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Psychotic features in bipolar and unipolar depression
Abstract
While some prior studies have found higher rates of psychotic depression in those with bipolar disorder or a bipolar relative, others have failed to confirm these observations. We examined the relationship of psychotic depression to polarity in several large familial samples of mood disorder.
A total of 4,724 subjects with major mood disorder in three family studies on the genetics of bipolar I disorder (BPI) or recurrent major depressive disorder (MDDR) were administered semi-structured interviews by clinicians. Determination of psychotic features was based on a report of hallucinations and/or delusions during the most severe depressive episode in the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or the Diagnostic Interview for Genetic Studies interview. Rates of psychotic depression were calculated by diagnostic category and comparisons were made between diagnoses within and across studies using the generalized estimating equation.
A diagnosis of BPI disorder was strongly predictive of psychotic features during depression compared to MDDR [odds ratio (OR) = 4.61, p < 0.0005]. Having bipolar II compared to MDDR was not predictive of psychosis (OR = 1.05, p = 0.260), nor was having a family history of BPI in MDDR subjects (OR = 1.20, p = 0.840).
Psychotic features during a depressive episode increased the likelihood of a BPI diagnosis. Prospective studies are needed to confirm these findings. The potential genetic underpinnings of psychotic depression warrant further study.
... In this regard, both cross-sectional and longitudinal studies have pointed out that the neurocognitive and functional trajectory may be mediated by the clinical course [38,39]. Thus, some studies have suggested the possibility that clinical characteristics, such as the presence of episodes with psychotic symptoms, have a deleterious effect on the neurocognitive or functional trajectory of this disorder, although there are discrepant results [20,28,29,[40][41][42][43]. Long-term studies are necessary to confirm these results [44]. ...
... In addition, BD-P had a worse level of psychosocial functioning than BD-NP, in a way that we could not replicate the findings of our previous cross-sectional study [29]. However, the present results are in accordance with other authors which also reported that patients with BD-P had a worse functional performance than patients with BD-NP [20,[40][41][42][43]. Therefore, the psychosocial functioning of BD-P would occupy an intermediate position between the functional impairment of patients with BD-NP and that of patients with SZ [23]. ...
BACKGROUND:
Bipolar disorder (BD) and schizophrenia (SZ) are characterized by neurocognitive and functional deficits with marked heterogeneity. It has been suggested that BD with a history of psychotic symptoms (BD-P) could constitute a phenotypically homogeneous subtype characterized by greater neurocognitive and functional impairments, or by a distinct trajectory of such deficits. The aim of this study was to compare the neurocognitive and functional course of euthymic BD-P, euthymic BD patients without a history of psychosis (BD-NP), stabilized patients with schizophrenia and healthy subjects, during a five-year follow-up.
METHODS:
Neurocognitive and psychosocial function was examined in 100 euthymic patients with BD (50 BD-P, 50 BD-NP), 50 stabilized patients with schizophrenia (SZ), and 51 healthy controls (HC) at baseline (T1), and after a 5-year follow-up (T2).
RESULTS:
The course of both neurocognitive performance and functional outcome of patients with SZ and BD (BD-P and BD-NP) is stable. The profile of neurocognitive impairment of patients with SZ or BD (BD-P and BD-NP), is similar, with only quantitative differences circumscribed to certain domains, such as working memory. The subgroup of patients with BD-NP does not show functional deterioration.
CONCLUSIONS:
We have not found evidence of progression in the neurocognitive or psychosocial impairment in any of the three groups of patients, although it cannot be dismissed the possibility of a subset of patients with a progressive course. Other longitudinal studies with larger samples and longer duration are necessary to confirm these findings.
... Despite its importance, bipolar depression remains remarkably understudied (Fountoulakis et al., 2017). This is particularly true for psychotic bipolar depression, even though 25% of the individuals with BD-I experience psychotic symptoms during at least one depressive episode (Frankland et al., 2015;Goes et al., 2007), and, by definition, individuals with BD-II only experience psychosis during depressive (rather than hypomanic) episodes (American Psychiatric Association, 2013). Psychotic features are more frequent and more recurrent in bipolar depression compared to major depressive disorder (MDD) (Frankland et al., 2015;Goes et al., 2007;Mitchell et al., 2001;Zaninotto et al., 2015), and more than a third of individuals who experience their first psychotic unipolar depressive episode are likely to switch diagnoses to BD or schizoaffective disorder (Tohen et al., 2012), particularly if this occurs before age 30 (Akiskal et al., 1995;Goldberg, Harrow, & Whiteside, 2001). ...
... This is particularly true for psychotic bipolar depression, even though 25% of the individuals with BD-I experience psychotic symptoms during at least one depressive episode (Frankland et al., 2015;Goes et al., 2007), and, by definition, individuals with BD-II only experience psychosis during depressive (rather than hypomanic) episodes (American Psychiatric Association, 2013). Psychotic features are more frequent and more recurrent in bipolar depression compared to major depressive disorder (MDD) (Frankland et al., 2015;Goes et al., 2007;Mitchell et al., 2001;Zaninotto et al., 2015), and more than a third of individuals who experience their first psychotic unipolar depressive episode are likely to switch diagnoses to BD or schizoaffective disorder (Tohen et al., 2012), particularly if this occurs before age 30 (Akiskal et al., 1995;Goldberg, Harrow, & Whiteside, 2001). Psychotic features in bipolar depression are associated with worse suicidality and worse functioning (Caldieraro et al., 2017). ...
Background:
The impact of psychosis on the treatment of bipolar depression is remarkably understudied. The primary aim of this study was to compare treatment outcomes of bipolar depressed individuals with and without psychosis. The secondary aim was to compare the effect of lithium and quetiapine, each with adjunctive personalized treatments (APTs), in the psychotic subgroup.
Methods:
We assessed participants with DSM-IV bipolar depression included in a comparative effectiveness study of lithium and quetiapine with APTs (the Bipolar CHOICE study). Severity was assessed by the Bipolar Inventory of Symptoms Scale (BISS) and by the Clinical Global Impression Scale-Severity-Bipolar Version (CGI-S-BP). Mixed models were used to assess the course of symptom change, and Cox regression survival analysis was used to assess the time to remission.
Results:
Psychotic features were present in 10.6% (n = 32) of the depressed participants (n = 303). Those with psychotic features had higher scores on the BISS before (75.2 ± 17.6 vs. 54.9 ± 16.3; P < .001) and after (37.2 ± 19.7 vs. 26.3 ± 18.0; P = .003) 6-month treatment. The CGI-S-BP yielded similar results. Participants with and without psychosis had similar course of symptom improvement and similar time to remission. There was no significant difference in the treatment outcomes of lithium (n = 11) and quetiapine (n = 21) among the psychotic subgroup.
Conclusion:
Bipolar depressive episodes with psychotic features are more severe, and compared to nonpsychotic depressions, present a similar course of improvement. Given the small number of participants presenting psychosis, the lack of statistically significant difference between lithium- and quetiapine-based treatment of psychotic bipolar depressive episodes needs replication in a larger sample.
... Major depressive episodes with psychotic features are more common in bipolar disorder (BD) than in major depressive disorder (MDD) [1][2][3], and a recent study has reported that depressed bipolar patients with psychotic features have worse illness outcomes [4]. Most treatment guidelines have recommended either the combination of an antidepressant with an antipsychotic or electroconvulsive therapy (ECT) for the treatment of MDD with psychotic features [5,6]; however, there is little information on the optimal treatment for bipolar depression with psychotic features. ...
... Most studies of psychotic symptoms in BD focus on manic episodes with psychotic features because psychotic symptoms are more common in manic episodes [10,11], and there are some suggestions for manic episodes with psychotic features in a recent review of treatment guidelines for BD [12]. On the other hand, the prevalence of psychotic features in depressive episode could be higher in BD, especially bipolar I disorder, than MDD [1,2]; however, there are few studies of pharmacotherapy for bipolar depression with psychotic features. A recent study, which investigated the differences in psychopharmacological treatment between psychotic and non-psychotic episodes in BD, reported that psychotic bipolar depression was associated with treatment with antipsychotics and the combination of an antipsychotic and an antidepressant [13]. ...
Background
Major depressive episodes with psychotic features are more common in bipolar disorder than in major depressive disorder; however, there is little information on the optimal treatment for bipolar depression with psychotic features.
Case presentation
The patient was a 69-year-old man. At the age of 66, he was admitted to the hospital for the treatment of bipolar depression with psychotic features. He was treated with a combination therapy of antipsychotics and antidepressants during long-term hospitalization. At the age of 69, he relapsed and was admitted to the hospital again. He was initially treated with olanzapine and lithium for the treatment of bipolar depression with psychotic features. He partially responded to the combination therapy, and psychomotor retardation and delusion of guilt disappeared; however, he developed psychomotor agitation and delusion of persecution, which was a mood-incongruent psychotic feature. Finally, he fully recovered with an additional dosage of lamotrigine, and had no experience of relapse after discontinuation of olanzapine.
Conclusions
This case report implicates the utility of lamotrigine for bipolar depression with psychotic features, and further studies are needed to establish the optimal treatment.
... According to Fountoulakis et al. (2016), the prevalence of psychosis in bipolar depression could be as high as 66% in historical descriptions. More recent studies report lower but still significant prevalence: 10.4% for a current episode (Mantere et al., 2004) and 10-28% for lifetime bipolar depressive episodes (Frankland et al., 2015;Goes et al., 2007;Rosenthal et al., 1980). Moreover, major depressive episodes with psychosis are more frequent (Frankland et al., 2015;Goes et al., 2007;Zaninotto et al., 2015) and more recurrent (Mitchell et al., 2001) in BD than in unipolar depression. ...
... More recent studies report lower but still significant prevalence: 10.4% for a current episode (Mantere et al., 2004) and 10-28% for lifetime bipolar depressive episodes (Frankland et al., 2015;Goes et al., 2007;Rosenthal et al., 1980). Moreover, major depressive episodes with psychosis are more frequent (Frankland et al., 2015;Goes et al., 2007;Zaninotto et al., 2015) and more recurrent (Mitchell et al., 2001) in BD than in unipolar depression. First episodes of psychotic depression in 30% of cases are likely to switch diagnosis to bipolar disorder (Tohen et al., 2012). ...
Background:
Psychotic bipolar depressive episodes remain remarkably understudied despite being common and having a significant impact on bipolar disorder. The aim of this study is to identify the characteristics of depressed bipolar patients with current psychosis compared to those without psychosis.
Methods:
We used baseline data of a comparative effectiveness study of lithium and quetiapine for bipolar disorder (the Bipolar CHOICE study) to compare demographic, clinical, and functioning variables between those with and without psychotic symptoms. Of the 482 participants, 303 (62.9%) were eligible for the present study by meeting DSM-IV criteria for an acute bipolar depressive episode. Univariate analyses were conducted first, and then included in a model controlling for symptom severity.
Results:
The sample was composed mostly of women (60.7%) and the mean age was 39.5±12.1 years. Psychosis was present in 10.6% (n=32) of the depressed patients. Psychotic patients had less education, lower income, and were more frequently single and unemployed. Psychosis was also associated with a more severe depressive episode, higher suicidality, more comorbid conditions and worse functioning. Most group differences disappeared when controlling for depression severity.
Limitations:
Only outpatients were included and the presence of psychosis in previous episodes was not assessed.
Conclusion:
Psychosis during bipolar depressive episodes is present even in an outpatient sample. Psychotic, depressed patients have worse illness outcomes, but future research is necessary to confirm if these outcomes are only associated with the severity of the disorder or if some of them are independent of it.
... Schizophrenia (SZ) and bipolar disorder (BP) are ostensibly separate clinical entities with distinct clinical courses and outcomes, but substantial overlap in phenomenology (1), cognition (2-4), brain structure (5-8), brain function (9, 10) and disease risk genes (11-14), especially for SZ and the psychotic subtype of BP (5-8). Approximately 60% of Bipolar I patients display psychotic symptoms (15,16), suggesting that the psychosis domain represents a useful starting point to compare commonalities and differences between these disorders. Similarities may originate in similarly disturbed neurophysiology, (17,18). ...
... Large meta-analytic linkage studies based on clinical SZ and BP phenotypes report several overlapping genetic risk loci (12,13,19). SZ and affective psychoses co-occur within kindreds, suggesting shared familial risk, consistent with shared genes conferring risk for both disorders (11,20,21), again especially for SZ and psychotic BP (15,22). Finally, psychotic symptoms aggregate familially in BP (23). ...
Schizophrenia and bipolar disorder share overlapping symptoms and genetic etiology. Functional brain dysconnectivity is seen in both disorders.
We compared 70 schizophrenia and 64 psychotic bipolar probands, their respective unaffected first-degree relatives (n = 70, and n = 52), and 118 healthy subjects, all group age-, gender-, and ethnicity-matched. We used functional network connectivity analysis to measure differential connectivity among 16 functional magnetic resonance imaging resting state networks. First, we examined connectivity differences between probands and control subjects. Next, we probed these dysfunctional connections in relatives for potential endophenotypes. Network connectivity was then correlated with Positive and Negative Syndrome Scale (PANSS) scores to reveal clinical relationships.
Three different network pairs were differentially connected in probands (false-discovery rate corrected q < .05) involving five individual resting-state networks: (A) fronto/occipital, (B) anterior default mode/prefrontal, (C) meso/paralimbic, (D) fronto-temporal/paralimbic, and (E) sensory-motor. One abnormal pair was unique to schizophrenia, (C-E), one unique to bipolar, (C-D), and one (A-B) was shared. Two of these three combinations (A-B, C-E) were also abnormal in bipolar relatives but none was normal in schizophrenia relatives (nonsignificant trend for C-E). The paralimbic circuit (C-D), which uniquely distinguished bipolar probands, contained multiple mood-relevant regions. Network relationship C-D correlated significantly with PANSS negative scores in bipolar probands, and A-B with PANSS positive and general scores in schizophrenia.
