Failure to differentiate bipolar disorder from schizophrenia on measures of neuropsychological function

30 inpatients diagnosed with schizophrenia were compared to 35 inpatients with bipolar affective disorder, manic type, on a large group of neuropsychological measures. Separate factor analyses were performed on measures of verbal, spatial, and speed variables in order to generate summary scales. Controlling for the effects of age, education, sex, duration of illness, number of previous hospitalizations, and medications at time of testing, there were no significant differences between diagnostic groups on the three factors or on individual test variables. Patients on medication performed more poorly on speed variables than those off medication. These findings call into question the notion of differential patterns of cognitive deficit among psychotic diagnoses.     

Comorbidity of attention deficit hyperactivity disorder with early- and late-onset bipolar disorder

OBJECTIVE: The relationship between attention deficit hyperactivity disorder (ADHD) and earlier age at onset of affective illness was examined in probands with a history of bipolar disorder. METHOD: The authors assessed 56 adult bipolar subjects. Those with a history of childhood ADHD (N=8) were age and sex matched with bipolar subjects without a history of childhood ADHD (N=8). RESULTS: The age at onset of the first affective episode was lower for the subjects with bipolar disorder and a history of childhood ADHD (mean=12.1 years, SD=4.6) than for those without a history of childhood ADHD (mean=20. 0 years, SD=11.3). CONCLUSIONS: ADHD in children of bipolar probands might identify children at highest risk for development of bipolar disorder.     

Replicated psychometric correlates of schizophrenia

OBJECTIVE: The authors' goals are to use scales from the MMPI hypothesized in their previous research to be correlates of liability to schizophrenia to differentiate DSM-III schizophrenia from bipolar and unipolar affective illness and to cross-validate these correlates in an independently ascertained sample of patients with Research Diagnostic Criteria (RDC) schizophrenia or affective disorder. METHOD: The criterion sample consisted of 83 patients consecutively admitted to a state-operated community mental health center. Diagnosis of schizophrenia; bipolar disorder, manic; and major depression were assigned by using DSM-III. The replication sample consisted of 60 adults with RDC diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, and unipolar disorder who were parents of children in two samples collected for a study of offspring at high risk for schizophrenia and other psychopathology. After the patients in the criterion sample were classified by logistic regression analysis, the results were used to classify patients in the replication sample. RESULTS: The MMPI indicators had adequate sensitivity, specificity, and predictive power for classifying schizophrenia, and there was a moderately high rate of diagnostic agreement between the MMPI and DSM-III. Cross-validation in the replication sample was successful. Overall, the MMPI index was an adequate inclusion and exclusion criterion not only for DSM-III-defined but also for RDC-defined schizophrenia. CONCLUSIONS: A psychometric index composed of the paranoid schizophrenia, psychoticism, and manifest hostility scales from the MMPI would be a cost-effective measure to increase diagnostic efficacy in future schizophrenia research and clinical practice.     

Implicit motives and cognitive variables: Specific links to vulnerability for unipolar or bipolar disorder

Cognitive variables contribute to the etiology of affective disorders. With the differentiation between explicit and implicit measures some studies have indicated underlying depressogenic schemata even in bipolar disorders. We tested for differences in implicit motives and cognitive variables between patients with remitted unipolar and bipolar disorder compared to controls and in a high-risk sample. Additionally we investigated whether affective symptoms relate to those variables. We cross-sectionally examined N=164 participants (53 with bipolar disorder, 58 with major depression, and 53 without affective disorders) and a high-risk sample (N=49) of adolescent children of either parents with unipolar or bipolar disorder or of healthy parents. The Multi-Motive-Grid was used to measure the implicit motives achievement, affiliation, and power, in addition to the cognitive measures of self-esteem, dysfunctional attitudes, and perfectionism. Unipolar and bipolar groups did not differ from healthy controls in implicit motives but showed higher scores in the cognitive factors. Adolescents at high risk for unipolar disorder showed lower scores in the power and achievement motives compared to adolescents at low risk. Subsyndromal depressive symptoms were related to the cognitive variables in both samples. Our results underline the importance of cognitive-behavioral treatment for both unipolar and bipolar disorder.     

Differentiation of primary affective illness from situational, symptomatic, and secondary depressions.

