How Social Stress Produces Depression
When Scott Russo and his team exposed 24 small, subordinate mice to larger, dominant mice for 10 minutes a day, 14 of them became socially withdrawn and more timid. Blood, tissue, and DNA samples showed a cascade of responses to the stress. First, activity decreased in genes in the nucleus accumbens (NAc), resulting in a 40% drop in production of the protein claudin-5, which secures the integrity of the blood-brain barrier. Up to 30% of vessels lining the blood-brain barrier in the NAc showed breaches, allowing the inflamatory substance interleukin-6 and a type of white blood cells called monocytes to pass into the NAc and disrupt signaling. Because the NAc helps evaluate threats and awards, presumably this disruption led to the altered emotional behavior.
     When the team examined the brains of deceased individuals they found that many of the ones who had depression had 50% lower levels of claudin-5. The study supports the role of inflammation in depression, and suggests that efforts to strengthen the blood-brain barrier or to reduce interleukin-6 (already being studied) or monocytes might be effective as depression treatments. Nature Neuroscience, Vol 20, 1752-1760.

"As Needed" Deep Brain Stimulation
Studies are in the works to deliver therapeutic deep brain stimulation (DBS) only when it is needed. Two will be used with patients with treatment-resistant mood disorders to deliver stimulation only when the electrodes detect a pattern of neural activity associated with mood disorder. A recent year-long study failed to produce significant improvement, so it is hoped this new approach will work better than the usual continuous stimulation. Another study will use a similar approach to treat bipolar disorder. If successful, researchers hope the DBS can be replaced with non-invasive stimulation through the skull. Nature News, November 22, 2017.

Magnetic Brain Stimulation Alters Negative Emotion
Repetitive transcranial magnetic stimulation (rTMS), which is delivered noninvasively to the scalp, can increase or decrease emotional responses to fearful images. The stimulation was delivered over the right dorsolateral prefrontal cortex; excitatory rTMS shortened reaction times in responding to fearful faces and reduced emotional arousal; inhibitory stimulation increased both measures. Interestingly, depression is often treated by applying inhibitory rTMS. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Vol 3, 329-336.

The Psychedelic Psilocybin May Help With Depression
Among 19 patients with treatment-resistant major depression who were given two doses of psilocybin seven days apart, nine responded positively and four showed remission; gains were maintained for the six-month period of the investigation. Psychopharmacology, 235, 399-408. In a follow-up study, depressive symptoms were reduced by 50% in seven out of twelve patients. Psilocybin was more likely to be effective in patients who used the fewest positive words during the baseline interview. Journal of Affective Disorders, Vol 230, 84-86.

Fifty New Schizophrenia Gene Locations Found
By examining data from 100,000 people, 40,000 of whom were diagnosed with schizophrenia, a team of Cardiff University researchers has identiied 145 DNA locations related to schizophrenia, 50 of which are new. Candidate genes were identified in 33 of the regions. Most of the genes have small effects, which helps explain why they have not been selected against in evolution. Nature Genetics, Vol 50, 381-389.

Forty-Four Genes Linked With Depression
By comparing the entire genomes of 135,000 people with depression with 345,000 controls, a team of over 200 researchers has linked depression with 44 genes, 30 of which have not been identified before. Some of the genes have previously been linked to schizophrenia, strengthening evidence for a partially shared etiology. Major depression was also associated with lower educational attainment and higher body mass. Nature Genetics, 50, 668-681.

Four Obsessive-Compulsive Genes Found
By comparing over 600 genes in 592 people with OCD and 560 controls, researchers have identified four OCD genes. The genes affect postsynaptic proteins, synapse management, and vesicle trafficing. All of the genes are active in the circuit linking the striatum, the thalamus, and regions of the cortex; the striatum is involved in learning and sends messages through the thalamus to the cortex, where decisions are made. Previous research has shown that disruption of activity in this circuit makes it harder to tell whether a situation is safe or risky. Nature Communications, Vol 8, DOI: 10.1038/s41467-017-00831.

Major Disorders Share Gene Expression Patterns
The etiology of psychological disorders involves not just genes, but which genes are expressed in the brain. Using 700 cortical samples from the brains of deceased individuals who had one of five major disorders, researchers found common gene expressions across some disorders, and unique patterns in others. For example, one gene was upregulated in schizophrenia and autism, but not in bipolar disorder, major depression, or alcoholism. Evidence indicated that these patterns of expression are themselves genetic in origin. Science, Vol 359, 693-697.

Ketamine Nasal Spray Reduces Suicidal Thoughts
You learn on page 424 of the text that ketamine has shown promise in alleviating treatment-resistant depression; ketamine activates AMPA receptors, implicating the glutamate system. Now a nasal spray containing ketamine (in the form of esketamine) has reduced depressive mood in patients who were at imminent suicide risk and had not responded to at least two previous treatments. Suicidal thinking improved, along with mood. Though the results were temporary the improvement occurred within four hours, indicating that this could be an effective and easily administered emergency intevention to prevent suicide. American Journal of Psychiatry, DOI: 10.1176/appi.ajp.2018.17060720.