Colom F, Vieta E, Martinez-Aran A, Reinares M, Benabarre A, Gasto C.
Clinical factors associated with treatment noncompliance in euthymic bipolar patients.
J Clin Psychiatry 2000 Aug;61(8):549-55
"BACKGROUND: Noncompliance with medication is a very common feature among bipolar patients. Rates of poor compliance may reach 64% for bipolar disorders, and noncompliance is the most frequent cause of recurrence. Knowledge of the clinical factors associated with noncompliance would enhance clinical management and the design of strategies to achieve a better outcome for bipolar patients. Although most patients withdraw from medication during maintenance treatment, compliance studies in euthymic bipolar samples are scarce. METHOD: Compliance treatment and its clinical correlates were assessed at the end of 2-year follow-up in 200 patients meeting Research Diagnostic Criteria for bipolar I or bipolar II disorder by means of compliance-focused interviews, measurements of plasma concentrations of mood stabilizers, and 2 structured interviews: the Schedule for Affective Disorders and Schizophrenia and the Structured Clinical Interview for DSM-III-R Axis II disorders. Well-compliant patients and poorly compliant patients were compared with respect to several clinical and treatment variables. RESULTS: The rate of mildly and poorly compliant patients was close to 40%. Comorbidity with personality disorders was strongly associated with poor compliance. Poorly compliant patients had a higher number of previous hospitalizations, but reported fewer previous episodes. The type of treatment was not associated with compliance. CONCLUSION: Clinical factors, especially comorbidity with personality disorders, are more relevant for treatment compliance than other issues such as the nature of pharmacologic treatment. Compliant patients may have a better outcome in terms of number of hospitalizations, but not necessarily with respect to the number of episodes. Bipolar patients, especially those with personality disorders, should be monitored for treatment compliance." [Abstract]

Pierson A, Jouvent R, Quintin P, Perez-Diaz F, Leboyer M.
Information processing deficits in relatives of manic depressive patients.
Psychol Med 2000 May;30(3):545-55
"BACKGROUND: The importance of genetic factors in the aetiology of manic-depressive illness (MDI) has been repeatedly confirmed and indicators of vulnerability to the illness in families with affective disorders are needed. Abnormal event-related potentials (ERP) may be markers of genetic vulnerability to mental illness. Long latency and low amplitude of P300 have consistently been reported in schizophrenic patients and their relatives. A few studies have also shown P300 deficits in MDI patients, but no ERP study has been performed on their relatives. METHODS: ERPs were recorded during an auditory oddball task in 19 relatives belonging to families with two or more bipolar patients and in controls with no familial or personal history of affective disorders. The relatives were selected as having no affective disorders on a lifetime basis, but eight had an anxiety disorder. RESULTS: In all relatives, a lower P300 amplitude and a longer P300 latency was found, with much longer reaction time and post-N200 duration till button-press than controls. A lack of P300 amplitude dominance in the right hemisphere was also found in relatives in comparison with controls. There also appeared to be a frontal predominance of ERP abnormalities in relatives. CONCLUSION: We report the first evidence of deficits in reaction time and in P300 amplitude and latency, and a lack of P300 right-sided dominance, in relatives of manic-depressive patients. This pattern may constitute an endophenotypic marker of manic-depressive disorder." [Abstract]

MacQueen GM, Young LT, Robb JC, Marriott M, Cooke RG, Joffe RT.
Effect of number of episodes on wellbeing and functioning of patients with bipolar disorder.
Acta Psychiatr Scand 2000 May;101(5):374-81
"OBJECTIVE: To examine the relationship between number of episodes and inter-episode functioning in bipolar disorder. METHOD: Sixty-four euthymic subjects with bipolar affective disorder completed the Medical Outcomes Questionnaire Short Form and the Global Assessment of Functioning Scale. Goodness-of-fit models were used to define the relation between episode number and level of function. RESULTS: Non-linear logarithmic and power relations best described the association between number of episodes and outcome. Number of past depressions was a stronger determinant of outcome than past manias. CONCLUSION: Strategies to minimize the number of episodes experienced by patients with bipolar illness must be pursued aggressively if function is to be maintained, with particular attention given to minimizing episodes of depression." [Abstract]

Vilela C, Vallet M, Salazar J, Tabares R, Selva G, Valanza V, Leal C.
[P300 and neuropsychological tests in schizophrenia and bipolar patients]
Rev Neurol 1999 Mar 16-31;28(6):608-12
"INTRODUCTION: A smaller P300 amplitude has been found in schizophrenic patients in the majority of the studies done. And this occur in spite of treatment, sex, clinical stage and evolution time of the illness. It has been already described an association between this amplitude reduction and a poor result on the neuropsychological tests. But these changes in the P300 amplitude are not specific of the schizophrenic patients and they can be found in affective patients. OBJECTIVES: This study try to value the influence of the clinical stage and the cognitive results on the P300 values in the bipolar patients and to compare these results with the schizophrenic patients. PATIENTS AND METHODS: It has been evaluated the evoked potentials and the results of a neuropsychological battery of tests in three patient groups: schizophrenics in patients with acute symptomatology (n = 18), schizophrenic out patients without acute symptomatology (n = 15) and bipolar in patients during a maniac period (n = 16). RESULTS: It has not been found any differences between schizophrenic and maniac patients nor in the amplitude or in the latency of the P300. The results of the neuropsychological tests have not any relation with P300 amplitude and latency except for the verbal fluidity (VF) which has a good correlation with a longer P300 latency. At the same time this was the only test in which schizophrenic patients have smaller results than affective patients with a good correlation. CONCLUSIONS: These results suggest a similar pattern of neuropsychological and neurophysiological damage in schizophrenic and affective patients in acute period of mania." [Abstract]