Analysis of family history and antidepressant drug response variables of 100 "neurotic" depressives followed up prospectively over three to four years disclosed that primary depressions (unipolar and bipolar) could be distinguished from nonprimary cases by (1) the early occurrence of "pharmacological-hypomania;" (2) family history of bipolar illness; (3) family history for affective disorder in two or three consecutive generations, especially when "loaded." Although each of these variables alone occurred in only one fifth to one third of the primary group, they individually displayed better than 95% specificity for it. Thus, the confidence with which the diagnosis of primary affective illness could be made in the presence of any of these variables ranged from 88% to 100%. These findings argue for considering such nonsymptomatological variables for their potential in strengthening the phenomenologic diagnostic criteria for depressive illness.     

Interdependency of lithium ratio, plasma lithium level and clinical state in patients with affective disorders

The interrelationship between lithium ratio, lithium plasma level and the different clinical phases of 31 patients with bipolar affective disorder has been investigated. the interdependency of these variables was followed longitudinally during different phases of the illness while under lithium therapy. Although positive correlations between lithium ratio and lithium plasma levels were evident, the lithium ratio values in the euthymic group were significantly higher than those in the manic and depressive groups, independently of the plasma lithium level. Our data suggested that RBC/plasma lithium ratio might be a sensitive state dependent index in affective bipolar illness.     

Gender differences in prevalence,risk, and clinical correlates of alcoholism comorbidity in bipolar disorder

OBJECTIVE: The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have previously received little systematic study. METHOD: The prevalence of lifetime alcoholism in 267 outpatients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV. Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered questionnaires. RESULTS: As in the general population, more men (49%, 57 of 116) than women with bipolar disorder (29%, 44 of 151) met the criteria for lifetime alcoholism. However, the risk of having alcoholism was greater for women with bipolar disorder (odds ratio=7.35) than for men with bipolar disorder (odds ratio=2.77), compared with the general population. Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder. CONCLUSIONS: This study suggests that there are gender differences in the prevalence, risk, and clinical correlates of alcoholism in bipolar illness. Although this study is limited by the retrospective assessment of illness variables, the magnitude of these gender-specific differences is substantial and warrants further prospective study.     

Evolution of cognitive impairment in bipolar disorder: a systematic review of cross-sectional evidence

OBJECTIVES: The notion that sufferers of bipolar disorder achieve complete syndromal and functional recovery between illness episodes has been brought into question by evidence that a large proportion of patients fail to regain premorbid levels of functioning after the resolution of major affective symptoms. A growing body of evidence suggests that bipolar patients exhibit neuropsychological impairment that persists even during the euthymic state, which may be a contributory factor to poor psychosocial outcome. However, the aetiology of such impairment and its relation to progression of illness are not well understood. This review aims to consider evidence from studies investigating both the relationship between cognitive impairment and clinical outcome and studies of neurocognitive function in unaffected first-degree relatives (FDRs) of bipolar sufferers to address issues of the temporal evolution of cognitive impairment in bipolar disorder. METHODS: Systematic literature review. RESULTS: The weight of evidence suggests that greater neuropsychological dysfunction in bipolar disorder is associated with a worse prior course of illness, particularly the number of manic episodes, hospitalizations and length of illness. The most consistent finding was a negative relationship between the number of manic episodes and verbal declarative memory performance. Impairment in unaffected FDRs was reported in verbal declarative memory and some facets of executive function. CONCLUSIONS: Cognitive impairment may be a trait vulnerability factor for bipolar disorder that is present before illness onset and worsens as the illness progresses. Further investigation into the causal relationship between cognitive impairment and illness course is essential.     

The Maudsley Bipolar Disorder Project: the effect of medication,family history,and duration of illness on IQ and memory in bipolar I disorder

BACKGROUND: Despite the growing recognition of the importance of cognitive impairment in psychiatric disorders, the effect of clinical factors, such as medication use and family history of affective disorders, on cognition in bipolar I disorder patients still remains unclear. This study examines the contribution of known and potential predictors to both general intellectual function and memory in a representative population of bipolar I disorder patients. METHOD: Of the 425 patients receiving treatment within a defined catchment area, 63 were identified as having bipolar I disorder. Of these patients, 43 were enrolled in the study and participated in a personal interview by a psychiatrist. All patients were invited to participate in a personal interview by a psychiatrist, and information on family history, past psychiatric history, past and current treatments, duration of illness, and age at onset was collected, in addition to demographic data. Cognitive performance was assessed using the Wechsler Adult Intelligence Scale-Revised, the National Adult Reading Test, and the Wechsler Memory Test III. RESULTS: Forty-three patients with DSM-IV bipolar I disorder were enrolled into the Maudsley Bipolar Disorder Project. Patients on treatment with antipsychotic drugs had a lower current full scale IQ, lower general memory scores, and lower working memory scores. A family history of affective disorders was associated with a higher full scale IQ, but not with either general or working memory measures. Duration of illness was negatively associated with general memory scores, but had no effect on either IQ or working memory measures. CONCLUSION: Current antipsychotic medication, duration of illness, and family history of affective disorder were the most significant predictors of IQ and memory function in bipolar I disorder patients.     

