Anxiety Disorders: Sher L

Sher L. · No affiliation provided · QJM. · Pubmed #14702505 links to  free full text

This publication has no abstract.

Sher L. · Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, NY 10032, USA. · Minerva Pediatr. · Pubmed #18971900 No free full text.

Abstract: Post-traumatic stress disorder (PTSD) is a common psychiatric disorder which is frequently comorbid with major depressive disorder (MDD). It has been suggested that some or all individuals diagnosed with comorbid PTSD and MDD have a separate psychobiological condition that can be termed ''post-traumatic mood disorder'' (PTMD). The idea was based on the fact that a significant number of studies suggested that patients suffering from comorbid PTSD and MDD differed clinically and biologically from individuals with PTSD alone or MDD alone. Individuals with comorbid PTSD and MDD are characterized by greater severity of symptoms and the higher level of impairment in social and occupational functioning compared to individuals with PTSD alone or MDD alone. Neurobiological evidence supporting the concept of PTMD includes the findings from neuroendocrine challenge, cerebrospinal fluid, neuroimaging, sleep and other studies. It has been demonstrated that child abuse increases the risk for PTSD, MDD, and suicidal behavior in adolescents and adults. Many victims of childhood abuse develop comorbid PTSD and depression, i.e., they develop PTMD. PTMD is associated with suicidal behavior. The link between childhood abuse, suicidal behavior in adolescents and PTMD indicates that it is important to develop interventions to prevent PTMD in victims of child abuse; to develop measures to prevent suicidal behavior in adolescents with PTMD; and to study psychobiology of PTMD in order to develop treatments for PTMD. Priorities for intervening to reduce adolescent suicidal behavior lie with interventions focused upon the improved recognition, treatment and management of adolescents with psychiatric disorders including PTMD.

Sher L. · Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA. · Minerva Pediatr. · Pubmed #18449137 No free full text.

Abstract: Depression and suicidal behavior in adolescents are frequently comorbid with alcohol and drug abuse. Alcohol abuse may lead to the deficiency of micronutrients including selenium, an essential trace element. In addition, dietary intake of selenium in some geographic areas is low. The combination of these two factors may result in significant selenium deficiency. Selenium plays an important role in brain function. Selenium is a potent protective agent for neurons through the expression of selenoproteins. Studies suggest that low selenium status is associated with depressed mood, anxiety, and cognitive decline. A tremendous amount of structural and functional brain development takes place during the teenage years. Many of the changes that take place during the second decade of life are novel and do not simply represent the remnants of childhood plasticity. Considerable evidence suggests that alcohol affects brain function and behavior differently during adolescence than during adulthood. Adolescents are more vulnerable to the long-term effects of alcohol abuse. The adolescent brain may be especially sensitive to a harmful combination of alcohol abuse and selenium deficiency. This combination may contribute to depression and suicidal behavior in adolescents. Recent research opens new avenues for the potential development of selenium containing compounds as preventive or therapeutic agents in psychiatric and neurological conditions. Healthy nutrition and possibly mineral supplementations should be a part of the treatment plan of adolescents with alcohol use disorders especially when alcohol misuse is comorbid with depression.

Makhija NJ, Sher L. · Department of Neuroscience, New York State Psychiatric Institute, New York 10032, USA. · Int J Adolesc Med Health. · Pubmed #17458324 No free full text.

Abstract: Adolescent suicide is an escalating crisis that needs to be addressed by clinicians and researchers. Alcohol use has consistently been implicated in adolescent suicide and it is generally assumed that alcohol use leads to an increased risk in suicidality, suicide attempts and completed suicides. It can lead to adolescent suicidality through alcohol myopia, disinhibition, and impaired judgment. Multiple genetically related intermediate phenotypes might contribute to the risk of alcohol misuse and suicidal behavior in adolescents. Genetic variations that enhance the risk for mood and anxiety symptoms or susceptibility to stress might increase risk through different mechanisms. Comorbid disorders such as depression are frequently exhibited in adolescents who misuse alcohol, therefore any adolescent who appears to be at risk for alcoholism or depression should always be screened for all other psychiatric disorders and for suicidality; some signs suicidal adolescents may exhibit include withdrawal, personality change, and a loss of interest in pleasurable activities. While assessment is important, prevention is crucial in any attempt to decrease the incidence of adolescent suicide. The US Center for Disease Control and Prevention (CDC) has established a set of seven guidelines that can be implemented from kindergarten through high school in order to establish alcohol prevention efforts in schools. Through beginning prevention efforts at a young age, it is hopeful that both alcohol misuse and adolescent suicide can be reduced.