Benazzi F.
Psychotic versus nonpsychotic bipolar outpatient depression.
Eur Psychiatry 1999 Dec;14(8):458-61
"Psychotic bipolar depression was compared with nonpsychotic bipolar depression. Psychotic (n = 59) and nonpsychotic (n = 176) bipolar depressed outpatients were SCID-DSM-IV interviewed. Psychotic bipolar depression had significantly higher severity, more chronicity, fewer atypical features and axis I co-morbidity, more bipolar I, and fewer bipolar II patients. Age at onset, duration of illness, gender, and recurrences, were not significantly different." [Abstract]

Carlson GA, Bromet EJ, Sievers S.
Phenomenology and outcome of subjects with early- and adult-onset psychotic mania.
Am J Psychiatry 2000 Feb;157(2):213-9
"OBJECTIVE: This study examined clinical differences between subjects with early-onset and adult-onset psychotic mania. METHOD: Subjects were from an epidemiologically derived, hospitalized sample who met criteria for definite bipolar disorder after 24 months of follow-up and whose index episode had been manic. Information collected regarding demographic characteristics, psychotic and depressive symptoms, childhood behavior problems and school functioning, substance/alcohol use disorders, and episode recurrence for two subgroups were compared: those whose illness first emerged before age 21 (early onset) (N=23) and those whose first episode occurred after age 30 (adult onset) (N=30). RESULTS: A larger proportion of the early-onset subjects were male, had childhood behavior disorders, had substance abuse comorbidity, exhibited paranoia, and experienced complete episode remission less frequently during 24-month follow-up than the adult-onset subjects. CONCLUSIONS: These data add to the body of evidence that has suggested that many subjects with early-onset psychotic mania have a more severe and developmentally complicated subtype of bipolar disorder." [Abstract]

Swann AC, Petty F, Bowden CL, Dilsaver SC, Calabrese JR, Morris DD.
Mania: gender, transmitter function, and response to treatment.
Psychiatry Res 1999 Oct 18;88(1):55-61
"Noradrenergic and GABA systems may be involved in mania, but there is little information about relationships between the function of these systems and response to specific antimanic treatments. We investigated relationships between indices of catecholamine or GABA system function, pretreatment mania severity and antimanic response to divalproex, lithium, or placebo. Plasma GABA and urinary excretion of catecholamine metabolites were measured before randomization to lithium, divalproex or placebo in patients hospitalized for manic episodes. Severity of mania was evaluated using the Manic Syndrome, Behavior and Ideation and Mania Rating Scale scores from the SADS-C. Multiple regression analysis showed that pretreatment plasma GABA was related to severity of manic symptoms. This relationship seemed stronger in women. Multiple regression analysis showed that pretreatment levels of urinary MHPG correlated with improvement in manic syndrome scores. These data suggest that GABA and norepinephrine may be related to different aspects of the manic state and to its pharmacologic sensitivity." [Abstract]

Martinez-Aran A, Vieta E, Colom F, Reinares M, Benabarre A, Gasto C, Salamero M.
Cognitive dysfunctions in bipolar disorder: evidence of neuropsychological disturbances.
Psychother Psychosom 2000;69(1):2-18
"Although cognitive dysfunctions in psychosis have classically been associated with schizophrenia, there is clinical evidence that some bipolar patients show cognitive disturbances either during acute phases or in remission periods. The authors critically review the data on cognitive impairment in bipolar disorder. The main computerized databases (Medline, Psychological Abstracts, Current Contents) have been consulted crossing the terms 'cognitive deficits', 'neuropsychology', 'intellectual impairment', 'mania', 'depression' and 'bipolar disorder'. Changes in the fluency of thought and speech, learning and memory impairment, and disturbances in associational patterns and attentional processes are as fundamental to depression and mania as are changes in mood and behavior. Moreover, a significant number of bipolar patients show persistent cognitive deficits during remission from affective symptoms. However, there are several methodological pitfalls in most studies such as unclear remission criteria, diagnostic heterogeneity, small sample sizes, absence of longitudinal assessment, practice effect and poor control of the influence of pharmacological treatment. Most studies point at the presence of diffuse cognitive dysfunction during the acute phases of bipolar illness. Most of these deficits seem to remit during periods of euthymia, but some of them may persist in approximately one third of bipolar patients. Methodological limitations warrant further research in order to clear up the relationship between neuropsychological functioning and clinical, demographic and treatment variables in bipolar disorder. Copyright 2000 S. Karger AG, Basel." [Abstract]

Callahan AM, Bauer MS.
Psychosocial interventions for bipolar disorder.
Psychiatr Clin North Am 1999 Sep;22(3):675-88, x
"The limitations of pharmacotherapy and the emergence of data supporting a role for psychosocial factors in the course of bipolar disorder have led to increased interest in the use of psychosocial interventions to improve outcomes. Although this area of study has suffered from a lack of systematic data, preliminary evidence suggests that the combined use of psychosocial interventions and medication is superior to pharmacologic treatment alone. Further research is necessary to identify and the psychosocial risk factors associated with bipolar disorder to design effective interventions to diminish their effects and improve outcome. The introduction of formal, manual-based psychotherapeutic interventions that include specific educational components has been particularly promising." [Abstract]

