Decision-making strategies by panic disorder subjects are more sensitive to errors

BACKGROUND: Decision-making is a complex process, which can be assessed experimentally by the two-choice prediction task. Error-rate, i.e. the frequency of incorrect predictions during this task, is an important factor for the response selection during decision-making. This investigation examined whether the frequency of incorrect predictions has an augmented effect on the number of different strategies underlying decision-making in patients with panic disorder. METHODS: Patients with a DSM-IV diagnosis of panic disorder (PD; N=18), unipolar major depressive disorder (MDD; N=18) and normal comparison subjects (C; N=35) were tested with the two-choice prediction task using three error-rate conditions (20, 50, or 80%). The dynamical entropy of the response sequences was used to quantify the number of different strategies generated during the different error-rates. RESULTS: At 20% error-rates, panic disorder subjects when compared to MDD and C subjects generated more strategies and switched more frequently between strategies as measured by the dynamical entropy and the range of local dynamical entropies. Response bias measures during the two-choice prediction task and post-test self-assessment did not differ between panic disorder subjects and MDD or C subjects. LIMITATIONS: First, panic disorder subjects were medicated. Second, the frequency and intensity of panic attacks and the degree of avoidance behaviors, was not assessed. Third, subjects were tested once only. CONCLUSIONS: Panic disorder subjects show uniformly high response sequence unpredictability in the presence of low error-rates, which is consistent with continued search for an optimal response strategy even when the error-rate is low.     

The quantitative assessment of motor activity in mania and schizophrenia

BackgroundIncreased motor activity is a cardinal feature of the mania of Bipolar Disorder (BD), and is thought to reflect dopaminergic dysregulation. Motor activity in BD has been studied almost exclusively with self-report and observer-rated scales, limiting the ability to objectively quantify this behavior. We used an ambulatory monitoring device to quantify motor activity in BD and schizophrenia (SCZ) patients in a novel exploratory paradigm, the human Behavioral Pattern Monitor (BPM).Method28 patients in the manic phase of BD, 17 SCZ patients, and 21 nonpatient (NC) subjects were tested in the BPM, an unfamiliar room containing novel objects. Motor activity was measured with a wearable ambulatory monitoring device (LifeShirt).ResultsManic BD patients exhibited higher levels of motor activity when exploring the novel environment than SCZ and NC groups. Motor activity showed some modest relationships with symptom ratings of mania and psychosis and was not related to smoking or body mass index.LimitationsAlthough motor activity did not appear to be impacted significantly by antipsychotic or mood-stabilizing medications, this was a naturalistic study and medications were not controlled, thus limiting conclusions about potential medication effects on motor activity.ConclusionManic BD patients exhibit a unique signature of motoric overactivity in a novel exploratory environment. The use of an objective method to quantify exploration and motor activity may help characterize the unique aspects of BD and, because it is amenable to translational research, may further the study of the biological and genetic bases of the disease.     

Decision-making cognition in mania and depression

BACKGROUND: Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. Recent work has suggested that differences may emerge on cognitive tasks requiring affective processing, such as decision-making. The present study sought to compare decision-making cognition in mania and depression in order to clarify the current profiles of impairment for these disorders and to contribute to our more general understanding of the relationship between mood and cognition. METHODS: Medicated manic patients, depressed patients, and normal healthy controls completed a computerized decision-making task. All subjects were asked to win as many points as possible by choosing outcomes based on variably-weighted probabilities and by placing 'bets' on each decision. RESULTS: Both patient groups were impaired on this task, as evidenced by slower deliberation times, a failure to accumulate as many points as controls and suboptimal betting strategies. Manic, but not depressed, patients made suboptimal decisions--an impairment that correlated with the severity of their illness. CONCLUSIONS: These findings are consistent with a growing consensus that manic and depressed patients are characterized by significant impairments in cognitive and particularly executive, functioning. Furthermore, the distinct patterns of observed impairment in manic and depressed patients suggests that the nature and extent of cognitive impairment differ between these two groups. Viewed in the context of other recent studies, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.     

