Repeated transcranial magnetic stimulation (rTMS) is a treatment for depression in which magnets placed near the skull stimulate electrical impulses in the brain. In a poster presented at the 2015 meeting of the Society of Biological Psychiatry, Martin Lan and colleagues presented results of the first study of structural changes in the brain following rTMS.
In the study, 27 patients in an episode of major depression underwent magnetic resonance brain scans before and after receiving rTMS treatment over their left prefrontal cortices. Lan and colleagues reported that several cortical regions related to cognitive appraisal, the subjective experience of emotion, and self-referential processing increased in volume following rTMS treatment: the anterior cingulate, the cingulate body, the precuneous, right insula, and gray matter in the medial frontal gyrus. The increases ranged from 5.3% to 15.7%, and no regions decreased in volume. More than 92% of the participants showed increased gray matter in all of these regions.
The brain changes were not correlated with antidepressant response to rTMS, but suggest a possible mechanism by which rTMS is effective in some people. Lan and colleagues concluded that rTMS likely had neuroplastic effects in areas of the brain that are important for emotion regulation.
N-acetylcysteine (NAC) is an anti-oxidant nutritional supplement that has been found to reduce a wide range of habitual behaviors, including drug and alcohol use, smoking, trichotillomania (compulsive hair-pulling), and gambling. It also improves depression, anxiety, and obsessive behaviors in adults, as well as irritability and repeated movements in children with autism. A new study suggests NAC may also be able to reduce non-suicidal self-injury, often thought of as “cutting,” in girls aged 13–21.
The open study, presented in a poster by researcher Kathryn Cullen at the 2015 meeting of the Society for Biological Psychiatry, compared magnetic resonance imaging (MRI) scans of 15 healthy adolescent girls to scans of 22 girls who had been engaging in self-injury, both before and after this latter group received eight weeks of treatment with N-acetylcysteine. Doses were 1200 mg/day for the first two weeks, 2400mg/day for the next two weeks, and 3600mg/day for the final four weeks. The girls also reported their self-injury behaviors.
Treatment with NAC reduced the girls’ self-injury behaviors. The brain scans showed that NAC also increased resting-state functional connectivity between the amygdala and the insula. Connectivity in this region helps people regulate their emotional responses. At baseline, the girls who engaged in self-harm had had deficient connectivity between the amygdala, the prefrontal cortex, insula, and the posterior cingulate cortices compared to the healthy girls, and this improved with the NAC treatment.
A recent study of 93 adults with bipolar disorder suggests that midday bright light therapy can be an effective adjunctive treatment for bipolar depression. The study by Dorothy Sit and colleagues was presented at the 2015 meeting of the Society for Biological Psychiatry. Participants had been diagnosed with bipolar I or II disorder, were in a current episode of depression, and were taking stable doses of mood stabilizing medication. They were randomized to receive either 7000-lux broad spectrum light for 45 to 60 minutes each day for six weeks or 50 lux dim red light. The comparison was dramatic: remission rates were 56.5% among those exposed to the 7000-lux light, and 14.3% among those who were exposed to the dim light. Those who received the bright light also reported better sleep quality and less suicidality.
Editor’s Note: These results are striking and raise the issue of whether midday bright light is more effective than early morning bright light, the usual recommendation for seasonal affective disorder (SAD) and other forms of depression. Until comparative studies are available, using midday light may be the way to go.
Studies of rodents with depression-like behaviors revealed that the combination of low (sub-therapeutic) doses of lithium and infusions of ketamine produced antidepressant-like effects. Researchers believed this might mean that in humans, lithium might have a unique effect potentiating the effects of ketamine.
In a small study by Mark J. Niciu presented at the 2015 meeting of the Society for Biological Psychiatry, patients with bipolar depression taking lithium or valproate mood stabilizers were given ketamine infusions or control infusions. In the 23 patients taking lithium and the 13 taking valproate, ketamine’s antidepressant effects were significantly better than placebo, but there was no difference between lithium and valproate with regard to these antidepressant effects. These preliminary data in a small number of subjects do not support the proposition that lithium augments the effects of ketamine in depression.
Intravenous ketamine can bring about rapid improvement in depressive symptoms among people with treatment-resistant depression. Because of its rapid effects, which can appear after only two hours, ketamine is being investigated as a treatment for people with suicidal thoughts.
At the 2015 meeting of the Society of Biological Psychiatry, Laili Soleimani and colleagues presented a poster about their recent double blind, randomized, controlled pilot study of ketamine inpatients and outpatients who scored highly on a measure of suicidal ideation. The 24 participants were randomized to receive either a single intravenous infusion of ketamine (0.5mg/kg) or a single infusion of midazolam (0.045 mg/kg), which shares ketamine’s anxiety-reducing effects but does not have antidepressant effects. They reported suicidal thoughts at 24 hours post-infusion, 48 hours, 72 hours, and 7 days. At 48 hours, those who received ketamine reported significantly reduced suicidal ideation compared to those who received midazolam, but this effect was no longer significant at the 72-hour mark.
The findings show that ketamine can briefly reduce suicidal ideation, and that the treatment is safe and tolerable for patients. This pilot study paves the way for further study of ketamine to reduce suicidal thinking in people who are at high risk for suicidal behavior.