Baldessarini RJ.
Treatment research in bipolar disorder: issues and recommendations.
CNS Drugs 2002;16(11):721-9
"Bipolar (manic-depressive) disorder is one of the most common of the severe mental illnesses. Officially recognised forms comprise type I (with mania), type II (with hypomania), cyclothymia and a rapid-cycling subtype. International lifetime prevalence estimates are 1 to 5% of the general population, and bipolar disorder accounts disproportionately for idiopathic psychoses. Psychiatric and substance-abuse comorbidities are common complications, and mortality rates are increased as a result of high suicidal risks, accidents, complications of substance abuse and increased fatality of stress-sensitive medical illnesses. Complex and labile symptomatic presentations, a tendency for patients to deny illness and reject treatment, and diagnostic heterogeneity severely complicate the design, conduct and interpretation of experimental treatment trials in bipolar disorder. Progress in the short-term treatment of mania with certain antiepileptic drugs and atypical antipsychotic agents has advanced greatly in recent years; however, long-term treatment trials other than with lithium remain rare, as are studies of type II disorder, bipolar depression and mixed states, and there is limited information on treatment effectiveness against comorbidity, dysfunction and mortality. There is a growing realisation that bipolar disorder represents a major, largely unmet, international public health challenge and that innovative methods for carrying out reliable and generalisable long-term pharmacological treatment trials, alone and in combination with cost-effective psychosocial and rehabilitative interventions, are urgently required." [Abstract]

Torrey EF.
Epidemiological comparison of schizophrenia and bipolar disorder.
Schizophr Res 1999 Sep 29;39(2):101-6; discussion 159-60
"Schizophrenia and bipolar disorder share many epidemiological features in common, but there are also differences. Both disorders share some risk factors, suggesting etiological antecedents that date to the perinatal period; these include excess of winter-spring births, abnormal dermatoglyphics, and probably an excess of perinatal complications. By contrast, an excess of urban births and an excess of minor physical anomalies are present in schizophrenia, but apparently not in bipolar disorder. Bipolar disorder also may be found in geographic, presumably genetic, isolates and in higher prevalence in higher socio-economic groups, which also differentiates it from schizophrenia. It is hypothesized that a subset of individuals with bipolar disorder constitutes a distinct disease entity, but that the majority share some common etiological antecedents with schizophrenia and may represent a disease continuum." [Abstract]

Benedetti F, Serretti A, Colombo C, Campori E, Barbini B, di Bella D, Smeraldi E.
Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression.
Am J Psychiatry 1999 Sep;156(9):1450-2
"OBJECTIVE: A functional polymorphism in the transcriptional control region upstream of the coding sequence of the 5-hydroxytryptamine transporter (5-HTT) has been reported. This polymorphism has been shown to influence the antidepressant response to fluvoxamine and paroxetine. The authors tested the hypothesis that the allelic variation of the 5-HTT-linked polymorphic region (5-HTTLPR) could influence the response of depressed patients to total sleep deprivation. METHOD: Sixty-eight drug-free inpatients with bipolar depression underwent a night of total sleep deprivation. 5-HTTLPR was genotyped in these patients. Changes in perceived mood were rated on a visual analogue scale and analyzed by using repeated measures analysis of covariance. RESULTS: Patients who were homozygotic for the long variant of 5-HTTLPR showed a significantly better mood amelioration after total sleep deprivation than those who were heterozygotic and homozygotic for the short variant. CONCLUSIONS: The influence of 5-HTTLPR on response to total sleep deprivation is similar to its observed influence on response to serotonergic drug treatments. This finding supports the hypothesis of a major role for serotonin in the mechanism of action of total sleep deprivation in depression." [Abstract]

Shulman KI, Herrmann N.
Bipolar disorder in old age.
Can Fam Physician 1999 May;45:1229-37
"OBJECTIVE: To review the classification, clinical characteristics, and epidemiology of bipolar disorders in old age with a special focus on neurologic comorbidity, high mortality, and management. QUALITY OF EVIDENCE: Most available data is gleaned from retrospective chart reviews and cohort studies. Treatment recommendations are based on evidence from younger populations and a few anecdotal case reports and series involving elderly people. MAIN MESSAGE: While relatively rare in the community setting, mania in old age frequently leads to hospitalization. It is associated with late-onset neurologic disorders (especially cerebrovascular disease) involving the right hemisphere and orbitofrontal cortex. Prognosis is relatively poor; morbidity and mortality rates are high. Management of bipolarity includes cautious use of mood stabilizers, especially lithium and divalproex. CONCLUSIONS: Mania in old age should trigger a careful assessment of underlying neurologic disease, especially cerebrovascular disease. Close clinical follow up is essential." [Abstract]

Clarke RP.
Outline of a theory of manic-depressive illness.
Med Hypotheses 1998 Jul;51(1):37-40
"Manic-depressive illness is characterized by locking into extreme states and alternation between those extremes. Locking into extreme states is also characteristic of a bistable, a basic electronic device of which the essential feature is a positive feedback loop with greater than unity gain. An argument is presented that under natural selection there has evolved a well-known and advantageous tendency for perceptions of successes to increase confidence, and that it is in the nature of confidence to increase perceptions of successes. Thus arises a positive feedback loop, in which perceptions of successes increase confidence, which further increases perceptions of successes, and so on, and the converse with failure and inconfidence. When the gain of the loop exceeds unity then locking into mania or depression will result. The feedback gain depends on both internal 'biological' factors and external situational factors. As a result of natural fluctuations the gain will occasionally fall temporarily below unity, releasing from the extreme state. Escape from mania will bias towards depression, whereas escape from depression will be elating. The physical embodiment of confidence may be serotonergic (or closely related) activity." [Abstract]

