A large study of retired Americans found that those with high levels of the inflammatory marker C-reactive protein in the blood had more depression and anxiety. Higher CRP also predicted severity of depression and anxiety four years later.
The study, by researchers Joy E. Lin and Aoife O’Donovan, included 18,603 people over age 50 from the Health and Retirement Study. It was presented at the 2016 meeting of the Society of Biological Psychiatry.
Lin and O’Donovan hope that treating or preventing inflammation may be the key to preventing symptoms of depression and anxiety.
A recent study shows that psychotherapy can not only improve depression symptoms, but may also reduce the inflammation that often accompanies them.
Researcher Jean Pierre Oses and colleagues randomly assigned participants with depression to receive Supportive-Expressive psychodynamic therapy, which is designed to help patients understand conflictual relationship patterns, or an alternative therapy. Among the 47 participants who received Supportive-Expressive therapy, depression improved significantly after 16 sessions, and blood levels of the inflammatory markers interleukin-6 and TNF alpha also dropped.
The research was presented at the 2016 meeting of the Society of Biological Psychiatry.
In new research presented at the 2016 meeting of the Society of Biological Psychiatry, researcher Tracy Barbour and colleagues revealed that youth with a family history of depression showed more amygdala activation in response to a threat than people without a family history of depression. This amygdala hyperactivity was linked to low resilience to stress and predicted worsening depressive symptoms over the following year.
In the study, 72 non-depressed youth were shown images of cars or human faces or cars that seemed to loom in a threatening way. Brain scans showed increased amygdala activity in participants with a family history of depression compared to those without such a history.
The amygdala is an almond-shaped part of the brain in the temporal lobe that has been linked to emotional reactions and memory, decision-making, and anxiety.
A recent study suggests that women who experienced moderate or severe abuse in childhood secrete less oxytocin while breastfeeding their own children. Oxytocin is a hormone that promotes emotional bonding. The study included 53 women. They breastfed their newborn children while blood samples were collected from the women via IV. Those women with a history of moderate or severe abuse (emotional, physical, or sexual) or neglect (emotional or physical) had lower measures of oxytocin in their blood during breastfeeding than women with no history or abuse in childhood or a history of mild abuse.
A history of abuse or neglect was more common among women with current depression compared to women with a history of depression or anxiety. Women who had never experienced depression or anxiety were least likely to have a history of abuse or neglect.
The study by Alison Steube and colleagues, presented at the 2016 meeting of the Society of Biological Psychiatry, suggests that traumatic events that occur during childhood may have long-lasting effects. These experiences may modulate the secretion of oxytocin in adulthood. Low oxytocin has been linked to depression.
A large study in Denmark suggests that taking selective serotonin reuptake inhibitor (SSRI) antidepressants alongside cholesterol-lowering statin drugs improved depression more than SSRIs alone. The findings, by Ole Köhler and colleagues were reported in the American Journal of Psychiatry in 2016.
The study included 872,216 people in Denmark’s national health care database who took SSRIs between 1997 and 2012. The most common SSRIs were citalopram, sertraline, and escitalopram. Of these people taking SSRIs, 13.0% also took a statin drug, typically simvastatin. Those patients who were taking both an SSRI and a statin were less likely than those taking an SSRI alone to be hospitalized for any psychiatric problem, or for depression specifically.
Depression is known to be correlated with inflammation throughout the body. Statins reduce this inflammation as well as lowering cholesterol. A 2013 study by Ahmad Ghanizadeh and Arvin Hedayati in the journal Depression and Anxiety showed that the SSRI fluoxetine and the statin lovastatin reduced depression severity compared to fluoxetine alone.
The combination of SSRIs and statins did not seem to reduce deaths or suicidal behavior compared to SSRIs alone. Statins have some side effects, but combining them with antidepressants did not increase the risks associated with their use.
A 2016 article by Heli Malm and colleagues in the Journal of the American Academy of Child and Adolescent Psychiatry suggests that in utero exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may increase the risk of depression in adolescence. However, the study included potentially confounding factors. It is possible that women who took SSRIs during pregnancy had more severe depression than those who went unmedicated during pregnancy. The mothers in the study who took SSRIs also had more comorbid conditions such as substance abuse.
Editor’s Note: Women should balance the risks and benefits of antidepressant use during pregnancy, since depression itself can have adverse effects on both mother and fetus. It has recently been established that SSRI use during pregnancy does not cause birth defects, so women with depression that has not responded to non-pharmaceutical interventions such as psychotherapy, omega-3 fatty acid supplementation, exercise, mindfulness, and repeated transcranial magnetic stimulation (rTMS) may still want to consider SSRIs.
