Early clinical predictors and correlates of long-term morbidity in bipolar disorder

OBJECTIVES: Identifying factors predictive of long-term morbidity should improve clinical planning limiting disability and mortality associated with bipolar disorder (BD). METHODS: We analyzed factors associated with total, depressive and mania-related long-term morbidity and their ratio D/M, as %-time ill between a first-lifetime major affective episode and last follow-up of 207 BD subjects. Bivariate comparisons were followed by multivariable linear regression modeling. RESULTS: Total % of months ill during follow-up was greater in 96 BD-II (40.2%) than 111 BD-I subjects (28.4%; P=0.001). Time in depression averaged 26.1% in BD-II and 14.3% in BD-I, whereas mania-related morbidity was similar in both, averaging 13.9%. Their ratio D/M was 3.7-fold greater in BD-II than BD-I (5.74 vs. 1.96; P<0.0001). Predictive factors independently associated with total %-time ill were: [a] BD-II diagnosis, [b] longer prodrome from antecedents to first affective episode, and [c] any psychiatric comorbidity. Associated with %-time depressed were: [a] BD-II diagnosis, [b] any antecedent psychiatric syndrome, [c] psychiatric comorbidity, and [d] agitated/psychotic depressive first affective episode. Associated with %-time in mania-like illness were: [a] fewer years ill and [b] (hypo)manic first affective episode. The long-term D/M morbidity ratio was associated with: [a] anxious temperament, [b] depressive first episode, and [c] BD-II diagnosis. CONCLUSIONS: Long-term depressive greatly exceeded mania-like morbidity in BD patients. BD-II subjects spent 42% more time ill overall, with a 3.7-times greater D/M morbidity ratio, than BD-I. More time depressed was predicted by agitated/psychotic initial depressive episodes, psychiatric comorbidity, and BD-II diagnosis. Longer prodrome and any antecedent psychiatric syndrome were respectively associated with total and depressive morbidity

Aggression among 216 patients with a first-psychotic episode of bipolar I disorder

Background: Aggression by patients with bipolar I disorder (BD-I) is not uncommon. Identifying potential risk factors early in the illness-course should inform clinical management and reduce risk. Methods: In a study sample of 216 initially hospitalized, first-psychotic episode subjects diagnosed with DSM-IV-TR BD-I, we identified recent (within 1&nbsp;month before hospitalization) aggression by ratings on the Brief Psychiatric Rating Scale-Expanded and review of detailed clinical research records. We compared subjects with versus without aggressive behavior for associations with selected demographic and clinical factors. Results: Aggression was identified in 23/216 subjects (10.6%). It was associated significantly with recent suicide attempt (OR = 4.86), alcohol abuse (OR = 3.63), learning disability (OR = 3.14), and initial manic episode (OR = 2.59), but not with age, sex, onset-type, personality disorder, time to recovery, or functional status. Conclusions: Among first-major episode BD-I patients with psychotic features, recent serious aggression towards others was identified in 10.6%. The odds of aggression increased by 4.9-times in association with a recent suicide attempt, more than 3-times with alcohol-abuse or learning disability, and by 2.6-times if the episode polarity was manic. The findings encourage closer management of alcohol misuse, suicide risk, and manic symptoms, and early detection of learning problems in BD-I patients

Incomplete oedipism and chronic suicidality in psychotic depression with paranoid delusions related to eyes

Self-enucleation or oedipism is a term used to describe self-inflicted enucleation. It is a rare form of self-mutilation, found mainly in acutely psychotic patients. We propose the term incomplete oedipism to describe patients who deliberately and severely mutilate their eyes without proper enucleation. We report the case of a 32-year-old male patient with a five-year history of psychotic depression accompanied by paranoid delusions centered around his belief that his neighbors criticized him and stared at him. A central feature of his clinical picture was an eye injury that the patient had caused by pouring molten lead into his right eye during a period of deep hopelessness and suicidality when the patient could not resolve his anhedonia and social isolation. Pharmacotherapy and psychotherapy dramatically improved his disorder

Synapsin II Is Involved in the Molecular Pathway of Lithium Treatment in Bipolar Disorder

Bipolar disorder (BD) is a debilitating psychiatric condition with a prevalence of 1–2% in the general population that is characterized by severe episodic shifts in mood ranging from depressive to manic episodes. One of the most common treatments is lithium (Li), with successful response in 30–60% of patients. Synapsin II (SYN2) is a neuronal phosphoprotein that we have previously identified as a possible candidate gene for the etiology of BD and/or response to Li treatment in a genome-wide linkage study focusing on BD patients characterized for excellent response to Li prophylaxis. In the present study we investigated the role of this gene in BD, particularly as it pertains to Li treatment. We investigated the effect of lithium treatment on the expression of SYN2 in lymphoblastoid cell lines from patients characterized as excellent Li-responders, non-responders, as well as non-psychiatric controls. Finally, we sought to determine if Li has a cell-type-specific effect on gene expression in neuronal-derived cell lines. In both in vitro models, we found SYN2 to be modulated by the presence of Li. By focusing on Li-responsive BD we have identified a potential mechanism for Li response in some patients

Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature

A systematic search of the literature reveals limited evidence to support use of aripiprazole, a second-generation antipsychotic medication, in maintenance therapy of bipolar disorder, despite widespread use

Morphophysiological responses of wheat cultivars in competition with diploid and tetraploid ryegrass.