Schizophrenia and psychotic bipolar probands share several abnormal resting state network connections, but there are also unique neural network underpinnings between disorders. We identified specific connections that might also be candidate psychosis endophenotypes.
... Pattern completion is believed to be disrupted in 29 psychiatric conditions such as schizophrenia, and may have a role in the formation of 30 delusions [21][22][23]. Given the genetic relatedness of BD and schizophrenia [24], and BD's 31 November 19, 2023 2/15 association with both psychosis [25] and declarative memory impairments [5,[26][27][28][29], it is 32 plausible that similar hypothesized pattern completion deficits may be found in BD. 33 Several lines of research suggest that CA3 structure, function, and electrophysiology 34 may be impaired in BD, which we review below. 35 First, many genetic variants associated with BD and lithium responsiveness are also 36 implicated in CA3 structure and function. ...
Patients with bipolar disorder (BD) demonstrate episodic memory deficits, which may be hippocampal-dependent and may be attenuated in lithium responders. Induced pluripotent stem-cell derived CA3 pyramidal cell-like neurons show significant hyperexcitability in lithium responsive BD patients, while lithium nonresponders show marked variance in hyperexcitability. We hypothesize that this variable excitability will impair episodic memory recall, as assessed by cued retrieval (pattern completion) within a computational model of the hippocampal CA3.
We simulated pattern completion tasks using a computational model of the CA3 with different degrees of pyramidal cell excitability variance. Since pyramidal cell excitability variance naturally leads to a mix of hyperexcitability and hypoexcitability, we also examined what fraction (hyper- vs. hypoexcitable) was predominantly responsible for pattern completion errors in our model.
Pyramidal cell excitability variance impaired pattern completion (linear model beta =-1.94, SE=0.01, p<0.001). The effect was invariant to the number of patterns stored in the network, as well as general inhibitory tone and pyramidal cell sparsity in the network. Excitability variance, and more specifically hyperexcitability, increased the number of spuriously active neurons, increasing false alarm rates and producing pattern completion deficits. Excessive inhibition also induces pattern completion deficits by limiting the number of correctly active neurons during pattern retrieval.
Excitability variance in CA3 pyramidal cell-like neurons observed in lithium nonresponders may predict pattern completion deficits in these patients. These cognitive deficits may not be fully corrected by medications that minimize excitability. Future studies should test our predictions by examining behavioural correlates of pattern completion in lithium responsive and nonresponsive BD patients.
... This may reflect a greater likelihood of Black individuals to present with dysphoric or mixed rather than euphoric manic syndromes. Furthermore, the higher occurrence of hallucinatory experiences and mood-incongruent delusions, which are more prevalent during manic episodes than depressive episodes, (Goes et al. 2007) can lead to a presentation characterized by increased irritability, paranoia, and atypical psychotic symptoms. ...
Background
Across clinical settings, black individuals are disproportionately less likely to be diagnosed with bipolar disorder compared to schizophrenia, a traditionally more severe and chronic disorder with lower expectations for remission. The causes of this disparity are likely multifactorial, ranging from the effects of implicit bias, to developmental and lifelong effects of structural racism, to differing cultural manifestations of psychiatric symptoms and distress. While prior studies examining differences have found a greater preponderance of specific psychotic symptoms (such as persecutory delusions and hallucinations) and a more dysphoric/mixed mania presentation in Black individuals, these studies have been limited by a lack of systematic phenotypic assessment and small sample sizes. In the current report, we have combined data from two large multi-ethnic studies of bipolar disorder with comparable semi-structured interviews to investigate differences in symptoms presentation across the major clinical symptom domains of bipolar disorder.
Results
In the combined meta-analysis, there were 4423 patients diagnosed with bipolar disorder type I, including 775 of self-reported as Black race. When symptom presentations were compared in Black versus White individuals, differences were found across all the major clinical symptom domains of bipolar disorder. Psychotic symptoms, particularly persecutory hallucinations and both persecutory and mood-incongruent delusions, were more prevalent in Black individuals with bipolar disorder type I (ORs = 1.26 to 2.45). In contrast, Black individuals endorsed fewer prototypical manic symptoms, with a notably decreased likelihood of endorsing abnormally elevated mood (OR = 0.44). Within depression associated symptoms, we found similar rates of mood or cognitive related mood symptoms but higher rates of decreased appetite (OR = 1.32) and weight loss (OR = 1.40), as well as increased endorsement of initial, middle, and early-morning insomnia (ORs = 1.73 to 1.82). Concurrently, we found that black individuals with BP-1 were much less likely to be treated with mood stabilizers, such as lithium (OR = 0.45), carbamazepine (OR = 0.37) and lamotrigine (OR = 0.34), and moderately more likely to be on antipsychotic medications (OR = 1.25).
Conclusions
In two large studies spanning over a decade, we found highly consistent and enduring differences in symptoms across the major clinical symptom domains of bipolar disorder. These differences were marked by a greater burden of mood-incongruent psychotic symptoms, insomnia and irritability, and fewer prototypical symptoms of mania. While such symptoms warrant better recognition to reduce diagnostic disparities, they may also represent potential targets of treatment that can be addressed to mitigate persistent disparities in outcome.
... Using PP for computational phenotyping (Schwartenbeck & Friston, 2016), one can conceptualize how the genetic factor impacts precision assignment in a particular functional domain. For example, people who exhibit high precision in beliefs regarding what causes the sensory data may show proneness to psychotic symptoms (e.g., delusions), which are more common in bipolar and schizophrenia than unipolar depression (Cuellar et al., 2005;Goes et al., 2007). Different phenotypes may emerge from different levels of sensory precision. ...
Most theories of psychopathology have focused on etiology at a specific level (e.g., genetic, neurobiological, psychological, or environmental) to explain specific symptoms or disorders. A few biopsychosocial theories have provided explanations that attempt to integrate different levels and disorders to some extent. However, these theories lack a framework in which different levels of analysis are integrated and thus do not explain the mechanism by which etiological factors interact and perturb neurobiology which in turn leads to psychopathology. We propose that predictive processing (PP), which originated in theoretical neurobiology literature, may provide a conceptually parsimonious and biologically plausible framework to achieve such integration. In PP, the human brain can be cast as implementing a generative model whose task is to minimize the surprise of sensory evidence by inferring its causes and actively controlling future sensory signals via action. This account offers a unifying model of perception, action, and emotion implicated in psychopathology. Furthermore, we show that PP can explain how different factors or levels result in psychopathology via updates of the generative model (the depth of the PP framework). Finally, we demonstrate the transdiagnostic appeal of PP by showing how perturbations within this framework can explain a broad range of psychopathology (the breadth of the PP framework), with a focus on bridging well-established psychosocial theories of psychopathology and PP. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
... In BD, however, even normal participation in spiritual/religious practice has been known to trigger (hypo)manic episodes, and individuals prone to hyperreligiosity may be especially vulnerable to severe mania and psychosis (Proudfoot, Doran, Manicavasangar, & Parker, 2011). SREs or religiously-themed delusions and hallucinations can also arise in the context of depressive episodes; however, their occurrence is relatively rare, ostensibly due to the sense of meaninglessness and diminishment of religious faith characteristic of severe depression (Goes et al., 2007;Ouwehand, Muthert, Zock, Boeije, & Braam, 2018). ...
Spiritual/religious experiences (SREs) are a hallmark of bipolar disorder (BD), and their subjective influence often persists post-episode. However, difficulty disentangling SRE meaning from illness narratives is common in BD, and can negatively impact illness coping and treatment engagement. While individuals with pre-existing spiritual/religious beliefs may benefit from access to adaptive interpretive frameworks shared by supportive social contexts, such resources are less readily available to atheists, who may be especially vulnerable to maladaptive SRE coping and outcomes.
The present study aimed to understand ways in which atheist adults with BD interpret their SREs, and which coping and treatment experiences are involved. Eleven medication-adherent Canadian and U.S. adults diagnosed with BD completed semi-structured interviews. A grounded theory analysis resulted in the following themes: SRE descriptions and mental health contexts; experiences influencing SRE interpretation; SRE explanations & related views; conflicting values and beliefs; helpful conceptual approaches; (predominantly negative) sharing and help-seeking experiences; spiritual/religious coping; relapse prevention; and personal growth and wellbeing. All participants endorsed agnostic and/or spiritual/religious worldviews after their SREs.
Interpretation of the results employed a cognitive approach to belief formation. The resulting middle-range theory proposes that SRE interpretation in atheists with BD is significantly influenced by cognitive dissonance between the lasting meaning/value of the SRE, acceptance of illness, and pre-existing atheist values and beliefs. Explanatory efforts may involve online and offline research, community exploration, and counselling/psychotherapy, and may be influenced by social pressures (e.g., effects of stigma, marginalization); consequences for self-esteem (e.g., internalized stigma, self-enhancing beliefs); existential concerns (e.g., coping with mortality); and mood fluctuations. Hybrid biomedical–spiritual/religious explanatory models may be common in this group, serving to reconcile SRE meaning/value with illness acceptance and pre-existing atheist values. Residual uncertainty, which can be persistent and pervasive, may be managed using various cognitive and behavioural strategies.
Clinical implications of the findings are examined and support a range of recommendations for clinical practice in assessment and treatment with this population. The study’s key contributions, limitations, and recommendations for future research are discussed, followed by some reflections from the researcher.
... De façon très intéressante, il existe également des variations circadiennes et des troubles du sommeil en lien avec le suicide . Certaines études se sont même intéressées au lien avec les TB (Goes et al., 2007). C'est pourquoi nous nous sommes ensuite intéressés à ce sous-type particulier de patients dont le risque suicidaire est majeur. ...
Dans la littérature scientifique actuelle, des études ont mis en évidence par une approche transdiagnostique, l’implication de facteurs cliniques, biologiques et génétiques spécifiques des conduites suicidaires indépendamment d’un diagnostic de trouble psychiatrique de l’Axe I ou II du Manuel Diagnostique et Statistique des Troubles Mentaux (DSM) (1–3). De plus, l’existence d’un trouble psychiatrique n’apparaît pas être discriminante pour définir certains types de profils de patients à risque de suicide (4–6). En effet, le suicide peut toucher à la fois des personnes dites en situation de crise mais il est largement reconnu que les pathologies psychiatriques restent à haut risque de suicide, notamment les troubles de l’humeur tels que les troubles bipolaires et les dépressions unipolaires, et plus particulièrement avec caractéristiques psychotiques (7,8). De plus, des facteurs de risque spécifiques de suicide ont été retrouvés dans chacune de ces différentes populations (9,10). Ainsi, avec cette conception moderne du suicide, il semble pertinent d’étudier le risque suicidaire dans diverses populations de suicidants, souffrant ou non de troubles psychiatriques, et en utilisant une approche tant épidémiologique, dynamique avec l’actigraphie, et biologique (3,11,12). En me basant sur cette approche, mon projet de thèse s’articule en 3 axes décrits ci-après, et consiste à identifier des facteurs de risque de récidive de tentative de suicide ainsi qu’à définir des profils de patients suicidants dans des populations différentes. Pour cela, plusieurs études coordonnées permettront de réaliser une évaluation multi-échelles de la vulnérabilité suicidaire de façon transdiagnostique et de façon ciblée dans les troubles de l’humeur uni- et bi-polaires.
... When depressed mood co-occurs with psychotic symptoms such as delusions and hallucinations, it is termed psychotic depression. This condition occurs in 10%− 28% of bipolar patients (Mantere et al., 2004;Frankland et al., 2015;Goes et al., 2007), although actual rates may be considerably higher, as psychotic features are often missed by diagnosing clinicians (Rothschild et al., 2008). Few studies have examined this condition in bipolar patients, as most inquiry into psychosis in BD has concerned its presence in mania. ...
Background
: Psychotic symptoms during bipolar depressive episodes, especially in outpatients, are under recognized and studied by clinicians and researchers. We examined the relationship between psychotic symptoms during a depressive episode and suicidal ideation in bipolar patients.
Methods
: Participants (N=351) were adult, depressed, outpatients with bipolar disorder (BD) in a comparative effectiveness study of quetiapine versus lithium. Psychotic symptoms were assessed via Bipolar Inventory of Signs and Symptoms Scale (BISS) and depressive episodes via Mini-International Neuropsychiatric Interview (MINI). Because only 4.84% (N=17) endorsed psychotic symptoms, we performed iterative multivariate matching with non-psychotic participants. On every matched population, a multiple regression analysis examined whether psychotic symptoms were associated with suicidal ideation, via the Concise Health Risk Taking scale (CHRT-12).
Results
: Averaged across the 50 matched populations, current psychotic symptoms predicted active suicidal ideation on the CHRT, but not a passive propensity toward suicide or total CHRT scores, after adjusting for common correlates of suicidality (e.g., previous suicidal behavior) (β=0.59, p=.01, R2= .41).
Limitations
: Our study was limited by three factors. First, the generalizability of our study was limited as the sample included only outpatients. Next, the analysis was cross-sectional and does not allow for causal interpretation. Lastly, our study lacked information regarding the content and mood congruency of participants’ psychosis.
Conclusion
: While a small proportion of BD outpatients had current symptoms of psychosis during their depressive episode, those who did were more likely to endorse active suicidal thoughts, including suicide methods and plans.
... • Early (pre-adolescent) age at onset of first mood disorder episode 6 • Family history of BD, highly recurrent depression, or psychosis 12,13 • Psychosis when depressed. 7,14 A number of other characteristics of depressive illness-including seasonal depression, atypical depressive features, suicidality, irritability, anxiety or substance use comorbidity, postpartum mood episodes, and brief recurrent depressive episodes-have been described in the literature as potential correlates of a bipolar diathesis; none have proved to be robust or pathognomonic of a BD diagnosis, as opposed to a unipolar diagnosis. ...