Platelet serotonin and serum lipids in psychotic mania

BACKGROUND: The role of serotonergic system and lipid status in the etiology of mania and its subtypes is not clear. The aims of the study were to determine platelet serotonin (5-HT) concentration, platelet monoamine oxidase (MAO) activity, and serum total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) and triglycerides (TG) in patients with psychotic and nonpsychotic subtypes of mania and in healthy control subjects. METHODS: The serum lipids, platelet 5-HT and MAO were determined in 40 (17 psychotic, 23 nonpsychotic) drug free male inpatients with type I bipolar affective disorder, current episode mania (DSM-IV criteria), and in 32 healthy male subjects. RESULTS: Platelet 5-HT levels in manic patients were similar to the values in healthy controls. Serum cholesterol and LDL values were significantly lower in manic patients than in healthy controls. Patients with psychotic features had increased platelet 5-HT concentrations and decreased levels of cholesterol and LDL as compared to the nonpsychotic manic patients and healthy controls. There was no significant difference in age, body mass index, platelet MAO activity, serum levels of TG and HDL between psychotic and nonpsychotic manic patients and healthy subjects. LIMITATION: Data on physical activity, dietary habits and alcohol consumption before hospitalization were not collected. CONCLUSION: The results of the present study suggest that biological differences between subtypes of mania might depend upon the presence of the psychotic symptoms. Our data confirm our previous results showing the increased platelet 5-HT concentration in psychotic disorders across the different diagnoses.     

Psychotic symptoms in patients with bipolar mania

BACKGROUND: Psychosis has been identified in as many as 68% of patients with bipolar mania. This analysis identified psychotic symptoms in these patients. METHODS: Data were from two placebo-controlled, 3-week studies in patients with an acute episode of bipolar mania. Symptoms were identified by the 30-item Positive and Negative Syndrome Scale (PANSS; item ratings, 1 = absent to 7 = extremely severe), the Young Mania Rating Scale, and the Global Assessment Scale. RESULTS: Psychotic features at study entry were diagnosed in 264 (51.3%) of the 515 patients. At baseline, these patients had significantly more severe scores on the PANSS, Young Mania Rating Scale, and Global Assessment Scale than patients without psychotic features. Patients with psychotic features had mean (+/-SD) scores of mild (3) or greater on six PANSS items: grandiosity (4.5+/-1.4), delusions (4.4+/-1.4), lack of judgment/insight (4.1+/-1.5), excitement (3.9+/-1.3), suspiciousness/persecution (3.1+/-1.6), and hostility (3.1+/-1.5). Grandiosity symptoms of delusional proportions (scores > or = 4) were noted in 205 (78%) of patients with a diagnosis of psychotic features and in 113 (45%) patients without the diagnosis. LIMITATIONS: The study was not specifically designed to assess patients with psychotic features and the PANSS was developed to evaluate symptoms of schizophrenia. CONCLUSIONS: These findings support prior reports indicating high rates of psychosis in patients with bipolar mania and identify the most prominent symptoms in these patients.     

Ethnic differences in first clinical presentation of bipolar disorder: results from an epidemiological study

BACKGROUND: Although high incidence rates of mania have been described in some ethnic minority populations, little is known about any ethnic differences in the early clinical presentation of bipolar disorder. METHODS: All cases of operationalised DSM-IV bipolar I disorder (BPI), first manic episode, within a defined epidemiological catchment area over a 35-year period, were identified; sociodemographic data, including ethnicity, and clinical information were then extracted. The proportion of African-Caribbean (n=52), African (n=33) and white European (n=149) cases who experienced a depressive episode before onset of mania and psychotic symptoms at first mania were compared. RESULTS: African-Caribbean and African groups were significantly less likely to have experienced a depressive episode before onset of first mania, at 13.5% and 6.1%, respectively, compared with 28.1% in the white European group. African-Caribbean and African groups also experienced more severe psychotic symptoms at first mania, but there were no differences in mood incongruent or first rank symptoms between ethnic groups. LIMITATIONS: Data pertaining to diagnosis and clinical symptoms were extracted by retrospective case note review. CONCLUSIONS: Ethnic differences in clinical presentation of bipolar disorder may have implications for assessment and treatment of ethnic minority patients.     