Hantouche EG, Akiskal HS, Lancrenon S, Allilaire JF, Sechter D, Azorin JM, Bourgeois M, Fraud JP, Chatenet-Duchene L.
Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP).
J Affect Disord 1998 Sep;50(2-3):163-73
"BACKGROUND: This paper presents the methodology and clinical data in mid-stream from a French multi-center study (EPIDEP) in progress on a national sample of patients with DSM-IV major depressive episode (MDE). The aim of EPIDEP is to show the feasibility of validating the spectrum of soft bipolar disorders by practising clinicians. In this report, we focus on bipolar II (BP-II). METHOD: EPIDEP involves training 48 French psychiatrists in 15 sites; construction of a common protocol based on the criteria of DSM-IV and Akiskal (Soft Bipolarity), as well as criteria modified from the work of Angst (Hypomania Checklist), the Ahearn-Carroll Bipolarity Scale, HAM-D and Rosenthal Atypical Depression Scale; Semi-Structured Interview for Evaluation of Affective Temperaments (based on Akiskal-Mallya), self-rated Cyclothymia Scale (Akiskal), family history (Research Diagnostic Criteria); and prospective follow-up. RESULTS: Results are presented on 250 (of the 537) MDE patients studied thus far during the acute phase. The rate of BP-II disorder which was 22% at initial evaluation, nearly doubled (40%) by systematic evaluation. As expected from the selection of MDE by uniform criteria, inter-group comparison between BP-II vs unipolar showed no differences on the majority of socio-demographic parameters, clinical presentation and global intensity of depression. Despite such uniformity, key characteristics significantly differentiated BP-II from unipolar: younger age at onset of first depression, higher frequency of suicidal thoughts and hypersomnia during index episode, higher scores on Hypomania Checklist and cyclothymic and irritable temperaments, and higher switching rate under current treatment. Eighty-eight percent of cases assigned to cyclothymic temperament by clinicians (with a cut-off of 10/21 items on self-rated cyclothymia) were recognized as BP-II. Evaluation of this temperament by clinician and patient correlated at a highly significant level (r=0.73; p <0.0001). Cyclothymia and hypomania were also correlated significantly (r=0.51; p < 0.001). LIMITATION: In a study conducted in diverse clinical settings, it was not possible to assure that clinicians making affective diagnoses were blind to the various temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. CONCLUSION: With a systematic search for hypomania, 40% of major depressive episodes were classified as BP-II, of which only half were known to the clinicians at study entry. Cyclothymic temperamental dysregulation emerged as a robust clinical marker of BP-II disorder. These data indicate that clinicians in diverse practice settings can be trained to recognize soft bipolarity, leading to changes in diagnostic practice at a national level." [Abstract]

Malkoff-Schwartz S, Frank E, Anderson B, Sherrill JT, Siegel L, Patterson D, Kupfer DJ.
Stressful life events and social rhythm disruption in the onset of manic and depressive bipolar episodes: a preliminary investigation.
Arch Gen Psychiatry 1998 Aug;55(8):702-7
"BACKGROUND: The association between stressful life events and onset of bipolar episodes is unclear. The association between bipolar episode onset and types of life events that disrupt social routines, and potentially sleep, has not yet been investigated. METHODS: Thirty-nine bipolar patients with primarily manic (n = 20) or depressed (n = 19) index episodes were interviewed with the Bedford College Life Event and Difficulty Schedule to determine the presence of severe events during 8-week pre-onset and control periods. All life events were also rated for degree of social rhythm disruption (SRD). RESULTS: More bipolar subjects experienced at least 1 SRD event and severe event in the pre-onset vs control periods. When subjects were divided into those with manic or depressive onsets, the only significant pre-onset vs control difference was for manic patients with SRD events. Additionally, the proportion of subjects with a pre-onset SRD event was greater for manic than for depressed patients. CONCLUSIONS: We found evidence that life events characterized by SRDs routines are associated with the onset of manic, but not depressive, episodes. Severe events seem to be related to onset of bipolar episodes, although it remains unclear whether severe events relate differentially to depressive and manic onsets." [Abstract]

Gonzalez-Pinto A, Gutierrez M, Mosquera F, Ballesteros J, Lopez P, Ezcurra J, Figuerido JL, de Leon J.
First episode in bipolar disorder: misdiagnosis and psychotic symptoms.
J Affect Disord 1998 Jul;50(1):41-4
"BACKGROUND: This study explores factors that can influence other psychotic diagnoses in the first episode of a DSM-III-R bipolar disorder. METHODS: It includes all 163 bipolar in-patients and out-patients in the state of Alava, North of Spain (Basque country) from February 1994 to May 1996. Patients were divided into two non-overlapping groups: unstable diagnoses, bipolars with an initial diagnosis of schizophrenia (or other psychosis), and stable diagnoses of bipolar disorder. RESULTS: A logistic regression analysis using marital status, age at onset and mood incongruent psychotic symptoms found that the latter was the only independent factor significantly associated with an unstable diagnosis." [Abstract]

