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GME Research Review

GME Research Review is a monthly newsletter where internationally recognized experts select, summarize, and provide a clinical commentary on the latest published research in psychiatry. Each summary has been derived from the relevant article’s abstract and the clinical commentary has been provided by our expert.

 
 

Issue 29, August 2014: Guest Commentator—Vladimir Maletic, MD, University of South Carolina School of Medicine, Columbia, SC

 

 

Cognitive Effects of Major Depression Treatment with Repetitive Transcranial Magnetic Stimulation

Nadeu SE, Bowers D, Jones TL, et al.  
Cogn Behav Neurol. 2014;27:77-87.


Objective: A previous report from a randomized, sham-controlled trial of 5 Hz dorsolateral prefrontal left- and right-sided repetitive transcranial magnetic stimulation (rTMS) in 48 participants with medically refractory major depressive disorder (MDD) noted the greatest symptomatic improvement with right-side cranial stimulation, both rTMS and sham, and to a lesser degree with left rTMS. Depression is commonly associated with cognitive impairment. The present study attempted to determine whether participants experienced treatment-related cognitive improvement. If so, which cognitive domains (language, executive, visuospatial, verbal episodic memory, attention) benefited the most, and whether treatment-induced cognitive changes were related either to improvement in depression or to other treatment variables, such as right versus left treatment and rTMS versus sham.

Methods:
• The study utilized hierarchical regression analyses to determine how baseline or treatment-associated variables contributed to changes in neuropsychological functions.
• The variables were: neuropsychological function in the 5 domains, severity of depression, change in depression with treatment, rTMS versus sham, laterality of stimulation, and rTMS-laterality interaction.

Results: Compared to sham, right rTMS was associated with 1.24 standard deviations greater gain in language function, 1.09 standard deviations greater gain in visuospatial function, and 2.38 standard deviations greater gain in verbal episodic memory than left rTMS. Observed improvements did not appear to be directly related to the relief from depression.

Conclusions: Study results suggest that disorders of cognition and mood in depression may have different mechanisms, but right rTMS may treat both.

Clinical Commentary
Change in depression ratings, laterality of stimulation, even true vs sham rTMS, demonstrated no impact on neurocognitive function 3 months after treatment. The significant improvement in language, visuospatial function and verbal episodic memory was exclusively attributable to the difference between sham vs right hemisphere rTMS. Further study and reproduction of these results will be necessary. Since improvement in cognition with right rTMS appears independent of improvement in mood, it would be interesting to see if a similar procedure would ameliorate cognition in other neuropsychiatric conditions.

 

 

Relationship Between the Quality of Marital Interaction and Thickness of Carotid Artery Intima-Media

Joseph NT, Kamarck TW, Muldoon MF, et al.
Psychosom Med. 2014;76:347-354.


Objective: Studies have shown that marital status and quality of marriage are associated with cardiovascular health. The present study examined the association between marital interaction quality during daily life and subclinical cardiovascular disease (CVD).

Methods:
• The sample consisted of 281 healthy, employed middle-aged adults who were married or living with a partner in a marital-like relationship (mean age=42.0 years, 88% white, 52% men).
• Marital interaction quality was assessed using hourly real-time ecological momentary assessments for 4 days, with participants rating their current or recent partner interactions on positive and negative characteristics (e.g., agreeableness and conflict).
• Carotid artery intima-medial thickness (IMT) was assessed using ultrasound imaging.

Results: Adjusting for demographics, positive marital interaction was inversely associated with IMT (b=j0.02, F[1,275]=9.18, p=.002), and negative marital interaction was positively associated with IMT (b=0.02 F[1,275]=10.29, p=.001). These associations were not accounted for by behavioral and biological CVD risk factors and were consistent across age, sex, race, and education. The associations were also independent of marital interaction frequency, nonmarital social interaction quality, and personality factors. Global reports of marital quality, in contrast, were not associated with IMT.

Conclusions: Marital quality as measured during real-time interactions between partners was associated with subclinical CVD in healthy middle-aged adults. This study supports the use of real-time social interaction assessment for characterizing links between social relationships and cardiovascular health.

Clinical Commentary
This is a cross-sectional study and the direction of the effect cannot be determined. Furthermore, it is plausible to consider that the relationship between medical illness and marital difficulties may be bidirectional. Nevertheless, the study provides an important insight, given that mood disorders have an association with both cardiovascular illness and marital problems. Concurrent treatment of mood disorders and marital therapy may provide additional health benefits.

 

 

Association Between Elevated Maternal C-Reactive Protein and Schizophrenia in the Offspring

Canetta S, Sourander A, Surcel HM, et al.
Am J Psychiatry. 2014. In press.


Objective: Epidemiological and preclinical research has established a relationship between immune activation due to maternal infection and subsequent risk of schizophrenia in the offspring. The present study investigated an association between early gestational C-reactive protein, a known inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large, national birth cohort with an extensive serum biobank.

Method:
• A nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort was utilized.
• A total of 777 cases (schizophrenia, N=630; schizoaffective disorder, N=147) with maternal sera available for C-reactive protein testing were identified and matched to 777 control subjects.
• Maternal C-reactive protein levels were assessed using a latex immunoassay from archived maternal serum specimens.

Results: Increasing maternal C-reactive protein levels were significantly associated with schizophrenia in offspring (adjusted odds ratio=1.31, 95% confidence interval=1.10-1.56). This finding remained significant after adjusting for potential confounders, including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status.