Differentially methylated regions in bipolar disorder and suicide

The addition of a methyl group to, typically, a cytosine‐guanine dinucleotide (CpG) creates distinct DNA methylation patterns across the genome that can regulate gene expression. Aberrant DNA methylation of CpG sites has been associated with many psychiatric disorders including bipolar disorder (BD) and suicide. Using the SureSelect^XT system, Methyl‐Seq, we investigated the DNA methylation status of CpG sites throughout the genome in 50 BD individuals (23 subjects who died by suicide and 27 subjects who died from other causes) and 31 nonpsychiatric controls. We identified differentially methylated regions (DMRs) from three analyses: (a) BD subjects compared to nonpsychiatric controls (BD‐NC), (b) BD subjects who died by suicide compared to nonpsychiatric controls (BDS‐NC), and (c) BDS subjects compared to BD subjects who died from other causes (BDS‐BDNS). One DMR from the BDS‐NC analysis, located in ARHGEF38, was significantly hypomethylated (23.4%) in BDS subjects. This finding remained significant after multiple testing (P_Bootstrapped = 9.0 × 10^?3), was validated using pyrosequencing, and was more significant in males. A secondary analysis utilized Ingenuity Pathway Analysis to identify enrichment in nominally significant DMRs. This identified an association with several pathways including axonal guidance signaling, calcium signaling, β‐adrenergic signaling, and opioid signaling. Our comprehensive study provides further support that DNA methylation alterations influence the risk for BD and suicide. However, further investigation is required to confirm these associations and identify their functional consequences.     

Unipolar mania: a distinct disorder?

BACKGROUND: This study aimed to identify the differences between unipolar mania and classical bipolar disorder. METHODS: Patients with at least four manic episodes and at least 4 years of follow-up without any depressive episodes were classified as unipolar mania. This group was compared to other bipolar-I patients defined according to DSM-IV regarding their clinical and socio-demographic variables. RESULTS: The rate for unipolar mania as defined by the study criteria was found to be 16.3% in the whole group of bipolar-I patients. Unipolar manic patients tended to have more psychotic features and be less responsive to lithium prophylaxis compared to other bipolar-I patients. LIMITATIONS: Because it was a retrospective study, there may be some minor depressive episodes left unrecorded in the unipolar mania group despite careful and thorough investigation. In addition, even with our fairly strict criteria for the diagnosis of unipolar mania, the possibility of a future depressive episode cannot be excluded. CONCLUSIONS: Unipolar mania may be the presentation of a nosologically distinct entity.     

Differences of Clinical Characteristics and Phenotypes between Prepubertal- and Adolescent-Onset Bipolar Disorders

The aim of this study is to describe the clinical characteristics of prepubertal- and adolescent-onset bipolar disorder (BD) and to identify any clinical differences between patients with prepubertal- and adolescent-onset BD. We analyzed the clinical records of 53 inpatients with BD. These patients were divided into prepubertal-onset and adolescent-onset groups. We also divided the subjects into narrow, intermediate, and broad phenotypes according to the definitions proposed by Leibenluft and colleagues. Of the total sample, 16 patients (30.2%) were in the prepubertal-onset group and 37 (69.8%) were in the adolescent-onset group. Patients with prepubertal-onset BD were more likely to display an insidious clinical presentation, atypical features, and comorbid psychopathology. And the majority of the subjects, especially in the prepubertal-onset group, were classified under the intermediate and broad phenotypes. These results suggest that the clinical presentation of BD with prepubertal-onset is different from that of adolescent-onset BD. It is inferred that a significant number of patients with prepubertal- and adolescent-onset BD do not meet DSM-IV criteria for mania or hypomania from the results of this study.     