Simoneau TL, Miklowitz DJ, Saleem R.
Expressed emotion and interactional patterns in the families of bipolar patients.
J Abnorm Psychol 1998 Aug;107(3):497-507
"The predictive validity of expressed emotion (EE) may derive in part from its relationship to important interactional processes in families of patients with major psychiatric disorders. The authors examined the relationship between relatives' EE attitudes, assessed during patients' bipolar, manic, or mixed episodes, and the interactional behavior of bipolar patients (n = 48) and their relatives as revealed in problem-solving discussions during the postepisode period. High-EE relatives were more verbally negative than low-EE relatives in these discussions. Patients from high-EE families were more nonverbally negative than those from low-EE families, whereas patients from low-EE families were more nonverbally positive than those from high-EE families. Sequential analyses revealed that high-EE families engage in negative interchanges of up to 3 volleys. Thus, levels of EE are associated with stressful patterns of interaction between bipolar patients and their relatives during the postepisode period." [Abstract]

Huxley NA, Parikh SV, Baldessarini RJ.
Effectiveness of psychosocial treatments in bipolar disorder: state of the evidence.
Harv Rev Psychiatry 2000 Sep;8(3):126-40
"Cost-effective psychotherapeutic interventions can enhance pharmacotherapy and improve outcomes in major depression and schizophrenia, but they are rarely studied in bipolar disorder, despite its often unsatisfactory response to medication alone. Following a literature search, we compiled and evaluated research reports on psychotherapeutic interventions in bipolar disorder patients. We found 32 peer-reviewed reports involving 1052 patients-14 studies on group therapy, 13 on couples or family therapy, and five on individual psychotherapy-all supplementing standard pharmacotherapy. Methodological limitations were common in these investigations. Nevertheless, important gains were often seen, as determined by objective measures of increased clinical stability and reduced rehospitalization, as well as other functional and psychosocial benefits. The results should further encourage rising international interest in testing the clinical and cost-effectiveness of psychosocial interventions in these common, often severe and disabling disorders." [Abstract]

Scott J, Stanton B, Garland A, Ferrier IN.
Cognitive vulnerability in patients with bipolar disorder.
Psychol Med 2000 Mar;30(2):467-72
"BACKGROUND: No study has simultaneously explored key components of Beck's model of cognitive vulnerability to depression in people with bipolar disorders. METHODS: We compared 41 euthymic bipolar patients with 20 healthy control subjects. All subjects were assessed on the Hamilton Rating Scale for Depression, the Autobiographical Memory Test and the Mean Ends Problem-Solving procedure and also completed the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Sociotropy Autonomy Scale and the Rosenberg Self-Esteem Questionnaire. RESULTS: In comparison to control subjects, patients with bipolar disorder demonstrated significantly higher levels of dysfunctional attitudes (particularly perfectionism and need for approval) and sociotropy, significantly greater over-general recall on an autobiographical memory test and significantly less ability to generate solutions to social problem-solving tasks. These between group differences remained significant when age, intelligence, latency to respond to autobiographical memory test cue words, and subjective mood ratings were included as co-variates in the statistical analysis. Within the patient group, cognitive dysfunction was significantly correlated with level of morbidity (as measured by number of previous illness episodes). CONCLUSIONS: This study suggests that cognitive vulnerability in patients with bipolar disorder is similar to that described in unipolar disorders. It is not clear whether this dysfunction is a cause or an effect of repeated episodes of bipolar disorder. However, the findings may have implications for clinical treatment as well as suggesting a number of important new avenues of research into psychological models of affective disorder." [Abstract]

Valles V, Van Os J, Guillamat R, Gutierrez B, Campillo M, Gento P, Fananas L.
Increased morbid risk for schizophrenia in families of in-patients with bipolar illness.
Schizophr Res 2000 Apr 7;42(2):83-90
"BACKGROUND: It has been reported that relatives of probands with severe, psychotic forms of bipolar illness have increased rates of schizophrenia but not the relatives of individuals with milder, non-psychotic forms of disorder. In this study, we examined the prevalence of psychiatric disorders in the first degree relatives of a sample of 103 inpatients with bipolar disorder and in a matched control sample of 84 healthy individuals. METHOD: Relatives of cases and controls were interviewed using the FH-RDC to determine familial morbid risk for schizophrenia and bipolar disorder. Age- and sex-adjusted morbidity risks were calculated in both samples according to the method of Stromgren. RESULTS: The morbid risks for both bipolar disorder (4.9%) and schizophrenia (2.8%) were higher in relatives of patients than in relatives of controls (0.3% and 0.6% respectively). The relative risks were 14.2 [95% confidence interval (CI)=3.1-64.2] for bipolar disorder and 4.9 (95% CI=1.3-18.8) for schizophrenia. Relatives of women with early onset of bipolar illness had the highest morbid risks for both bipolar illness and schizophrenia. The presence of more than one patient with bipolar disorder in a family increased the risk for schizophrenia nearly fourfold (RR=3.5, 95% CI=1.2-10.2). There was no additional effect of presence of psychotic features. CONCLUSION: Our results suggest that the transmission of psychosis is not disorder-specific. Bipolar illness characterised by a high familial loading is associated with increased risk of schizophrenia in the relatives." [Abstract]

Tompson MC, Rea MM, Goldstein MJ, Miklowitz DJ, Weisman AG.
Difficulty in implementing a family intervention for bipolar disorder: the predictive role of patient and family attributes.
Fam Process 2000 Spring;39(1):105-20
"Family affect was examined as a predictor of difficulty implementing a 9-month, manual-based, psychoeducational family therapy for recently manic bipolar patients. Prior to therapy, family members were administered measures to assess both their expressed emotion and affective behavior during a family interaction task. Following family treatment, both therapists and independent observers rated the overall difficulty of treating the family, and therapists also rated each participant's problem behaviors during treatment, in the areas of affect, communication, and resistance. Therapists regarded affective problems among relatives and resistance among patients as central in determining the overall difficulty of treating the family. Relatives' critical behavior toward patients during the pretreatment interaction task predicted both independent observers' ratings of overall treatment difficulty and therapists' perceptions of relatives' affective problems during treatment. Moreover, patients' residual symptoms predicted independent observers' ratings of overall difficulty and therapists' perceptions of patients' resistance to the family intervention. Results suggest that difficulties in conducting a manual-based family intervention can be predicted from systematic, pretreatment family and clinical assessment." [Abstract]