When does mania signal bipolar disorder, another medical illness, or the adverse effects of a prescribed antidepressant? And what are the next steps to manage this development?
... Estimates suggest that 20 to 58% of patients experience psychotic symptoms during manic episodes (Goodwin and Jamison 1990;Perälä et al. 2007;Pope and Lipinski 1978). Furthermore, approximately 25% of individuals with bipolar II disorder experience psychotic features during a depressive episode (Frankland et al. 2015;Goes et al. 2007). The most commonly experienced psychotic symptoms are delusions (48%), formal thought disorders (19%), and hallucinations (15%; Goodwin and Jamison 1990); however, all features of psychosis are possible in mania (Dunayevich and Keck 2000). ...
Bipolar disorders are increasingly understood as part of a spectrum of clinical and subclinical symptoms and impairment. Upwards of 50% of patients with bipolar disorders experience psychotic symptoms as part of their mood episodes. However, studies largely have not examined the extent to which people with subclinical bipolar spectrum psychopathology experience psychotic-like or schizotypic symptoms. The present study examined the association of bipolar spectrum psychopathology (as assessed by the Hypomanic Personality Scale [HPS]) with interview ratings of psychotic-like and schizotypic experiences in a sample of 177 young adults. HPS scores were associated with positive and disorganized schizotypic symptoms, as well as with schizotypal and paranoid personality disorder traits. Contrary to hypotheses, questionnaire measures of positive, negative, and disorganized schizotypy did not moderate the associations of the HPS with measures of psychopathology and impairment. However, exploratory analyses suggested that the schizotypy subscales mediated the association of HPS scores with these outcomes. These findings indicate that subclinical expressions of bipolar spectrum psychopathology are associated with psychotic-like and schizotypic symptoms consistent with psychotic features that characterize bipolar disorders. Overall, this study supports a shared dimension of psychosis that extends through subclinical functioning both in the bipolar and schizophrenia spectrum psychopathologies.
... Regarding the investigation of psychiatric phenomena as a possible predictive factor of first manic episode, the high rate of occurrence of depressive episodes with psychotic or classic melancholic symptoms reported by our patients is consistent with earlier studies that suggests that a very early-onset depressive episode (before age 13 years) might be a frequent first manifestation of BD. Also, very early-onset psychotic depression may be a predictive factor for subsequent development of BD. 13,[34][35][36] The frequent occurrence of psychotic depression in our patients, who subsequently developed first manic episode with disorganization and psychotic features, highlights the possibility that psychosis and disorganization may be more related to specific, BD-related psychopathology and neurobiological dysfunction and less related to the age of onset. 9,11,13,34,37,38 Further investigations focused on disorganization symptoms during depressive episodes in children and adolescents may help differentiate unipolar depressive episode, BD, and schizophrenia. ...
Objective:
Presence of psychotic symptoms seems to be a commonplace in early-onset bipolar disorder (BD). However, few studies have examined their occurrence in adolescent-onset BD. We sought to investigate the frequency of affective and psychotic symptoms observed during the first manic episode in adolescents.
Methods:
Forty-nine adolescents with bipolar I disorder (DSM-IV criteria) were admitted to a psychiatric hospital during their first acute manic episode. Assessment for current psychiatric diagnosis was performed by direct clinical interview and the DSM-IV version of the Diagnostic Interview for Children and Adolescents (DICA).
Results:
Teenage inpatients with BD consistently exhibited typical manic features, such as euphoria, grandiosity, and psychomotor agitation. In addition, disorganization and psychotic symptoms were present in 82 and 55% of the total sample, respectively. There was no significant difference in symptoms between early- and late-adolescent subgroups. Remarkably, most patients (76%) reported previous depressive episode(s); of these, 47% had prominent psychotic features in the prior depressive period.
Conclusion:
These findings suggest that disorganization and psychotic symptoms during the first manic episode are salient features in adolescent-onset BD, and that psychotic depression frequently may precede psychotic mania. Nevertheless, differential diagnosis with schizophrenia should be routinely ruled out in cases of early-onset first psychotic episode.
... Die wichtige Bedeutung genetischer Faktoren für Äthiologie der wahnhaften Depression wurde bereits in den 80er Jahren herausgestellt. Klassische Heritabilitätsuntersuchungen stellten bereits damals die PMD eher in die Nähe "biologisch determinierter" Depressionen (39), wie sie auch im Rahmen der Bipolaren Störungen (insbesondere Bipolar-I) auftreten (25,47). Dennoch beschäftigen sich nur wenige Studien mit der Genetik der PMD, obwohl die genetischen Grundlagen der MD insgesamt Gegenstände umfangreicher Forschungen sind (36). ...
Zusammenfassung
Psychotische Major Depressionen zeichnen sich gegenüber schweren depressiven Episoden ohne psychotische Symptome nicht nur durch das Vorliegen bestimmter inhaltlicher Denkstörungen oder Wahrnehmungsstörungen aus, sondern zeigen auch in ihren klinischen Erscheinungsbildern, ihren Verläufen, ihrer ätiologischen und epidemiologischen Faktoren sowie ihrer Therapiemöglichkeiten einige Besonderheiten. Im Vergleich mit einer schweren nicht-psychotischen Depression ist der Krankheitsverlauf hinsichtlich Symptomausprägung, Rezidivneigung, Residualsymptomen, Episodendauer, Gesamtbeeinträchtigung, Komorbiditäten und Mortalität schwerwiegender. Im vorliegenden Artikel werden epidemiologische Daten, Studien zu Verlauf, Symptomkonstellationen, Neurobiologie und Therapie auf die Frage hin untersucht, ob es sich bei der psychotischen Depression um eine eigenständige Krankheitsentität handelt und eine Stellung zwischen den affektiven und den schizophrenen Psychosen in einem gedachten „schizoaffektiven Spektrum“ einnimmt.
... psychotic symptoms during the depressive episode, and more frequent recurrences of depressive episodes. [18][19][20][21][22] Also, depressive episodes during the postpartum period indicate a higher risk of BPD than do episodes in women outside the postpartum period, with a hazard ratio (HR) of 1.66 (95% CI, 1.12-2.48). 23 The risk is much greater when postpartum depressive episodes are associated with anxiety symptoms (HR=10.15; ...
Used together, brief assessment tools, such as the PDQ9 and MDQ, have greater sensitivity and accuracy than clinician assessment alone.
... Another finding from our study that overlapped with those reported in the meta-analysis by Ratheesh et al. (9) was that psychotic depression at index was associated with subsequent BD. This association has been reported consistently over decades based on studies of both clinical and epidemiological cohorts (7,(26)(27)(28)(29)(30)(31)(32)(33). In further support of the close connection between psychotic depression and BD, prior studies have shown that when relatives of patients with BD become depressed, they have an increased prevalence of psychotic symptoms compared to depressed relatives of individuals without BD (34). ...
Objective:
Conversion from unipolar depression (UD) to bipolar disorder (BD) is a clinically important event that should lead to treatment modifications. Unfortunately, recognition of this transition is often delayed. Therefore, the objective of this study was to identify predictors of diagnostic conversion from UD to BD.
Method:
Historical prospective cohort study based on 91 587 individuals diagnosed with UD in Danish hospital psychiatry between 1995 and 2016. The association between a series of potential predictors and the conversion from UD to BD during follow-up (702 710 person-years) was estimated by means of Cox regression with death as competing risk.
Results:
During follow-up, 3910 individuals with UD developed BD. The cumulative incidence of conversion was slightly higher in females (8.7%, 95% CI: 8.2-9.3) compared to males (7.7%, 95% CI: 7.0-8.4). The strongest predictor of conversion from UD to BD was parental history of BD (adjusted hazard ratio (aHR) = 2.60, 95% CI: 2.20-3.07)). Other predictors included psychotic depression at the index UD episode (aHR = 1.73, 95% CI: 1.48-2.02), a prior/concomitant non-affective psychosis (aHR = 1.73, 95% CI: 1.51-1.99), and in-patient treatment at the index episode (aHR = 1.76, 95% CI: 1.63-1.91).
Conclusion:
Diagnostic conversion from UD to BD is predicted by severe depression requiring in-patient treatment, psychotic symptomatology, and parental history of BD.
... Most BDETs and AETs excluded patients with suicidal ideation at the time of screening for the treatment study, and most also excluded patients with a history of substance use disorders. The studies of bipolar disorder were significantly less likely to exclude patients with psychotic features, a potentially important difference because patients with bipolar I depression are more likely to have psychotic symptoms than patients with nonbipolar depression [34]. ...
Background
Concerns about the generalizability of pharmacotherapy efficacy trials to “real-world” patients have been raised for more than 40 years. Almost all of this literature has focused on treatment studies of major depressive disorder (MDD). Objective
The aim of the study was to review the psychiatric inclusion and exclusion criteria used in placebo-controlled trials that assessed the efficacy of medications for bipolar depression (bipolar disorder efficacy trials [BDETs]) and compare the criteria used in BDETs with those used in efficacy trials of antidepressants to treat MDD (antidepressant efficacy trials [AETs]). Methods
We searched the MEDLINE, Embase, and PsycINFO databases for articles published from January 1995 through December 2014. We identified 170 placebo-controlled AETs and 22 BDETs published during these 20 years. Two of the authors independently reviewed each article and completed a pre-specified information extraction form listing the psychiatric inclusion and exclusion criteria used in the study. ResultsSix inclusion/exclusion criteria were used in at least half of the BDETs: minimum severity on a depression symptom severity scale, significant suicidal ideation, diagnosis of alcohol or drug use disorder, presence of a comorbid nondepressive, nonsubstance use Axis I disorder, current episode of depression being too long, and absence of current manic symptoms. BDETs were significantly less likely than AETs to exclude patients with a history of psychotic features/disorders, borderline personality disorder, and post-traumatic stress disorder and more likely to exclude individuals who scored too low on the first item of the Hamilton Depression Rating Scale. Nearly two-thirds of the BDETs placed an upper limit on the duration of the current depressive episode, three times higher than the rate in the AETs. There was no difference on other variables between the AETs and BDETs. Conclusions
Similar to treatment studies of nonbipolar MDD, the treatment studies of bipolar depression frequently excluded patients with comorbid psychiatric and substance use disorders and insufficient severity of depressive symptoms as rated on standardized scales. These findings indicate that concerns about the generalizability of data from trials of recently approved medications for the treatment of bipolar depression are as relevant as the concerns that have been raised about studies of antidepressants for nonbipolar depression.
... Die wichtige Bedeutung genetischer Faktoren für Äthiologie der wahnhaften Depression wurde bereits in den 80er Jahren herausgestellt. Klassische Heritabilitätsuntersuchungen stellten bereits damals die PMD eher in die Nähe "biologisch determinierter" Depressionen (39), wie sie auch im Rahmen der Bipolaren Störungen (insbesondere Bipolar-I) auftreten (25,47). Dennoch beschäftigen sich nur wenige Studien mit der Genetik der PMD, obwohl die genetischen Grundlagen der MD insgesamt Gegenstände umfangreicher Forschungen sind (36). ...
Major depression with psychotic features (PMD) is not only characterised by certain symptoms such as delusions or hallucinations. In comparison with non-psychotic major depression clinical manifestations, course of disease, etiological and epidemiological traits show some distinctive features. The course of PMD is more severe in terms of symptomatology, tendency to recurrence, residual symptoms, duration of episodes, overall impairment, comorbidities and mortality. In this paper, data on epidemiology, course, symptoms, neurobiology and treatment options are discussed to shed light on the question if PMD can be considered a distinct entity of mental illness and if it should be placed somewhere in the range of a putative "schizoaffective continuum".
... Patients experience recurrent depressive, and (mixed-) manic episodes characterized by increased mood and arousal and reduced sleep [Saunders and Goodwin, 2010]. In addition, the majority of bipolar I disorder patients suffer psychotic symptoms [Dunayevich and Keck, 2000; Goes et al., 2007] and cognitive deficits [Kumar and Frangou, 2010; Mart ınez- Ar an et al., 2000; Martino et al., 2014; Quraishi and Frangou, 2002; Robinson et al., 2006]. Psychiatric symptoms such as these have been suggested to relate to aberrant integration of neural information among functionally specialized brain circuits [Buckholtz and Meyer-Lindenberg, 2012]. ...
The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections-i.e., the connectome-suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected "rich club" organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, interhemispheric connections) of the brain's network. We find that bipolar I disorder patients exhibit reduced global efficiency (-4.4%, P =0.002) and that this deficit relates (r = 0.56, P < 0.001) to reduced connectivity strength of interhemispheric connections (-13.0%, P = 0.001). Bipolar disorder patients were found not to show predominant alterations in the strength of brain hub connections in general, or of connections spanning brain hubs (i.e., "rich club" connections) in particular (all P > 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency in association with disruptions in interhemispheric connectivity, while the central "rich club" system appears not to be particularly affected. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
... However, psychotic symptoms only occurred in a few individuals, and these results should be interpreted with caution. Early psychotic symptoms that lead to later mood disorders are more clearly aligned with BPD than unipolar depressive disorders [91][92][93]. This association is also in line with previous studies emphasizing the role of the psychotic features related to early onset mood disorder and the increased risk of BPDs or schizoaffective disorder in long-term follow-up studies [94][95][96][97][98][99][100]. ...
Background: We aimed to outline the early risk factors for adult bipolar disorder (BPD) in adolescents with mood disorders. Methods: Adolescents (16–17 years old) with mood disorders (n = 287; 90 participants with hypomania spectrum episodes and 197 with major depressive disorder [MDD]) were identified from a community sample. Fifteen years later (at 30–33 years of age), mood episodes were assessed (n = 194). The risk of developing BPD (n = 22), compared with MDD (n = 104) or no mood episodes in adulthood (n = 68), was estimated via logistic regression. Adolescent mood symptoms, non-mood disorders, and family characteristics were assessed as potential risk factors.
