Comorbid depressive and anxiety disorders in 509 individuals with an at-risk mental state: impact on psychopathology and transition to psychosis

Paolo Fusar-Poli, Barnaby Nelson, Lucia Valmaggia, Alison R Yung, Philip K McGuire, Paolo Fusar-Poli, Barnaby Nelson, Lucia Valmaggia, Alison R Yung, Philip K McGuire

Abstract

Background: The current diagnostic system for subjects at enhanced clinical risk of psychosis allows concurrent comorbid diagnoses of anxiety and depressive disorders. Their impact on the presenting high-risk psychopathology, functioning, and transition outcomes has not been widely researched.

Methods: In a large sample of subjects with an At-Risk Mental State (ARMS, n = 509), we estimated the prevalence of DSM/SCID anxiety or depressive disorders and their impact on psychopathology, functioning, and psychosis transition. A meta-analytical review of the literature complemented the analysis.

Results: About 73% of ARMS subjects had a comorbid axis I diagnosis in addition to the "at-risk" signs and symptoms. About 40% of ARMS subjects had a comorbid diagnosis of depressive disorder while anxiety disorders were less frequent (8%). The meta-analysis conducted in 1683 high-risk subjects confirmed that baseline prevalence of comorbid depressive and anxiety disorders is respectively 41% and 15%. At a psychopathological level, comorbid diagnoses of anxiety or depression were associated with higher suicidality or self-harm behaviors, disorganized/odd/stigmatizing behavior, and avolition/apathy. Comorbid anxiety and depressive diagnoses were also associated with impaired global functioning but had no effect on risk of transition to frank psychosis. Meta-regression analyses confirmed no effect of baseline anxiety and/or depressive comorbid diagnoses on transition to psychosis.

Conclusions: The ARMS patients are characterized by high prevalence of anxiety and depressive disorders in addition to their attenuated psychotic symptoms. These symptoms may reflect core emotional dysregulation processes and delusional mood in prodromal psychosis. Anxiety and depressive symptoms are likely to impact the ongoing psychopathology, the global functioning, and the overall longitudinal outcome of these patients.

Keywords: ARMS; anxiety; attenuated psychosis; depression; prodromal; psychosis; psychosis risk; schizophrenia; ultra high risk.

Figures

Fig. 1.
Fig. 1.
Meta-analysis of comorbid baseline anxiety and depressive diagnoses in subjects at high clinical risk for psychosis. Anxiety 15.3%, 95% CI 8.9%–25%; Depression 40.7%, 95% CI 32.5%–49.4%. Random-effect models applied.
Fig. 2.
Fig. 2.
Impact of comorbid depressive and/or anxiety disorders on the baseline GAF scores of individuals with an ARMS (Kruskall-Wallis test = 0.004, Jonckheere-Terpstra

Fig. 3.

Kaplan-Meier survival estimates of transition…

Fig. 3.

Kaplan-Meier survival estimates of transition risks stratified for ARMS subgroups ( n =…

Fig. 3.
Kaplan-Meier survival estimates of transition risks stratified for ARMS subgroups (n = 509) over follow-up (mean = 3.65 years). APS, Attenuated Psychosis Syndrome; BLIP, Brief Limited Intermittent Psychotic episode; GRD, Genetic Risk and Deterioration syndrome; Mixed, a mixture of the above subgroups.

Fig. 4.

Hypothesized proportion of each type…

Fig. 4.

Hypothesized proportion of each type of attenuated psychotic symptoms (psychotic-like experience, PLE) in…

Fig. 4.
Hypothesized proportion of each type of attenuated psychotic symptoms (psychotic-like experience, PLE) in different populations.
Fig. 3.
Fig. 3.
Kaplan-Meier survival estimates of transition risks stratified for ARMS subgroups (n = 509) over follow-up (mean = 3.65 years). APS, Attenuated Psychosis Syndrome; BLIP, Brief Limited Intermittent Psychotic episode; GRD, Genetic Risk and Deterioration syndrome; Mixed, a mixture of the above subgroups.
Fig. 4.
Fig. 4.
Hypothesized proportion of each type of attenuated psychotic symptoms (psychotic-like experience, PLE) in different populations.