Sher L. · Division of Neuroscience, Department of Psychiatry, Columbia University, New York, NY 10032, USA. · Acta Psychiatr Scand. · Pubmed #16390364 No free full text.

Abstract: OBJECTIVE: The purpose of this paper was to provide a clinical review of the literature on the relation of alcoholism to suicidal behavior. METHOD: Studies of alcoholism and suicidal behavior available in MEDLINE, Institute for Scientific Information Databases (Science Citation Index Expanded, Social Sciences Citation Index, and Arts & Humanities Citation Index), EMBASE, and Cochrane Library were identified and reviewed. RESULTS: Alcoholism is associated with a considerable risk of suicidal behavior. Individuals with alcoholism who attempt or complete suicide are characterized by major depressive episodes, stressful life events, particularly interpersonal difficulties, poor social support, living alone, high aggression/impulsivity, negative affect, hopelessness, severe alcoholism, comorbid substance, especially cocaine abuse, serious medical illness, suicidal communication, and prior suicidal behavior. Partner-relationship disruptions are strongly associated with suicidal behavior in individuals with alcoholism. CONCLUSION: All individuals with alcoholism should receive a suicide risk assessment based on known risk factors.

Sher L. · Division of Neuroscience, Department of Psychiatry, Columbia University, New York, NY 10032, USA. · Forsch Komplementarmed Klass Naturheilkd. · Pubmed #15604626 No free full text.

Abstract: The concept of the placebo effect has received a considerable attention over the past several decades. The placebo effect has been observed in different psychiatric disorders, including post-traumatic stress disorder (PTSD), a chronic and severe disorder precipitated by exposure to a psychologically distressing event. The placebo response rates in patients with PTSD range from 19% to 62%. A considerable number of research publications suggest that endogenous opioids are involved in the mechanisms of the placebo effect. Endogenous opioid peptides play an important role in stress response and in the pathophysiology of PTSD. Therefore, endogenous opioids may be involved in the neurobiology of the placebo effect in PTSD. Possibly, the endogenous opioid system mediates the effect of placebo on all 3 PTSD symptom clusters (re-experiencing symptoms, avoidance and numbing, and physiologic arousal). The placebo effect-related activation of the endogenous opioid system may result in an improvement in intrusive symptomatology and symptoms of increased arousal because the administration of exogenous opioids improve these symptoms. The placebo effect-related activation of the endogenous opioid system may have a mood-enhancing effect, and, consequently, diminish avoidance and numbing. Multiple neurotransmitter and neuroendocrine pathways may be involved in the mechanisms of the placebo effect in PTSD. Further studies of the neurobiology of the placebo effect on patients with PTSD and other psychiatric disorders may produce interesting and important results.

Flensborg-Madsen T, Mortensen EL, Knop J, Becker U, Sher L, Grønbaek M. · Centre of Alcohol Research, National Institute of Public health, University of Southern Denmark, Copenhagen K, Denmark. · Compr Psychiatry. · Pubmed #19486728 No free full text.

