Tracing the Circuits of Self-Loathing in the Depressed Brain

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They say there’s a fine line between love and hate, as evidenced by the fact that the same brain circuitry processes both intense love and severe hatred. Now a new study finds that that the key wiring that connects brain regions in this circuit is weakened in people suffering from depression.

At first glance, weakening the brain connections necessary to feel hate might seem like a recipe for calmer and more peaceful feelings, but the researchers think the decoupling may actually contribute to feelings of self-loathing, which is clearly associated with depression.

Meanwhile, because the same brain-circuitry problems interfere with the ability to feel love, it may further cause feelings of self-hatred in people with depression, who commonly say they feel unloved and unlovable, even when there is affectionate evidence to the contrary.

MORE: Study: How Chronic Stress Can Lead to Depression

Using magnetic resonance imaging, researchers performed brain scans on 15 people with untreated depression, 24 people whose depression had not responded to multiple antidepressants and 37 healthy controls, who were matched by age, gender and education to the depressed people.

The researchers found that compared to the control group, depressed people showed weakened connections between the superior and inferior orbitofrontal cortex (OFC) on the left side of the brain, but stronger connections on the right side of the brain. Previous research suggests that the right OFC responds more to punishment, while the left is more responsive to reward. The new brain-scan results fall neatly in line with the experience of depression, in which pleasures are dulled while emotional pain — especially rejection — feels more acute.

The study also found weaker connections in a circuit known for the presence of mirror neurons, which become active not when we perform an action, but when we watch others do so. For example, if you see someone else smile, your mirror neurons turn on in response, and even send a preparatory signal to the muscles involved with grinning in kind, whether you or not you ultimately do.

Mirror neurons are believed to help people recognize the thoughts and intentions of others, which helps encourage understanding and feelings of connectedness. The uncoupling of mirror neuron circuits in depressed people may make them feel more isolated and unable to relate to friends and loved ones.

In addition, researchers discovered stronger connections between brain regions that have been linked to attention to negative experience.

But why does such brain circuitry increase depressed people’s self-hate more than their hatred for others? The authors write:

One possibility is that the uncoupling of this hate circuit could be associated with impaired ability to control and learn from social or other situations, which provoke feelings of hate towards self or others. This in turn could lead to an inability to deal appropriately with feelings of hate and an increased likelihood of both uncontrolled self-loathing and withdrawal from social interactions.

Alternatively, given the involvement of hate-related circuitry, the new research could support the Freudian notion that at least some part of depression may be due to “anger turned inward.” Research has found that in men in particular a key symptom of depression is often anger.

MORE: Why Patients Don’t Open Up to Doctors About Depression

Whether the dysfunctions in these regions involve reduced ability to feel love or increased feelings of self-hate, or both, understanding the circuitry may potentially help researchers develop more effective treatments.

The research [PDF] was published in Molecular Psychiatry and led by Jianfeng Feng of the University of Warwick in England.

Maia Szalavitz is a health writer at TIME.com. Find her on Twitter @maiasz. You can also continue the discussion on TIME Healthland’s Facebook page and on Twitter @TIMEHealthland.

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