Wheat crop growth and development can be affected by weed infestation, especially ryegrass. Thus, the objective of this study was to evaluate the competitive ability of wheat cultivars wit h the diploid and tetraploid ryegrass biotypes. Greenhouse experiments were conducted in a completely randomized design with four replications. BRS Parrudo and TBIO Sinuelo wheat cultivars and the competitors ryegrass diploid and tetraploid were used. The population of each species was defined and then the replacement series experiments were carried out, containing the following proportions of wheat and ryegrass plants: 100:0, 75:25, 50:50, 25:75; and 0:100%, equivalent to 32:0; 24:8; 16:16; 8:24; and 0:32 plants per pot. Fifty days after species emergence, physiological traits, such as photosynthetic activity ( A ), stomatal conductance ( g S ), transpiration rate E ), internal concentration of mesophyll CO 2 (C i ), water use efficiency (WUE), and carboxylation ef ficiency (CE), were evaluated, along with the morphological traits of leaf area (LA), stem diameter (SD), number of tillers (NT), and shoot dry mass (DM). Competitiveness analysis was performed by means of diagrams applied to substitutive experiments using relative competitiveness indices. The ryegrass, both diploid and tetraploid, had a negative effect on the variables related to A , WUE and also those associated with plant growth. The ryegrass negatively changed the LA, DM, SD, and NT of the cultivars BRS Parrudo and TBIO Sinuelo, which demonstrates competition between the cultivars of wheat and the weed ryegrass with mutual damage to the species involved in th recommended for wheat cultivation

Treatment and outcomes of an Australian cohort of outpatients with bipolar 1 or schizoaffective disorder over twenty-four months : implications for clinical practice

Background The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with &lsquo;real-world&rsquo; treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.Methods Participants prescribed either conventional mood stabilizers (CMS; n&thinsp;=&thinsp;155) alone, or olanzapine with, or without, CMS (olanzapine&thinsp;&plusmn;&thinsp;CMS; n&thinsp;=&thinsp;84) were assessed every 3&thinsp;months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale &ndash; Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.Results On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24&thinsp;months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine&thinsp;&plusmn;&thinsp;CMS (61%;) cohorts.Conclusions Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.<br /

S -Adenosyl- l -homocysteine in brain

Administration of methionine sulfoximine (MSO) to rats and mice significantly decreased cerebral levels of S -adenosyl- l -homocysteine (AdoHcy). Concurrent administration of methionine prevented this decrease and, when methionine was given alone, significantly elevated AdoHcy levels resulted in both species. Regionally, AdoHcy levels varied from 20 nmol/g in rat cerebellum and spinal cord to about 60 nmol/g in hypothalamus and midbrain. MSO decreased AdoHcy in all regions tested except striatum, midbrain, and spinal cord. AdoMet/AdoHcy ratios (methylation index) varied from 0.48 in hypothalamus to 2.4 in cerebellum, and MSO administration decreased these ratios in all regions except hypothalamus. AdoHcy hydrolase activity was lowest in hypothalamus, highest in brainstem and, generally, varied inversely with regional AdoHcy levels. MSO decreased AdoHcy hydrolase activity in all regions except hypothalamus and spinal cord. Cycloleucine administration resulted in significantly decreased levels of mouse brain AdoHcy, whereas the administration of dihydroxyphenylalanine (DOPA) failed to affect AdoHcy levels. It is concluded that (a) cerebral AdoHcy levels are more tightly regulated than are those of AdoMet after MSO administration, (b) slight fluctuations of AdoHcy levels may be important in regulating AdoHcy hydrolase activity and hence AdoHcy catabolism in vivo, (c) the AdoMet/AdoHcy ratio reflects the absolute AdoMet concentration rather than the transmethylation flux, (d) the decreased AdoMet levels in midbrain, cortex, and striatum after MSO with no corresponding decrease in AdoHcy suggest an enhanced AdoMet utilization, hence an increased transmethylation in the MSO preconvulsant state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45411/1/11064_2004_Article_BF00966019.pd

Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression

Depression is a highly prevalent and recurrent neuropsychiatric disorder associated with alterations in emotional and cognitive domains. Neuroplastic phenomena are increasingly considered central to the etiopathogenesis of and recovery from depression. Nevertheless, a high number of remitted patients experience recurrent episodes of depression, remaining unclear how previous episodes impact on behavior and neuroplasticity and/or whether modulation of neuroplasticity is important to prevent recurrent depression. Through re-exposure to an unpredictable chronic mild stress protocol in rats, we observed the re-appearance of emotional and cognitive deficits. Furthermore, treatment with the antidepressants fluoxetine and imipramine was effective to promote sustained reversion of a depressive-like phenotype; however, their differential impact on adult hippocampal neuroplasticity triggered a distinct response to stress re-exposure: while imipramine re-established hippocampal neurogenesis and neuronal dendritic arborization contributing to resilience to recurrent depressive-like behavior, stress re-exposure in fluoxetine-treated animals resulted in an overproduction of adult-born neurons along with neuronal atrophy of granule neurons, accounting for an increased susceptibility to recurrent behavioral changes typical of depression. Strikingly, cell proliferation arrest compromised the behavior resilience induced by imipramine and buffered the susceptibility to recurrent behavioral changes promoted by fluoxetine. This study shows that previous exposure to a depressive-like episode impacts on the behavioral and neuroanatomical changes triggered by subsequent re-exposure to similar experimental conditions and reveals that the proper control of adult hippocampal neuroplasticity triggered by antidepressants is essential to counteract recurrent depressive-like episodes.FCT (IF/01079/2014). This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the FCT, under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersio