should be a big step forward for treatment of BP.

PMID: 27663044 [PubMed - as supplied by publisher]

Suicide in older men: The health in men cohort study (HIMS).

Prev Med. 2016 Sep 20;

Authors: Almeida OP, McCaul K, Hankey GJ, Yeap BB, Golledge J, Flicker L

Suicide rates are high in later life, particularly among older men. Mood disorders are known risk factors, but the risk of suicide associated with poor physical health remains unclear. We completed a cohort study of a community representative sample of 38,170 men aged 65-85 in 1996 who were followed for up to 16years. Data on suicide attempts and completion were obtained from the Western Australia Data Linkage System, as was information about medical and mental health diagnoses. 240 (0.6%) participants had a recorded history of past suicide attempt, most commonly by poisoning (85%). Sixty-nine men died by suicide during follow up (0.3% of all deaths), most often by hanging (50.7%). Age-adjusted competing risk regression showed that past suicide attempt was not a robust predictor of future suicide completion (sub-hazard ratio, SHR=1.58, 95%CI=0.39, 6.42), but bipolar (SHR=7.82, 95%CI=3.08, 19.90), depressive disorders (SHR=2.26, 95%CI=1.14, 4.51) and the number of health systems affected by disease (SHR for 3-4 health systems=6.02, 95%CI=2.69, 13.47; SHR for ?5 health systems=11.18, 95%CI=4.89, 25.53) were. The population fraction of suicides attributable to having 5 or more health systems affected by disease was 79% (95%CI=57%, 90%), and for any mood disorder (bipolar or depression) it was 17% (95%CI=3%, 28%). Older Australian men with multiple health morbidities have the highest risk of death by suicide, even after taking into account the presence of mood disorders. Improving the overall health of the population may be the most effective way of decreasing the rates of suicide in later life.

PMID: 27663430 [PubMed - as supplied by publisher]

Bipolar Disorder and Early Affective Trauma.

Psychiatr Danub. 2016 Sep;28(Suppl-1):4-8

Authors: de Codt A, Monhonval P, Bongaerts X, Belkacemi I, Tecco JM

BACKGROUND: Bipolar disorder is a chronic psychiatric disease with a high prevalence and is a major psychosocial and medical burden. The exact etiological pathways of bipolar disorder are not fully understood. Genetic factors are known to play an important role in the etiology of bipolar disorder. However, high rates of discordance among identical twins and a growing body of evidence that environmental factors such as early stress can influence the onset and course of psychiatric diseases underline the importance of additional etiological mechanisms of bipolar disorders. There has been little investigation about early trauma in bipolar disorder. The aim of this study was to review the literature on the association between early traumatic interactions like child neglect, mistreatment, abuse or early parental separation and the occurrence of bipolar disorder in adulthood or impact on the course of the disease.
METHODS: Studies investigating associations between child neglect, mistreatment, abuse or early parental separation and occurrence of bipolar disorder in adulthood or impact on the course of the disease were searched in the Pubmed database. More than 700 articles were sorted independently by two of the authors using predefined criteria. Only research articles, reviews and meta-analyses were selected for this review.
RESULTS: 53 articles met the inclusion criteria. To date, four systematic reviews partially addressed our research question. Early trauma is more frequently found in the past of bipolar patients than in the general population. Studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a worse prognosis.
CONCLUSIONS: Early trauma is more often found in the past of bipolar adult patients than the general population and studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a worse prognosis. In further studies attention should be paid to the age of trauma occurrence and the definition of trauma. The findings also support the importance of additional psychoanalytic oriented psychotherapy for the treatment of bipolar disorder.

PMID: 27663796 [PubMed - as supplied by publisher]

An approach to treat bipolar disorders mixed states.

Psychiatr Danub. 2016 Sep;28(Suppl-1):9-12

Authors: Tavormina G

Very often clinicians meet great difficulties in making a correct diagnosis of mood disorders which they are assessing, above all when mixed states are present: this because the patients mainly focus on their own symptoms of depressive uneasiness; mixed symptoms can insidiously infiltrate into the mood and life of the patients causing a chronic and worsening clinical state. It is essential not to forget that the depression is only one phase of a broader bipolar mood disorder, and this has to be the illness to be treated by psychiatrists and, generally, by clinicians managing an appropriate polytherapy with mood-stabilisers and antidepressants.

