Prodromal Mania and Psychosis

Predicting mania versus psychosis: Researchers performed a retrospective study of prodromal symptoms, risk factors, and vulnerability markers in first-episode mania and psychosis.



“Charlie” is an 18-year-old Caucasian male with recently diagnosed bipolar disorder. He has no significant family psychiatric history. His early growth and development was typical, although he was a colicky baby. In early elementary school, he was demanding and outspoken, with increased energy. At age 10, his parents noticed some mood changes and that he was overly sensitive. Charlie had worsening mood lability at age 13, with periods of irritability and depression. At times, he was active and bossy on the playground—other times, he preferred to isolate inside and read during recess. He had some intermittent sleep difficulties and periodic anger outbursts at home. He also occasionally reported some unusual experiences. At age 16, his symptoms dramatically worsened, and he was hospitalized for a first episode of mania.

There is a recent increased effort to identify at-risk subjects for major psychiatric disorders, including schizophrenia and bipolar disorder, and to predict individuals with prodromal symptoms who will progress to full-threshold disorder.1,2 First-episode mania (FEM) has been less frequently studied than first-episode psychosis (FEP). Furthermore, studies of FEP do not typically distinguish between affective and non-affective FEP,3 and the diagnosis may change over time.4 Risk/vulnerability markers include a family history of mood disorders and attention-deficit/hyperactivity disorder for bipolar disorder, perinatal complications, worse premorbid adjustment, and increased cannabis use in schizophrenia.

The Current Study

Verdolini and colleagues5 aimed to identify symptomatic and temporal differences between the prodromal phases of FEM and FEP with onset in young adulthood or adulthood, as well as differences in risk factors and vulnerability markers. The authors performed a retrospective cross-sectional analysis, as part of a larger 2-year study in Spain. Diagnosis was confirmed using a semi-structured interview according to DSM-5 criteria. Inclusion criteria were outpatients aged 18 to 45 and a FEM or FEP in the past 4 years. They excluded subjects with intellectual disability, severe medical conditions (eg, HIV or cancer), alcohol or other substance dependence, or electroconvulsive therapy in the past year.

Data on clinical features at illness onset, current clinical symptoms and treatments, and medical histories were collected. Data on prodromal symptoms (within 3 years of onset) were obtained retrospectively from patients (and caregivers), including using the semistructured Bipolar Prodrome Symptom Scale-Retrospective. Data on risk factors, including family history of psychiatric disorders, life stressors, childhood trauma, delayed language or psychomotor development, nocturnal enuresis, and difficulties in writing and reading were assessed. Clinical information on mental health services during youth (including diagnoses and medications) were also obtained. Logistic regression models were used to investigate prodromal symptoms as predictors of FEM and FEP. Differences in the duration of prodromal symptoms in FEM and FEP were assessed using Student’s t-test.

The study sample included 108 subjects (n=72 with FEM and n=36 with FEP). There were no sociodemographic differences between subject groups, except worse psychosocial functioning in patients with FEP. Subjects with FEM had a significantly shorter duration of untreated psychosis. There were no significant differences in the number of total prodromal symptoms between FEM and FEP. Social isolation was significantly associated with the prodromal stage of FEP, and increased energy or goal-directed activity with the prodromal stage of FEM. FEP was associated with a longer and more gradual onset and slower deterioration than FEM. The depression symptom “physically slowed down” was most associated with a gradual onset pattern, whereas “increased energy” was most associated with more rapid onset. There were higher rates of obstetric complications and reading/writing difficulties in FEP than FEM. Impaired premorbid adjustment was characteristic of FEP; otherwise, there were no differences in vulnerability factors.

Study Conclusions

The authors concluded that different clinical symptoms were associated with the prodromal phases of FEP and FEM; FEP was associated with a longer prodrome; reading/writing difficulties differentiated FEP and FEM; and impaired premorbid adjustment was more characteristic of FEP. The main study strength was the use of comprehensive and exhaustive assessments. Study limitations included the relatively small sample size (particularly for FEP) and the potential for recall bias with retrospective assessments.

The Bottom Line

The psychosis and mania prodromes, coupled with risk and vulnerability markers, may contribute to identification of individuals at increased risk of conversion to fulminant disorders. Together, this information may help identify targeted early treatment strategies based on individual characteristics.

Dr Miller is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric TimesTM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.


1. Arango C, Díaz-Caneja CM, McGorry PD, et al. Preventive strategies for mental health. Lancet Psychiatry. 2018;5(7):591-604.

2. Vieta E, Salagre E, Grande I, et al. Early intervention in bipolar disorder. Am J Psychiatry. 2018;175(5):411-426.

3. Barajas A, Pelaez T, González O, et al. Predictive capacity of prodromal symptoms in first-episode psychosis of recent onset. Early Interv Psychiatry. 2019;13(3):414-424.

4. Fusar-Poli P, Cappucciati M, Rutigliano G, et al. Diagnostic stability of ICD/DSM first episode psychosis diagnoses: meta-analysis. Schizophr Bull. 2016;42(6):1395-1406.

5. Verdolini N, Borras R, Sparacino G, et al. Prodromal phase: differences in prodromal symptoms, risk factors and markers of vulnerability in first episode mania versus first episode psychosis with onset in late adolescence or adulthood. 2022. Online ahead of print.