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Objectives: Bipolar disorder (BD) is a debilitating illness that often starts at an early age. Prevention of first and subsequent mood episodes, which are usually preceded by a period characterized by subthreshold symptoms is important. We compared demographic and clinical characteristics including severity and duration of subsyndromal symptoms across adolescents with three different bipolar-spectrum disorders. Methods: Syndromal and subsyndromal psychopathology were assessed in adolescent inpatients (age = 12-18 years) with a clinical mood disorder diagnosis. Assessments included the validated Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P). We compared phenomenology across patients with a research consensus conference-confirmed DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnoses of BD-I, BD-not otherwise specified (NOS), or mood disorder (MD) NOS. Results: Seventy-six adolescents (age = 15.6 ± 1.4 years, females = 59.2%) were included (BD-I = 24; BD-NOS = 29; MD-NOS = 23) in this study. Median baseline global assessment of functioning scale score was 21 (interquartile range = 17-40; between-group p  = 0.31). Comorbidity was frequent, and similar across groups, including disruptive behavior disorders (55.5%, p  = 0.27), anxiety disorders (40.8%, p  = 0.98), and personality disorder traits (25.0%, p  = 0.21). Mania symptoms (most frequent: irritability = 93.4%, p  = 0.82) and depressive symptoms (most frequent: depressed mood = 81.6%, p  = 0.14) were common in all three BD-spectrum groups. Manic and depressive symptoms were more severe in both BD-I and BD-NOS versus MD-NOS ( p  < 0.0001). Median duration of subthreshold manic symptoms was shorter in MD-NOS versus BD-NOS (11.7 vs. 20.4 weeks, p  = 0.002) and substantial in both groups. The most used psychotropics upon discharge were antipsychotics (65.8%; BD-I = 79.2%; BD-NOS = 62.1%; MD-NOS = 56.5%, p  = 0.227), followed by mood stabilizers (43.4%; BD-I = 66.7%; BD-NOS = 31.0%; MD-NOS = 34.8%, p  = 0.02) and antidepressants (19.7%; BD-I = 20.8%; BD-NOS = 10.3%; MD-NOS = 30.4%). Conclusions: Youth with BD-I, BD-NOS, and MD-NOS experience considerable symptomatology and are functionally impaired, with few differences observed in psychiatric comorbidity and clinical severity. Moreover, youth with BD-NOS and MD-NOS undergo a period with subthreshold manic symptoms, enabling identification and, possibly, preventive intervention of those at risk for developing BD or other affective episodes requiring hospitalization.

Objective: The aim of the present study was to investigate the psychometric properties of the Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P), the first specific interview for emerging bipolar disorder (BD) symptoms., Methods: A total of 205 youth aged 12-23 years and/or their caregivers underwent BPSS-P interviews: 129 patients with mood spectrum disorders [depression spectrum disorder (n = 77), mood disorder not otherwise specified (NOS) (n = 27), BD-NOS (n = 14), bipolar I disorder (BD-I)/bipolar II disorder (BD-II)/cyclothymia (n = 11), 34 with non-mood spectrum disorders, and 42 healthy controls (HCs)]. We used Cronbach's α to assess internal consistency; intra-class correlation (ICC) for inter-rater reliability; Spearman's rho for convergent validity with the Young Mania Rating Scale (YMRS), General Behavior Inventory-10-item Mania Form (GBI-M-10), and Cyclothymic-Hypersensitive Temperament (CHT) scale; and analysis of variance for discriminatory power between diagnostic groups., Results: Internal consistency was good to very good for the BPSS-P Mania (Cronbach's α = 0.87), Depression (Cronbach's α = 0.89), and General Symptom indices (Cronbach's α = 0.74). Inter-rater reliability was high for the BPSS-P Total score (ICC = 0.939), and BPSS-P Mania (ICC = 0.934), Depression (ICC = 0.985), and General (ICC = 0.981) indices. Convergent validity was large (ρ ≥ 0.50) between the BPSS-P Mania Index and YMRS, GBI-M-10, and CHT; BPSS-P Depression Index and Montgomery-Åsberg Depression Rating Scale (MADRS) and CHT; and BPSS-P General Index and GBI-M-10 and CHT. Expectedly, convergent validity was small (ρ = 0.10 to < 0.30) between the BPSS-P Mania Index and MADRS, and BPSS-P Depression Index and YMRS. Furthermore, the BPSS-P and its