Subtypes of manic episodes according to ICD-10-prediction of time to remission and risk of relapse

BACKGROUND: The long-term predictive ability of the ICD-10 subtypes of hypomania, mania without psychosis and mania with psychosis has not been investigated. METHODS: All patients who got a diagnosis of a single hypomanic episode, single manic episode without psychosis or single manic episode with psychosis in a period from 1994 to 1999 at the first discharge ever in Denmark were identified. The time to discharge from first admission and the risk of relapse leading to readmission were compared for the three groups of patients. RESULTS: Totally, 41 patients with a hypomanic episode, 149 patients with a manic episode without psychotic symptoms and 202 patients with a manic episode with psychotic symptoms at first discharge ever were identified. Patients with mania and psychotic symptoms were admitted longer than patients with mania without psychosis, and patients with mania without psychosis were admitted longer than patients with hypomania. No differences were found in the risk of relapse leading to readmission between the three groups of patients. LIMITATIONS: The results apply to hospitalised patients only. CONCLUSIONS: The ICD-10 subclassification of manic episodes does only partially predict long-term outcome.     

Increased plasma levels of brain-derived neurotrophic factor in patients with long-term bipolar disorder

Recent data indicate that neurotrophins may play a role in the physiopathology of bipolar disorder (BD) and may be useful as biomarkers of the disease. The aim of this study was to evaluate the plasma concentrations of brain-derived neurotrophic factor (BDNF) in BD patients, and to correlate their levels with clinical parameters. BDNF was measured in plasma from 53 BD type I subjects (34 during mania and 19 during euthymia) and 38 healthy controls by enzyme-linked immuno-sorbent assay (ELISA). Patients were assessed by a structured clinical interview (Mini-plus), Young mania and Hamilton depression rating scales. Plasma BDNF levels were significantly increased in patients with mania (P ≤ 0.001) and euthymia (P ≤ 0.001) when compared with controls, but did not correlate with any clinical parameters. BDNF concentration was higher in BD patients with 10 or more years of disease. BDNF plasma levels were increased in BD patients, mainly in those with a longer course of disease. In line with previous studies, it is conceivable that BDNF may play a role in the pathophysiology of BD.     

Linguistic analyses of speech disorder in psychosis

Much theory and research has been devoted to characterizing speech disorders in psychotic individuals and to understanding the connections between language productions and underlying cognitive processes. Studies in the literature have used primarily traditional clinical assessments and experimental task methods to study speech phenomena in psychotic patients. More recently, however, the range of study methods has expanded to include models based on normal language use, borrowed from the field of psycholinguistics. This article reviews linguistic studies of the discourse of psychotic patients with a focus on understanding speech disorders in the context of schizophrenia and mania. The studies are grouped according to the method of analysis used, including frequency counts, type-token ratios, cloze analyses, contextual constraint, pause and hesitation patterns, and discourse level analyses. Methodological problems and theoretical issues are summarised, followed by a statement of current status. The use of multiple measures applied to whole discourse speech samples offers particular promise for clarifying diagnostic issues and testing hypotheses based on cognitive models.     

