Enrique Baca-Garcia

New perspectives in glutamate and anxiety

Anxiety and stress-related disorders, namely posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (ODC), social and specific phobias, and panic disorder, are a major public health issue. A growing body of evidence suggests that glutamatergic neurotransmission may be involved in the biological mechanisms underlying stress response and anxiety-related disorders. The glutamatergic system mediates the acquisition and extinction of fear-conditioning. Thus, new drugs targeting glutamatergic neurotransmission may be promising candidates for new pharmacological treatments. In particular, N-methyl-d-aspartate receptors (NMDAR) antagonists (AP5, AP7, CGP37849, CGP39551, LY235959, NPC17742, and MK-801), NMDAR partial agonists (DCS, ACPC), α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) antagonists (topiramate), and several allosteric modulators targeting metabotropic glutamate receptors (mGluRs) mGluR1, mGluR2/3, and mGluR5, have shown anxiolytic-like effects in several animal and human studies. Several studies have suggested that polyamines (agmatine, putrescine, spermidine, and spermine) may be involved in the neurobiological mechanisms underlying stress-response and anxiety-related disorders. This could mainly be attributed to their ability to modulate ionotropic glutamate receptors, especially NR2B subunits. The aim of this review is to establish that glutamate neurotransmission and polyaminergic system play a fundamental role in the onset of anxiety-related disorders. This may open the way for new drugs that may help to treat these conditions.

Is impulsivity a link between childhood abuse and suicide

Childhood abuse and neglect are known to affect psychological states through behavioral, emotional, and cognitive pathways. They increase the risk of having psychiatric diseases in adulthood and have been considered risk factors for suicidal behavior in all diagnostic categories. Early, prolonged, and severe trauma is also known to increase impulsivity, diminishing the capacity of the brain to inhibit negative actions and to control and modulate emotions. Many neurobiological studies hold that childhood maltreatment may lead to a persistent failure of the inhibitory processes ruled mainly by the frontal cortex over a fear-motivated hyperresponsive limbic system. Multiple neurotransmitters and hormones are involved in the stress response, but, to our knowledge, the two major biological consequences of the chronic exposure to trauma are the hypofunction of the serotonergic system and changes in the hypothalamic-pituitary-adrenal axis function. Some of these findings overlap with the neurobiological features of impulsivity and of suicidal behavior. Impulsivity has also been said to be both a consequence of trauma and a risk factor for the development of a pathological response to trauma. Thus, we suggest that impulsivity could be one of the links between childhood trauma and suicidal behavior. Prevention of childhood abuse could significantly reduce suicidal behavior in adolescents and adults, in part, through a decrease in the frequency of impulsive behaviors in the future.

Issues for DSM-V: Suicidal Behavior as a Separate Diagnosis on a Separate Axis

Suicidal behavior (death and attempts) is usually a complication of psychiatric conditions, most commonly mood disorders (1). However, it also occurs in schizophrenia, substance use disorders (particularly with alcohol), and personality and anxiety disorders, among others (1). About 10% of those who commit or attempt suicide have no identifiable psychiatric illness. However, our current nomenclature considers suicidal behavior a symptom of major depressive episode or borderline personality disorder.

Family history of suicidal behavior and early traumatic experiences : Additive effect on suicidality and course of bipolar illness?

BACKGROUND Bipolar disorder (BD) is associated with a high prevalence of suicide attempt and completion. Family history of suicidal behavior and personal history of childhood abuse are reported risk factors for suicide among BD subjects. METHODS BD individuals with family history of suicidal behavior and personal history of childhood abuse (BD-BOTH), BD individuals with family history of suicidal behavior or personal history of childhood abuse (BD-ONE), and BD individuals with neither of these two risk factors (BD-NONE) were compared with regard to demographic variables and clinical measures. RESULTS Almost 70% of the sample had a history of a previous suicide attempt. There were significantly higher rates of previous suicide attempts in the BD-BOTH and BD-ONE relative to the BD-NONE group. BD-BOTH were significantly younger at the time of their first suicide attempt and had higher number of suicide attempts compared with BD-NONE. BD-BOTH were significantly younger at the time of their first episode of mood disorder and first psychiatric hospitalization and had significantly higher rates of substance use and borderline personality disorders compared to BD-NONE. LIMITATIONS Retrospective study. Use of semi-structured interview for the assessment of risk factors. CONCLUSIONS BD individuals with a familial liability for suicidal behavior and exposed to physical and/or sexual abuse during childhood are at a greater risk to have a more impaired course of bipolar illness and greater suicidality compared to those subjects with either only one or none of these risk factors. Prospective studies are needed to confirm these findings.

Toward a Biosignature for Suicide

OBJECTIVE Suicide, a major cause of death worldwide, has distinct biological underpinnings. The authors review and synthesize the research literature on biomarkers of suicide, with the aim of using the findings of these studies to develop a coherent model for the biological diathesis for suicide. METHOD The authors examined studies covering a large range of neurobiological systems implicated in suicide. They provide succinct descriptions of each system to provide a context for interpreting the meaning of findings in suicide. RESULTS Several lines of evidence implicate dysregulation in stress response systems, especially the hypothalamic-pituitary-adrenal axis, as a diathesis for suicide. Additional findings related to neuroinflammatory indices, glutamatergic function, and neuronal plasticity at the cellular and circuitry level may reflect downstream effects of such dysregulation. Whether serotonergic abnormalities observed in individuals who have died by suicide are independent of stress response abnormalities is an unresolved question. CONCLUSIONS The most compelling biomarkers for suicide are linked to altered stress responses and their downstream effects, and to abnormalities in the serotonergic system. Studying these systems in parallel and in the same populations may elucidate the role of each and their interplay, possibly leading to identification of new treatment targets and biological predictors.