... In recent decades, studies have attempted to identify features of illness that help distinguish patients with bipolar depression from those with MDD. Several of these features have been consistently found to be more prominent in bipolar depression: earlier age at onset, increased number of depressive episodes, and greater propensity for hypersomnia, psychomotor abnormalities, and psychotic symptoms (Mitchell et al. 2001(Mitchell et al. , 2011Serretti et al. 2002;Perlis et al. 2006;Goes et al. 2007;Souery et al. 2012;Tondo et al. 2014). However, differing phenotype assessments and widely varying ascertainment schemes have limited the comparison of anything but broad trends across studies. ...
Distinguishing bipolar disorder (BP) from major depressive disorder (MDD) has important relevance for prognosis and treatment. Prior studies have identified clinical features that differ between these two diseases but have been limited by heterogeneity and lack of replication. We sought to identify depression-related features that distinguish BP from MDD in large samples with replication.
Using a large, opportunistically ascertained collection of subjects with BP and MDD we selected 34 depression-related clinical features to test across the diagnostic categories in an initial discovery dataset consisting of 1228 subjects (386 BPI, 158 BPII and 684 MDD). Features significantly associated with BP were tested in an independent sample of 1000 BPI cases and 1000 MDD cases for classifying ability in receiver operating characteristic (ROC) analysis.
Seven clinical features showed significant association with BPI compared with MDD: delusions, psychomotor retardation, incapacitation, greater number of mixed symptoms, greater number of episodes, shorter episode length, and a history of experiencing a high after depression treatment. ROC analyses of a model including these seven factors showed significant evidence for discrimination between BPI and MDD in an independent dataset (area under the curve = 0.83). Only two features (number of mixed symptoms, and feeling high after an antidepressant) showed an association with BPII versus MDD.
Our study suggests that clinical features distinguishing depression in BPI versus MDD have important classification potential for clinical practice, and should also be incorporated as 'baseline' features in the evaluation of novel diagnostic biomarkers.
... reporting on the high rates of psychomotor retardation and other "melancholic" features, 5,23 psychosis, 26 and atypical depressive symptoms 5 in BP-I depression. Both psychomotor retardation and psychotic symptoms remained significant in the multivariate model, confirming their status as cardinal features of BP-I depression. ...
In a prior study of bipolar disorder pedigrees, we demonstrated distinct clinical differences between depressive episodes in bipolar disorder and major depressive disorder (MDD), including differentiation between these conditions using the Probabilistic Approach to Bipolar Depression. The aim of this retrospective study was to compare the phenomenology of the most severe lifetime depressive episodes between bipolar I (BP-I) and II (BP-II) disorder subtypes and MDD in these pedigrees.
Patients with DSM-IV diagnoses of BP-I (n = 202), BP-II (n = 44), and MDD (n = 120) from bipolar disorder pedigrees were assessed using the Diagnostic Interview for Genetic Studies between 1998 and 2012. Multivariate logistic regression was used to identify distinguishing clinical features. The utility of the Probabilistic Approach in distinguishing BP-I and BP-II depression from MDD was assessed.
BP-I differed from MDD in terms of greater rates of psychomotor retardation (P < .05) and psychotic features (P < .05). BP-II was distinguished from MDD (P < .01) by the greater likelihood of mixed features. Patients with BP-II had a greater likelihood of mixed features (P < .001) and a lesser likelihood of psychomotor retardation (P < .05) compared to those with BP-I. The Probabilistic Approach significantly differentiated both BP-I and BP-II from MDD (P < .01 to P < .001, depending on cutoff) but did not robustly distinguish between BP-I and BP-II.
First, the differentiation of BP-II from both BP-I depression and MDD in terms of the presence of mixed symptoms is of particular interest given the current debate over "mixed specifiers" for these conditions in DSM-5. Second, the Probabilistic Approach to Bipolar Depression was demonstrated for the first time to significantly distinguish both bipolar disorder subtypes from MDD.
© Copyright 2015 Physicians Postgraduate Press, Inc.
... However, psychotic symptoms only occurred in a few individuals, and these results should be interpreted with caution. Early psychotic symptoms that lead to later mood disorders are more clearly aligned with BPD than unipolar depressive disorders [91][92][93]. This association is also in line with previous studies emphasizing the role of the psychotic features related to early onset mood disorder and the increased risk of BPDs or schizoaffective disorder in long-term follow-up studies [94][95][96][97][98][99][100]. ...
Background
We aimed to outline the early risk factors for adult bipolar disorder (BPD) in adolescents with mood disorders.Methods
Adolescents (16¿17 years old) with mood disorders (n¿=¿287; 90 participants with hypomania spectrum episodes and 197 with major depressive disorder [MDD]) were identified from a community sample. Fifteen years later (at 30¿33 years of age), mood episodes were assessed (n¿=¿194). The risk of developing BPD (n¿=¿22), compared with MDD (n¿=¿104) or no mood episodes in adulthood (n¿=¿68), was estimated via logistic regression. Adolescent mood symptoms, non-mood disorders, and family characteristics were assessed as potential risk factors.ResultsAmong the adolescents with mood disorders, a family history of BPD was the strongest predictor of developing BPD compared with having no mood episodes in adulthood (OR¿=¿5.94; 95% CI¿=¿1.11-31.73), whereas disruptive disorders significantly increased the risk of developing BPD compared with developing MDD (OR¿=¿2.94; CI¿=¿1.06-8.12). The risk that adolescents with MDD would develop adult BPD, versus having no mood episodes in adulthood, was elevated among those with an early disruptive disorder (OR¿=¿3.62; CI¿=¿1.09-12.07) or multiple somatic symptoms (OR¿=¿6.60; CI¿=¿1.70-25.67). Only disruptive disorders significantly predicted adult BPD among adolescents with MDD versus continued MDD in adulthood (OR¿=¿3.59; CI¿=¿1.17-10.97). Only a few adolescents with hypomania spectrum episodes continued to have BPD as adults, and anxiety disorders appeared to increase this risk.Conclusions
Although most of the identified potential risk factors are likely general predictors of continued mood disorders, disruptive disorders emerged as specific predictors of developing adult BPD among adolescents with MDD.
... 22 In addition to these knowledges compulsive writing behavior can be ob-served in schizophrenia and frontotemporal dementia. 10 In light of the review of the literature, any studies couldn't be found about the association between dandy walker variant or other cerebellar malformations and hypergraphy. ...
Cerebellum is known to play an important role in coordination and motor functions. In some resent studies it is also considered to be involved in modulation of mood, cognition and psychiatric disorders. Dandy Walker Malformation is a congenital malformation that is characterized by hypoplasia or aplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of the posterior fossa. When the volume of posterior fossa is normal, the malformation is called Dandy Walker Variant. Case is a 32 year old male with a 12 year history of Bipolar I Disorder presented with manic and depresive symptoms, including dysphoric and depressive affect, anhedonia, suicidal thoughts and behaviours, thoughts of fear about future, overtalkativeness and graphomania, increased energy, irregular sleep, loss of appetite, increased immersion in projects, irritability, agressive behavior, impulsivity. Cranial Magnetic Resonance Imaging was compatible to the morphological features of Dandy Walker Variant.
... Our results revealed a number of robust differences in the clinical picture of Psychotic Mood Disorders (PMD), when compared to affective disorders with no history of psychotic symptoms. In line with previous findings, a number of negative prognostic factors were associated with PMD: a higher prevalence of BP-I diagnosis (Goes et al., 2007), a younger age at the first hospitalization (Jager et al., 2005), a higher number of mood episodes lifetime (Leyton et al., 1995;Coryell et al., 1996;Coryell et al., 2001), a younger age at illness onset (Lenzi et al., 1996) and, above all, a higher prevalence of early onset (before the age of 21) of mood symptoms. Other studies had also found a higher number of hospitalizations (Jager et al., 2005) in PMD patients, but in our sample lifetime duration of hospitalization was not different between groups. ...
The nosological and clinical implications of psychotic features in the course of mood disorders have been widely debated. Currently, no specification exists for defining a subgroup of lifetime Psychotic Mood Disorder (PMD) patients.
A total of 2178 patients were examined, including subjects with Bipolar Disorder (BP) type I (n=519) and II (n=207) and Major Depressive Disorder (n=1452). Patients were divided between PMD (n=645) and non-psychotic Mood Disorders (MD) (n=1533) by the lifetime presence of at least one mood episode with psychotic features. Subjects having a depressive episode at the time of assessment were also examined: HAM-D and YMRS scores were compared between MD and PMD subjects, both with and without current psychotic features.
A diagnosis of BP-I, a higher familial load for BP, a higher number of mood episodes lifetime, and a higher prevalence of OCD and somatic comorbidities were all associated to PMD. A diagnosis of BP (OR=4.48) was the only significant predictor for psychosis. PMD with non-psychotic depression were apparently less severe than MD patients and had a lower rate of "non-responders" to AD treatment. Sub-threshold manic symptoms and suicidal risk were also more pronounced among PMD.
The lack of information about number and polarity of previous psychotic mood episodes may be the major limitations of our study.
BP diagnosis is the most significant predictor for psychosis in mood disorders. Non-psychotic mood episodes in PMD patients may be characterized by a distinctive symptom profile and, possibly, a different response to treatment.
... Among adults, previous research suggests that psychosis linked with mood is associated with poorer functioning, more severe symptomatology, and a worsened prognosis and psychosocial functioning in comparison to non-psychotic mood disorders. [26][27][28][29][30][31] Some groups have suggested or debated whether psychotic mood disorders may represent a separate subtype of mood disorders. 26 Other studies have examined the disease course and prognosis in psychotic and nonpsychotic juveniles with BPD. ...
Few studies have examined the correlates of psychosis in children and adolescents with bipolar disorder (BPD). We examined psychiatric comorbidity, familiality, and psychosocial functioning in multiple domains in BPD children and adolescents with and without psychotic features.
As part of 2 ongoing family-based studies of children and adolescents with DSM-IV-defined BPD, we compared youth and their families with psychotic symptoms (BPD+P) and without psychotic symptoms (BPD-P). All youth and family members were assessed using indirect and direct structured psychiatric interviews (Kiddie Schedule for Affective Disorders-Epidemiologic Version and DSM-IV Structured Clinical Interview) in a blinded manner. One study was conducted from January 2000 through December 2004, and the other study was conducted from February 1997 through September 2006.
Of the 226 youth with BPD, 33% manifested psychotic symptoms, as defined by the presence of hallucinations or delusions. We found that BPD+P youth had a greater number of BPD episodes (P < .01), more psychiatric hospitalizations (P < .01), and significantly higher rates of psychiatric comorbidity compared to BPD-P youth (all P values < .05). Additionally, a higher percentage of BPD+P youth had a family history of psychosis (P = .01). There was a lower processing speed (P = .03) and lower arithmetic scaled score (P = .04) in BPD+P youth, but no other meaningful differences in cognitive variables were identified between the 2 BPD groups. Psychosis in BPD was also associated with decreased family cohesion (P = .04) and poorer overall global functioning (P < .01).
In children and adolescents with BPD, those who manifest psychotic features have higher rates of comorbid psychopathology, family history of psychosis, and poorer overall functioning in multiple domains than BPD children without psychosis. Future studies should examine neuroimaging correlates, medication response, and longitudinal course of children and adolescents with BPD who manifest psychosis as part of their clinical picture.
... 4 Bipolar disorder is a chronic and life-long condition which is characterized by shifts in energy level, mood state, behaviours 5 and psychotic symptoms such as hallucinations and delusions. 6 The cerebellum is suggested to interfere in the pathophysiology of bipolar disorder. 7 It has connections via thalamus to several brain regions such as dorsolateral prefrontal cortex, medial frontal cortex, anterior cingulate and the posterior hypotha-lamus which are all associated with behaviour and cognition. ...
Mega cisterna magna is a part of "Dandy-Walker Complex" and it is characterized by the enlargement of the cisterna magna, morphologically intact vermis and cerebellar hemispheres. We report a case of manic attack in a 23-year-old man with mega cisterna magna. The patient was treated with quetiapine 1,000 mg/day and sodium valproate 1,500 mg/day and the symptoms were ameliorated within 2.5 months. In this case, mega cisterna magna and manic symptoms may be found together coincidentally or any cerebellar dysfunction due to mega cisterna magna may cause or contribute to the appearance of affective symptoms. To our knowledge, this is the first case reporting manic attack with psychotic symptoms associated with mega cisterna magna. This report suggests that any lesion in the cerebellum might contribute to the occurrences of some affective and psychotic symptoms seen in bipolar disorder.
Background and objective:
Caused by shared genetic risk factors and similar neuropsychological symptoms, bipolar disorder (BD) and major depressive disorder (MDD) are at high risk of misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. We aimed to develop a machine learning (ML)-based diagnostic system, based on electronic medical records (EMR) data, to mimic the clinical reasoning of human physicians to differentiate MDD and BD (especially BD depressive episodes) patients about to be admitted to a hospital and, hence, reduce the misdiagnosis of BD as MDD on admission. In addition, we examined to what extent our ML model could be made interpretable by quantifying and visualizing the features that drive the predictions.
Methods:
By identifying 16,311 patients admitted to a hospital located in western China between 2009 and 2018 with a recorded main diagnosis of MDD or BD, we established three sub-cohorts with different combinations of features for both the MDD-BD cohort and the MDD-BD depressive episodes cohort, respectively. Four different ML algorithms (logistic regression, extreme gradient boosting (XGBoost), random forest, and support vector machine) and four train-test splits were used to train and validate diagnostic models, and explainable methods (SHAP and Break Down) were utilized to analyze the contribution of each of the features at both population-level and individual-level, including feature importance, feature interaction, and feature effect on prediction decision for a specific subject.