Abstract: BACKGROUND: Understanding the comorbidity of alcohol use disorders (AUD) and other psychiatric disorders may have important implications for treatment and preventive interventions. However, information on the epidemiology of this comorbidity is lacking. The objective of this study was to present results on lifetime psychiatric comorbidity of AUD in a large Danish community population. METHODS: A prospective cohort study was used, comprising 3 updated measures of sets of lifestyle covariates and 26 years of follow-up data on 18,146 individuals from the Copenhagen City Heart Study, Denmark. The study population was linked to national Danish hospital registers and a greater Copenhagen alcohol unit treatment register to detect registrations with AUD and other psychiatric disorders. RESULTS: Of the individuals invited to the study, 7.6% were registered with AUD, and among these, 50.3% had a lifetime comorbid psychiatric disorder. Personality disorders were the most common comorbid disorders (24%) together with mood disorders (16.8%) and drug abuse (16.6%). The risk of developing a psychiatric disorder in individuals who were already registered with AUD was larger than the risk of developing AUD in individuals who were already registered with another psychiatric disorder; these differences in risk were especially noticeable for anxiety disorders, personality disorders, and drug abuse. CONCLUSIONS: AUD is frequently comorbid with other psychiatric disorders, and it is likely that AUD is both an etiologic factor in other mental disorders and a consequence of mental disease. However, in interpreting these complex and perhaps circular causal links, it is important to consider that AUD is registered before a comorbid psychiatric diagnosis more often than the reverse temporal order.

Flensborg-Madsen T, Knop J, Mortensen EL, Becker U, Sher L, Grønbaek M. · Institute of Preventive Medicine, Copenhagen University Hospital, Centre for Health and Society, and Department of Health Psychology, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark. · Psychiatry Res. · Pubmed #19359047 No free full text.

Abstract: Knowledge of the epidemiology of suicide is a necessary prerequisite for developing prevention programs. The aim of this study was to analyze the risk of completed suicide among individuals with alcohol use disorders (AUD), and to assess the role of other psychiatric disorders in this association. A prospective cohort study was used, containing three updated sets of lifestyle covariates and 26 years follow-up of 18,146 individuals between 20 and 93 years of age from the Copenhagen City Heart Study in Denmark. The study population was linked to four different registers in order to detect: Completed suicide, AUD, Psychotic disorders, Anxiety disorders, Mood disorders, Personality disorders, Drug abuse, and Other psychiatric disorders. Individuals registered with AUD were at significantly increased risk of committing suicide, with a crude hazard ratio (HR) of 7.98 [Confidence interval (CI): 5.27-12.07] compared to individuals without AUD. Adjusting for all psychiatric disorders the risk fell to 3.23 (CI: 1.96-5.33). In the stratified sub-sample of individuals without psychiatric disorders, the risk of completed suicide was 9.69 (CI: 4.88-19.25) among individuals with AUD. The results indicate that individuals registered with AUD are at highly increased risk of completed suicide, and that registered co-morbid psychiatric disorders are neither sufficient nor necessary causes in this association.

Carballo JJ, Harkavy-Friedman J, Burke AK, Sher L, Baca-Garcia E, Sullivan GM, Grunebaum MF, Parsey RV, Mann JJ, Oquendo MA. · Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, NY 10032, United States. · J Affect Disord. · Pubmed #18221790 No free full text.

Abstract: 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.

Arendt M, Rosenberg R, Foldager L, Sher L, Munk-Jørgensen P. · Centre for Basic Psychiatric Research, Aarhus University Hospital, Risskov, Denmark. · Am J Addict. · Pubmed #18058411 No free full text.

Abstract: This is the first follow-up study on the association between cannabis withdrawal symptoms and risk of relapse to cannabis use. Withdrawal symptoms were assessed in 36 subjects seeking treatment for cannabis dependence. All were free of other substance use or alcohol abuse in the month before abstinence from cannabis. Follow-up was performed 26+/-4 months later, and at this point, the withdrawal symptoms were re-assessed. The following symptoms were significantly elevated after abstinence compared with follow-up: irritability, anger, depression, restlessness, craving, sleep problems, strange dreams, increased appetite, violent outbursts, sweating, hot flashes, chills, and shakiness. This offers further validation of a cannabis withdrawal syndrome. Average withdrawal scores at baseline did not differ with gender, age, treatment type, extent of cannabis use, or a lifetime history of anxiety or affective disorders. Withdrawal scores at baseline did not predict relapse during follow-up.

