Brain metabolism mediates inherited anxiety

New research demonstrates that metabolic over-activity in the brain associated with anxiety and depression is passed from parents to children.

The study, published in PNAS, looked at 592 young rhesus monkeys from a large, multigenerational family. Some of these monkeys displayed an anxious temperament, similar to that seen in some children.

Brain imaging showed that these anxious monkeys displayed increased metabolic activity in their prefrontal-limbic-midbrain circuit, while genetic analysis showed that this metabolic difference was also inherited.

'Over-activity of these three brain regions are inherited brain alterations that are directly linked to the later-life risk to develop anxiety and depression,' said senior author Professor Ned Kalin of the Department of Psychiatry at the University of Wisconsin in Madison.

The young monkeys were exposed to a mildly threatening situation, comparable to a child encountering a stranger who does not make eye contact. Using positron emission tomography (PET) scanning, combined with assessing their behavioural and physiological responses, the researchers identified that this neural circuit in the brain associated with an anxious temperament. However, it was the increased metabolic activity, rather than the size of these areas of the brain , that was linked to a genetic predisposition to developing anxious disorders.

Professor Kalin suggested that these findings could be combined with publicly available data on gene-expression levels to help identify the genes, and therefore the molecular mechanisms, that trigger this over-activity.

'This is a big step in understanding the neural underpinnings of inherited anxiety and begins to give us more selective targets for treatment,' he said.

'To a certain extent, anxiety can provide an evolutionary advantage because it helps an individual recognise and avoid danger. But when the circuits are over-active, it becomes a problem and can result in anxiety and depressive disorders,' explained Professor Kalin.

Previous studies in humans have shown that parents with anxiety or depression are more likely to have children with an extremely anxious temperament, who are themselves at increased risk of developing anxiety or depressive disorders later in life. In addition to environmental influences, such as parent—child interactions, genetic factors contribute around 35 percent of the risk that a child will go on to develop an anxiety disorder.