Results:
The XGBoost algorithm provided the best test performance (AUC: 0.838 (0.810-0.867), PPV: 0.810 and NPV: 0.834) for separating patients with BD from those with MDD. Core predictors included symptoms (mood-up, exciting, bad sleep, loss of interest, talking, mood-down, provoke), along with age, job, myocardial enzyme markers (creatine kinase, hydroxybutyrate dehydrogenase), diabetes-associated marker (glucose), bone function marker (alkaline phosphatase), non-enzymatic antioxidant (uric acid), markers of immune/inflammation (white blood cell count, lymphocyte count, basophil percentage, monocyte count), cardiovascular function marker (low density lipoprotein), renal marker (total protein), liver biochemistry marker (indirect bilirubin), and vital signs like pulse. For separating patients with BD depressive episodes from those with MDD, the test AUC was 0.777 (0.732-0.822), with PPV 0.576 and NPV 0.899. Additional validation in models built with self-reported symptoms removed from the feature set, showed test AUC of 0.701 (0.666-0.736) for differentiating BD and MDD, and AUC of 0.564 (0.515-0.614) for detecting patients in BD depressive episodes from MDD patients. Validation in the datasets without removing the patients with comorbidity showed an AUC of 0.826 (0.806-0.846).
Conclusion:
The diagnostic system accurately identified patients with BD in various clinical scenarios, and differences in patterns of peripheral markers between BD and MDD could enrich our understanding of potential underlying pathophysiological mechanisms of them.
Learning objectives after participating in this cme activity, the psychiatrist should be better able to:
• Analyze and compare the different bipolar disorder (BD) types.• Identify markers that distinguish BD types and explain how the DSM-IV defines the disorder.
Abstract:
Since the status of type II bipolar disorder (BD2) as a separate and distinct form of bipolar disorder (BD) remains controversial, we reviewed studies that directly compare BD2 to type I bipolar disorder (BD1). Systematic literature searching yielded 36 reports with head-to-head comparisons involving 52,631 BD1 and 37,363 BD2 patients (total N = 89,994) observed for 14.6 years, regarding 21 factors (with 12 reports/factor). BD2 subjects had significantly more additional psychiatric diagnoses, depressions/year, rapid cycling, family psychiatric history, female sex, and antidepressant treatment, but less treatment with lithium or antipsychotics, fewer hospitalizations or psychotic features, and lower unemployment rates than BD1 subjects. However, the diagnostic groups did not differ significantly in education, onset age, marital status, [hypo]manias/year, risk of suicide attempts, substance use disorders, medical comorbidities, or access to psychotherapy. Heterogeneity in reported comparisons of BD2 and BD1 limits the firmness of some observations, but study findings indicate that the BD types differ substantially by several descriptive and clinical measures and that BD2 remains diagnostically stable over many years. We conclude that BD2 requires better clinical recognition and significantly more research aimed at optimizing its treatment.
This Clinical Handbook for the Management of Mood Disorders will equip clinicians with the knowledge to refine their diagnostic skills and implement treatment plans for mood disorders based on the most up-to-date evidence on interventions that work. Covering the widest range of treatments and techniques, it provides clear guidance for the management of all types and subtypes of both minor and major depression. Chapters cover the latest and most innovative treatments, including use of ketamine, deep brain stimulation and transcranial magnetic stimulation, effective integration of pharmacological and psychotherapeutic approaches, as well as providing a thought-provoking look at the future research agenda and the potential for reliable biomarkers. This is the most comprehensive review of depression available today. Written and edited by leading experts mostly from Columbia University, this is an essential resource for anyone involved in the care and treatment of patients with mood disorders.
This Clinical Handbook for the Management of Mood Disorders will equip clinicians with the knowledge to refine their diagnostic skills and implement treatment plans for mood disorders based on the most up-to-date evidence on interventions that work. Covering the widest range of treatments and techniques, it provides clear guidance for the management of all types and subtypes of both minor and major depression. Chapters cover the latest and most innovative treatments, including use of ketamine, deep brain stimulation and transcranial magnetic stimulation, effective integration of pharmacological and psychotherapeutic approaches, as well as providing a thought-provoking look at the future research agenda and the potential for reliable biomarkers. This is the most comprehensive review of depression available today. Written and edited by leading experts mostly from Columbia University, this is an essential resource for anyone involved in the care and treatment of patients with mood disorders.
Os princípios e questões gerais envolvidos no tratamento da depressão bipolar incluem a avaliação inicial, objetivos do tratamento, cenário, farmacoterapia, duração de um ensaio clínico adequado, monitoramento, psicoterapia adjuvante e comorbidade. O transtorno bipolar é um transtorno de humor caracterizado por períodos de elevação patológica do humor (mania ou hipomania). Os pacientes com transtorno bipolar I apresentam episódios maníacos e quase sempre apresentam episódios hipomaníacos e episódios depressivos maiores. O transtorno bipolar II é caracterizado por pelo menos um episódio de hipomania e um ou mais episódios depressivos maiores. Além disso, características psicóticas, como delírios e alucinações, frequentemente acompanham episódios depressivos bipolares, particularmente em pacientes com transtorno bipolar I. O termo droga antimaníaca é utilizado para nos referir a medicamentos que podem reduzir os sintomas agudos de mania/hipomania, sem causar uma mudança para a polaridade oposta, exemplos incluem lítio, antiepilépticos, como carbamazepina e valproato, e antipsicóticos de segunda geração, como aripiprazol, cariprazina, lurasidona, olanzapina, quetiapina e risperidona. Os pacientes com depressão bipolar I podem não responder ou tolerar a monoterapia com quetiapina e monoterapia com lurasidona.
Background:
Lifetime psychotic symptoms are present in over half of the patients with bipolar disorder (BD) and can have an adverse effect on its course, outcome, and treatment. However, despite a considerable amount of research, the impact of psychotic symptoms on BD remains unclear, and there are very few systematic reviews on the subject.
Aim:
To examine the extent of psychotic symptoms in BD and their impact on several aspects of the illness.
Methods:
The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. An electronic literature search of six English-language databases and a manual search was undertaken to identify published articles on psychotic symptoms in BD from January 1940 to December 2021. Combinations of the relevant Medical Subject Headings terms were used to search for these studies. Articles were selected after a screening phase, followed by a review of the full texts of the articles. Assessment of the methodological quality of the studies and the risk of bias was conducted using standard tools.
Results:
This systematic review included 339 studies of patients with BD. Lifetime psychosis was found in more than a half to two-thirds of the patients, while current psychosis was found in a little less than half of them. Delusions were more common than hallucinations in all phases of BD. About a third of the patients reported first-rank symptoms or mood-incongruent psychotic symptoms, particularly during manic episodes. Psychotic symptoms were more frequent in bipolar type I compared to bipolar type II disorder and in mania or mixed episodes compared to bipolar depression. Although psychotic symptoms were not more severe in BD, the severity of the illness in psychotic BD was consistently greater. Psychosis was usually associated with poor insight and a higher frequency of agitation, anxiety, and hostility but not with psychiatric comorbidity. Psychosis was consistently linked with increased rates and the duration of hospitalizations, switching among patients with depression, and poorer outcomes with mood-incongruent symptoms. In contrast, psychosis was less likely to be accompanied by a rapid-cycling course, longer illness duration, and heightened suicidal risk. There was no significant impact of psychosis on the other parameters of course and outcome.
Conclusion:
Though psychotic symptoms are very common in BD, they are not always associated with an adverse impact on BD and its course and outcome.
Symptomatic overlap of depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) is a major diagnostic and therapeutic problem. Mania in medical history remains the only reliable distinguishing marker which is problematic given that episodes of depression compared to episodes of mania are more frequent and predominantly present at the beginning of BD. Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive, task-free, and well-tolerated method that may provide diagnostic markers acquired from spontaneous neural activity. Previous rs-fMRI studies focused on differentiating BD from MDD depression were inconsistent in their findings due to low sample power, heterogeneity of compared samples, and diversity of analytical methods. This meta-analysis investigated resting-state activity differences in BD and MDD depression using activation likelihood estimation. PubMed, Web of Science, Scopus and Google Scholar databases were searched for whole-brain rs-fMRI studies which compared MDD and BD currently depressed patients between Jan 2000 and August 2020. Ten studies were included, representing 234 BD and 296 MDD patients. The meta-analysis found increased activity in the left insula and adjacent area in MDD compared to BD. The finding suggests that the insula is involved in neural activity patterns during resting-state that can be potentially used as a biomarker differentiating both disorders.
The two major subtypes of bipolar disorder (BD), BD-I and BD-II, are distinguished based on the presence of manic or hypomanic episodes. Historically, BD-II was perceived as a less severe form of BD-I. Recent research has challenged this concept of a severity continuum. Studies in large samples of unrelated patients have described clinical and genetic differences between the subtypes. Besides an increased schizophrenia polygenic risk load in BD-I, these studies also observed an increased depression risk load in BD-II patients. The present study assessed whether such clinical and genetic differences are also found in BD patients from multiplex families, which exhibit reduced genetic and environmental heterogeneity. Comparing 252 BD-I and 75 BD-II patients from the Andalusian Bipolar Family (ABiF) study, the clinical course, symptoms during depressive and manic episodes, and psychiatric comorbidities were analyzed. Furthermore, polygenic risk scores (PRS) for BD, schizophrenia, and depression were assessed. BD-I patients not only suffered from more severe symptoms during manic episodes but also more frequently showed incapacity during depressive episodes. A higher BD PRS was significantly associated with suicidal ideation. Moreover, BD-I cases exhibited lower depression PRS. In line with a severity continuum from BD-II to BD-I, our results link BD-I to a more pronounced clinical presentation in both mania and depression and indicate that the polygenic risk load of BD predisposes to more severe disorder characteristics. Nevertheless, our results suggest that the genetic risk burden for depression also shapes disorder presentation and increases the likelihood of BD-II subtype development.
Catatonia is a complex neuropsychiatric syndrome characterized by motor signs, disturbances of volition, inability to suppress complex motor activities, stereotypies, and autonomic instability. It has been reported to occur in more than 10% among hospitalized acute psychiatric patients. In DSM-5, catatonia syndrome is defined as a specifier to major mood, psychotic disorders, and general medical conditions. Cotard's syndrome is a particular cluster of psychotic symptoms characterized by nihilistic delusions. It has been described among depressive psychotic disorders and in bipolar depression. Even though the concurrent presence of these two psychopathological conditions is rare, they can be associated with medical internal complications as dehydration, pneumonia, and thromboembolic disease, due to the lack of movements (immobilization). These syndromes are complex and difficult to treat, needing multiple psychopharmacological choices (antidepressants, mood stabilizers, antipsychotics). Here we describe the case of a young woman with bipolar disorder, who presented catatonia and Cotard's syndrome during a depressive psychotic episode; she required hospitalization because of the severity of symptoms. The recovery from the acute phase was obtained only after several months of treatment and rehabilitation. © Springer International Publishing AG, part of Springer Nature 2019. All rights reserved.
Background:
More than 50% of individuals with bipolar disorder (BD) do not reach full psychosocial functioning, even during periods of euthymia. It has been suggested that history of psychotic symptoms is one of the factors which are associated with a worse functional outcome. The objective was to compare psychosocial functioning between patients with BD, with (BD-P), and without (BD-NP) a history of psychotic symptoms, and to examine whether the history of psychotic symptoms, or other clinical or neurocognitive variables predict psychosocial functioning.
Methods:
Psychosocial functioning and neurocognition were examined in 100 euthymic patients with bipolar I disorder (50 BD-P, and 50 BD-NP), compared to 50 stabilised patients with schizophrenia (SZ), and 51 healthy controls (HC).
Results:
1) There were no differences between BD-P and BD-NP in the GAF-F score or in the FAST total score. 2) The two groups of patients with BD had better scores than SZ both in the GAF-F, and in all measures of the FAST, except for the subscale leisure time. 3) The neurocognitive composite index, verbal memory and subclinical depressive symptoms were the variables which explained a higher percentage of the variance of functional outcome.
Limitations:
The cross-sectional design, and the relatively small sample size are the main limitations.
Conclusions:
A history of psychotic symptoms has no relevant impact on the level of psychosocial functioning in BD. Neurocognitive dysfunction and subclinical depressive symptoms are the variables that best explain the functional impairment. These findings have important clinical implications.
Background:
The presence of psychotic symptoms in bipolar disorder (BD) is considered a feature of higher severity of illness and, in particular, of manic episodes in bipolar I disorder (BD I). However, the possibility to apply the "with psychotic features" specifier to major depressive episodes in either bipolar II disorder (BD II) or BD I highlights the need for additional research in this area.
Methods:
The present study assessed the lifetime presence of psychotic symptoms and related socio-demographic and clinical features in a large sample of BD patients (N=360), with (BDPs, N=207) and without a lifetime history of psychosis (BDNPs, N=153).
Results:
An overall less favorable socio-demographic profile was observed in BDPs vs BDNPs. In terms of clinical variables, BDPs vs BDNPs had: earlier age at onset (27.7±10.5 vs 30.1±12.3years; p=0.02), higher rates of BD I diagnosis (95.7% vs 45.8%; p<0.001), more elevated (manic/hypomanic/mixed) polarity of first (55.2% vs 24.4%; p<0.001) and most recent episode (69.8% vs 35.6%; p<0.001), more comorbid alcohol/substance use disorder (38.1% vs 21.9%; p=0.002), more lifetime hospitalizations (3.8±6.1 vs 2±3; p=0.002) and involuntary commitments (1±1.9 vs 0.1±0.4; p<0.001), more history of psychosocial rehabilitation (17.9% vs 5.7%; p=0.001), more current antipsychotic use (90.1% vs 70.9%; p<0.001), and lower GAF (62.3±14.2 vs 69.3±12.5; p<0.001), but shorter duration of most recent episode (34.1±45.4 vs 50.3±65.7days; p=0.04), lower rates of comorbid anxiety disorders (23.9% vs 38.2%; p=0.005), and antidepressant use (19.4% vs 56.6%; p<0.001).
