Temperamental traits and adverse experiences during childhood may together offer clues to vulnerability to major psychiatric disorders, a transdiagnostic study by researchers at NIMHANS has found.
The study, published recently in the Journal of Affective Disorders, examined 1,162 adults, including 532 people with psychiatric disorders, 457 unaffected first-degree relatives (FDRs) and 173 healthy controls. The participants were drawn from 393 multiplex families – families in which multiple members had been diagnosed with psychiatric disorders – involving schizophrenia, bipolar disorder, obsessive-compulsive disorder (OCD) and alcohol use disorder (AUD).
The researchers examined four broad dimensions of adult temperament – negative affectivity, extraversion/surgency, effortful control and orienting sensitivity – along with adverse childhood experiences (ACEs).
“Our findings suggest that temperament does not map onto psychiatric disorders in a simple, one-to-one manner. Rather, different combinations of temperamental characteristics are associated with different disorders, and some of these characteristics are also seen among unaffected family members,” said Srinivas Balachander, corresponding author and one of the lead researchers of the study.
Temperament shared within families
Using data from the erstwhile Accelerator programme for Discovery in Brain disorders using Stem cells (ADBS) project, (funded by the Department of Biotechnology and Pratiksha Trust), now known as the Rohini Nilekani Centre for Brain and Mind, at NIMHANS, the researchers found evidence of familial sharing across all four temperamental domains.
This was observed despite considerable variation in the psychiatric diagnoses within the same families. The finding is of interest because temperament is known to have a substantial heritable component, although the study did not directly establish that the temperamental characteristics observed were caused by specific genetic variants.
“In our study, considering the significant within-family heterogeneity in terms of different diagnoses, there was still a significant degree of shared temperament,” Dr. Balachander said.
Among affected participants, schizophrenia and bipolar disorder were associated with lower extraversion/surgency and orienting sensitivity. OCD was associated with higher negative affectivity and orienting sensitivity, along with lower effortful control and extraversion/surgency. Participants with AUD showed higher negative affectivity and orienting sensitivity and lower effortful control.
Some of these patterns were also observed among unaffected first-degree relatives. Relatives of people with schizophrenia showed lower extraversion/surgency, while relatives of people with OCD showed higher negative affectivity and lower effortful control.
“These findings are particularly interesting because some temperamental characteristics were evident even in individuals who did not have the disorder but belonged to families carrying a higher degree of familial risk,” Dr. Balachander said.
Childhood adversity and alcohol use disorder
The researchers also examined whether adverse childhood experiences altered the relationship between temperament and psychiatric disorders.
The clearest evidence for an interaction between temperament and childhood adversity emerged in alcohol use disorder. The overall ACE score was significantly associated with AUD, and interactions between childhood adversity and two temperamental domains – extraversion/surgency and effortful control – were also observed.
“Childhood adversity appears to add another layer to the relationship between temperament and psychiatric vulnerability. In our study, the evidence for this interaction was particularly apparent in alcohol use disorder, rather than uniformly across all four disorders,” Dr. Balachander said.
The researchers, however, cautioned against interpreting the findings as evidence that a particular temperament or childhood experience causes a psychiatric disorder.
The study was cross-sectional, meaning that the assessments were made at one point in time. The adult temperament measures were self-reported and could be influenced by current illness, treatment, illness duration or an individual’s perception of their own past Reports of childhood adversity may also be affected by recall and measurement biases.
Testing the findings
To examine whether the findings extended beyond the genetically enriched family sample, the researchers tested their statistical model using an independent community-based cohort from the Consortium for Vulnerability to Externalizing Disorders and Addiction (c-VEDA).
The analysis included 2,485 adults aged 18 to 23 years for whom the relevant temperament, ACE and psychiatric assessments were available.
The model showed an area under the curve (AUC) of 0.822 for alcohol use disorder, 0.742 for bipolar disorder and 0.752 for OCD. Its performance for schizophrenia was close to chance level, with an AUC of 0.526.
“The external validation gives us some indication that the associations identified in the family-based sample may extend to community populations for some disorders. However, the findings for schizophrenia did not replicate well, which is an important limitation and needs further investigation,” Dr. Balachander said.
The researchers said the findings point to the need for prospective studies that follow unaffected family members over time. Such studies could help determine whether particular temperamental characteristics precede the onset of psychiatric illness or are partly consequences of illness and its treatment.
“Temperament and childhood adversity may eventually become useful components of broader risk assessment frameworks, but we need prospective longitudinal evidence before we can say that they have predictive or preventive value,” Dr. Balachander said.
The researchers said that studying temperament alongside childhood adversity could eventually provide a more nuanced understanding of psychiatric vulnerability than considering family history alone. However, they stressed that the present findings do not establish that these measures can predict who will develop a psychiatric disorder.
The researchers said continued longitudinal follow-up of the cohort would be important to establish whether the observed temperamental patterns have value in identifying individuals at increased risk before the emergence of clinically significant symptoms.