Conclusions: This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders.

Clinical Commentary
This study provides further support to the inflammatory hypothesis of schizophrenia etiopathogenesis. Furthermore, it provides us with a clear target for preventive interventions, focused on detecting and subsequently addressing maternal infection and inflammation.

 

 

Changes in Antidepressant Use After the FDA Warning

Lu CY, Zhang F, Lakoma M, et al.
BMJ. 2014. In press


Objective: Widely publicized US Food and Drug Administration warnings in 2003 about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people. The present study has attempted to investigate the consequences of the warning-related changes in the prescribing practices.

Methods: This Quasi-experimental study assessed changes in outcomes after the warnings, controlling for pre-existing trends.
• Information was extracted from the Automated healthcare claims data (2000–10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network.
• Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million).
• The main outcome measures were rates of antidepressant dispensing, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides.

Results: Trends in antidepressant use and poisonings changed abruptly after the warnings (Table). In the second year after the warnings, relative changes in antidepressant use were −31.0% among adolescents, −24.3% among young adults, and −14.5% among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100,000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents and young adults, but not among adults. These reflected absolute increases of 2 and 4 poisonings per 100,000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group.

 

Adolescents

Young Adults

Adults

Changes in Antidepressant Use post warnings

–31%
(95% CI, –33% to –29%)

–24.3%
(–25.4% to –23.2%)

–14.5%
(–16% to –12.9%)

Reduction in medication dispensing per 100,000 ppl.

696

1,216

1,621

Psychotropic drug poisoning

21.7%
(95% CI, 4.9% to 38.5%)

33.7%
(95% CI, 26.9% to 40.4%)

5.2%
(95% CI, −6.5% to 16.9%)

Conclusions: Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people.

Clinical Commentary
FDA warnings and ensuing media publicity generated a drastic change in antidepressant prescribing practice associated with unintended and concerning consequences. The actual impact of FDA warning may be underestimated as not all individuals who have attempted suicidal poisoning seek medical attention. Not only treatment, but also lack of antidepressant treatment may put young patients in jeopardy. Consequences of FDA advisories require extended scrutiny.

 

Depressive Symptom Clusters Predict a 6-Year Increase in Insulin Resistance

Khambaty T, Stewart JC, Muldoom MF, et al.
Psychosom Med. 2014;76:363-369.


Objective: To examine longitudinal bidirectional associations between two depressive symptom clusters (the cognitive-affective and somatic-vegetative clusters) and insulin resistance, a marker of prediabetes.

Methods:
• Participants were 269 adults aged 50 to 70 years without diabetes enrolled in the Pittsburgh Healthy Heart Project, a prospective cohort study.
• At baseline and 6-year visits, participants completed the Beck Depression Inventory-II (BDI-II) and underwent a blood draw to quantify fasting insulin and glucose.
• Researchers examined the total baseline BDI-II, cognitive-affective, and somatic-vegetative scores as predictors of 6-year change in the homeostatic model of assessment (HOMA) score, an estimate of insulin resistance calculated from fasting insulin and glucose.
• Study evaluated baseline HOMA score as a predictor of 6-year change in BDI-II total and subscale scores.

Results: Regression analyses, adjusted for demographic factors and baseline HOMA score, found that the baseline BDI-II somatic-vegetative score (A = 0.14, p = .025), but not the cognitive-affective (A = 0.001, p = .98) or total (A = 0.10, p = .11) scores, predicted 6-year HOMA change. This result persisted in models controlling for anxiety symptoms and hostility. Several factors were examined as candidate mediators; however, only change in body mass index was a significant mediator (p = .042), accounting for 23% of the observed association. Baseline HOMA score did not predict 6-year change in BDI-II total or subscale scores (Table; all p values = 9.56). Regression Analyses Examining Depressive Symptoms as Predictors of 6-Year Change in HOMA Score

                                                                        Demographic-Adjusted Models

 

B

SE B

b

R2

DR2

DF

Baseline BDI-II Total

0.04

0.03

0.10

0.12

0.01

2.56

Baseline BDI-II cognitive-affective score

0.001

0.06

0.001

0.01

0.00

0.00

Baseline BDI-II somatic-vegetative score

0.08

0.03

0.14*

0.03

0.02

5.07

n=269. BDI-II=Beck Depression Inventory-II; HOMA=Homeostatic Model of Assessment; SE=standard error. aAdjusted for age, sex, race/ethnicity, education, and baseline HOMA score.
*p< .05.

Conclusions: Among adults aged 50 to 70 years, the somatic-vegetative symptoms of depression (e.g., fatigue, sleep disturbance, and appetite changes) may worsen insulin resistance and increase diabetes risk, partly, by increasing body mass index.

Clinical Commentary
The study confirmed a link between somatic-vegetative signs of depression and development of insulin resistance. Insulin resistance, in turn, did not prognosticate future depression. We can only speculate about the relevant pathophysiological mechanisms. Immune, autonomic, and hypothalamic-pituitary-adrenal disturbances have all been associated with somatic-vegetative symptoms of depression and are plausible risk factors for the vascular disease. In further support of this hypothesis, obesity was identified as a relevant mediator. However, inflammatory indicators, such as IL-6 and CRP did not mediate development of vascular disorder. Unfortunately, the study did not examine other indicators of inflammation and oxidative stress, nor balance between inflammatory and anti-inflammatory cytokines.

 


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