Conclusions:
The present findings indicate an overall worse profile of socio-demographic and certain clinical characteristics associated with the lifetime presence of psychotic symptoms in bipolar patients.
Modern approach distinguishes between ‘mood’ which is the long-lasting internal emotional tone and largely characteristic of the individual; ‘affect’ which is the general emotional status during the last few days or weeks, and it is observable through the individual’s behaviour; and ‘emotion’ which corresponds to the transient emotional state which also manifests itself through motor behaviours (face mimics, body movements, complex behaviours, etc.). Mood has an enduring nature, tends to be unfocused and diffused, involves expectation of the future and is manifested in subtle ways, while, in contrast, emotions tend to be short lived and to have a clear focus.
The present study aims at exploring associations between a continuous measure of distorted thought contents and a set of demographic and clinical features in a sample of unipolar/bipolar depressed patients.
Our sample included 1,833 depressed subjects. Severity of mood symptoms was assessed by the 21 items Hamilton Depression Rating Scale (HAM-D). The continuous outcome measure was represented by a delusion (DEL) factor, extracted from HAM-D items and including items: 2 ("Feelings of guilt"), 15 ("Hypochondriasis"), and 20 ("Paranoid symptoms"). Each socio-demographic and clinical variable was tested by a generalized linear model test, having depressive severity (HAM-D score?DEL score) as the covariate.
A family history of major depressive disorder (MDD; p=0.0006), a diagnosis of bipolar disorder, type I ( p=0.0003), a comorbid general anxiety disorder (p<0.0001), and a higher number of manic episodes during lifetime (p<0.0001), were all associated to higher DEL scores. Conversely, an older age at onset (p<0.0001) and a longer duration of hospitalization for depression over lifetime (p=0.0003) had a negative impact over DEL scores. On secondary analyses, only the presence of psychotic features (p<0.0001) and depressive severity (p<0.0001) were found to be independently associated to higher DEL scores.
The retrospective design and a non validated continuous measure for distorted thought contents were the main limitations of our study. Excluding the presence of psychotic features and depressive severity, no socio-demographic or clinical variable was found to be associated to our continuous measure of distorted thinking in depression.
Recent studies have indicated that the 11-item Psychotic Depression Assessment Scale (PDAS), consisting of the 6-item melancholia subscale (HAM-D6) of the Hamilton Depression Rating Scale and 5 psychosis items from the Brief Psychiatric Rating Scale (BPRS), is a valid measure for the severity of psychotic depression. The aim of this study was to subject the PDAS, and its depression (HAM-D6) and psychosis (BPRS5) subscales to further validation.
Patients diagnosed with psychotic depression at Danish psychiatric hospitals participated in semi-structured interviews. Video recordings of these interviews were assessed by two experienced psychiatrists (global severity rating of psychotic depression, depressive symptoms and psychotic symptoms) and by two young physicians (rating on 27 symptom items, including the 11 PDAS items). The clinical validity and responsiveness of the PDAS and its subscales was investigated by Spearman correlation analysis of the global severity ratings and the PDAS, HAM-D6, and BPRS5 total scores. The unidimensionality of the scales was tested by item response theory analysis (Mokken).
Ratings from 39 participants with unipolar psychotic depression and nine participants with bipolar psychotic depression were included in the analysis. The Spearman correlation analysis indicated that the PDAS, HAM-D6 and BPRS5 were clinically valid (correlation coefficients from 0.78 to 0.85, p<0.001) and responsive (correlation coefficients from 0.72 to 0.86, p<0.001) measures of psychotic depression. According to the Mokken analysis, all three scales were unidimensional.
The clinical validity, responsiveness and unidimensionality of the PDAS and its subscales were confirmed in an independent sample of patients with psychotic depression.
Copyright © 2014. Published by Elsevier B.V.
Objective:
To assess the association of neural development-related genes LIS1and TSNAX with bipolar disorder in a Chinese Han population.
Methods:
Three hundred and eight five patients (including 188 males and 197 females) from Guangzhou Brain Hospital with bipolar disorder meeting the Diagnostic and Statistic Manual of Bipolar Disorder (BDI) (Fourth Edition) criteria and 475 healthy controls from the local community were recruited. Ten single nucleotide polymorphisms (SNPs) of the LIS1 and TSNAX genes were genotyped by GoldenGate genotyping assay on an Illumina Beadstation 500 machine. Association analyses of SNPs and haplotypes were performed with Plink 1.07 software.
Results:
Analysis of the total sample has failed to find any association of SNP or haplotype of the two genes with BDI (P> 0.05). When patients were divided into subgroups with or without psychotic symptom, no significant association of the two genes was found with psychotic BDI or non-psychotic BDI (P> 0.05). No significant association was found between any SNP and haplotype of two genes and female BDI or male BDI, nor were significant association found between age of onset and LIS1 and TSNAX gene polymorphisms.
Conclusion:
Our results indicated that LIS1 and TSNAX genes are not associated with susceptibility to bipolar I disorder in Chinese Han population.
Patients with unipolar psychotic depression (PD) are at high risk of developing bipolar disorder (BD). This conversion has important implications for the choice of treatment. This study, therefore, aimed to identify risk factors associated with diagnostic conversion from PD to BD.
We conducted a population-based, historical prospective cohort study by merging data from Danish registers. Patients assigned an ICD-10 diagnosis of PD between 1 January 1995 and 31 December 2007 were identified in the Danish Central Psychiatric Research Register and were followed until the development of BD, death, loss to follow-up, or 31 December 2007. Potential risk factors for conversion to BD, also defined through various Danish registers, were tested in multiple logistic regression analyses with risk expressed as adjusted odds ratios (AOR).
We identified 8,588 patients with PD, of whom 609 (7.1%) developed BD during follow-up. The following characteristics were significantly associated with diagnostic conversion from PD to BD: early onset of PD [AOR = 0.99 (per year of increasing age), p = 0.044], recurrent depression [AOR = 1.02 (per episode), p = 0.036], living alone (AOR = 1.29, p = 0.007), receiving a disability pension (AOR = 1.55, p < 0.001), and the highest educational level being a technical education (AOR = 1.55, p < 0.001), short-cycle higher education (AOR = 2.65, p < 0.001), or medium-cycle higher education (AOR = 1.75, p < 0.001).
Diagnostic conversion to BD was prevalent among patients with PD. The following characteristics were significantly associated with this conversion: early onset of PD, recurrent depression, living alone, receiving a disability pension, and the highest educational level being a technical education, short-cycle higher education, or medium-cycle higher education.
Psychotic depressed patients were found to have more severe cognitive deficits, poorer treatment response and higher suicidal risk respect to non-psychotic depressives. Aim of the present research was to compare clinical variables and outcome between psychotic and non-psychotic major depressive patients.
A sample of 36 major depressed patients was divided into two groups according to the presence of psychotic symptoms. Structured Clinical Interview for DSM (SCID-I) and Hamilton Depression Rating Scale (HAM-D) were administered to the patients at baseline by trained raters. One-way analysis of variance (ANOVAs) and chi-square tests were performed to compare the two groups. Binary logistic regression was performed to assess the risk of lack of response/remission in patients with psychotic symptoms and the risk of developing psychotic symptoms in major depressives with a family history of schizophrenia or bipolar disorder.
Psychotic major depressives presented more severe illness as showed by HAM-D baseline scores (F=17.20, p<0.001), a longer duration of hospitalization (F=7.64, p=0.009) and they were more frequently treated with clomipramine (χ(2)=16.22, p=0.027). Psychotic symptoms were predictive of lack of remission (OR=4.09, p=0.05) and family history of schizophrenia/psychotic bipolar disorder was associated with psychotic major depression (OR=10.81, p=0.04).
Patients with psychotic symptoms present a more severe course of illness as showed by long hospitalizations and lower rates of remission. Psychotic depressives show more frequently a family history of "major psychoses" suggesting a continuum in psychotic disorders and a genetic association of major psychotic depression with bipolar disorder and schizophrenia.
Background:
The Semantic Object Retrieval Task (SORT) requires participants to indicate whether word pairs recall a third object. Schizophrenia individuals (SZ) tend to report associations between nonassociated word pairs; this overretrieval is related to formal thought disorder (FTD). Since semantic memory impairments and psychosis are also found in bipolar disorder (BP), we examined whether SORT impairments and their relationship to symptoms are also present in BP.
Methods:
Participants (n = 239; healthy control subjects [HC] = 133; BP = 32; SZ = 74) completed SORT while undergoing functional magnetic resonance imaging (fMRI) scanning.
Results:
Retrieval accuracy negatively correlated with negative symptoms and no-retrieval accuracy negatively correlated with FTD severity in SZ but not BP. Retrieval versus no-retrieval trials activated a distributed fronto-parieto-temporal network; bilateral inferior parietal lobule (IPL) activity was larger in HC versus SZ and HC versus BP, with no difference in SZ versus BP. Right IPL activity positively correlated with positive and general psychosis symptoms in SZ but not BP.
Conclusions:
SZ reported more associations between unrelated word pairs than HC; this overretrieval increased with FTD severity. Schizophrenia individuals were also more likely to fail to find associations between related word pairs; this underretrieval increased with negative symptom severity. fMRI symptom correlations in IPL in SZ are consistent with arguments that IPL abnormality relates to loosening of associations in SZ. By comparison, BP showed intermediate impairments on SORT, uncorrelated with symptoms, suggesting that the relationship between SORT performance, fMRI activity, and psychotic symptoms is schizophrenia-specific.
To determine the frequency with which bipolar II disorder (BD II) was diagnosed in clinics held in four rural towns in New South Wales (NSW).
A retrospective case file audit was conducted for patients referred for psychiatric assessment and treatment in four towns in rural NSW over a period of two years and nine months.
Of 559 patients seen for the first time during the study period, 113 (20.2%) were diagnosed with BD II, and of these this diagnosis was made for the first time in 69 patients (61%). Associated clinical findings in BD II patients are presented and a comparison is made with patients with non-bipolar depression seen during the same period.
BD II was commonly seen in these rural clinics, and appears to be often under-diagnosed in general practice, as has been found to be the case in urban centres. This is seen as a serious public health problem, which needs to be addressed by educational steps directed at general practitioners (GPs), mental health clinicians, and perhaps also the general public.
Depression accompanied by psychotic symptoms is referred to as delusional or psychotic depression (PD). PD is classified as a subtype of severe unipolar depression/ severe depression in bipolar disorder in the two current major diagnostic systems, namely the 10th revision of the International Classification of Disease (ICD-10) and the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). We discuss the arguments in favour of and against classifying PD as a distinct syndrome under the affective disorders.
Although genetic epidemiological studies have confirmed increased rates of major depressive disorder among the relatives of people with bipolar affective disorder, no report has compared the clinical characteristics of depression between these two groups.
To compare clinical features of depressive episodes across participants with major depressive disorder and bipolar disorder from within bipolar disorder pedigrees, and assess the utility of a recently proposed probabilistic approach to distinguishing bipolar from unipolar depression. A secondary aim was to identify subgroups within the relatives with major depression potentially indicative of 'genetic' and 'sporadic' subgroups.
Patients with bipolar disorder types 1 and 2 (n = 246) and patients with major depressive disorder from bipolar pedigrees (n = 120) were assessed using the Diagnostic Interview for Genetic Studies. Logistic regression was used to identify distinguishing clinical features and assess the utility of the probabilistic approach. Hierarchical cluster analysis was used to identify subgroups within the major depressive disorder sample.
Bipolar depression was characterised by significantly higher rates of psychomotor retardation, difficulty thinking, early morning awakening, morning worsening and psychotic features. Depending on the threshold employed, the probabilistic approach yielded a positive predictive value ranging from 74% to 82%. Two clusters within the major depressive disorder sample were found, one of which demonstrated features characteristic of bipolar depression, suggesting a possible 'genetic' subgroup.
A number of previously identified clinical differences between unipolar and bipolar depression were confirmed among participants from within bipolar disorder pedigrees. Preliminary validation of the probabilistic approach in differentiating between unipolar and bipolar depression is consistent with dimensional distinctions between the two disorders and offers clinical utility in identifying patients who may warrant further assessment for bipolarity. The major depressive disorder clusters potentially reflect genetic and sporadic subgroups which, if replicated independently, might enable an improved phenotypic definition of underlying bipolarity in genetic analyses.
This article reports on the development and reliability of the Diagnostic Interview for Genetic Studies (DIGS), a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions. The DIGS, which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health (NIMH) Genetics Initiative, has the following additional features: (1) polydiagnostic capacity; (2) a detailed assessment of the course of the illness, chronology of psychotic and mood syndromes, and comorbidity; (3) additional phenomenologic assessments of symptoms; and (4) algorithmic scoring capability. The DIGS is designed to be employed by interviewers who exercise significant clinical judgment and who summarize information in narrative form as well as in ratings. A two-phase test-retest (within-site, between-site) reliability study was carried out for DSM-III-R criteria-based major depression, bipolar disorder, schizophrenia, and schizoaffective disorder. Reliabilities using algorithms were excellent (0.73 to 0.95), except for schizoaffective disorder, for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability. A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions. The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders, schizophrenia, and related conditions.
Symptomatic overlap between affective disorders and schizophrenia has long been noted. More recently, family and linkage studies have provided some evidence for overlapping genetic susceptibility between bipolar disorder and schizophrenia. If shared genes are responsible for the psychotic manifestations of both disorders, these genes may result in clustering of psychotic symptoms in some bipolar disorder pedigrees. The authors tested this hypothesis in families ascertained for a genetic study of bipolar disorder.