Early physical and sexual abuse associated with an adverse course of bipolar illness.

BACKGROUND: There is growing awareness of the association between physical and sexual abuse and subsequent development of psychopathology, but little is known, however, about their relationship to the longitudinal course of bipolar disorder. METHODS: We evaluated 631 outpatients with bipolar I or II disorder for general demographics, a history of physical or sexual abuse as a child or adolescent, course of illness variables, and prior suicide attempts, as well as SCID-derived Axis I and patient endorsed Axis II comorbidity. RESULTS: Those who endorsed a history of child or adolescent physical or sexual abuse, compared with those who did not, had a history of an earlier onset of bipolar illness, an increased number of Axis I, II, and III comorbid disorders, including drug and alcohol abuse, faster cycling frequencies, a higher rate of suicide attempts, and more psychosocial stressors occurring before the first and most recent affective episode. The retrospectively reported associations of early abuse with a more severe course of illness were validated prospectively. CONCLUSIONS: Greater appreciation of the association of early traumatic experiences and an adverse course of bipolar illness should lead to preventive and early intervention approaches that may lessen the associated risk of a poor outcome.     

Platelet 3H-imipramine binding and familial transmission of affective disorders

We studied platelet 3H-imipramine binding and family history of affective illness in 26 patients with bipolar affective disorder and 24 patients with unipolar affective disorder. The density of platelet 3H-imipramine binding sites (Bmax) was significantly lower in bipolar patients with family history of affective illness than in healthy controls; however, there was a considerable overlap in Bmax values between the familial cases and the normal controls. A similar trend was observed in familial cases of unipolar disorder but the differences fell short of statistical significance. The nonfamilial cases of affective disorder did not differ from the healthy controls. The possible role of reduced platelet 3H-imipramine binding as a genetic vulnerability 'marker' in affective disorder was discussed.     

Individual and familial risk factors for bipolar affective disorders in Denmark

BACKGROUND: Few population-based studies have addressed risk factors for bipolar affective disorder. OBJECTIVE: To study the possible association between bipolar affective disorder and history of mental illness in a parent or sibling; urbanicity of birth place; season of birth; sibship characteristics, including birth order; influenza epidemics during pregnancy; and early parental loss. DESIGN: We used a population-based cohort of 2.1 million individuals based on data from the Danish Civil Registration System linked with the Danish Psychiatric Central Register. SETTING: Nationwide population-based sample of all individuals hospitalized or in outpatient clinic contact for the first time with bipolar affective disorder.Patients Overall, 2299 individuals were first diagnosed with bipolar affective disorder during the 31.8 million person-years of follow-up. RESULTS: Risk of bipolar affective disorder was associated with a history of bipolar affective disorder as well as other psychiatric disorders, including schizophrenia and schizoaffective disorder, in parents or siblings. People with a first-degree relative with bipolar affective disorder had a 13.63-fold (95% confidence interval, 11.81-15.71) increased risk of bipolar affective disorder. No other consistent associations were found with the exception of an association between early parental loss, in particular maternal, and bipolar affective disorder. Children who experienced maternal loss before their fifth birthday had a 4.05 (95% confidence interval, 1.68-9.77) increased risk of bipolar affective disorder. CONCLUSIONS: Early parental loss may represent both environmental and genetic risk factors for bipolar affective disorder. Most of the risk factors included in our study that previously have been associated with schizophrenia were not associated with bipolar affective disorder, supporting that the 2 disorders may be at least partially separate etiological entities.     