Intravenous ketamine is known for its fast-acting antidepressant effects, which can appear within two hours of an infusion. Researchers are now investigating its use for the reduction of suicidal thoughts. In a study presented in a poster at the 2015 meeting of the Society of Biological Psychiatry, Jennifer L. Vande Voort and colleagues compared the sleep of patients whose suicidal thoughts decreased after a single ketamine infusion (0.5 mg/kg over 40 minutes) to those whose suicidal thoughts remained.
Study participants whose suicidal thoughts diminished after one infusion of ketamine had better sleep quality the following night, with fewer disruptions in sleep than among those who did not have an anti-suicidal response to ketamine. The participants who responded well to ketamine had sleep quality similar to that of healthy controls.
Vande Voort and colleagues hope that these new findings about ketamine’s effect on sleep may provide clues to the biological mechanism behind ketamine’s effect on suicidal ideation.
Progressive losses in gray matter have been observed in the cortex of people with schizophrenia, and those at high risk for the illness. In the past, studies have shown that the amount of antipsychotics a patient is exposed to is correlated with the extent of their deficits in gray matter, suggesting that antipsychotic treatment could exacerbate gray matter loss.
A new meta-analysis by Antotonio Vita and colleagues in the journal Biological Psychiatry shows that first-generation antipsychotics were associated with greater losses in gray matter compared with atypical antipsychotics, which seemed to slow the loss of gray matter.
The meta-analysis analyzed data from 18 longitudinal studies comparing a total of 1155 patients with schizophrenia to 911 healthy control participants. Magnetic resonance imaging (MRI) scans showed that over time, patients with schizophrenia lost more cortical gray matter volume. The patients’ cumulative intake of any kind of antipsychotic between MRI scans was associated with gray matter losses. But when Vita and colleagues drilled down to find differences between patients taking first-generation antipsychotics and those taking second-generation atypical antipsychotics, they found that patients with higher average daily intake of first-generation antipsychotics had greater losses in gray matter, while patients with higher average daily intake of atypical antipsychotics had less progressive losses in gray matter.
This study is the first to compare the effects of first-generation antipsychotics, which were developed in the 1960s, with those of atypical antipsychotics, which came into frequent use in the late 1980s, on cortical gray matter loss in schizophrenia. While first-generation antipsychotics are associated with the side effect of tardive dyskinesia, involuntary movements of the face and jaw, atypical antipsychotics are most commonly associated with weight gain.
Three studies have randomly assigned patients with schizophrenia to receive either first-generation or atypical antipsychotics. In these studies as well, second-generation antipsychotics were associated with smaller losses in gray matter.
The authors speculate that either second-generation antipsychotics may have neuroprotective effects, or first-generation antipsychotics may have neurotoxic effects. They also suggest that first-generation antipsychotics may not have the capacity to interfere with the natural progression of schizophrenia in terms of gray matter losses.
Future studies may investigate differences between specific antipsychotic medications’ effects on gray matter volume. Vita and colleagues reported that in the analysis, the atypical antipsychotic clozapine was associated with the least loss of gray matter of any medication in the included studies.
Editor’s Note: This study is important because it adds to findings questioning the conclusions of a large National Institute of Mental Health–sponsored study known as CATIE and a meta-analysis by John Geddes published in the journal BMJ in 2000, in which he wrote that “There is no clear evidence that atypical antipsychotics are more effective or better tolerated than conventional (first generation) antipsychotics.” Read more
A new long-term study of omega-3 polyunsaturated fatty acids for psychosis prevention shows that almost seven years after a 3-month stint of receiving these dietary supplements daily, adolescents and young adults at high risk for psychosis showed fewer symptoms of conversion to full-blown psychosis than those who received placebo during the same period.
The research team, led by Paul Amminger, originally found that among 81 youth (mean age 16.5) at high risk of developing psychosis due to their family histories, the 41 who received 12 weeks of daily supplementation with 700mg of eicosapentaenoic acid (EPA) omega-3s and 480 mg of docosahexaenoic acid (DHA) omega-3s showed reduced likelihood of conversion to psychosis one year later than the 40 who received placebo.
The team followed up an average of 6.7 years later with 71 of the original 81 participants. Among those who had received the omega-3 intervention, 9.8% had developed psychosis. Among the placebo group, 40% had developed psychosis, and they had done so earlier.
In addition, the omega-3 participants were better functioning, they had required less antipsychotic medication, and they had lower rates of any psychiatric disorder than the placebo group.
Amminger wrote in the journal Nature Communications, “Unlike antipsychotics, fish oil tablets have no side effects and arent’s stigmatizing to patients.”
Editor’s Note: Because of their lack of side effects, a good case can be made for omega-3 fatty acids for patients at high risk for psychosis. The novel thing about this study is that short-term treatment with omega-3 fatty acids had preventive effects almost 7 years later.
At the 2015 meeting of the Society of Biological Psychiatry in May, researcher Daniel Blumberger reported to this editor (Robert M. Post) that he has found repeated transcranial magnetic stimulation (rTMS) to be effective for depression in late life. Blumberger noted that it may be necessary to use higher intensity stimulation (i.e. at 120% of motor threshold instead of the usual 110% of motor threshold) in the elderly in order to overcome the gap between the skull and the brain, which can grow with age due to brain atrophy.
Blumberger has also successfully used rTMS as a followup treatment to a successful course of electroconvulsive therapy (ECT), administering rTMS twice a week for up to 66 treatments in a given patient in order to maintain remission of their depression.