subscales discriminated each patient group from HCs and from non-mood spectrum patients (except for the BPSS-P General Index). Moreover, the BPSS-P Total score discriminated BD-I/BD-II/cyclothymia from depression spectrum patients, and the BPSS-Mania Index differentiated all three bipolar spectrum groups from depression spectrum patients., Conclusions: The BPSS-P has good to excellent psychometric properties. Its use across multiple settings and predictive validity requires further investigation., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The aim of the present study was to systematically evaluate the prodrome to mania in youth., Methods: New-onset/worsening symptoms/signs of ≥ moderate severity preceding first mania were systematically assessed in 52 youth (16.2 ± 2.8 years) with a research diagnosis of bipolar I disorder (BD-I). Youth and/or caregivers underwent semi-structured interviews, using the Bipolar Prodrome Symptom Scale-Retrospective., Results: The mania prodrome was reported to start gradually in most youth (88.5%), with either slow (59.6%) or rapid (28.8%) deterioration, while a rapid-onset-and-deterioration prodrome was rare (11.5%). The manic prodrome, conservatively defined as requiring ≥ 3 symptoms, lasted 10.3 ± 14.4 months [95% confidence interval (CI): 6.3-14.4], being present for ≥ 4 months in 65.4% of subjects. Among prodromal symptoms reported in ≥ 50% of youth, three were subthreshold manic in nature (irritability: 61.5%, racing thoughts: 59.6%, increased energy/activity: 50.0%), two were nonspecific (decreased school/work functioning: 65.4%, mood swings/lability: 57.7%), and one each was depressive (depressed mood: 53.8%) or subthreshold manic/depressive (inattention: 51.9%). A decreasing number of youth had ≥ 1 (84.6%), ≥ 2 (48.1%), or ≥ 3 (26.9%) 'specific' subthreshold mania symptoms (i.e., elation, grandiosity, decreased need for sleep, racing thoughts, or hypersexuality), lasting 9.5 ± 14.9 months (95% CI: 5.0-14.0), 3.5 ± 3.5 months (95% CI: 2.0-4.9), and 3.0 ± 3.2 months (95% CI: 1.0-5.0) for ≥ 1, ≥ 2, or ≥ 3 specific symptoms, respectively., Conclusions: In youth with BD-I, a relatively long, predominantly slow-onset mania prodrome appears to be common, including subthreshold manic and depressive psychopathology symptoms. This suggests that early clinical identification and intervention may be feasible in bipolar disorder. Identifying biological markers associated with clinical symptoms of impending mania may help to increase chances for early detection and prevention before full mania., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: There is an increased interest in early intervention strategies for severe mental disorders with hopes of mitigating the emergence and impact of the illness. Individuals at clinical high-risk (CHR) for schizophrenia have been primarily identified by the presence of attenuated positive symptoms. Although bipolar disorder and schizophrenia may have overlapping etiologies, few studies have investigated the potential prodrome in bipolar disorder. We sought to determine if there is a prodrome to bipolar disorder and if clinical or neurocognitive measures could distinguish between the bipolar and schizophrenia prodromes., Methods: We examined subjects who were initially identified as CHR for schizophrenia during the prodromal phase of the illness and followed them prospectively. Unexpectedly, eight subjects developed bipolar disorder. Baseline data from subjects who eventually developed bipolar disorder (pre-BP; N=8), schizophrenia or a psychotic disorder (pre-SZ; N=24) and a non-converter comparison group (NCC; N=115) were compared., Results: The pre-BP and pre-SZ groups did not differ on attenuated positive symptom severity, global measures of functioning or on the global neurocognitive score. Compared to NCC individuals, both pre-BP and pre-SZ patients reported more severe attenuated positive symptoms and were more likely to be on antipsychotic medication at baseline. The pre-SZ group had a significantly lower current IQ and was significantly more impaired than the NCC group on the overall neurocognitive score., Conclusions: This study provides preliminary support for a bipolar prodrome, which may be indistinguishable from the schizophrenia prodrome based on clinical and neurocognitive