Impairments of attention and effort among patients with major affective disorders

Impairments of attention are common among people with major affective disorders, yet the influence of effortful task demands on attentional performance in unipolar and bipolar illness has been little studied. The authors compared psychiatric inpatients with primary diagnoses of unipolar or bipolar affective disorder (n=27) and age-matched normal control subjects (n=20) on a battery of eight neuropsychological tasks designed to measure different attentional functions. There were low-effort and high-effort versions of each task. Significant group differences were consistently observed on tasks demanding sustained and focused attention, but not on tasks requiring visual selective attention. Although affective disorder patients showed impairments on most tasks regardless of level of task effort, group differences were greatest on high-effort conditions. Results indicate that patients with major affective disorders show significant attentional impairments on most measures of effortful attention, and the magnitude of these impairments increases as the effortful demands of the task increase.     

Frequency of comorbid personality disorders in bipolar and unipolar affective disorders

One expression of the complex relationship between personality and affective disorder is the comorbidity of personality disorders (PDs) with affective disorders. In a sample of 117 patients with unipolar and 60 with bipolar affective disorders, we assessed DSM-III-R PDs with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) and compared them with personality factors as obtained by the five-factor model (FFM-NEO Five-Factor Inventory). Fifty-one percent of the unipolar and 38% of the bipolar disorders fulfilled criteria for a comorbid PD. The three most frequent PDs were obsessive-compulsive PD, borderline PD, and narcissistic (bipolar) or avoidant (unipolar) PD. Cluster C PDs and especially avoidant PD occurred significantly more frequently in unipolar than in bipolar patients, while narcissistic PD occurred significantly more often in bipolar than in unipolar patients. The FFM results supported the validity of our PD diagnoses. In a logistic regression analysis, higher depression score at the time of the SCID-II interview and shorter duration of the illness were weakly related to a higher frequency of PDs. Our results indicate that PDs are frequent in affective disorders and that there are subtle differences between unipolar and bipolar patients concerning such comorbid disorders.     

Rates and clinical correlates of treatment non-adherence in schizoaffective bipolar patients

Murru A, Pacchiarotti I, Nivoli AMA, Bonnin CM, Patrizi B, Amann B, Vieta E, Colom F. Rates and clinical correlates of treatment non‐adherence in schizoaffective bipolar patients. Objective: To analyze demographical, clinical, and therapeutic variables that may be associated with pharmacological non‐adherence in a sample of schizoaffective patients, bipolar type. Method: Adherence to treatment and its clinical correlates were assessed at the end of a 10‐year follow‐up in 76 patients meeting DSM‐IV‐TR diagnosis of schizoaffective disorder, bipolar type. Adherent and poorly adherent patients were compared regarding clinical and therapeutic variables. Results: The rate of poorly adherent patients was 32/76 (41.2%) of the sample. Adherent patients were more likely to have presented an affective episode at illness onset and to have fewer purely – non‐affective – psychotic episodes. Demographic or other clinical variables were not found to be associated to treatment adherence. Family history for psychiatric disorders or suicide did not correlate either, and neither did any specific pharmacological agent. Conclusion: Rates of non‐adherence in schizoaffective disorder are high. Adherence seems to be associated to a more affective course of illness (affective first episode and fewer purely psychotic episodes). Patients with more prominent schizophrenia‐like characteristics could be at higher risk for poor adherence and need to be closely followed and monitored. Even when properly treated, schizoaffective disorder is a disabling and severe disorder with high risk for recurrences.     

Bipolar affective disorder and creativity: implications and clinical management

Research on the relationship between creativity and mental illness is summarized, and studies documenting a relationship in writers between creativity and affective illness (particularly bipolar illness) are described. Writers have a high prevalence of affective illness, and both affective illness and creativity have increased frequency in their first-degree relatives. The clinical management of the creative individual is challenging. In general, creative individuals are most productive when their affective symptoms are under good control.     