Rates of psychotic symptoms-defined as hallucinations or delusions-during affective episodes were compared in families of 47 psychotic and 18 nonpsychotic probands with bipolar I disorder. The analysis included 202 first-degree relatives with major affective disorder.
Significantly more families of psychotic probands than families of nonpsychotic probands (64% versus 28%) contained at least one relative who had affective disorder with psychotic symptoms. Significantly more affectively ill relatives of psychotic probands than of nonpsychotic probands (34% versus 11%) had psychotic symptoms. An analysis of clustering of psychotic subjects across all families revealed significant familial aggregation. Clustering of psychosis was also apparent when only bipolar I disorder was considered the affected phenotype.
Psychotic bipolar disorder may delineate a subtype of value for genetic and biological investigations. Families with this subtype should be used to search for linkage in chromosomal regions 10p12-13, 13q32, 18p11.2, and 22q11-13, where susceptibility genes common to bipolar disorder and schizophrenia may reside. Putative schizophrenia-associated biological markers, such as abnormal evoked response, oculomotor, and neuroimaging measures, could similarly be explored in such families.
The purpose of this study was to assess 65 pedigrees ascertained through a Bipolar I (BPI) proband for evidence of linkage, using nonparametric methods in a genome-wide scan and for possible parent of origin effect using several analytical methods. We identified 15 loci with nominally significant evidence for increased allele sharing among affected relative pairs. Eight of these regions, at 8q24, 18q22, 4q32, 13q12, 4q35, 10q26, 2p12, and 12q24, directly overlap with previously reported evidence of linkage to bipolar disorder. Five regions at 20p13, 2p22, 14q23, 9p13, and 1q41 are within several Mb of previously reported regions. We report our findings in rank order and the top five markers had an NPL>2.5. The peak finding in these regions were D8S256 at 8q24, NPL 3.13; D18S878 at 18q22, NPL 2.90; D4S1629 at 4q32, NPL 2.80; D2S99 at 2p12, NPL 2.54; and D13S1493 at 13q12, NPL 2.53. No locus produced statistically significant evidence for linkage at the genome-wide level. The parent of origin effect was studied and consistent with our previous findings, evidence for a locus on 18q22 was predominantly from families wherein the father or paternal lineage was affected. There was evidence consistent with paternal imprinting at the loci on 13q12 and 1q41.
Linkage studies of bipolar disorder and schizophrenia have found overlapping evidence for susceptibility genes in four chromosomal regions-10p12-14, 13q32, 18p11.2, and 22q12-13. The authors previously demonstrated familial clustering of psychotic symptoms-defined as hallucinations and/or delusions-in some bipolar disorder pedigrees. In this study they used stratified linkage analysis to test the hypothesis that those bipolar disorder pedigrees most enriched for psychotic symptoms would show greater evidence of linkage to the regions of previous bipolar disorder/schizophrenia linkage overlap.
Nonparametric linkage analyses using GENEHUNTER and ASPEX were performed on 65 bipolar disorder families. Family subsets were defined by the number of family members with psychotic mood disorder.
The 10 families in which three or more members had psychotic mood disorder showed suggestive evidence of linkage to 13q31 (nonparametric linkage score=3.56; LOD score=2.52) and 22q12 (nonparametric linkage score=3.32; LOD score=3.06). These results differed significantly from those for the entire study group of 65 families, which showed little or no linkage evidence in the two regions. The 10 families with three or more psychotic members did not show evidence of linkage to 10p12-14 or 18p11.2. The 95% confidence interval on 22q12 spanned 4.3 centimorgans (2.6 megabases) and was congruent with previous findings.
Bipolar disorder families in which psychotic symptoms cluster may carry susceptibility genes on chromosomal regions 13q31 and 22q12. Replication should be attempted in similar families and perhaps in schizophrenia families in which mood symptoms cluster because these overlapping phenotypes may correlate most closely with the putative susceptibility genes. The localization of the 22q12 finding particularly encourages further study of this region.
We conducted a 9-cM genome scan in a large bipolar pedigree sample from the National Institute of Mental Health genetics initiative (1060 individuals from 154 multiplex families). We performed parametric and nonparametric analyses using both standard diagnostic models and comorbid conditions thought to identify phenotypic subtypes: psychosis, suicidal behavior, and panic disorder. Our strongest linkage signals (genome-wide significance) were observed on chromosomes 10q25, 10p12, 16q24, 16p13, and 16p12 using standard diagnostic models, and on 6q25 (suicidal behavior), 7q21 (panic disorder) and 16p12 (psychosis) using phenotypic subtypes. Several other regions were suggestive of linkage, including 1p13 (psychosis), 1p21 (psychosis), 1q44, 2q24 (suicidal behavior), 2p25 (psychosis), 4p16 (psychosis, suicidal behavior), 5p15, 6p25 (psychosis), 8p22 (psychosis), 8q24, 10q21, 10q25 (suicidal behavior), 10p11 (psychosis), 13q32 and 19p13 (psychosis). Over half the implicated regions were identified using phenotypic subtypes. Several regions - 1p, 1q, 6q, 8p, 13q and 16p - have been previously reported to be linked to bipolar disorder. Our results suggest that dissection of the disease phenotype can enrich the harvest of linkage signals and expedite the search for susceptibility genes. This is the first large-scale linkage scan of bipolar disorder to analyze simultaneously bipolar disorder, psychosis, suicidal behavior, and panic disorder.
The purpose of this study was to assemble and validate a database of phenotypic variables that were collected from families with bipolar disorder as a resource for genetic and other biological studies.
Participants were ascertained for two bipolar disorder genetic linkage studies: the University of Chicago, Johns Hopkins, and National Institute of Mental Health (NIMH) Intramural Program (CHIP) Collaboration and the NIMH Genetics Initiative project. All participants underwent detailed, phenotypic assessment with either the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or one of four versions of the Diagnostic Interview for Genetic Studies. Clinicians reviewed the interview items and derived variable definitions that were used to extract data from the original datasets. The combined data were subjected to range and logic assessments, and a subset was re-verified against the original data. Inconsistent data and variables that were deemed unreliable were excluded. Several of the resulting variables were characterized in the total cohort and tested for familial clustering, heritability, and statistical power in genetic linkage and association studies.
The combined database of phenotypic variables contained 197 variables on 5,721 subjects in 1,177 families. Deoxyribonucleic acid (DNA) samples are available for 5,373 of these subjects. The clinical presentation of bipolar disorder varied markedly. Most subjects suffered from serious and often disabling illness. Many phenotypic variables are strongly familial, and some quantitative variables are highly heritable. The cohort assembled in this study offers substantial power to carry out genetic linkage and association studies that use specific clinical features as covariates or as primary phenotypes.
This is the largest database of phenotypic variables yet assembled for bipolar disorder, and it is now available to the research community. Researchers and clinicians can use this database to explore the connections between phenomenology and genetics in a cohort that is adequately powered to detect even modest genetic effects in bipolar disorder.
• The Schedule for Affective Disorders and Schizophrenia (SADS) was developed to reduce information variance in both the descriptive and diagnostic evaluation of a subject. The SADS is unique among rating scales in that it provides for (1) a detailed description of the features of the current episode of illness when they were at their most severe; (2) a description of the level of severity of manifestations of major dimensions of psychopathology during the week preceding the evaluation, which can then be used as a measure of change; (3) a progression of questions and criteria, which provides information for making diagnoses; and (4) a detailed description of past psychopathology and functioning relevant to an evaluation of diagnosis, prognosis, and overall severity of disturbance. This article reports on initial scale development and reliability studies of the items and the scale scores.
This the Diagnostic Interview for Genetic Studies (DIGS), a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions. The DIGS, which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health (NIMH) Genetics Initiative, has the following additional features: (1) polydiagnostic capacity; (2) a detailed assessment of the course of the illness, chronology of psychotic and mood syndromes, and comorbidity; (3) additional phenomenologic assessments of symptoms; and (4) algorithmic scoring capability. The DIGS is designed to be employed by interviewers who exercise significant clinical judgment and who summarize information in narrative form as well as in ratings. A two-phase test-retest (within-site, between-site) reliability study was carried out for DSM-III-R criteria—based major depression, bipolar disorder, schizophrenia, and schizoaffective disorder. Reliabilities using algorithms were excellent (0.73 to 0.95), except for schizoaffective disorder, for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability. A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions. The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders, schizophrenia, and related conditions.
Four sites collaborated with the NIMH to develop a resource for the genetic study of bipolar (BP) illness. Common methods of ascertainment and assessment were developed in 1989. A series of families with a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar type (SA/BP) first-degree relative has been studied. We now report initial data from a genomic survey with an average intermarker interval of 10 cM on 540 subjects from 97 families. This is the largest commonly ascertained and assessed linkage sample for bipolar illness reported to date; it includes 232 subjects with BPI, 32 SA/BP, 72 bipolar II (BPII), and 88 unipolar, recurrent (UPR). Nonparametric methods of analysis were employed, with all sites using affected sib pair analysis. The strongest findings thus far appear to be on chromosomes 1, 6, 7, 10, 16, and 22. Support has also been found for some previously reported linkages, including 21q and possibly Xq26. All these areas (as well as others) will be followed up with additional markers and further analyses. No locus tested thus far meets stringent criteria for an initial finding of significant linkage. Am. J. Med. Genet. 74:227–237, 1997. © 1997 Wiley-Liss, Inc.
The Schedule for Affective Disorders and Schizophrenia (SADS) was developed to reduce information variance in both the descriptive and diagnostic evaluation of a subject. The SADS is unique among rating scales in that it provides for (1) a detailed description of the features of the current episodes of illness when they were at their most severe; (2) a description of the level of severity of manifestations of major dimensions of psychopathology during the week preceding the evaluation, which can then be used as a measure of change; (3) a progression of questions and criteria, which provides information for making diagnoses; and (4) a detailed description of past psychopathology and functioning relevant to an evaluation of diagnosis, prognosis, and overall severity of disturbance. This article reports on initial scale development and reliability studies of the items and the scale scores.
Delusions and hallucinations are often part of the symptomatology in patients with affective disorders. The frequency of these symptoms in an outpatient population has been documented in a recent article by Guze et al.1 They found that primary bipolar (BP) patients reported delusions and hallucinations in 53% of cases and primary unipolar (UP) patients in only 17% of the cases. These data suggest that there might be differentiating clinical symptoms that could distinguish BP depressed from UP patients.An earlier attempt was made to separate UP from BP depressed patients by Beigel and Murphy2 on the basis of symptom complex. They found in this inpatient group matched for age, sex, and level of depression that there was no statistical difference (p > .05) in the psychotic symptoms between UP () and BP () depressed patients. Though these did not reach statistical significance, the trend was the opposite of that reported by Guze.This contradiction could be explained by the rather apparent differences between these studies. Guze did not distinguish in his paper whether he was working with BP manic phase, BP depressed phase, or both. One would assume both. Beigel rated his BP patients specifically during the depressed phase of illness for at least two weeks.It has been noted that bipolar illness is characterized by a greater family history of affective disorder than unipolar illness; therefore, it may be considered more “genetic” or biological.3 This finding makes it worthwhile to compare bipolar and unipolar depressions on the variable of organic (sensorium) symptoms as well as on psychotic symptoms.
The prevalence of hallucinations and delusions was studied in 1,715 patients with unipolar or bipolar affective disorders hospitalized at a tertiary care facility. The authors found that the presence of psychotic features was significantly associated with diagnostic subtype. Bipolar manics were more likely than primary depressives, secondary depressives, and bipolar depressives to have hallucinations and/or delusions; primary depressives were significantly more likely than secondary depressives to have psychotic features. Among psychotic patients, bipolar manics were more likely than the other diagnostic groups to have delusions only and less likely to have hallucinations only. Possible explanations for these findings are discussed.
Data on prior course, characteristics of index episode, and familial aggregation of patients with bipolar II disorder is discussed. The data supports the separation of this condition from both bipolar I and recurrent unipolar disorder.
To quantify the contribution of genetic factors in the pathogenesis of delusional depression, the incidence of major depression in the first degree relatives of 77 delusional, 76 nondelusional depressive patients, and 153 age- and sex-matched controls was calculated in a case-control study. The morbid risk for psychiatric disorders, including major depression and bipolar I disorder, did not distinguish the two proband groups. The segregation analysis showed that the model of multifactorial inheritance fits best to our results. Heritability was estimated on the basis of a threshold model for multifactorial inheritance, and a high contribution of genetic factors for both subgroups was found.
Longitudinal data sets are comprised of repeated observations of an outcome and a set of covariates for each of many subjects. One objective of statistical analysis is to describe the marginal expectation of the outcome variable as a function of the covariates while accounting for the correlation among the repeated observations for a given subject. This paper proposes a unifying approach to such analysis for a variety of discrete and continuous outcomes. A class of generalized estimating equations (GEEs) for the regression parameters is proposed. The equations are extensions of those used in quasi-likelihood (Wedderburn, 1974, Biometrika 61, 439-447) methods. The GEEs have solutions which are consistent and asymptotically Gaussian even when the time dependence is misspecified as we often expect. A consistent variance estimate is presented. We illustrate the use of the GEE approach with longitudinal data from a study of the effect of mothers' stress on children's morbidity.
Family psychiatric history was compared in the 472 first-degree relatives of 31 delusional and 35 nondelusional inpatients who met DSM III criteria for major depression with melancholia. Morbid risks for psychiatric illness or for psychiatric treatment variables did not differ between the two groups. Specifically, rates of affective and psychotic illnesses in families did not distinguish delusional from nondelusional probands. The findings do not support the hypothesis of a genetic relationship of nonaffective psychosis to delusional depression.
In a family study of major depression, the prevalence of bipolar illness was nearly six times as high among the relatives of delusionally depressed probands as among the relatives of nondelusionally depressed probands or of controls.
