Characteristics, symptomatology and naturalistic treatment in individuals at-risk for bipolar disorders: Baseline results in the first 180 help-seeking individuals assessed at the dresden high-risk project

doi:10.1016/j.jad.2013.10.009

Journal of Affective Disorders

Volumes 152–154, January 2014, Pages 427-433

https://doi.org/10.1016/j.jad.2013.10.009 Get rights and content

Abstract

Background

Considering results from the early recognition and intervention in psychosis, identification and treatment of individuals with at-risk states for the development of bipolar disorders (BD) could improve the course and severity of illness and prevent long-term consequences. Different approaches to define risk factors and groups have recently been published, data on treatment options are still missing.

Methods

Help-seeking persons at the early recognition center in Dresden, Germany, were assessed with a standardized diagnostic procedure including following risk factors for BD: familial risk, increasing mood swings, subsyndromal (hypo)manic symptoms, specific sleep and circadian rhythm disturbances, anxiety/fearfulness, affective disorder, decreased psychosocial functioning, increasing periodic substance use, and attention-deficit/hyperactivity disorder. Based on symptomatology and current and/or life-time psychiatric diagnosis, subjects with an at-risk state were offered individual treatment options.

Results

Out of 180 referred and screened persons, 29 (16%) met criteria for at-risk state for BD. Altogether, 27 (93%) at-risk individuals fulfilled criteria for a current and/or life-time mental illness other than BD; 14 (48%) had received pharmacological and/or psychotherapeutic treatment in the past. Treatments recommended included psychoeducation (100%), psychotherapy alone (62%), pharmacotherapy alone (17%), and psychotherapy+pharmacotherapy (14%).

Conclusions

To identify at-risk states for BD, a multifactorial approach including all known risk markers should be used. As most at-risk patients meet criteria for other mental disorders, the short- and long-term impact of different treatment strategies on symptomatic, functional and diagnostic outcomes requires detailed investigation.

Limitations

Small sample size of at-risk individuals, lack of sufficient prospective data and control groups.

Section snippets

Background

Considering the success of early recognition and intervention programs focusing on prodromal syndromes for psychosis (Correll et al., 2010, Fusar-Poli et al., 2013, McGorry et al., 1996, McGorry et al., 2009, Schultze-Lutter et al., 2008), related, yet different approaches were developed recently to identify prodromal states of bipolar disorders (BD) (Bechdolf et al., 2010, Brietzke et al., 2012b, Conus et al., 2008, Correll et al., 2007b, Leopold et al., 2012).

The diagnosis of bipolar I or II

Methods

The early recognition center at the university hospital in Dresden, Germany, was established for help-seeking young people from the age of 12 until 40 years. Individuals can also be referred to the center by psychologists, psychiatrists or primary care physicians in case of suspected development of BD or psychosis. After a first contact, subjects are assessed by clinical psychologists and psychiatrists with a standardized diagnostic battery, including psychiatric and medical history,

Results

Between May 2009 and June 2012, 284 young individuals had at least one contact with the early recognition center. 180 (63%) individuals (mean age=25.2±6.7 years, 50% female) underwent diagnostic procedures because of undiagnosed but suspected, manifest and/or prodromal psychiatric disorder(s). Out of these 180 individuals, 29 (16%) met criteria for a bipolar at-risk state and completed the entire battery of the complex diagnostic procedures. Except for a significantly younger age in at-risk

Discussion

Major findings of the presented data are that (1) of the young, help-seeking individuals screened at the early recognition center, 16% met criteria for bipolar at-risk state; (2) 93% of those subjects fulfilled criteria for a current and/or life-time diagnosis of a DSM-IV psychiatric disorder other than bipolar disorder; and (3) only 48% had received any kind of treatment before contacting the early recognition center. In all of those cases, treatment decisions were made without

Limitations

The results of the presented analysis have to be interpreted within its limitations. These include the small sample size of BD at-risk individuals, lack of sufficient prospective data to test the sensitivity and specificity of individual risk markers and constellations, and lack of control groups. However, the summarized data provide a basis for further investigation in the nascent area of early identification and prevention of BD before the first full (hypo)manic episode.