The association between course of illness and subsequent morbidity in bipolar I disorder

OBJECTIVE: We examined the relationship between certain bipolar I disorder clinical course variables over 5 years with outcome over the subsequent 5-year period. METHODS: Prospective observational follow-up data of 123 bipolar I subjects were analyzed. Predictive clinical variables included the frequency and direction of switches, and the quantity, polarity and length of affective periods. Outcome variables were an affective burden index (ABI) accounting for week-by-week severity and weeks hospitalized. Bivariate analyses guided the selection of predictors for multivariable analyses against the outcome variables. RESULTS: Affective burden index: while the number and direction of switches, the number of polyphasic episodes, weeks in hypomania/mania/mixed state, weeks in minor/major depression, weeks in at least marked affective syndrome, and weeks in any affective syndrome all had bivariate correlation (p<0.01) with the ABI, only weeks in hypomania/mania/mixed state and weeks in minor/major depression made significant contributions in the multivariable analysis (p<0.01) with the ABI. Weeks hospitalized: weeks in at least marked affective syndrome were significantly correlated with weeks hospitalized in bivariate analysis (p<0.01), and maintained a contribution to weeks hospitalized in the multivariable analysis (p<0.01). CONCLUSIONS: The quantity and severity of weeks in symptomatic affective states are possibly greater predictors of affective burden in bipolar I patients than the quantity and direction of affective switches.     

Familiality of polarity at illness onset in bipolar affective disorder

OBJECTIVE: Bipolar affective disorder is clinically heterogeneous, and clinical features that run in families may help define more homogeneous phenotypes. The authors sought to establish whether polarity at illness onset, which is related to severity and course, is a familial feature of bipolar affective disorder. METHOD: The authors studied 971 subjects from 507 families ascertained through sibling pairs with bipolar I or schizoaffective bipolar disorder. Self-reported ages at onset of mania and major depression were used to code polarity at onset as manic, major depressive, or both (mania and major depression in the same onset year). Familial clustering was estimated by using mixed-effects regression analysis, and the relationship between polarity at onset and several other clinical features was assessed. As a preliminary test of genetic validity, the authors assessed the impact of polarity at onset on genetic linkage findings previously detected in this sample. RESULTS: Polarity at onset was significantly familial in this sample. This largely reflected relative pairs concordant for mania at onset, which occurred significantly more frequently than would be expected by chance. Mania at onset substantially increased the genetic linkage signal on chromosome 16p (maximum lod score=4.5) but had no effect on linkage to chromosome 6q. Mania at onset occurred at a later age on average than major depression at onset and was less likely to be complicated by panic attacks or alcoholism. CONCLUSIONS: Polarity at illness onset is a familial feature of bipolar affective disorder and is associated with important clinical indicators, which may help define more homogeneous subtypes of bipolar affective disorder.     

Neurocognition in bipolar disorder: A review of the current research

Altered neurocognitive processing ability is an important feature of bipolar illness and deficits are observed in a number of neuropsychologic domains including executive function, learning and memory, attention, and psychomotor speed. Recent studies have demonstrated that cognitive deficits are present across clinical states with some evidence of both trait and state clustering. Number of hospitalizations and affective episodes, as well as duration of illness and other illness variables, have also been shown to be associated with the neuropsychologic performance of bipolar patients. Presently, it appears that functions mediated by frontal and temporal systems including attention and verbal learning and memory are the cognitive domains most consistently affected in bipolar patients. One important implication of these deficits is that they may be associated with loss of self-regulation and modulation of affective response. Characterization of these changes may provide new insight into the pathophysiology and treatment of bipolar disorder.     

Risk or resilience? Empathic abilities in patients with bipolar disorders and their first-degree relatives

Endophenotypes are intermediate phenotypes which are considered a more promising marker of genetic risk than illness itself. While previous research mostly used cognitive deficits, emotional functions are of greater relevance for bipolar disorder regarding the characteristic emotional hyper-reactability and deficient social-emotional competence. Hence, the aim of the present study was to clarify whether empathic abilities can serve as a possible endophenotype of bipolar disorder by applying a newly developed task in bipolar patients and their first-degree relatives. Three components of empathy (emotion recognition, perspective taking and affective responsiveness) have been assessed in a sample of 21 bipolar patients, 21 first-degree relatives and 21 healthy controls. Data analysis indicated significant differences between controls and patients for emotion recognition and affective responsiveness but not for perspective taking. This shows that in addition to difficulties in recognizing facial emotional expressions, bipolar patients have difficulties in identifying emotions they would experience in a given situation. However, the ability to take the perspective of another person in an emotional situation was intact but decreased with increasing severity of residual hypomanic and depressive symptoms. Relatives performed comparably bad on emotion recognition but did not differ from controls or patients in affective responsiveness. This study is the first to show that deficient emotion recognition is the only component of empathy which forms a possible endophenotype of bipolar disorder. This has important implications for prevention strategies. Furthermore, changes in affective responsiveness in first-degree relatives show a potential resilience marker.