Fundamentals for Future Mobile-Health (mHealth): A Systematic Review of Mobile Phone and Web-Based Text Messaging in Mental Health

Background Mobile phone text messages (short message service, SMS) are used pervasively as a form of communication. Almost 100% of the population uses text messaging worldwide and this technology is being suggested as a promising tool in psychiatry. Text messages can be sent either from a classic mobile phone or a web-based application. Reviews are needed to better understand how text messaging can be used in mental health care and other fields of medicine. Objective The objective of the study was to review the literature regarding the use of mobile phone text messaging in mental health care. Methods We conducted a thorough literature review of studies involving text messaging in health care management. Searches included PubMed, PsycINFO, Cochrane, Scopus, Embase and Web of Science databases on May 25, 2015. Studies reporting the use of text messaging as a tool in managing patients with mental health disorders were included. Given the heterogeneity of studies, this review was summarized using a descriptive approach. Results From 677 initial citations, 36 studies were included in the review. Text messaging was used in a wide range of mental health situations, notably substance abuse (31%), schizophrenia (22%), and affective disorders (17%). We identified four ways in which text messages were used: reminders (14%), information (17%), supportive messages (42%), and self-monitoring procedures (42%). Applications were sometimes combined. Conclusions We report growing interest in text messaging since 2006. Text messages have been proposed as a health care tool in a wide spectrum of psychiatric disorders including substance abuse, schizophrenia, affective disorders, and suicide prevention. Most papers described pilot studies, while some randomized clinical trials (RCTs) were also reported. Overall, a positive attitude toward text messages was reported. RCTs reported improved treatment adherence and symptom surveillance. Other positive points included an increase in appointment attendance and in satisfaction with management and health care services. Insight into message content, preventative strategies, and innovative approaches derived from the mental health field may be applicable in other medical specialties.

Severity of personality disorders and suicide attempt

Objective:  Severity of personality disorders (PDs) may be more useful in estimating suicide risk than the diagnosis of specific PDs. We hypothesized that suicide attempters with severe PD would present more attempts and attempts of greater severity/lethality.

Low plasma cholesterol levels in suicidal males: A gender- and body mass index-matched case-control study of suicide attempters and nonattempters

Findings from animal and human studies suggest an association between low cholesterol levels and suicidal behaviors. The purpose of this case-control study was to test whether cholesterol levels in suicide attempters are lower than in controls without suicide attempt history matched by gender, age, and body mass index (BMI). Suicide attempters (n=177: 68 men and 109 women) and controls (177 blood donors) were assessed. Serum cholesterol levels were significantly lower in suicide attempters than in controls. After gender stratification, the difference remained significant in men, but not in women.

Dimensions of suicidal behavior according to patient reports

Abstract.Five factor analyses with limitations explored the Suicidal Intent Scale (SIS) subscales reflecting suicidal behavior dimensions. This larger sample study conducts an exploratory factor analysis of the SIS. Two large samples of suicide attempters (N= 435 and N= 252) from a general hospital were studied. The validity of SIS subscales obtained from the factor analysis was investigated by examining the association between the subscales and clinical variables. There were two factors: expected lethality and planning. In both samples, male gender and depression tended to be associated with higher scores in both subscales (small to medium effect sizes). Hospitalization was associated with higher scores in both SIS subscales (medium to large effects) suggesting that these subscales were reasonably good predictors of suicide attempt severity. Clinicians assessing patient reports to establish the severity of suicide attempts need to ask questions regarding both dimensions: expected lethality and planning.

Perceived quality of life in obsessive-compulsive disorder: related factors

BackgroundObsessive-compulsive disorder (OCD) affects young adults and has great impact on the social, emotional and work spheres.MethodsWe measured perceived quality of life (QOL) in OCD patients, in order to analyse socio-demographic and clinical factors that may be associated with QOL perception. 64 OCD outpatients were assessed with the Mini International Neuropsychiatric Interview for DSM-IV, the Yale-Brown Obsessions and Compulsions scale (Y-BOCS), Hamiltons depression scale and the SF-36 self-administered global QOL perception scale.ResultsWe found a correlation among Hamiltons scale scores and all SF-36 subscales. The severity of the obsessive-compulsive disorder was correlated with all SF-36 subscales and with the highest scores in Hamiltons scale. The obsessions subscale was correlated to all SF-36 subscales, while the compulsions subscale was correlated only to social functioning, emotional role, mental health and vitality. Compulsions were not related to general health perception. There were significant differences between OCD patients and the Spanish general population in all SF-36 subscales except those related to physical health and pain. Gender, age, age of onset of the disorder, years of evolution and marital status of the patients did not significantly affect quality of life perception. Being employed was related to better scores in the subscale of physical role. Patients with medical comorbidity scored lower in the subscales of general health, social functioning and mental health. Patients with comorbid psychiatric disorders had worse scores in the subscales of pain, general health, social functioning and mental health.ConclusionQuality of life perception was different in OCD patients and the general population. Quality of life perception was related to severity of the disorder, physical and psychiatric comorbidity and employment status.