Personalized medicine: Prediction of disease vulnerability in mood disorders

Personalized or precision medicine is a medical discipline that proposes tailoring health care to each individual by integrating data from their genetic makeup, epigenetic modifications, other biomarkers, clinical symptoms and environmental exposures. Currently, patients typically present for treatment of mood disorders relatively late in the disease course and this is of great concern both because delay in attaining remission reduces the success of subsequent treatment and depressive episodes have negative cumulative effects on the brain and body. In this article we will discuss progress in personalized medicine for predicting disease vulnerability for major depressive disorder and bipolar disorder. We will review non-biological risk factors, genetic factors, epigenetic factors, as well as the roll of neuroimaging and electroencephalograms. Putting together this information will poise psychiatrists to make biological, system-based evaluations for their patients

Impulsive choice and psychological pain in acutely suicidal depressed patients

Despite identification of several risk factors, suicide prediction and prevention is still a clinical challenge. Suicide can be seen as a consequence of poor decision making triggered by overwhelming psychological pain. We examined the relationship of choice impulsivity and psychological pain in depressed patients with acute suicidality. Impulsive choice (delay discounting), psychological pain, and clinical characteristics were assessed in four groups of adults (N = 20-22): a) depressed patients within 72 hours after a suicide attempt, b) depressed patients with active suicidal ideation, c) nonsuicidal depressed patients, and d) healthy controls. Impulsive choice was higher in the suicide attempt (0.114 [0.027]) and ideation (0.099 [0.020]) groups compared with nonsuicidal depressed (0.079 [0.020]) and healthy (0.066 [0.019]) individuals (F(3,79) = 3.06, p = .042). Psychological pain data showed a similar profile (F(3,78) = 43.48, p < .001), with 43.4 (2.9) rating of psychological pain for the suicide attempt, 54.3 (2.2) for suicide ideation, 37.0 (3.2) for nonsuicidal depressed, and 13.7 (0.5) for healthy groups. Within the suicide attempt group, persisting suicidal ideation was associated with more severe depression (36.6 [2.9] versus 21.5 [3.1], p = .007) and choice impulsivity (0.134 [0.03] versus 0.078 [0.04], p = .015). Both measures normalized within a week: depression (29.9 [2.6] versus 14.4 [3.0], p = .006) and choice impulsivity (0.114 [0.026] versus 0.066 [0.032], p = .019). Transient impulsive choice abnormalities are found in a subset of those who attempt suicide. Both, suicidal ideation and behavior were associated with choice impulsivity and intense psychological pain

Gender-specific effects of depression and suicidal ideation in prosocial behaviors.

Prosocial behaviors are essential to the ability to relate to others. Women typically display greater prosocial behavior than men. The impact of depression on prosocial behaviors and how gender interacts with those effects are not fully understood. We explored the role of gender in the potential effects of depression on prosocial behavior.We examined prosocial behaviors using a modified version of the Trust Game in a clinical population and community controls. Study participants were characterized on the severity of depression and anxiety, presence of suicidal ideation, history of childhood trauma, recent stressful life events, and impulsivity. We correlated behavioral outcomes with gender and clinical variables using analysis of variance and multiple regression analysis.The 89 participants comprised four study groups: depressed women, depressed men, healthy women and healthy men (n = 16-36). Depressed men exhibited reciprocity more frequently than healthy men. Depression induced an inversion of the gender-specific pattern of self-centered behavior. Suicidal ideation was associated with increased reciprocity behavior in both genders, and enhancement of the effect of depression on gender-specific self-centered behavior.Depression, particularly suicidal ideation, is associated with reversal of gender-specific patterns of prosocial behavior, suggesting abnormalities in sexual hormones regulation. This explanation is supported by known abnormalities in the hypothalamus-pituitary-adrenal and hypothalamus-pituitary-gonadal axes found in depression

Behavior of depressed patients and healthy participants in the modified Trust Game.

<p>Bonferroni correction was used for multiple comparison;</p>a<p>compared to suicide attempter group;</p>b<p>compared to suicidal ideation group;</p>c<p>compared to depressed control group;</p>d<p>compared to healthy control group.</p><p>Behavior of depressed patients and healthy participants in the modified Trust Game.</p

Relationship between offer amount during the baseline condition and reciprocity behavior in healthy women, depressed women, healthy men and depressed men.

<p>Relationship between offer amount during the baseline condition and reciprocity behavior in healthy women, depressed women, healthy men and depressed men.</p

Effect of depression and presence of suicidal ideation in prosocial behavior in men and women.

<p>A. Reciprocity behavior during baseline condition in healthy participants and depressed patients. B. Self-centered behavior during emotionally challenging condition in healthy participants and depressed patients. C. Reciprocity behavior during baseline condition in depressed non suicidal and depressed suicidal patients. D. Self-centered behavior during emotionally challenging condition in in depressed non suicidal and depressed suicidal patients. * Different between healthy and depressed participants, # different from all other groups; p<0.05.</p

Demographic and clinical characteristics of depressed patients and healthy participants.

<p>Bonferroni correction was used for multiple comparison;</p>a<p>compared to suicide attempter group;</p>b<p>compared to suicidal ideation group;</p>c<p>compared to depressed control group;</p>d<p>compared to healthy control group;</p><p>*Yates chi square.</p><p>Demographic and clinical characteristics of depressed patients and healthy participants.</p

The neural correlates of reciprocity are sensitive to prior experience of reciprocity

Reciprocity is central to human relationships and is strongly influenced by multiple factors including the nature of social exchanges and their attendant emotional reactions. Despite recent advances in the field, the neural processes involved in this modulation of reciprocal behavior by ongoing social interaction are poorly understood. We hypothesized that activity within a discrete set of neural networks including a putative moral cognitive neural network is associated with reciprocity behavior. Nineteen healthy adults underwent functional magnetic resonance imaging scanning while playing the trustee role in the Trust Game. Personality traits and moral development were assessed. Independent component analysis was used to identify task-related functional brain networks and assess their relationship to behavior. The saliency network (insula and anterior cingulate) was positively correlated with reciprocity behavior. A consistent array of brain regions supports the engagement of emotional, self-referential and planning processes during social reciprocity behavior