Cannabis use and expression of mania in the general population

BACKGROUND: Cannabis use is common in patients with bipolar disorder, however little is known about cannabis as a risk factor for mania. In order to investigate the association between exposure to cannabis and subsequent development of manic symptoms whilst controlling for psychotic symptoms, a longitudinal population-based study was carried out. METHODS: 4815 individuals aged 18 to 64 years were interviewed using the Composite International Diagnostic Interview at baseline, 1 year follow up and 3 year follow up, including assessment of substance use, manic symptoms and psychotic symptoms. RESULTS: Use of cannabis at baseline increased the risk for manic symptoms during follow-up (adjusted OR 2.70, 95% CI: 1.54, 4.75), adjusted for age, sex, educational level, ethnicity, single marital status, neuroticism, use of other drugs, use of alcohol, depressive symptoms and manic symptoms at baseline. The association between cannabis use and mania was independent of the prevalence and the incidence of psychotic symptoms. There was no evidence for reverse causality, as manic symptoms at baseline did not predict the onset of cannabis use during follow-up (OR = 0.35, 95% CI: 0.03, 3.49). LIMITATIONS: As 3 years is a relative short period of follow-up, long-term effects of cannabis use on mania outcomes could not be detected. CONCLUSION: The results suggest that cannabis use may affect population expression of manic symptoms (and subsequent risk to develop bipolar disorder [Regeer, E.J., Krabbendam, L., R, DE Graaf, Ten Have, M., Nolen, W.A., Van Os, J., 2006. A prospective study of the transition rates of subthreshold (hypo)mania and depression in the general population. Psychol Med, 1-9.]). These findings may not be due to the emergence of psychotic symptoms or the effects of self-medication.     

Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN)

Background: This research derives from the French national multisite collaborative study on the clinical epidemiology of mania (EPIMAN). Our aim is to establish the validity of dysphoric mania along a “spectrum of mixity” extending into mixed mania with subthreshold depressive manifestations; to demonstrate the feasibility of obtaining clinically meaningful data on this entity on a national level; and to characterize the contribution of temperamental attributes and gender in its origin. Methods: EPIMAN involves training 23 French psychiatrists in four different sites, representing four regions of France; to rigorously apply a common protocol deriving from the criteria of DSM-IV and McElroy et al.; the use of such instruments as the Beigel-Murphy, Ahearn-Carroll, modified HAM-D; and measures of affective temperaments based on the Akiskal-Mallya criteria; obtaining data on comorbidity, and family history (according to Winokur's approach as incorporated into the FH-RDC); and prospective follow-up for at least 12 months. The present report concerns the clinical and temperamental features of 104 manic patients during the acute hospital phase. Results: Dysphoric mania (DM defined conservatively with fullblown depressive admixtures of five or more symptoms) occurred in 6.7%; the rate of dysphoric mania defined broadly (DM, presence of ≥2 depressive symptoms) was 37%. Depressed mood and suicidal thoughts had the best positive predictive values for mixed mania. In comparison to pure mania (0–1 depressive symptoms), DM was characterized by female over-representation; lower frequency of such typical manic symptomatology as elation, grandiosity, and excessive involvement; higher prevalence of associated psychotic features; higher rate of mixed states in first episodes; and complex temperamental dysregulation along primarily depressive, but also cyclothymic, and irritable dimensions; such irritability was particularly apparent in mixed mania at the lowest threshold of depressive admixtures of two symptoms only. Limitation: In a study involving hospitalized affectively unstable psychotic patients, it was difficult to assure that psychiatrists making the clinical diagnoses would be blind to the temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. Conclusions: Mixed mania, defined cross-sectionally by the simultaneous presence of at least two depressive symptoms, represents a prevalent and clinically distinct form of mania. Subthreshold depressive admixtures with mania actually appear to represent the more common expression of dysphoric mania. Moreover, an irritable dimension appears to be relevant to the definition of the expression of mixed mania with the lowest threshold of depressive symptoms. Neither an extreme, nor an endstage of mania, “mixity” is best conceptualized as intrusion of mania into its “opposite” temperament – especially that defined by lifelong depressive traits – and favored by female gender. These data suggest that reversal from a temperament to an episode of “opposite” polarity represents a fundamental aspect of the dysregulation that characterizes bipolar disorder. In both men and women with hyperthymic temperament, there appears “protection” against depressive symptom formation during a manic episode which, accordingly, remains relatively “pure”. Because men have higher rates of this temperament, pure mania is overrepresented in men; on the other hand, the depressive temperament in manic women seems to be a clinical marker for the well-known female tendency for depression, hence the higher prevalence of mixed mania in women.     