In August 2011, the US Food and Drug Administration issued a warning that doses of the selective serotonin reuptake inhibitor (SSRI) antidepressant citalopram (Celexa) that exceeded 40mg/day could prolong the QT interval, a measure of heart rate used to diagnose abnormal heart rhythms. A study of records from the Veterans Health Administration showed that 35,848 veterans whose dose of citalopram was reduced from an average of 64mg/day to under 40mg/day faced increased deaths, hospitalizations for any cause, and hospitalizations for depression specifically after the reductions.
The FDA warning meant to prevent heart problems had the unintended consequence of increasing hospitalizations and deaths among the veterans affected. These findings by Thomas S. Rector and colleagues were published in the American Journal of Psychiatry in 2016.
Editor’s Note: There are some similarities between this case and findings by researchers Andrew Nierenberg and Andrew Stoll, who noticed that patients taking 40mg/day of fluoxetine (Prozac) had better long-term outcomes than those taking 20mg/day, even though those taking 40mg were more ill and more likely to relapse at the start of the study.
Researchers Ellen Frank and David Kupfer found that 90% of unipolar depressed patients relapsed when their antidepressant doses were halved, even though they had been stable for 5 years before the change.
These and the findings from Rector and colleagues lead this editor to believe that reducing the dosage of effective treatments should not be done without reason—that is, in the absence of side effects, or simply to achieve the minimal effective dose. Dose reductions without cause not only may increase the risk of relapse, but may also put the patient at increased risk of developing tolerance to the medication, for example hastening the onset of ‘Prozac poop-out.’
When long-term maintenance drug therapy is going well, it may be best to be conservative and stay the course. Conversely, in the absence of a good long-term response, be as active and creative as possible to achieve mood stabilization.
Ketamine, which is used as an anesthetic at higher doses, can also relieve depression within hours when delivered intravenously. A 2016 study by Morteza Jafarinia and colleagues in the Journal of Affective Disorders suggests that oral ketamine may be helpful in the treatment of mild to moderate depression in people with chronic pain.
The study compared 150mg daily doses of oral ketamine to 150mg daily doses of the anti-inflammatory pain reliever diclofenac over 6 weeks. When interviewed at week 3 and week 6, the ketamine group reported significantly fewer symptoms of depression than the diclofenac group.
A systematic review of research on the value of pharmaceutical-grade nutritional supplements, or ‘nutraceuticals,’ in depression treatment has found that several do indeed improve depression symptoms.
The 2016 review by Jerome Sarris and colleagues in the American Journal of Psychiatry found that the following nutraceuticals primarily produced positive results compared to placebo: omega-3 fatty acids (primarily EPA or ethyl-EPA); vitamin D; l-methylfolate (a more potent form of folic acid); and S-adenosyl methionine or SAMe, a beneficial compound created from toxic homocysteine with the help of folate.
Editor’s Note: Most of these compounds can also be useful in bipolar depression. Omega-3 fatty acids and vitamin D are helpful to many patients. L-methylfolate is particularly helpful to the 30% of the population with a MTHFR deficiency that interferes with the ability of folate to break down homocysteine. SAMe is an exception—while it is effective in unipolar depression, it may cause switching into mania in patients with bipolar disorder.
The researchers identified a few additional nutraceuticals that each had one study supporting their use—creatine, sometimes used by weightlifters to provide extra energy to muscles; folinic acid, which can protect bone marrow and other cells during chemotherapy; and a combination of amino acids.
Results from studies that compared other compounds to placebo were mixed. Those included studies of zinc, folic acid, vitamin C, and the amino acid tryptophan. A study of inositol, a compound found in plants that is not normally digestible, had nonsignificant results.
No serious side effects were observed in any of the studies of nutraceuticals, though some caused minor digestive disturbances.
Editor’s Note: Another beneficial nutraceutical that did not appear in the review article is N-acetylcysteine. In 6- to 8-week studies, NAC improved depression and anxiety compared to placebo. It also improved bipolar depression and reduced many habits and additions in non-bipolar patients. These include cocaine and gambling addition, alcohol and nicotine use, trichotillomania (compulsive hair-pulling) and obsessive compulsive disorder (OCD).
Vitamin B12 deficiency is a risk associated with a vegan diet. B12 deficiency can lead to depression, anemia, and even irreversible neuron damage, according to researcher Drew Ramsey, who spoke on the topic at the 2016 meeting of the American Psychiatric Association.
A study of vegans showed that 52% were deficient in vitamin B12, while another 23% had insufficient levels of the vitamin. B12 is found in the highest concentrations in certain seafoods and liver. It is also found in dairy products, eggs, fortified breakfast cereals, and is available in supplement form.
Women who eat a vegan diet while pregnant may not be providing their offspring with enough nutrients, according to researcher Emily Deans, who also spoke at the meeting. A case report on 30 vegan mothers found that 60% of their offspring had developmental delays and 37% showed cerebral atrophy.
Deans said that eating no meat is associated with higher rates of depression, anxiety, and worse quality of life.
Ramsey believes that while the North American diet is probably weighted too heavily toward animal products, seafood remains an important source of B12.