Role of funding source

No funding.

Conflict of interest

C.U. Correll has been a consultant and/or advisor to or has received honoraria from: Actelion, Alexza; Bristol-Myers Squibb, Cephalon, Eli Lilly, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, Medavante, Medscape, Merck, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Takeda, Teva, and Vanda. He has received grant support from BMS, Janssen/J&J, and Otsuka.

M. Bauer has received grant/research support from The Stanley Medical Research Institute, NARSAD, Deutsche

Acknowledgment

None.

References (66)

A. Bechdolf et al.
A preliminary evaluation of the validity of at-risk criteria for bipolar disorders in help-seeking adolescents and young adults
J. Affect. Disord.
(2010)
E. Brietzke et al.
A theoretical framework informing research about the role of stress in the pathophysiology of bipolar disorder
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2012)
E. Brietzke et al.
Towards a multifactorial approach for prediction of bipolar disorder in at risk populations
J. Affect. Disord.
(2012)
A. Duffy et al.
Early stages in the development of bipolar disorder
J. Affect. Disord.
(2010)
J.A. Egeland et al.
Prodromal symptoms before onset of manic-depressive disorder suggested by first hospital admission histories
J. Am. Acad. Child Adolesc. Psychiatry
(2000)
E.L. Fergus et al.
Is there progression from irritability/dyscontrol to major depressive and manic symptoms? A retrospective community survey of parents of bipolar children
J. Affect. Disord.
(2003)
P. Fusar-Poli et al.
Can antidepressants prevent psychosis?
Lancet
(2007)
B. Geller et al.
Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency
J. Am. Acad. Child Adolesc. Psychiatry
(1998)
B.I. Goldstein et al.
Prevalence and correlates of bipolar I disorder among adults with primary youth[hyphen (true graphic)]onset anxiety disorders
J. Affect. Disord.
(2007)
K. Leopold et al.
Risk constellations prior to the development of bipolar disorders: rationale of a new risk assessment tool
J. Affect. Disord.
(2012)

J.D. Lish et al.

The National Depressive and Manic-Depressive Association (Dmda) Survey of Bipolar Members

J. Affect. Disord.

(1994)

D.J. Miklowitz et al.

Early intervention for symptomatic youth at risk for bipolar disorder: a randomized trial of family-focused therapy

J. Am. Acad. Child Adolesc. Psychiatry

(2013)

C. O’Donovan et al.

Antidepressant monotherapy in pre-bipolar depression; predictive value and inherent risk

J. Affect. Disord.

(2008)

K.J. Oedegaard et al.

A study of age at onset and affective temperaments in a Norwegian sample of patients with mood disorders

J. Affect. Disord.

(2009)

R.H. Perlis et al.

Long-term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD)

Biol. Psychiatry

(2004)

R.M. Post

Kindling and sensitization as models for affective episode recurrence, cyclicity, and tolerance phenomena

Neurosci. Biobehav. Rev.

(2007)

R.M. Post et al.

Neurobiological correlates of illness progression in the recurrent affective disorders

J. Psychiatr. Res.

(2012)

D.V. Skjelstad et al.

Symptoms and signs of the initial prodrome of bipolar disorder: a systematic review

J. Affect. Disord.

(2010)

T. Svirskis et al.

Axis-I disorders and vulnerability to psychosis

Schizophr. Res.

(2005)

H.S. Akiskal et al.

Switching from unipolar to bipolar-Ii – an 11-year prospective-study of clinical and temperamental predictors in 559 patients

Arch. Gen. Psychiatry

(1995)

C. Baethge et al.

Sequencing of substance use and affective morbidity in 166 first-episode bipolar I disorder patients

Bipolar Disord.