References

    1. Fusar-Poli P, Borgwardt S, Bechdolf A, et al. The psychosis high risk state: a comprehensive state of the art review. Arch Gen Psychiatry. In press.
    1. Fusar-Poli P, Yung AR. Should attenuated psychosis syndrome be included in DSM-5? Lancet. 2012; 379: 591–592
    1. Fusar-Poli P, Bonoldi I, Yung AR, et al. Predicting psychosis: a meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry. 2012; 69: 1–10
    1. Fusar-Poli P, Bechdolf A, Taylor M, et al. At risk for schizophrenic or affective psychosis? A meta-analysis of DSM/ICD diagnostic outcomes in individuals at high clinical risk. [published online ahead of print May 15, 2012]. Schizophr Bull. 10.1093/schbul/sbs060
    1. Fusar-Poli P, Deste G, Smieskova R, et al. Cognitive functioning in prodromal psychosis: a meta-analysis. Arch Gen Psychiatry. 2012; 69: 1–10
    1. Fusar-Poli P, Howes OD, Allen P, et al. Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis. Mol Psychiatry. 2011; 16: 67–75
    1. Velthorst E, Nieman DH, Linszen D, et al. Disability in people clinically at high risk of psychosis. Br J Psychiatry. 2010; 197: 278–284
    1. Häfner H, Löffler W, Maurer K, Hambrecht M, an der Heiden W. Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia. Acta Psychiatr Scand. 1999; 100: 105–118
    1. Woods SW, Addington J, Cadenhead KS, et al. Validity of the prodromal risk syndrome for first psychosis: findings from the North American Prodrome Longitudinal Study. Schizophr Bull. 2009; 35: 894–908
    1. Salokangas RK, Ruhrmann S, von Reventlow HG, et al. Axis I diagnoses and transition to psychosis in clinical high-risk patients EPOS project: prospective follow-up of 245 clinical high-risk outpatients in four countries. Schizophr Res. 2012;138:192–197.;
    1. Wigman JT, van Nierop M, Vollebergh WA, et al. Evidence that psychotic symptoms are prevalent in disorders of anxiety and depression, impacting on illness onset, risk, and severity—implications for diagnosis and ultra-high risk research. Schizophr Bull. 2012; 38:247–257
    1. Cannon TD, Cadenhead K, Cornblatt B, et al. Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Arch Gen Psychiatry. 2008; 65: 28–37
    1. Fusar-Poli P, Byrne M, Badger S, McGuire PK, Valmaggia L. Outreach and Support in South London (OASIS), 2001–2011: ten years of early diagnosis and treatment for young individuals at clinical high risk for psychosis. Eur Psychiatry. 10.1016/j.eurpsy.2012.08.002.
    1. Yung AR, McGorry PD, Francey SM, et al. PACE: a specialised service for young people at risk of psychotic disorders. Med J Aust. 2007; 187: S43–S46
    1. Yung AR, Yuen HP, McGorry PD, et al. Mapping the onset of psychosis: the Comprehensive Assessment of At-Risk Mental States. Aust N Z J Psychiatry. 2005; 39: 964–971
    1. Hall RC. Global assessment of functioning. A modified scale. Psychosomatics. 1995; 36: 267–275
    1. Nelson B, Yuen K, Yung AR. Ultra high risk (UHR) for psychosis criteria: are there different levels of risk for transition to psychosis? Schizophr Res. 2011; 125: 62–68
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009; 339: b2535
    1. Borenstein MHL, Higgins J, Rothstein H. Comprehensive Meta-analysis Version 2. Englewood, NJ: Biostat; 2005.
    1. Nielssen O, Large M. Rates of homicide during the first episode of psychosis and after treatment: a systematic review and meta-analysis. Schizophr Bull. 2010; 36: 702–712
    1. Lipsey M, Wilson D. Practical Meta-analysis. Thousand Oaks, CA: Sage Publications; 2000;
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315: 629–634
    1. Wigman JT, van Nierop M, Vollebergh WA, et al. Evidence that psychotic symptoms are prevalent in disorders of anxiety and depression, impacting on illness onset, risk, and severity–implications for diagnosis and ultra-high risk research. Schizophr Bull. 2012; 38: 247–257
    1. Demjaha A, Valmaggia L, Stahl D, Byrne M, McGuire P. Disorganization/cognitive and negative symptom dimensions in the at-risk mental state predict subsequent transition to psychosis. Schizophr Bull. 2012;38:351–359;
    1. Seidman LJ, Giuliano AJ, Meyer EC, et al. North American Prodrome Longitudinal Study (NAPLS) Group Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Arch Gen Psychiatry. 2010; 67: 578–588
    1. Fusar-Poli P, Byrne M, Valmaggia L, et al. Social dysfunction preducts two years clinical outcomes in people at ultrahigh risk for psychosis. J Psychiatr Res. 2009; 44: 294–301