PMID: 27663797 [PubMed - as supplied by publisher]

Risk and efficacy in cognitive functions in Bipolar Disorder II with atypical antipsychotic augmentation.

Psychiatr Danub. 2016 Sep;28(Suppl-1):13-17

Authors: Franza F

BD-II has been consistently associated with cognitive dysfunction across a broad range of cognitive domains. Atypical antipsychotic drugs, or SGAs are effective antipsychotics in these diseases, often in combination with antidepressants and mood stabilizers. Data on the possible effect of antipsychotics on neuro-cognition are rare and conflicting. The main objective of our study was to assess the effectiveness and possible risks to cognitive function in a group of inpatients affected by BD-II. Forty-five inpatients with Bipolar II Disorder (DSM-5) were included in a two-year observational study. They were treated with sodium valproate as a mood stabiliser, atypical antipsychotics and SSRIs. The utilized SGA augmentation were quetiapine (n=13); aripiprazole (n=10); olanzapine (n=11); asenapine (n=11). All inpatients were administered some psychopathological scales and evaluated for neuropsychological variables (for example, attention, verbal memory domains, etc.). After two years of treatment with SGAs, there has been no significant reduction of previous levels. In particularly, quetiapine and asenapine groups showed a better performance in learning task, short-term task and recognition tasks, in accordance with previous studies. Our small observational study shown that atypical antipsychotics cause an improvement in symptoms in BD, and particularly BD II. In particular, they do not induce significant alterations in overall cognitive performance generally. On the contrary, some SGAs, such as quetiapine and asenapine, seem to demonstrate a not statistically significant mild improvement in cognition.

PMID: 27663798 [PubMed - as supplied by publisher]

Should Assessment for Bipolar Disorder and mixed affective state be a standard part of assessment for suicide risk?

Psychiatr Danub. 2016 Sep;28(Suppl-1):18-20

Authors: Annear D, Agius M

The risk of suicide is high amongst individuals with bipolar affective disorder and mixed affective state. Research has shown that the suicide risk increases during both rapid-cycling and mixed affective states in bipolar. This article reviews the recent research of patients with bipolar and mixed affective state and suicide risk and highlights the reasons and potential benefits of factoring the potential risks into the assessment for suicide risk.

PMID: 27663799 [PubMed - as supplied by publisher]

Cardiovascular diseases in Patients with Bipolar disease: Pragmatic Management.

Psychiatr Danub. 2016 Sep;28(Suppl-1):21-24

Authors: Jesus C, Jesus I, Agius M

BACKGROUND: Bipolar disorder (BD), also known as manic-depressive illness, is a condition characterized by unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks. Bipolar disorder is known to be a chronic and disabling disease associated with higher incidence of obesity, diabetes, metabolic syndrome, dyslipidemias, hypertension and tobacco use which all together are known risk factors for the development of Cardiovascular diseases. With this research we wish to collect evidence to show how Cardiovascular diseases (CVD) affect Patients with Bipolar disease, the burden it can have in patients lives, to understand how this problem has been assessed so far and present suggestions that may improve the health care of these patients.
METHODS: Our study is a literature based research.
CONCLUSION: With our study we concluded that patients with BD are at higher risk of CVD and at an earlier age compared with the general population. Also, there is a lack of proper monitoring and consideration of the cardiovascular risk factors in patients with Bipolar disorder whether by primary care physicians or psychiatrists even though it plays a critical role in the general outcome of this patients and also leads to increase in mortality and morbidity rates.

PMID: 27663800 [PubMed - as supplied by publisher]

Are SSRIs responsible for precipitating suicidal ideation in teenagers with 'subsyndromal' bipolar affective disorder who have been misdiagnosed with unipolar depression?