(2008)

A. Bechdolf et al.

Rationale and first results of developing at-risk (prodromal) criteria for bipolar disorder

Curr. Pharm. Des.

(2012)

S. Behrendt et al.

The role of mental disorders in the risk and speed of transition to alcohol use disorders among community youth

Psychol. Med.

(2011)

M. Berk et al.

Does stage of illness impact treatment response in bipolar disorder? Empirical treatment data and their implication for the staging model and early intervention

Bipolar Disord.

(2011)

D.J. Bond et al.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid attention-deficit/hyperactivity disorder

Ann. Clin. Psychiatry

(2012)

K.D. Chang et al.

Divalproex monotherapy in the treatment of bipolar offspring with mood and behavioral disorders and at least mild affective symptoms

J. Clin. Psychiatry

(2003)

Consoli, A., Deniau, E., Huynh, C., Purper, D., Cohen, D., 2007. Treatments in child and adolescent bipolar disorders....

P. Conus et al.

The proximal prodrome to first episode mania – a new target for early intervention

Bipolar Disord.

(2008)

B.A. Cornblatt et al.

Can antidepressants be used to treat the schizophrenia prodrome? Results of a prospective, naturalistic treatment study of adolescents

J. Clin. Psychiatry

(2007)

C.U. Correll et al.

Type and duration of subsyndromal symptoms in youth with bipolar-I disorder prior to their first mania episode

Bipolar Disord.

(2013)

C.U. Correll et al.

Differentiation in the preonset phases of schizophrenia and mood disorders: evidence in support of a bipolar mania prodrome

Schizophr. Bull.

(2007)

C.U. Correll et al.

Early identification and high-risk strategies for bipolar disorder

Bipolar Disord.

(2007)

C.U. Correll et al.

Research in people with psychosis risk syndrome: a review of the current evidence and future directions

J. Child Psychol. Psychiatry

(2010)

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These state, trait, and familial characteristics (Scott et al., 2017) can be monitored prospectively through a critical period of enhanced risk (Leopold et al., 2014), such as being in the age of onset range for BD onset. At-risk groups are heterogeneous and screening is complicated (Leopold et al., 2014) due to the variety of risk constellations, the episodic course of BD, the multiplicity of subthreshold symptoms, and the symptomatic overlap with other mental disorders in a vulnerable age group (Hauser and Correll, 2013). As several different symptoms might be present prior to BD, a cluster of features, including distal and more enduring symptoms, such as personality traits, and more proximal, recently emerging or worsening clinical symptoms, including depressive and manic/hypomanic symptomatology, might best capture the bipolar prodrome.
To assess the occurrence and frequency of bipolar at-risk symptoms in a large sample of previously undiagnosed students using the new screening tool Bochumer Screeningbogen Bipolar (BSB). 2329 students of the Ruhr-University Bochum, Germany completed online demographic data as well as various self-rating questionnaires (BSB; Hypomania Checklist 32; Altman Self-Rating Mania Scale; Beck Depression Inventory). Within the student cohort (64.4% female, mean age 24.3 years) every fifth student currently suffered from moderate to severe depressive symptoms; every sixth student had already thought about suicide and every other student reported a history of mood swings. The most frequently reported depressive symptoms included physical exhaustion, depressed mood, and tiredness. The most frequently reported (hypo)manic symptoms included physical agitation, feeling extremely energetic, and lack of concentration. The BSB showed good convergent validity with other established questionnaires capturing depressive or (hypo)manic symptoms, as well as a stable administration of underlying constructs. The BSB correlated significantly with the already established applied questionnaires. The predictive power of the BSB regarding the development of bipolar disorder cannot be correctly quantified at present. The further purpose of this exploratory web-based study should be to examine the validity of the presented measures in a longitudinal design.
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This is important because an early detection in BD may slow illness progression, alleviate medical burden and improve long-term functional outcome [100]. Current psychosocial prevention strategies involve targeting ultra-high risk groups such as healthy bipolar offspring (HBO), first degree relatives of BD patients, individuals exposed to early trauma in childhood, and adolescents with substance use disorders (SUDs) [101–103]. However, it is still not possible to identify individuals who will develop bipolar illness based solely on psychopathological traits or early phenomenology [98].
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The focus of this study was on clarifying the clinical features that precede the onset of BD, by examining, first, rates of clinical features in the AR group compared to controls, and second, clinical features that predicted later onset of affective disorders in the BD group. First, this study extends previous reports in demonstrating that young subjects at high genetic risk for BD were also at significantly increased risk for developing a broad range of psychopathology (Birmaher et al., 2009; Duffy et al., 2010, 2014; Hillegers et al., 2005; Leopold et al., 2014; Nurnberger et al., 2011; Vandeleur et al., 2012; Wals et al., 2001; Whalley et al., 2011). Specifically, we found that AR subjects were more likely to develop depressive, anxiety and behavioural disorders compared to controls.
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Research reportCharacteristics, symptomatology and naturalistic treatment in individuals at-risk for bipolar disorders: Baseline results in the first 180 help-seeking individuals assessed at the dresden high-risk project