Arnold LM, Witzeman KA, Swank ML, McElroy SL, Keck PE Jr.
Health-related quality of life using the SF-36 in patients with bipolar disorder compared with patients with chronic back pain and the general population.
J Affect Disord 2000 Jan-Mar;57(1-3):235-9
"BACKGROUND: The purpose of this study was to assess and compare the health-related quality of life of patients with bipolar disorder and chronic back pain and, in turn, to compare these results with those previously generated for the general population. METHODS: Subjects were patients with bipolar disorder (n=44), a comparison group of chronic back pain patients (n=30), and a population-based control sample (n=2,474). Health-related quality of life was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), a self-administered questionnaire in which lower scores are indicative of greater impairment. RESULTS: Patients with bipolar disorder had lower mean scores than the general population on all scales except Physical Functioning. Bipolar patients had significantly higher scores than chronic back pain patients in the categories of Physical Functioning, Role Limitations--Physical, Bodily Pain, and Social Function. There were no significant differences between bipolar disorder and chronic back pain groups in the Mental Health and Role Limitations - Emotional categories. LIMITATIONS: The results of the study are limited by the relatively small sample sizes of the bipolar and back pain patient groups. CONCLUSIONS: Patients with bipolar disorder had substantial impairment in health-related quality of life in comparison with the general population. Bipolar patients were less compromised in areas of physical and social functioning than chronic back pain patients but had similar impairment in mental health." [Abstract]

Merette C, Roy-Gagnon MH, Ghazzali N, Savard F, Boutin P, Roy MA, Maziade M.
Anticipation in schizophrenia and bipolar disorder controlling for an information bias.
Am J Med Genet 2000 Feb 7;96(1):61-8
"Anticipation was investigated in schizophrenia (SZ) and bipolar disorder (BP) while addressing several biases in 18 large families (154 subjects) from Eastern Quebec densely affected by SZ, BP, or both over three generations. In particular, we controlled for an information bias using a measure of quality and quantity of clinical information (QOI) concerning the subjects' illness. Otherwise, spurious anticipation could have arisen because we found that QOI varied with the generations as well as with the severity of illness. Although anticipation was investigated separately for SZ and BP, both disorders were also included in one analysis that tested anticipation under the unitary hypothesis that the SZ and the BP spectrums represent a continuum of severity of the same disease. Age of onset (AOO) and five indices of severity were tested for anticipation. Two statistics were used: the difference in the mean AOO or severity between two successive generations, and the mean difference in parent-offspring pairs (POP). The study led to four main findings: 1) the choice of the statistics greatly influenced the results, POP yielding systematically greater biased estimates; 2) for SZ and BP, the evidence for anticipation with the five severity indices vanished after controlling for QOI; 3) as regards AOO a decrease of 8.6 years, p = 0.0001, and 5.3 years, p = 0.009 in AOO was found for SZ between Generations 1-2, and 2-3, respectively, despite controlling for QOI and addressing all biases; and 4) conversely for BP, anticipation with AOO may be due to censoring. Findings suggest that future anticipation studies should also control for QOI." [Abstract]

Reilly-Harrington NA, Alloy LB, Fresco DM, Whitehouse WG.
Cognitive styles and life events interact to predict bipolar and unipolar symptomatology.
J Abnorm Psychol 1999 Nov;108(4):567-78
"This study examined the interaction of cognitive style (as assessed self-report and information-processing battery) and stressful life events in predicting the clinician-rated depressive and manic symptomatology of participants with Research Diagnostic Criteria lifetime diagnoses of bipolar disorder (n = 49), unipolar depression (n = 97), or no lifetime diagnosis (n = 23). Bipolar and unipolar participants' attributional styles, dysfunctional attitudes, and negative self-referent information processing as assessed at Time 1 interacted significantly with the number of negative life events that occurred between Times 1 and 2 to predict increases in depressive symptoms from Time 1 to Time 2. Within the bipolar group, participants' Time 1 attributional styles and dysfunctional attitudes interacted significantly, and their self-referent information processing interacted marginally, with intervening life events to predict increases in manic symptoms from Time 1 to Time 2. These findings provide support for the applicability of cognitive vulnerability-stress theories of depression to bipolar spectrum disorders." [Abstract]