Carballo JJ, Bird H, Giner L, Garcia-Parajua P, Iglesias J, Sher L, Shaffer D. · Division of Child and Adolescent Psychiatry, Department of Psychiatry, Columbia University, New York, NY 10032, USA. · Int J Adolesc Med Health. · Pubmed #17458327 No free full text.

Abstract: OBJECTIVE: To compare the clinical and demographic characteristics of older adolescents and young adults with and without alcohol misuse in a primary care setting. METHODS: This study is a case-control study. Eighty-one 18-30 year old adolescents and young adults attending a primary care center were assessed with the CAGE questionnaire, the PRIME-MD instrument and the IPDE screening questionnaire. Sub-samples of positive screen for alcohol misuse (n = 21) and a negative age- and gender matched group (n = 21) were compared. RESULTS: Of those with alcohol misuse, 71.9% had a comorbid psychiatric diagnosis. Depressive and anxiety disorders appeared to be more prevalent among the subjects with alcohol misuse than among controls. Among those patients with depressive or anxiety disorders and alcohol misuse, 22.2% reported suicidal ideation as compared to none among the controls suffering from depressive or anxiety disorders. 69.1% of subjects with alcohol misuse had a comorbid personality disorder. Significantly more adolescents and young adults with alcohol misuse exhibited borderline personality traits (p = 0.03) and there was also a trend towards a greater proportion exhibiting histrionic traits (p = 0.07) than among those without alcohol misuse. CONCLUSIONS: Adolescents and young adults with alcohol misuse in a primary care center have a high prevalence of psychiatric comorbidity. Cluster B personality disorders may be more prevalent in the population with alcohol misuse. Adolescents and young adults with alcohol misuse may be more likely to report suicidal ideation while suffering from depressive or anxiety disorders. Further studies that evaluate the clinical and demographic characteristics of adolescents and young adults with alcohol misuse attended in a primary care center are needed.

Shoval G, Zalsman G, Apter A, Diller R, Sher L, Weizman A. · Department of Child and Adolescent Psychiatry, Geha Mental Health Center, Petah Tiqva 49100, Israel. · Compr Psychiatry. · Pubmed #17145274 No free full text.

Abstract: The comorbidity of schizophrenia/schizoaffective disorder and substance use is a major psychiatric concern that is associated with aggressive and suicidal behavior. This study investigated the clinical correlates and characterizes adolescent psychotic inpatients with and without comorbid substance use. We performed a retrospective study of 188 adolescent inpatients who were admitted between the years 1994 and 2004 to the inpatient unit of Geha Mental Health Center and who were diagnosed as suffering from either schizophrenia or schizoaffective disorder. The substance-using psychotic inpatients were found to have more relatives with substance-related disorders, fewer comorbid anxiety disorders, lower scores on the Brief Psychiatric Rating Scale and Hamilton Scale for Depression, higher scores on the Overt Aggression Scale, and they were more suicidal than the nonsubstance using inpatients. Adolescent inpatients with schizophrenia and schizoaffective who use substances possess differential clinical characteristics and particular correlates that justify adopting a specific approach to this high-risk clinical subgroup.

Shoval G, Zalsman G, Sher L, Apter A, Weizman A. · Adolescent Inpatient Unit, Geha Mental Health Center, Petah Tiqva, Israel. · Depress Anxiety. · Pubmed #16400622 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) is a common disorder in adolescents, usually treated in the outpatient setting. Our aim in this study was to evaluate the clinical characteristics of adolescents with severe OCD that required hospitalization. A total of 342 patients consecutively admitted to a psychiatric adolescent inpatient unit and 87 healthy volunteers were assessed by a semistructured interview for clinical diagnosis, suicide risk factors, aggression, ego defense mechanisms, and intelligence. Patients with OCD (n=40) were compared to other four diagnostic patient groups with psychotic, affective, conduct, and eating disorders, as well as to normal controls. Adolescent inpatients with OCD experienced less separation anxiety than all the other psychiatric groups (P < .01) and were less impulsive than controls (P < .001). They differed in aggressive/impulsive traits and hospital-related behaviors from other diagnostic groups. Adolescent inpatients with OCD consist of a unique subgroup in the inpatient unit in terms of their clinical characteristics and risk factors for suicide. These characteristics should be taken into account when developing a treatment plan for these difficult-to-treat inpatients.