Psychiatr Danub. 2016 Sep;28(Suppl-1):79-82

Authors: Hogg S, Ansari S, Masood Q, Agius M, Rihmer Z

Concerns have recently been raised about a possible link between suicidal ideation and the use of SSRIs in teenagers diagnosed with unipolar depression, such that the USA FDA and UK CSM have issued warnings regarding the use of SSRIs in adolescents with depression. We investigated this phenomenon first by recognizing that the initial presentation of unipolar and bipolar depression may only differ in subtle ways and with the result being that a significant number of patients are misdiagnosed at the expense of patient outcomes. This is especially pertinent as patients with bipolar disorder have increased lifetime rates of suicide as compared with those patients with unipolar depression. The normal developmental trajectory of bipolar disorder often involves recurrent depressive episodes in early adolescence before the development of hypomanic/manic episodes. Therefore, a misdiagnosis of bipolar disorder as unipolar depression in teenagers could explain the failure of SSRIs to adequately treat depressive episodes. A suboptimal response to SSRIs and so a lack of control of the depression is a risk factor for suicide. One reason for this suboptimal response is the markedly different neurotransmission involved in bipolar depression as compared to the neurotransmitter systems operated on by SSRIs. In bipolar disorder, dopamine is the principal neurotransmitter disrupted and we marshal structural, pharmacological and biochemical evidence to support this claim. One important strand of evidence involves polymorphisms in D1 and D2 dopamine receptors being implicated in the pathogenesis of bipolar affective disorder. Serotonin neurotransmission is affected by SSRIs, however the role of serotonin in bipolar disorder is much more ambiguous. The conclusion we arrive at is that the link between suicidality and SSRI use in adolescents diagnosed with unipolar depression may in fact be due to inappropriate treatment of misdiagnosed bipolar disorder that has yet to manifest with hypomanic/manic symptoms.

PMID: 27663811 [PubMed - as supplied by publisher]

Evaluation of the cortisol concentrations in patients with schizophrenia.

Psychiatr Danub. 2016 Sep;28(Suppl-1):162-164

Authors: Tobolska D, Wilczy?ski KM, Lorek M, Mazgaj E, Krysta K, Gawlik A, Krzystanek M

INTRODUCTION: The hypothalamus-pituitary-adrenal axis (HPAA) plays a pivotal role in response to a range of external and internal factors often described as a "stress". Growing evidence in a literature, suggest various dysregulations of HPAA, in course of numerous mental disorders. Patients with schizophrenia and bipolar disorder seem to have elevated basal cortisol secretion, what might be caused by the diminution of glucocorticoid receptors' amount. It was of the interest if the cortisol concentrations in patients with diagnosed schizophrenia who underwent treatment, differs from healthy individuals.
MATERIALS AND METHODS: Two groups of participants were included into the study. First group (study) consisted of 10 patients with diagnosed schizophrenia and control group which included 38 healthy individuals. Study was divided into two stages, first one (pilot) included only control group, and utilized cortisol concentrations measurement from saliva, blood and 24h urine sample. Second part (main study) involved both groups although focused on a salivary cortisol concentrations.
RESULTS: A mean salivary cortisol concentration in patients with schizophrenia who underwent treatment was significantly lower in comparison with healthy individuals.
CONCLUSIONS: Obtained results indicate that patients who underwent a treatment, and does not present notable clinical signs of schizophrenia may have moderately lowered levels of salivary cortisol. This may be a reflection of relenting psychotic symptoms as well as a direct effect of atypical antipsychotic drugs on a HPA axis activity.

PMID: 27663830 [PubMed - as supplied by publisher]

An unusual cause of cervical kyphosis.

Spine J. 2016 Sep 21;

Authors: Raj MS, Schwab JH

BACKGROUND CONTEXT: Acute fixed cervical kyphosis may be a rare presentation of conversion disorder, psychogenic dystonia, and potentially as a side effect from typical antipsychotic drugs. Haldol has been associated with acute dystonic reactions. In some cases, rigid deformities ensue. We are reporting a case of a fixed cervical kyphosis after the use of Haldol.
PURPOSE: To present a case of a potential acute dystonic reaction temporally associated with Haldol ingestion leading to fixed cervical kyphosis.
STUDY DESIGN: This is a case report.
METHODS: A patient diagnosed with bipolar disorder presented to the emergency room several times with severe neck pain and stiffness. The neck appeared fixed in flexion with extensive osteophyte formation over a three month period.
RESULTS: The patient's condition was resolved by a posterior-anterior-posterior surgical approach. It corrected the patient's cervical curvature from 88° to 5°.
CONCLUSION: Acute dystonic reactions have the potential to apply enough pressure on bone to cause rapid osteophyte formation.

PMID: 27664338 [PubMed - as supplied by publisher]

Redox Dysregulation in Schizophrenia Revealed by in vivo NAD+/NADH Measurement.