Behavioural and neurocognitive responses to sad facial affect are attenuated in patients with mania

BACKGROUND: The processing of facial emotion involves a distributed network of limbic and paralimbic brain structures. Many of these regions are also implicated in the pathophysiology of mood disorders. Behavioural data indicate that depressed subjects show a state-related positive recognition bias for faces displaying negative emotions. There are sparse data to suggest there may be an analogous, state-related negative recognition bias for negative emotions in mania. We used functional magnetic resonance imaging (fMRI) to investigate the behavioural and neurocognitive correlates of happy and sad facial affect recognition in patients with mania. METHOD: Functional MRI and an explicit facial affect recognition task were used in a case-control design to measure brain activation and associated behavioural response to variable intensity of sad and happy facial expressions in 10 patients with bipolar I mania and 12 healthy comparison subjects. RESULTS: The patients with mania had attenuated subjective rating of the intensity of sad facial expressions, and associated attenuation of activation in the subgenual anterior cingulate and bilateral amygdala, with increased activation in the posterior cingulate and posterior insula. No behavioural or neurocognitive abnormalities were found in response to presentation of happy facial expressions. CONCLUSIONS: Patients with mania showed a specific, mood-congruent, negative bias in sad facial affect recognition, which was associated with an abnormal profile of brain activation in paralimbic regions implicated in affect recognition and mood disorders. Functional imaging of facial emotion recognition may be a useful probe of cortical and subcortical abnormalities in mood disorders.     

Evidence of genetic overlap of schizophrenia and bipolar disorder: linkage disequilibrium analysis of chromosome 18 in the Costa Rican population.

The long-standing concept that schizophrenia (SC) and bipolar disorder (BP) represent two distinct illnesses has been recently challenged by findings of overlap of genetic susceptibility loci for these two diseases. We report here the results of a linkage disequilibrium (LD) analysis of chromosome 18 utilizing subjects with SC from the Central Valley of Costa Rica. Evidence of association (P < 0.05) was obtained in three chromosomal regions: 18p11.31 (D18S63), 18q12.3 (D18S474), and 18q22.3-qter (D18S1161, D18S70), all of which overlap or are in close proximity with loci previously shown to be in LD with BP, type I in this population. Since both the SC and bipolar samples contained cases with a history of mania and almost all cases of SC and BP had a history of psychosis, we performed an alternative phenotyping strategy to determine whether presence or absence of mania, in the context of psychosis, would yield distinct linkage patterns along chromosome 18. To address this issue, a cohort of psychotic patients (including a range of DSMIV diagnoses) was divided into two groups based on the presence or absence of mania. Regions that showed association with SC showed segregation of association when the sample was stratified by history of mania. Our results are compared with previous genetic studies of susceptibility to SC or BP, in Costa Rica as well as in other populations. This study illustrates the importance of detailed phenotype analysis in the search for susceptibility genes influencing complex psychiatric disorders in isolated populations and suggests that subdivision of psychoses by presence or absence of past mania syndromes may be useful to define genetic subtypes of chronic psychotic illness.     