Subjects who meet the criteria for an affective syndrome possibly are aetiologically heterogeneous. An approach to this possibility involves examining affectively ill subjects obtained by different methods of ascertainment. This study compares depressed and manic subjects who are related to affectively ill probands with affectively ill subjects who were obtained from a study of a control population, and, therefore, were less likely to be familial. The subjects were identified in a large collaborative study of depression where both family members as well as controls were personally interviewed and followed up for 6 years after admission to the study. Data were obtained on subtypes of affective disorder using the Research Diagnostic Criteria and information was gathered about psychiatric hospitalizations, suicide attempts, alcoholism and psychological functioning prior to admission. Similar assessments were made for the comparison groups for the 6 year period between intake and follow-up. Relatives of bipolar I/schizoaffective manic probands were more likely to show mania than affectively ill controls or relatives of unipolar/schizoaffective depressed probands. Affectively ill controls were less likely to be hospitalized and less likely to suffer from an incapacitating depression. They were also likely to have functioned in a more healthy fashion than the affectively ill relatives of the bipolars and unipolars, in the 5 years before admission to the study. In the 6 year follow-up, both the subjects themselves and raters assessed the depressed controls as functioning better than the affectively ill relatives of the probands. Further, assessment of global adjustment during the 6 year period was worse for the relatives of affectively ill probands than for the depressed controls. Length of major depression was longer in relatives of bipolar and unipolar probands than in controls. Though all of the subjects in this study met research criteria for an affective illness, there were marked differences in the qualitative aspects of these illnesses with the relatives of affectively ill probands, who functioned less well and had longer and more severe episodes and more hospitalizations.
Most efforts to describe the prognostic significance of psychotic features in depression have been limited to single assessments 1 year or less after the initial evaluation. However, the various biological and treatment response differences between patients with psychotic and nonpsychotic depression suggest that prognostic differences may be very long-term.
The 787 patients described here entered the study as they sought treatment at one of five academic medical centers; they had either RDC major depressive disorder or schizo-affective depression (other than the mainly schizophrenic subtype) and completed at least 6 months of follow-up. Of these, 144 (18.3%) had psychotic depression as defined here. Patients provided follow-up interviews at 6-month intervals for 5 years and annually thereafter; 98 of those with psychotic depression and 434 of those with non-psychotic depression were followed for 10 years.
Those who began follow-up with psychotic depression had fewer weeks with minimal symptoms in each of the 10 years of follow-up and reported more psychosocial impairment at both 5 and 10 years. Both the index episode and the first recurrence of psychotic depression lasted longer than nonpsychotic episodes, but nonpsychotic episodes among previously psychotic individuals were relatively brief. Intervals between episodes were significantly shorter for patients who had ever been psychotic.
Together with evidence that psychotic features are highly recurrent, these data show 1) that psychotic features denote a lifetime illness of greater severity and 2) that within individuals, psychotic features may emerge in only the more severe episodes.
The present study evaluated clinical and demographic features of subjects with delusional versus nondelusional major depressive disorder. Two hundred eighty-eight subjects with mood disorder (bipolar disorder, n = 94; major depressive disorder, n = 194) were included in the study. No differences were observed for gender, polarity of mood disorder, age of onset, duration of index episode, number of episodes, number of previous hospital admissions, frequency of illness episodes, and number of suicide attempts. On the other hand, delusional subjects showed a higher rate of cluster A personality disorder and a lower level of education. We also detected a larger number of cluster B personality disorders among nondelusionals. Our data suggest that subjects with delusional mood disorder do not differ substantially from nondelusionals in terms of the clinical and demographic variables considered in this study except for personality disorders.
To examine if melancholic depression is over-represented in those with 'bipolar depression' and, if confirmed, to use that phenomenon to assist the clinical definition of melancholia.
We contrast 83 bipolar and 904 unipolar depressed patients on three melancholic sub-typing systems (DSM, Clinical and CORE system) and compare representation of their clinical depressive features.
By all three melancholic sub-typing systems, the bipolar patients were more likely to receive diagnoses of 'melancholia' and of psychotic depression. To the extent that this differential prevalence of depressive sub-types was reflected in varying patterns of clinical features, we so indirectly identified a set of items defining 'melancholia'. By such a strategy, melancholia was most clearly distinguished by behaviourally-rated psychomotor disturbance. While a number of 'endogeneity symptoms' were significantly over-represented, logistic regression analyses refined the set to psychomotor disturbance (both as a symptom and as a sign) and pathological guilt. We also established a distinctly higher prevalence of bipolar depression in those where a refined diagnosis of melancholia was made.
Bipolar depression appears to be more likely to be 'melancholic' in type, thus providing an indirect strategy for the clinical definition of melancholia.
Despite a resurgence of interest in the treatment of bipolar depression, there have been few controlled studies of the clinical characteristics of this condition. Identification of any distinctive clinical "signatures" of bipolar depression would be helpful in determining treatment options in the clinical setting.
From a cohort of 270 inpatients and outpatients assessed in detail during a DSM-IV major depressive episode, 39 bipolar I disorder patients were identified and closely matched with 39 major depressive disorder patients for gender, age, and the presence or absence of DSM-IV melancholic subtype. Patients were compared on a broad range of parameters including the Hamilton Rating Scale for Depression (depression severity), 54 depressive symptoms, the Newcastle Endogenous Depression Diagnostic Index, 3 family history items, 2 physical health items, the CORE scale (psychomotor disturbance), and 5 history items.
Although the bipolar patients were no more severely depressed than the major depressive disorder controls, they were more likely to demonstrate psychomotor-retarded melancholic and atypical depressive features and to have had previous episodes of psychotic depression. These findings were largely duplicated even when the population was confined to those with DSM-IV melancholia.
The clinical admixture of psychomotor-retarded melancholic signs and symptoms, "atypical" features, and (less frequently) psychosis may provide a "bipolar signature" in clinical scenarios when there is uncertainty concerning the polarity of a depressive presentation.
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.
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.
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.
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.
Although the diagnostic reliability of major depression and mania has been well established, that of hypomania and bipolar II (BPII) disorder has not. This remains an important issue for clinicians, especially for those undertaking genetic studies of BP disorder since bipolar I (BPI) and BPII disorders often cluster in the same families. We have assessed our diagnostic reliability of BP disorders, recurrent unipolar disorder, and their constituent episodes (major depression, mania, and hypomania) using interview and best-estimate diagnostic procedures used in a genetic study of families with BPI disorder.
Reliability was assessed for (1) co-rated Schedule for Affective Disorders and Schizophrenia-Lifetime version interviews of 37 subjects including 15 with BP disorders; (2) test-retest Schedule for Affective Disorders and Schizophrenia-Lifetime version interviews of 26 subjects including 13 with BP disorders; and (3) best-estimate diagnoses made by 2 noninterviewing psychiatrists on 524 subjects in a genetic linkage study of BPI disorder. Diagnoses were based on Research Diagnostic Criteria for a Selected Group of Functional Disorders, except that recurrent major depression as well as hypomania was required for a diagnosis of BPII disorder.
On co-rated interviews, we observed complete agreement between interviewers for diagnosing major depressive, manic, and hypomanic episodes. For test-retest interviews, the Cohen kappa coefficients were 0.83 for manic, 0.72 for hypomanic, and 1.0 for major depressive episodes. At the best-estimate level, the Cohen kappa coefficients were 0.99 for BPI, 0.99 for BPII, and 0.98 for recurrent unipolar disorder.
Good interrater reliability for BPII can be achieved when the interviews and best-estimate diagnoses are done by experienced psychiatrists.
This is an initial report on a six-site collaborative project, Genetics of Recurrent Early-Onset Depression (GenRED). This is a study of a large sample of families with recurrent major depressive disorder (DSM-IV) beginning by the age 30 in probands or 40 in relatives. Evidence suggests that early onset and recurrence of depressive episodes predict substantially increased risk of depression in first-degree relatives compared with the general population, suggesting that susceptibility genes might be mapped with this phenotype. The projected sample of 800-1,000 affected sibling pairs (ASPs) and other relatives will be studied using genome scan methods. Biological materials and blinded clinical data will be made available through the NIMH cell repository program. The sample should have good-to-excellent power to detect a locus associated with a 24% or greater population-wide increase in risk to siblings. We describe 838 affected individuals from the first 305 families containing 434 independent ASPs, or 613 ASPs counting all possible pairs. The mean age at the onset was 18.5 years, with a mean of 7.3 episodes and longest episode of 655 days. Almost all subjects had experienced at least 4 weeks of depression with five or more additional symptom criteria. Frequencies of symptoms and psychiatric and medical comorbid are provided. Substance use was more common in males, and panic disorder in females. Within pairs of affected siblings, correlations were significant for age at onset, substance abuse/dependence, panic disorder, obsessive-compulsive disorder and nicotine initiation and persistence. We replicated previously reported associations among comorbid panic disorder and social phobia, chronicity of depression and suicidal behavior. This suggests comparability of our cases to those in earlier large family studies. This dataset should prove useful for genetic studies of a highly familial form of major depressive disorder.
To present the results of a systematic review of literature published between January 1, 1980, and December 31, 2000, that reports findings on the prevalence and incidence of mood disorders in both general population and primary care settings.
We conducted a literature search of epidemiologic studies of mood disorders, using Medline and HealthSTAR databases and canvassing English-language publications. Eligible publications were restricted to studies that examined subjects aged at least 15 years and over. We used a set of predetermined inclusion and exclusion criteria to identify relevant studies. We extracted and analyzed prevalence and incidence data for heterogeneity.
Of general population studies, a total of 18 prevalence and 5 incidence studies met eligibility criteria. We found heterogeneity across 1-year and lifetime prevalence of major depressive disorder (MDD), dysthymic disorder and bipolar I disorder. The corresponding pooled rates for 1-year prevalence were 4.1 per 100, 2.0 per 100, and 0.72 per 100, respectively. For lifetime prevalence, the corresponding pooled rates were 6.7 per 100, 3.6 per 100, and 0. per 100, respectively. Significant variation was observed among 1-year incidence rates of MDD, with a correspond ing pooled rate of 2.9 per 100.
The prevalence of mood disorders reported in high-quality studies is generally lower than rates commonly reported in the general psychiatric literature. When controlled for common methodological confounds, variation in prevalence rates persists across studies and deserves continued study. Methodological variation among studies that have examined the prevalence of depression in primary health care services is so large that comparative analyses cannot be achieved.
Significant proportion of patients treated for depression may have various types of bipolar mood disorders. The aim of the study was to assess the frequency of bipolar disorders among outpatients having at least one major depressive episode, treated by 96 psychiatrists, representing all regions of Poland.
The study included 880 patients (237 male, 643 female), identified to following diagnostic categories: bipolar I, bipolar II, bipolar spectrum disorder and major depressive disorder.
Bipolar mood disorders were found in 61.2% of patients studied, bipolar I more frequent in men and bipolar II in women, and bipolar spectrum in 12% of patients. Patients with age ranges 19-49 and 50-65 years did not differ as to the percentage of diagnostic categories. Patients with bipolar mood disorders compared to major depressive disorder had significantly more frequent family history of bipolar disorder, premorbid hyper- or cyclothymic personality, early onset of depression, symptoms of hypersomnia and hyperphagia, psychotic depression, post-partum depression, and treatment-resistant depression. Bipolar spectrum patients had most clinical features similar to classic types of bipolar disorders.
Neither structured interview for family history, nor formal criteria for a number of clinical manifestations were used. The population treated by psychiatrists may not be representative and present a subgroup with more severe mood disorders.
Bipolar mood disorders may be very prevalent among depressive outpatients treated by psychiatrists in Poland, which is confirmed by the results of recent studies. Bipolar patients (including bipolar spectrum) significantly differ from major depressive disorder as to numerous clinical features related mostly to depressive episode.
As there is very little research on the topic, we compared the frequency and the type hallucinations among hospitalized patients diagnosed with bipolar disorder (BPD) versus other major psychiatric illnesses.
At admission, all patients hospitalized at the Department of Psychiatry at the Freie Universität Berlin (1981-2001) underwent comprehensive assessments using the standardized Association for Methodology and Documentation in Psychiatry (AMDP) system. We used these data to compare risks and types of hallucinations and associated factors by bivariate and multivariate testing in patients diagnosed with BPD, major depression, or schizophrenia.
At admission, the cross-sectional prevalence of current hallucinations among 4972 hospitalized subjects ranked: schizophrenia (61.1%), bipolar mixed (22.9%), bipolar manic (11.2%), bipolar depressed (10.5%), unipolar depressed (5.9%). The most frequent hallucinations across all patients were auditory, followed by somatic and visual hallucinations. There were only minor age or sex differences in risk of hallucinations. Compared with patients diagnosed with schizophrenia, hallucinations among patients with BPD were less severe, more visual and less often auditory. Characteristics of hallucinations were similar among manic and both bipolar- and unipolar-depressed subjects. Among patients with major affective disorders, those with hallucinations were less well-educated, had higher anxiety scores, less insight into the illness, and their hospitalizations averaged 17% longer. Across all diagnoses, hallucinations, particularly olfactory, were significantly associated with delusions. Hallucinations in BPD were most often accompanied by persecutory delusions; delusions of grandeur were least associated with hallucinations.
This study provides detailed descriptive data regarding the frequency (cross-sectional) and characteristics of hallucinations in a large sample of patients with BPD, major depression or schizophrenia. Our results suggest a link of lower education and the presence of hallucinations in major affective disorders. The significance of this finding, as well as the role of anxiety in hallucinating patients, requires further study.
Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: a preliminary report
- Initiative Nimh
- Bipolar
- Group
NIMH Genetics Initiative Bipolar Group. Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: a preliminary report. Am J Med Genet 1997; 74: 227–237.
Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: a preliminary report
- NIMH Genetics Initiative Bipolar Group