Schizophr Bull. 2016 Sep 24;

Authors: Kim SY, Cohen BM, Chen X, Lukas SE, Shinn AK, Yuksel AC, Li T, Du F, Öngür D

Balance between the redox pair of nicotinamide adenine dinucleotides (oxidized NAD+ and reduced NADH), reflects the oxidative state of cells and the ability of biological systems to carry out energy production. A growing body of evidence suggests that an "immuno-oxidative" pathway including oxidative stress, mitochondrial dysfunction, neuroinflammation, and cell-mediated immune response may contribute to disruptions in brain activity in schizophrenia (SZ). The aim of this study is to assess possible redox imbalance in SZ patients by using a novel in vivo (31)P MRS technique. The participants included 40 healthy controls, 21 chronic SZ, 13 first-episode (FE) SZ, and 18 FE bipolar disorder (BD) patients (as a psychiatric control group). All participants initially underwent structural imaging at a 3 Tesla (3 T) and (31)P MRS measurements were performed on a 4 T MR scanner. NAD+ and NADH components were determined by nonlinear least-square fitting of the model simulated spectra; these incorporated prior chemical shift and coupling constant information to in vivo resonances obtained from (31)P MRS experiments. We found a significant reduction in the NAD+/NADH ratio in chronically ill SZ patients compared to a matched healthy control group, and in FE SZ patients compared to both a matched FE BD patient group and a matched healthy control group. These findings provide evidence for redox imbalance in the brain in all phases of SZ, potentially reflecting oxidative stress.

PMID: 27665001 [PubMed - as supplied by publisher]

Related Articles

Narrative exposure therapy for posttraumatic stress disorder associated with repeated interpersonal trauma in patients with severe mental illness: a mixed methods design.

Eur J Psychotraumatol. 2016;7:32473

Authors: Mauritz MW, Van Gaal BG, Jongedijk RA, Schoonhoven L, Nijhuis-van der Sanden MW, Goossens PJ

BACKGROUND: In the Netherlands, most patients with severe mental illness (SMI) receive flexible assertive community treatment (FACT) provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD) are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET) within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients.
OBJECTIVES: The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1) PTSD and dissociative symptoms changes and (2) changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients' experiences with NET and to identify influencing factors on treatment results.
METHODS: This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25) with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results enhance the understanding of quantitative outcomes.
DISCUSSION: The results of this study will provide more insight into influencing factors for clinical changes in this population.

PMID: 27658371 [PubMed]

'Non-criteria' neurologic manifestations of antiphospholipid syndrome: A hidden kingdom to be discovered.

CNS Neurol Disord Drug Targets. 2016 Sep 20;

Authors: Islam MA, Alam F, Kamal MA, Wong KK, Sasongko TH, Gan SH

Neurological manifestations or disorders associated with central nervous system (CNS) are one of the most common as well as important clinical characteristics of antiphospholipid syndrome (APS). Although in the last updated (2006) classification criteria of APS its neurological manifestations encompassed only transient ischemic attack (TIA) and stroke, diverse 'non-criteria' neurological disorders or manifestations (headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanism responsible for these abnormal neurological manifestations in APS remains unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titre of antiphospholipid antibodies (aPLs) in the neuro-pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have been successfully treated either solely or by combined therapy with anti-thrombotic regimens (i.e. anticoagulant and/or platelet antiaggregant), antineuralgic drugs (i.e. antidepressant, antipsychotic and antiepileptic) or immunosuppressive drugs, evidence-based guideline for the management of neurologic manifestations of APS is still unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and CNS in addition to conducting randomized controlled trails to facilitate the discovery of appropriate medications for respective 'non-criteria' neurologic manifestations of APS.

PMID: 27658514 [PubMed - as supplied by publisher]

Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia.

Exp Neurol. 2016 Sep 19;

Authors: Bordia T, Zhang D, Perez XA, Quik M

Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos(+) D2 MSNs and decreased c-Fos(+) non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD.

PMID: 27658674 [PubMed - as supplied by publisher]

Neuroprogression and illness trajectories in bipolar disorder.