Simon GE, Unutzer J.
Health care utilization and costs among patients treated for bipolar disorder in an insured population.
Psychiatr Serv 1999 Oct;50(10):1303-8
"OBJECTIVE: The study examined health care utilization and costs among patients treated for bipolar-spectrum disorders in an insured population. METHODS: Computerized data on prescriptions and on outpatient and inpatient diagnoses from a large health plan were used to identify patients treated for cyclothymia, bipolar disorder, or schizoaffective disorder. Three age- and sex-matched comparison groups consisting of general medical outpatients, patients treated for depression, and patients treated for diabetes were selected from health plan members. Utilization and cost of health services for the four groups over a six-month period were assessed using computerized accounting records. RESULTS: Total mean+/-SD costs for patients in the bipolar disorder group ($3,416+/-$6,862) were significantly higher than those in any of the comparison groups. Specialty mental health and substance abuse services accounted for 45 percent of total costs in the group with bipolar disorder (mean+/-SD=$1, 566+/-$3,243), compared with 10 percent in the group with depression. Among patients treated for bipolar disorder, 5 percent of patients accounted for approximately 40 percent of costs for specialty mental health and substance abuse services, 90 percent of inpatient costs for specialty mental health and substance abuse services, and 95 percent of out-of-pocket costs for inpatient care. In the bipolar disorder group, parity coverage of inpatient mental health and substance abuse services would increase overall health care costs by 6 percent. CONCLUSIONS: Health care costs for patients with bipolar disorder exceed those for patients treated for depression or diabetes, and specialty mental health and substance abuse treatment costs account for this difference. Costs to the insurer and costs borne by patients are accounted for by a small proportion of patients. Elimination of discriminatory mental health coverage would have a small effect on overall health care costs." [Abstract]

Kessing LV.
The effect of the first manic episode in affective disorder: a case register study of hospitalised episodes.
J Affect Disord 1999 Jun;53(3):233-9
"BACKGROUND: It is poorly understood how the course of illness in depressive patients is affected by a manic episode. METHOD: The course of hospitalised episodes was compared for patients with depressive episodes only, patients who presented with a manic or circular first episode and patients who presented with a depressive first episode and later developed mania. The Danish psychiatric central register was used as a study base, including all hospital admissions with primary affective disorder in Denmark during 1971-1993. RESULTS: A total of 17,447 patients presented with a depressive first episode and 2903 patients with a manic or circular first episode. Among the 17,447 depressive patients, 762 patients presented with mania at later episodes (4.4%). Younger age at onset was associated with increased risk of developing mania. Patients who had a late first manic episode had the same rate of subsequent recurrence as patients with mania at first episode and this rate was higher than the rate of recurrence for patients who remained having depressive episodes only. Time since first manic episode was without importance in relation to the risk of subsequent recurrence. CONCLUSION: Patients who present with depression and later develop mania have from onset the same risk of recurrence as initially bipolar patients. LIMITATION: The data relate to admissions rather than episodes. CLINICAL RELEVANCE: Younger patients who present with depression have increased risk of developing bipolar disorder." [Abstract]

Lattuada E, Serretti A, Cusin C, Gasperini M, Smeraldi E.
Symptomatologic analysis of psychotic and non-psychotic depression.
J Affect Disord 1999 Jul;54(1-2):183-7
"BACKGROUND: The aim of the present study is to evaluate the symptomatologic presentation of delusional compared to non-delusional major depressive episodes. METHODS: Two hundred and eighty-eight subjects suffering from mood disorder (144 bipolar, 133 unipolar) were assessed at admission by the Hamilton Depression Rating Scale (HAMD-21). RESULTS: Depressive symptomatology was more severe in the delusional sample, even after the exclusion of the items directly involved with delusional symptoms (P = 0.00002). CONCLUSIONS: Our data support the hypothesis of delusional depression as a more severe form of mood disorder." [Abstract]

Pallanti S, Quercioli L, Pazzagli A, Rossi A, Dell'Osso L, Pini S, Cassano GB.
Awareness of illness and subjective experience of cognitive complaints in patients with bipolar I and bipolar II disorder.
Am J Psychiatry 1999 Jul;156(7):1094-6
"OBJECTIVE: The authors' goal was to investigate the awareness of illness and subjective cognitive complaints of patients with either bipolar I disorder or bipolar II disorder during a phase of clinical stabilization. METHOD: They used a structured clinical interview, the Frankfurt Complaints Questionnaire, to determine subjective cognitive complaints, and the Scale of Unawareness of Mental Disorder to assess 57 consecutively enrolled patients with bipolar I or bipolar II disorder. RESULTS: Patients with bipolar II disorder had significantly less insight and a higher level of subjective complaints of stimulus overload than patients with bipolar I disorder. CONCLUSIONS: These results suggest that a severe deficit in self-awareness may constitute a distinguishing psychopathological characteristic of patients with bipolar II disorder. Further studies are required to determine if there are associated neuropsychological dysfunctions." [Abstract]

Meeks S.
Bipolar disorder in the latter half of life: symptom presentation, global functioning and age of onset.
J Affect Disord 1999 Jan-Mar;52(1-3):161-7
"BACKGROUND: Little is known about bipolar disorder in late life. Recent research has been in acute, in-patient, settings, and has focused on late-onset mania, or has produced samples with surprisingly late mean ages of onset. No recent study has used a larger out-patient sample to address late-life outcomes of bipolar disorder. METHODS: 86 community-residing, middle-aged and older adults who met RDC for bipolar I or II were interviewed using the Schedule for Affective Disorders and Schizophrenia, three times over 8 months. RESULTS: Participants were primarily unmarried and impoverished. Most were living alone or with immediate family members. The majority were in depressive episodes. Depressive symptoms were more common and more predictive of functioning than manic symptoms. Age of onset was related to global functioning. The effect of age of onset was mediated by number of depressive episodes. CONCLUSION: Most adults in this sample had supports to maintain them in the community in spite of chronic or intermittently cycling manifestations of affective disorder and limited medication. Consistent with prior research, early age of onset was related to poorer functioning, apparently by increasing the number and severity of depressive episodes. LIMITATIONS: Limitations stem from possible exclusion of those people with the worst and best outcomes. It also is a relatively young sample for a gerontological study. CLINICAL RELEVANCE: The study suggests that more attention needs to be paid to diagnosing and treating depressive episodes in later life." [Abstract]