青少年双相障碍不同亚型首发患者治疗前后甲状腺功能水平的差异

目的:了解青少年双相障碍不同亚型患者的临床特征及治疗前后甲状腺功能水平的差异。方法:采用电化学发光法分别在治疗前、治疗1月后测定住院双相障碍患儿149例和50例正常青少年对照组的血清三碘甲状腺原氨酸Ttriiodothyronine,T3)、甲状腺素(Thyroxine,T4)、游离三碘甲状腺原氨酸(Free triiodothyronine,FT3)、游离甲状腺素(Free thyroxine,FT4)和促甲状腺激素(Thyroid-stimulating hormone,TSH)水平,按照目前发作形式分为躁狂组49例、抑郁组80例和混合组20例,比较3组间临床特征及治疗前后甲状腺功能水平。结果:躁狂组在总病程(F=8.237,P0.001)和本次病程(F=5.228,P0.05)的时间上低于抑郁组和混合组,躁狂组非核心家庭(离异、丧偶)的比例高于抑郁组和混合组(χ~2=6.200,P0.05);混合组伴有精神病性症状的比例高于躁狂组和抑郁组(χ~2=7.449,P0.05)。躁狂组、抑郁组和混合组治疗前后的T3、T4值及治疗后的FT4值低于对照组(F=49.214,27.303,12.882,P0.001);躁狂组在治疗前的FT3值高于其他3组(F=5.512,P0.001);躁狂组治疗后的TSH值高于抑郁组和对照组,并且混合组治疗后的TSH值高于对照组(F=8.752,P0.001),差异有统计学意义。结论:青少年双相障碍不同亚型存在不同的临床特征,在治疗前后与正常青少年的比较中具有不同的甲状腺素水平。     

The significance of psychotic features in manic episodes: a report from the NIMH collaborative study

BACKGROUND: Psychotic features in the context of major depressive syndromes have correlates in symptom severity, acute treatment response and long-term prognosis. Little is known as to whether psychotic features have similar importance when they occur within manic syndromes. METHODS: These data derive from a multi-center, long-term follow-up of patients with major affective disorder. Raters conducted follow-up interviews at 6-month intervals for the first 5 years and annually thereafter. A sub-set of probands participated in a family study in which all available, adult, first-degree relatives were interviewed as well. RESULTS: Of 139 who entered the study in an episode of mania, 90 patients had psychotic features. Symptom severity ratings at intake were more severe for this group. Though time to first recovery and time to first relapse did not distinguish the groups, psychotic features were associated with a greater number of weeks ill during follow-up and the strength of this association was similar to that seen for psychotic features within depressed patients described in an earlier publication. Patients with psychotic mania at intake did not differ significantly from those with nonpsychotic mania by response to acute lithium treatment, suicidal behavior during follow-up, or risks for affective disorder among first-degree relatives. Psychotic features within manic syndromes were not associated with high psychosis ratings during follow-up. In contrast, when psychotic features accompanied depressive syndromes, they strongly predicted the number of weeks with psychosis during follow-up, particularly among individuals whose episodes at intake were less acute. CONCLUSIONS: As with major depressive syndromes, psychotic features in mania are associated with greater symptom severity and higher morbidity in the long-term. Psychotic features are much less predictive of future psychosis when they occur within a manic syndrome than when they occur within a depressive syndrome.     

Early improvement with lithium in classic mania and its association with later response

ObjectivesDespite lithium’s clinical efficacy in treating mania in bipolar disorder (BD), studies evaluating early improvement and subsequent treatment response are sparse. This study investigated whether early improvement (within one week) to lithium monotherapy predicted later response and remission in individuals with BD mania.MethodsBD-I patients (n=46) experiencing a manic episode received lithium monotherapy for four weeks (initial dose: 600 mg/d, adjusted to therapeutic levels); individuals experiencing a mixed episode, rapid cyclers, previous non-responders to lithium, and those with current drug abuse/dependence were excluded. Symptoms were rated using the Young Mania Rating Scale (YMRS) at baseline and at Days 7, 14, 21, and 28.ResultsThirty-three percent of the total sample responded to lithium within the first week of treatment, defined as a ≥50% decrease from baseline YMRS scores; 63% responded by study endpoint. In addition, 39% of the total sample showed early improvement (at least 20% decrease in YMRS scores) after one week of treatment. In this group, 79% responded to lithium by study endpoint. Among those showing less than 20% improvement at Week 1, only 23% responded to lithium by study endpoint.LimitationsHistory of episodes sequence was not assessed.ConclusionsEarly improvement in response to lithium monotherapy in subjects with BD mania predicted later response and remission. Most patients who did not show early improvement in response to lithium during the first week of treatment showed no response after one month. The findings provide a valuable clinical tool for early identification of those patients most likely to benefit from lithium in clinical practice.