Sex Differences in First-Episode Mania—Data from a Retrospective Chart Review

Dear Editor,

Sex differences in mental illness arise from multiple biological, social, and epidemiological factors that pose differential health risks in males and females. ¹ Bipolar I disorder (BD I) is reportedly not associated with sex differences in terms of prevalence and the polarity of onset, ² though certain studies show that males get more manic episodes. ³ Regarding the clinical presentation of mania, males are more likely to have increased libido, grandiosity, and suicidality, ² while mixed symptoms, hallucinations, and rapid cycling are more in females. However, findings on the prevalence of psychotic symptoms and suicidality have been inconsistent. ² Studies on sex differences in first-episode mania (FEM) are sparse in India. A previous study from our center, on a smaller sample, reported no sex differences in FEM except for increased activity levels and better treatment-response in females. ⁴

As part of a larger record-review examining the 10-year course of FEM, we performed a retrospective chart review of both inpatients and outpatients with FEM (ICD-10) or BD I with only prior depression who presented to us between 2008 and 2014. The data were abstracted using an electronic data sheet agreed upon by all the authors. The data was extracted by qualified psychiatrists NKC, SSK, PJ, KRK, TNS, and DR, and it was cross-verified by two senior psychiatrists, VK and KM. There was no blinding, and the patients were not contacted. Information extracted included sociodemographic, clinical, and treatment details of patients with FEM. This particular analysis aimed to look at sex differences in FEM with respect to clinical presentation and sociodemographic details. Institute Ethics Committee approved the study. Statistical analysis was done using IBM Statistical Package for the Social Sciences (SPSS) software, version 26.0. Chi-square test and independent-sample t-test were employed to examine group differences.

We reviewed 676 records and collected data from 275 (Males [M] = 167; Females [F] = 108) case records. Table 1 shows the statistically significant differences in demographic and clinical variables between the groups. Age (in years) at the onset of mania (M = 26.75 ± 8.51, F = 27.09 ± 8.3, t = 0.32, P = 0.97) and age at first contact (M = 26.74 ± 8.5, F = 27.09 ± 8.3, t = 0.33, P = 0.95) did not differ between the groups. There were no differences in the prevalence of prior depressive episode (M = 12.8%, F = 12.5%, χ² = 0.004, P = 0.94) or positive family history of any psychiatric illness (χ² = 1.08, P = 0.95). Other clinical features like suicidality (M = 6.9%, F = 6.7%, χ² = 0.003, P = 0.95) and other psychotic symptoms such as delusion of reference (M = 17.3%, F = 23.1%, χ² = 0.81, P = 0.36), delusion of persecution (M = 30.6%, F = 32.3%, χ² = 0.05, P = 0.81), or auditory hallucinations (M = 20.4%, F = 24.6%, χ² = 0.40, P = 0.52) did not statistically differ between the two groups (all P > 0.1). The severity of episode (as assessed with Clinical Global Impression-Severity scale (M = 4.65 ± 0.77, F = 4.52 ± 0.76, t = –1.15, P = 0.48), time to treatment (M = 1.35 ± 1.55, F = 1.31 ± 1.83, t = –0.172, P = 0.42), antipsychotics/mood stabilizers usage, and dose of antipsychotics (olanzapine equivalents in mg; M = 16.4 ± 6.05; F = 14.6 ± 6.04, t = –2.45, P = 0.48) did not differ (P > 0.1) between the groups.

Table 1.

Sex Differences in FEM

Variables	Percentage/Mean±SD		χ2/t	P Value
	Males (n = 167)	Females (n = 108)
Education—illiterate	8.3	18.7	10.89	0.01
Unemployed	9.5	40	37.83	<0.001
Married Single	36.5 61.7	63.9 36.5	25.51	<0.001
Substance dependence	94.1	5.9	28.59	<0.001
Irritable mania	68.9	54.8	3.88	0.04
Grandiose delusion	82.7	69.2	4.01	0.04
Time to remit	1.11 ± 1.14	0.90 ± .67	–1.39	0.02

FEM: first episode mania, SD: standard deviation.

A subset of our data with a smaller sample size was published earlier, which showed increased activity levels and better treatment-response in females than males. ⁴ But, with a larger sample size, these factors were not significant. Our study indicated significantly increased substance dependence and irritability in males, similar to previous studies.^5,6 In India, the prevalence of substance use is higher in males than females, which could be the reason for higher substance dependence in males. ⁷ In the Indian population, the age of marriage is earlier in females, a possible explanation for the predominance of married females in our sample. ⁸ Delusion of grandiosity was more prevalent in males, consistent with an earlier study ⁹ but contradicted another study with a female predominance. ¹⁰ There were no sex differences in the presence of prior depressive episodes, which is contrary to a study that reported female preponderance. ⁶ Studies show that the course of BD I has sex differences, ² but the differences are not very obvious in the FEM; it is likely that with illness progression, the course may change between men and women. Our study found males were more educated, single, and employed, with higher irritability, delusion of grandiosity, substance use, and increased time to remit. These are important factors that may cause sex-based differences in the course of the illness.

The strength of the study is the larger sample size of FEM. The study’s limitations include lack of information on risk factors like stressors and adverse childhood events, the retrospective nature, and not using rating scales to measure the severity and improvement. The study was exploratory in nature with no prespecified hypotheses and no correction for multiple testing. Further systematic studies are required on this clinically significant research area.