    1. Cornblatt B, Carrión R, Addington J, et al. Risk factors for psychosis: impaired social and role functioning. Schizophr Bull. 2012;38:1247–1257
    1. Ruhrmann S, Paruch J, Bechdolf A, et al. Reduced subjective quality of life in persons at risk for psychosis. Acta Psychiatr Scand. 2008; 117: 357–368
    1. Bechdolf A, Pukrop R, Köhn D, et al. Subjective quality of life in subjects at risk for a first episode of psychosis: a comparison with first episode schizophrenia patients and healthy controls. Schizophr Res. 2005; 79: 137–143
    1. Mishara AL. Klaus Conrad (1905–1961): delusional mood, psychosis, and beginning schizophrenia. Schizophr Bull. 2010; 36: 9–13
    1. van Os J, Linscott RJ. Introduction: The extended psychosis phenotype–relationship with schizophrenia and with ultrahigh risk status for psychosis. Schizophr Bull. 2012; 38: 227–230
    1. McGorry PD, Nelson B, Goldstone S, Yung AR. Clinical staging: a heuristic and practical strategy for new research and better health and social outcomes for psychotic and related mood disorders. Can J Psychiatry. 2010; 55: 486–497
    1. Tyrer P, Seivewright N, Ferguson B, Tyrer J. The general neurotic syndrome: a coaxial diagnosis of anxiety, depression and personality disorder. Acta Psychiatr Scand. 1992; 85: 201–206
    1. van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L. A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychol Med. 2009; 39: 179–195
    1. Perlis RH, Uher R, Ostacher M, et al. Association between bipolar spectrum features and treatment outcomes in outpatients with major depressive disorder. Arch Gen Psychiatry. 2011; 68: 351–360
    1. Maric N, Myin-Germeys I, Delespaul P, de Graaf R, Vollebergh W, Van Os J. Is our concept of schizophrenia influenced by Berkson’s bias? Soc Psychiatry Psychiatr Epidemiol. 2004; 39: 600–605
    1. Berkson J. Limitations of the application of fourfold table analysis to hospital data. Biometrics. 1946; 2: 47–53
    1. Fusar-Poli P, Van Os J. Lost in transition: setting the psychosis threshold in prodromal research [published online ahead of print November 9, 2012]. Acta Psychiatr Scand. 10.1111/acps.12028
    1. Yung AR, Nelson B, Thompson A, Wood SJ. The psychosis threshold in Ultra High Risk (prodromal) research: is it valid? Schizophr Res. 2010; 120: 1–6
    1. Addington J, Cornblatt BA, Cadenhead KS, et al. At clinical high risk for psychosis: outcome for nonconverters. Am J Psychiatry. 2011; 168: 800–805
    1. Yung AR, Nelson B, Baker K, Buckby JA, Baksheev G, Cosgrave EM. Psychotic-like experiences in a community sample of adolescents: implications for the continuum model of psychosis and prediction of schizophrenia. Aust N Z J Psychiatry. 2009; 43: 118–128
    1. Yung AR, Buckby JA, Cosgrave EM, et al. Association between psychotic experiences and depression in a clinical sample over 6 months. Schizophr Res. 2007; 91: 246–253
    1. Varghese D, Scott J, Welham J, et al. Psychotic-like experiences in major depression and anxiety disorders: a population-based survey in young adults. Schizophr Bull. 2011; 37: 389–393
    1. Werbeloff N, Drukker M, Dohrenwend BP, et al. Self-reported attenuated psychotic symptoms as forerunners of severe mental disorders later in life. Arch Gen Psychiatry. 2012;69:467–475;
    1. Morrison AP, French P, Stewart SL, et al. Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial. BMJ. 2012; 344: e2233
    1. Sacher J, Neumann J, Fünfstück T, Soliman A, Villringer A, Schroeter ML. Mapping the depressed brain: a meta-analysis of structural and functional alterations in major depressive disorder. J Affect Disord. 2012; 140: 142–148
    1. Radua J, van den Heuvel OA, Surguladze S, Mataix-Cols D. Meta-analytical comparison of voxel-based morphometry studies in obsessive-compulsive disorder vs other anxiety disorders. Arch Gen Psychiatry. 2010; 67: 701–711
    1. Fusar-Poli P, Borgwardt S, Crescini A, et al. Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis. Neurosci Biobehav Rev. 2011; 35: 1175–1185
    1. Fusar-Poli P, Radua J, McGuire P, Borgwardt S. Neuroanatomical maps of psychosis onset: voxel-wise meta-analysis of antipsychotic-naive VBM studies. Schizophr Bull. 2012;38:1297–1307
    1. Fusar-Poli P, Stone JM, Broome MR, et al. Thalamic glutamate levels as a predictor of cortical response during executive functioning in subjects at high risk for psychosis. Arch Gen Psychiatry. 2011; 68: 881–890

Source: PubMed

3
Suscribir