Abstract

Background

Methods

Results

Conclusions

Limitations

Section snippets

Background

Methods

Results

Discussion

Limitations

Role of funding source

Conflict of interest

Acknowledgment

J. Affect. Disord.

Prog. Neuropsychopharmacol. Biol. Psychiatry

J. Affect. Disord.

J. Affect. Disord.

J. Am. Acad. Child Adolesc. Psychiatry

J. Affect. Disord.

Lancet

J. Am. Acad. Child Adolesc. Psychiatry

J. Affect. Disord.

J. Affect. Disord.

J. Affect. Disord.

J. Am. Acad. Child Adolesc. Psychiatry

J. Affect. Disord.

J. Affect. Disord.

Biol. Psychiatry

Neurosci. Biobehav. Rev.

J. Psychiatr. Res.

J. Affect. Disord.

Schizophr. Res.

Switching from unipolar to bipolar-Ii – an 11-year prospective-study of clinical and temperamental predictors in 559 patients

Arch. Gen. Psychiatry

Sequencing of substance use and affective morbidity in 166 first-episode bipolar I disorder patients

Bipolar Disord.

Rationale and first results of developing at-risk (prodromal) criteria for bipolar disorder

Curr. Pharm. Des.

The role of mental disorders in the risk and speed of transition to alcohol use disorders among community youth

Psychol. Med.

Does stage of illness impact treatment response in bipolar disorder? Empirical treatment data and their implication for the staging model and early intervention

Bipolar Disord.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid attention-deficit/hyperactivity disorder

Ann. Clin. Psychiatry

Divalproex monotherapy in the treatment of bipolar offspring with mood and behavioral disorders and at least mild affective symptoms

J. Clin. Psychiatry

The proximal prodrome to first episode mania – a new target for early intervention

Bipolar Disord.

Can antidepressants be used to treat the schizophrenia prodrome? Results of a prospective, naturalistic treatment study of adolescents

J. Clin. Psychiatry

Type and duration of subsyndromal symptoms in youth with bipolar-I disorder prior to their first mania episode

Bipolar Disord.

Differentiation in the preonset phases of schizophrenia and mood disorders: evidence in support of a bipolar mania prodrome

Schizophr. Bull.

Early identification and high-risk strategies for bipolar disorder

Bipolar Disord.

Research in people with psychosis risk syndrome: a review of the current evidence and future directions

J. Child Psychol. Psychiatry

Research report
Characteristics, symptomatology and naturalistic treatment in individuals at-risk for bipolar disorders: Baseline results in the first 180 help-seeking individuals assessed at the dresden high-risk project