measures currently used in high-risk schizophrenia programs., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to examine predictors of diagnostic and symptomatic outcome in adolescents with either psychotic disorder not otherwise specified (PsyNOS) or brief psychotic disorder (BrPsy) followed in a schizophrenia prodromal program., Methods: As part of a naturalistic study of adolescents considered at clinical high risk for schizophrenia, 26 youths (mean age, 15.9 +/- 2.6 years, 65.4% male) with psychosis not fulfilling criteria for schizophrenia/schizoaffective disorder and diagnosed with PsyNOS or BrPsy were evaluated for predictors of diagnostic and symptomatic outcome after at least 6 (mean, 22.8 +/- 19.4) months follow up., Results: Progression to schizophrenia, schizoaffective disorder, or psychotic bipolar disorder (n = 10, 38.5%) was predicted by fulfilling criteria for schizotypal personality disorder at baseline (p = 0.046). Development of schizophrenia/schizoaffective disorder (n = 7, 27.0%) was associated with worse executive functioning (p = 0.029) and absence of anxiety disorders (p = 0.027). Conversely, progression to bipolar disorder (n = 4, 15.4%), with (n = 3, 11.5%) or without (n = 1, 3.8%) psychosis, was associated with the presence of anxiety disorders (p = 0.014). Remission of all psychotic as well as attenuated positive or negative symptoms (n = 5, 19.4%) was predicted by Hispanic ethnicity (p = 0.0047), an initial diagnosis of BrPsy (p = 0.014), longer duration of antidepressant treatment (p = 0.035), and better attention at baseline (p = 0.042)., Conclusions: Results from this preliminary study suggest that patients with PsyNOS, BrPsy, or schizotypal personality disorder features in adolescence should be followed as separate risk groups in prodromal studies of schizophrenia and bipolar disorder. Executive function deficits and absence of anxiety disorders may be risk markers for schizophrenia, while presence of anxiety disorders may be linked to bipolar disorder risk. After achieving full remission, patients with sudden onset of psychosis and brief episodes could once be given the option of careful, supervised treatment discontinuation. The potential salutary effect of antidepressants during the psychotic prodrome and presence of characteristics differentiating patients at risk for schizophrenia or bipolar disorder should be investigated further.

Objective: The presence and specificity of a bipolar prodrome remains questioned. We aimed to characterize the prodrome prior to a first psychotic and nonpsychotic mania and to examine the phenotypic proximity to the schizophrenia prodrome., Methods: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective, information regarding the mania prodrome was collected from youth with a research diagnosis of bipolar I disorder and onset before 19 years of age, and/or their caregivers. Only newly emerging, at least moderately severe, symptoms were analyzed. Prodromal characteristics were compared between patients with and without subsequent psychotic mania and with published bipolar and schizophrenia prodrome data., Results: In 52 youth (age at first mania: 13.4 +/- 3.3 years), the prodrome onset was predominantly "insidious" (>1 year, 51.9%) or "subacute" (1-12 months, 44.2%), while "acute" presentations (<1 month, 3.8%) were rare. The prodrome duration was similar in patients with (1.7 +/- 1.8 years, n = 34) and without (1.9 +/- 1.5 years, n = 18) subsequent psychotic mania (P = .70). Attenuated positive symptoms emerging late in the prodrome and increased energy/goal-directed activity were significantly more common in patients with later psychotic mania. Mania and schizophrenia prodrome characteristics overlapped considerably. However, subsyndromal unusual ideas were significantly more likely part of the schizophrenia prodrome, while obsessions/compulsions, suicidality, difficulty thinking/communicating clearly, depressed mood, decreased concentration/memory, tiredness/lack of energy, mood lability, and physical agitation were more likely part of the mania prodrome., Conclusions: A lengthy and symptomatic prodrome makes clinical high-risk research a feasible goal for bipolar disorder. The phenotypic overlap with the schizophrenia prodrome necessitates the concurrent study of both illness prodromes.