Does psychomotor agitation in major depressive episodes indicate bipolarity? : EEvidence from the Zurich Study

Psychiatric Hospital, Zurich University, Lenggstrasse 31, P.O. Box 1931, 8032 Zurich, Switzerland.
European Archives of Psychiatry and Clinical Neuroscience (Impact Factor: 3.53). 10/2008; 259(1):55-63. DOI: 10.1007/s00406-008-0834-7
Source: PubMed


Kraepelin's partial interpretation of agitated depression as a mixed state of "manic-depressive insanity" (including the current concept of bipolar disorder) has recently been the focus of much research. This paper tested whether, how, and to what extent both psychomotor symptoms, agitation and retardation in depression are related to bipolarity and anxiety.
The prospective Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults (N = 591) (aged 20 at first interview) by six interviews over 20 years (1979-1999). Psychomotor symptoms of agitation and retardation were assessed by professional interviewers from age 22 to 40 (five interviews) on the basis of the observed and reported behaviour within the interview section on depression. Psychiatric diagnoses were strictly operationalised and, in the case of bipolar-II disorder, were broader than proposed by DSM-IV-TR and ICD-10. As indicators of bipolarity, the association with bipolar disorder, a family history of mania/hypomania/cyclothymia, together with hypomanic and cyclothymic temperament as assessed by the general behavior inventory (GBI) [15], and mood lability (an element of cyclothymic temperament) were used.
Agitated and retarded depressive states were equally associated with the indicators of bipolarity and with anxiety. Longitudinally, agitation and retardation were significantly associated with each other (OR = 1.8, 95% CI = 1.0-3.2), and this combined group of major depressives showed stronger associations with bipolarity, with both hypomanic/cyclothymic and depressive temperamental traits, and with anxiety. Among agitated, non-retarded depressives, unipolar mood disorder was even twice as common as bipolar mood disorder.
Combined agitated and retarded major depressive states are more often bipolar than unipolar, but, in general, agitated depression (with or without retardation) is not more frequently bipolar than retarded depression (with or without agitation), and pure agitated depression is even much less frequently bipolar than unipolar. The findings do not support the hypothesis that agitated depressive syndromes are mixed states.
The results are limited to a population up to the age of 40; bipolar-I disorders could not be analysed (small N).

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Available from: Alex Gamma, Sep 10, 2014
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    • "Those differences may have influenced the results. Particularly, the authors of the Zurich Study discussed that their findings were negative because a population was limited up to age of 40 (Angst et al., 2009). In earlier findings, it was reported that mood-switching in MDD patients during pharmacotherapy may have emerged later in life (Akiskal et al., 2003). "
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    ABSTRACT: Background The relationship between psychomotor agitation in unipolar depression and mood-switching from depression to manic, hypomanic and mixed states has been controversial. We investigated the future risk of initial mood-switching as a function of psychomotor agitation in unipolar depression. Methods We identified 189 participants diagnosed with major depressive disorder (MDD). We divided all patients with MDD into two categories (1) agitated patients (n=74), and (2) non-agitated patients (n=115). These groups were prospectively followed and compared by time to mood-switching. Kaplan–Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazard ratio estimates for a multivariate model were conducted to examine the risk of mood-switching by psychomotor agitation. Results During follow-up, mood-switching occurred in 20.3% of the agitated patients and 7.0% of the non-agitated patients. In the Kaplan–Meier survival estimates for time to incidence of mood-switching with agitated or non-agitated patients, the cumulative probability of developing mood-switching for agitated patients was higher than those for non-agitated patients (log-rank test: χ2=7.148, df=1, p=0.008). Survival analysis was also performed using Cox proportional hazards regression within a multivariate model. The agitation remained significantly associated with incidence of mood-switching (HR=2.98, 95% CI: 1.18–7.51). Limitations We did not make a clear distinction between antidepressant-induced mood-switching and spontaneous switching. Conclusions The main finding demonstrated that MDD patients with agitation were nearly threefold as likely to experience mood-switching, suggesting that psychomotor agitation in MDD may be related to an indicator of bipolarity.
    Full-text · Article · Jan 2015 · Journal of Affective Disorders
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    • "In other words, these symptoms may be the clinical 'signature' of mixed states. Amongst these, psychomotor agitation and distractibility are of particular interest because both have been identified as putative drivers in mixed episodes (Benazzi, 2003) and are associated with poorer treatment outcomes (Angst et al., 2009). "
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    ABSTRACT: Background DSM׳s replacement of ‘mixed episodes’ with ‘mixed features’ has ironically created a specifier, which potentially lacks specificity because it overlooks two key symptoms: psychomotor agitation and distractibility. Therefore, the present study examined the presence of psychomotor agitation and distractibility across the mood disorder spectrum. Methods Two hundred patients were diagnosed and assigned to one of three groups (depression, bipolar spectrum disorder (BDspectrum) and bipolar disorder) based on clinical evaluation by a psychiatrist. On the basis of MDQ scores, the depression group was then further subdivided into two groups: unipolar depression (UP) and mixed depression (UPmix). These four groups were then compared to examine the relative distribution of psychomotor agitation and distractibility. Participants underwent a clinical evaluation by a psychiatrist and completed a series of questionnaires. Results Increased distraction, racing thoughts, and increased irritability were the most commonly reported manic symptoms amongst the unipolar depression group. Further, UPmix and BDspectrum had significantly higher psychomotor agitation and distractibility than the other two groups. Limitations The present study depended on self-report measures and did not include standardised measures of distractibility and psychomotor agitation. Future research needs to examine pure unipolar patients without any manic symptoms to clarify further how different this group would be from those with mixed features. Conclusions The present findings suggest that distractibility and psychomotor agitation may represent the core of mixed states, as they are more common in patients with mixed depression and bipolar spectrum disorder than patients diagnosed with unipolar depression and bipolar I disorder. Future research and clinical implications are discussed.
    Preview · Article · Apr 2014 · Journal of Affective Disorders
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    • "This interest has been stimulated by the observation that clinicians often initially underdiagnose bipolarity in patients in favour of a diagnosis of depression [8] [12] [19] [21]. Some studies have focused on agitated depression within mixed mood episodes [1] [5]. Among the different symptom dimensions that have been described in psychosis, the manic dimension appears to be the best discriminator between schizophrenia and affective psychosis [6]. "
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    ABSTRACT: To examine the predictive diagnostic value of affective symptomatology in a first-episode psychosis (FEP) sample with 5years' follow-up. Affective dimensions (depressive, manic, activation, dysphoric) were measured at baseline and 5years in 112 FEP patients based on a factor structure analysis using the Young Mania Rating Scale and Hamilton Depression Rating Scale. Patients were classified as having a diagnosis of bipolar disorder at baseline (BDi), bipolar disorder at 5years (BDf), or "other psychosis". The ability of affective dimensions to discriminate between these diagnostic groups and to predict a bipolar disorder diagnosis was analysed. Manic dimension score was higher in BDi vs. BDf, and both groups had higher manic and activation scores vs. "other psychosis". Activation dimension predicted a bipolar diagnosis at 5years (odds ratio=1.383; 95% confidence interval, 1.205-1.587; P=0.000), and showed high levels of sensitivity (86.2%), specificity (71.7%), positive (57.8%) and negative predictive value (90.5%). Absence of the manic dimension and presence of the depressive dimension were both significant predictors of an early misdiagnosis. The activation dimension is a diagnostic predictor for bipolar disorder in FEP. The manic dimension contributes to a bipolar diagnosis and its absence can lead to early misdiagnosis.
    Full-text · Article · Sep 2013 · European Psychiatry
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