Expert Rev Neurother. 2016 Sep 23;

Authors: Kapczinski NS, Mwangi B, Cassidy RM, Garcia DL, Bermudez MB, Kauer-Sant'Anna M, Kapczinski F, Passos IC

INTRODUCTION: The longitudinal course of bipolar disorder is highly variable, and a subset of patients seems to present a progressive course associated with brain changes and functional impairment.
AREAS COVERED: We discuss the theory of neuroprogression in bipolar disorder. This concept considers the systemic stress response that occurs within mood episodes and late-stage deficits in functioning and cognition as well as neuroanatomic changes. We also discuss treatment refractoriness that may take place in some cases of bipolar disorder. We searched PubMed for articles published in any language up to June 4(th), 2016. We found 315 abstracts and included 87 studies in our review. Expert Commentary: We are of the opinion that the use of specific pharmacological strategies and functional remediation may be potentially useful in bipolar patients at late-stages. New analytic approaches using multimodal data hold the potential to help in identifying signatures of subgroups of patients who will develop a neuroprogressive course.

PMID: 27659841 [PubMed - as supplied by publisher]

A Novel Relationship for Schizophrenia, Bipolar, and Major Depressive Disorder. Part 8: a Hint from Chromosome 8 High Density Association Screen.

Mol Neurobiol. 2016 Sep 22;

Authors: Chen X, Long F, Cai B, Chen X, Qin L, Chen G

Convergent evidence from genetics, symptomatology, and psychopharmacology implies that there are intrinsic connections between schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD); for example, any two or even three of these disorders could co-exist in some families. A total of 48,753 single nucleotide polymorphisms (SNPs) on chromosome 8 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (type I), 177 MDD patients, and 1000 controls. Associated SNP loci were comprehensively revealed, and outstanding susceptibility genes were identified including CSMD1, NRG1, PXDNL, SGCZ, and TMEM66. Unexpectedly, flanking genes for up to 95.9 % of the associated SNPs were replicated (P ? 9.9E-8) in the enlarged cohort of 986 SCZ patients. Considering convergent evidence, our results implicate that bipolar disorder and major depressive disorder might be subtypes of schizophrenia.

PMID: 27660274 [PubMed - as supplied by publisher]

Associations of Serum Cytokine Receptor Levels with Melancholia, Staging of Illness, Depressive and Manic Phases, and Severity of Depression in Bipolar Disorder.

Mol Neurobiol. 2016 Sep 23;

Authors: Siwek M, Sowa-Ku?ma M, Stycze? K, Misztak P, Nowak RJ, Szewczyk B, Dudek D, Rybakowski JK, Nowak G, Maes M

To examine cytokine receptor biomarkers in bipolar disorder (BD), we recruited 133 well-phenotyped BD patients and 50 normal controls and measured serum levels of soluble interleukin 1 receptor antagonist (sIL-1RA), soluble interleukin-2 receptor (sIL-2R), sIL-6R, and tumor necrosis factor receptor 60 and 80 kDa (sTNFR60/80). sIL-1RA and sTNFR80 are significantly higher in BD than in controls and sTNFR80 and higher in melancholic than in non-melancholic patients and controls. Kapczinski's stages 3 + 4 are characterized by lowered sIL-2R and increased sTNFR80 levels. Acute phase depression is characterized by increased sTNFR80 levels as compared with controls, manic, and euthymic patients. Both sTNFR60 and sTNFR80 levels are significantly and positively related with severity of depression but not mania. Logistic regression analysis showed that the significant predictors for BD are increased sIL-1RA levels, nicotine dependence and a family history of depression and alcoholism. The risk factors for stages 3 + 4 are lowered sIL-2R levels and nicotine dependence. Melancholia is predicted by higher sTNFR80 levels and female sex. Severity of depression is predicted by female sex, nicotine dependence, and increased sTNFR60 and sTNFR80 levels. Cell-mediated immunity is activated during a current episode of depression but not (hypo)mania or the euthymic state. There are no associations between the biomarkers and age at onset, duration of illness, severity of mania, bipolar (BP)2 or BP1 subtypes, rapid cycling, atypical depression, psychotic or suicidal symptoms, and a family history of psychiatric disease. The results show that increased sIL-1RA may be a trait marker of BD, increased sTNFR80 a state marker of the depressive phase, especially melancholia, while lower sIL-2R but higher sTNFR80 may be staging biomarkers.

PMID: 27660275 [PubMed - as supplied by publisher]

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