Brieger P, Marneros A.
[Dysthymia and cyclothymia--serious consequences of rarely diagnosed disorders]
Versicherungsmedizin 1998 Dec 1;50(6):215-8
"Dysthymia and cyclothymia are chronic affective disorders with a minimum duration of 2 years. Both ICD-10 and DSM-IV define cyclothymia as a bipolar disorder with low intensity. This disorder is rare and little research has been done on it. Its economic and social consequences vary from case to case. In contrast dysthymias, chronic depressive disorders, are frequent (prevalence 3-6%) and cause considerable distress. They have serious economic and social consequences, which are comparable to those caused by other chronic conditions such as arthritis or diabetes mellitus. Despite widely held conviction a majority of dysthymias improves under consequent pharmaco- and psychotherapy." [Abstract]

Angst J.
The emerging epidemiology of hypomania and bipolar II disorder.
J Affect Disord 1998 Sep;50(2-3):143-51
"The literature on the lifetime prevalence of the bipolar spectrum suggests rates of 3-6.5%. The Zurich cohort study identified a prevalence rate up to age 35 of 5.5% of DSM-IV hypomania/mania and a further 2.8% for brief hypomania (recurrent and lasting 1-3 days). The validity of DSM-IV hypomania and brief hypomania was demonstrated by a family history of mood disorders, a history of suicide attempts and treatment for depression. Comorbidity with anxiety disorders and substance abuse was found equally in both subtypes of hypomania. The study suggests that recurrent brief hypomania belongs to the bipolar spectrum. The findings should be verified on larger national cohorts in other epidemiological and clinical studies." [Abstract]

Leboyer M, Bellivier F, McKeon P, Albus M, Borrman M, Perez-Diaz F, Mynett-Johnson L, Feingold J, Maier W.
Age at onset and gender resemblance in bipolar siblings.
Psychiatry Res 1998 Nov 16;81(2):125-31
"In order to measure the intrafamilial correlation for age at onset and to examine gender resemblance among bipolar siblings, we assessed a sample of 130 bipolar patients belonging to 59 multiple affected sibships. To study the intrafamilial resemblance for age at onset and gender, we used the intraclass correlation and the sibship method, respectively. Within the whole sample, age at onset for affected siblings was correlated (rho = 0.42, P = 0.0001). Gender was randomly distributed among bipolar sibships, demonstrating the absence of gender resemblance among affected siblings. The existence of an intrafamilial correlation for age at onset among bipolar siblings suggests that this variable may assist in the identification of more heritable forms of the illness. No intrafamilial correlation was found for the gender of affected siblings, suggesting that familial vulnerability factors are not gender-specific." [Abstract]

Grigoroiu-Serbanescu M, Martinez M, Nothen MM, Propping P, Milea S, Mihailescu R, Marinescu E.
Patterns of parental transmission and familial aggregation models in bipolar affective disorder.
Am J Med Genet 1998 Sep 7;81(5):397-404
"Two recent studies [McMahon et al., 1995: Am J Hum Genet 56:1277-1286; Gershon et al., 1996: Am J Med Genet (Neuropsychiatr Genet) 67:202-207] reported an excess of maternal transmission in bipolar affective disorder in multiply affected families. In a sample of 130 families ascertained through a bipolar proband without regard to psychiatric family history we analysed the frequency of maternal (MAT) and paternal (PAT) transmissions, the morbid risk (MR) in relatives of transmitting mothers and fathers and the inheritance patterns in families with MAT vs. PAT transmission of the disease. In the total sample of 130 families we identified 39 families where the disease was transmitted from the paternal side (PAT families) and 35 families where the disease was transmitted from the maternal side (MAT families). Counting PAT and MAT transmissions in these unilineal families we found nearly equal numbers for both transmission types under a narrow (BP: bipolar disorder, schizoaffective-bipolar type disorder) and a broad definition (AFF: BP, recurrent unipolar depression) of the phenotype. The MRs for narrow and broad phenotypes were not significantly different in any type of PAT relative in PAT families vs. MAT relatives in MAT families. However, in PAT families there were two times more affected females than males with both disease models, while in MAT families there was no MR difference by relatives' sex. The transmission of BP was compatible with the Mendelian major gene model in PAT families and with the multifactorial model in MAT families. Extension of the relatives' phenotype led to borderline non-Mendelian major effects in PAT families and reproduced the multifactorial model in MAT families." [Abstract]

Kessing LV, Andersen PK, Mortensen PB, Bolwig TG.
Recurrence in affective disorder. I. Case register study.
Br J Psychiatry 1998 Jan;172:23-8
"BACKGROUND: In recent years, studies of the risk of recurrence in affective disorder in relation to the number of prior episodes have given contradictory results. METHOD: Survival analysis was used to calculate the rate of recurrence after successive episodes in a case register study including all hospital admissions with primary affective disorder in Denmark during 1971-1993. A total of 20,350 first-admission patients were discharged with a diagnosis of affective disorder, depressive or manic/cyclic type. RESULTS: The rate of recurrence increased with the number of previous episodes in both unipolar and bipolar disorder. Initially, the two types of disorders followed markedly different courses, but later in the course of the illness the rate of recurrence was the same for the two disorders. CONCLUSIONS: The course of severe unipolar and bipolar disorder seems to be progressive in nature despite the effect of treatment." [Abstract]