Gokhshtein U, Giner L, Mitrani M, Sharabi I, Gorlyn M, Sher L, Goldberg PH, Misgav S, Carballo JJ, Bolovik L, Ben-Dor DH. · Adolescent Inpatient Department, Geha Mental Health Center, Petach Tikva, Israel. · Int J Adolesc Med Health. · Pubmed #16231484 No free full text.

Abstract: Adolescents with acute mental illness or suicidal behavior are almost always hospitalized for safety and evaluation purposes. The tendency towards long-term or repeated hospitalizations has many adverse effects such as dependency on the mental health care system and increased chronicity of illness. The causes for these phenomena may be prevented in the early stages of hospitalization. We suggest a therapeutic model of supportive short-term family therapy. The family therapy component aims to enhance the quality of interaction and the level of support among family members. The therapy component dealing with the individual targets the patient's anxiety symptoms and coping strategies, and focuses on return to a healthy state. The child is encouraged to return home to a supportive family as soon as the treatment team feels this to be advisable. This paper discusses a case which highlights how a patient reacts in crisis, and ways in which a supportive environment can help bring about therapeutic success with reduced hospitalization.

Sher L, Oquendo MA, Conason AH, Brent DA, Grunebaum MF, Zalsman G, Burke AK, Mann JJ. · Division of Neuroscience, Department of Psychiatry, Columbia University, and New York State Psychiatric Institute, New York, NY 10032, USA. · Acta Psychiatr Scand. · Pubmed #16156833 No free full text.

Abstract: OBJECTIVE: To compare clinical features of depressed subjects without alcoholism but with a family history of alcoholism to a depressed group without alcoholism and without a family history of alcoholism. METHOD: Clinical and demographic data of 209 depressed subjects without a history of alcoholism in first-degree relatives and 73 depressed individuals with a history of alcoholism in first-degree relatives were compared. Subjects with a personal history of alcoholism were excluded. RESULTS: Depressed subjects with a family history of alcoholism have a significantly higher prevalence of reported childhood physical and sexual abuse and post-traumatic stress disorder (PTSD), make more suicide attempts, and have greater intent to die at the time of their most lethal suicide attempt, compared to depressed subjects without a family history of alcoholism. CONCLUSION: Depressed patients with a family history of alcoholism are at greater risk for suicidal behavior and PTSD and may require more careful management.

Tyano S, Zalsman G, Ofek H, Blum I, Apter A, Wolovik L, Sher L, Sommerfeld E, Harell D, Weizman A. · Child and Adolescent Division, Geha Mental Health Center, Petach Tikva, Israel. · Eur Neuropsychopharmacol. · Pubmed #16076550 No free full text.

Abstract: To evaluate the relationship between plasma serotonin (p5-HT) levels and psychometric measures in suicidal adolescents vs. controls, 211 adolescents from three sites in Israel were divided into four groups: suicidal psychiatric inpatients (n=35); non-suicidal psychiatric inpatients (n=30); adolescents referred to the emergency room (ER) due to a suicide attempt (n=51); and a community-based control group from 4 high schools in the same catchment areas (n=95). All were interviewed and assessed for violence, aggression, depression, impulsivity, anger, anxiety, and p5-HT. p5-HT levels were significantly lower in the control group compared to all other groups. A significant negative correlation was found between p5-HT level and suicidal behavior severity among the suicidal inpatients. p5-HT did not discriminate between the psychiatric diagnostic categories and was significantly lower in ER violent compared to non-violent subjects. Gender, depression, and anger were associated with suicidal behavior in all four groups. Beck Depression Inventory (BDI) scores together with p5-HT levels discriminated between healthy controls and other groups. p5-HT level in combination with some of the psychometric scales may serve as a safe and inexpensive peripheral marker of psychopathology, and may help to differentiate between sub-populations of suicidal adolescents. The biological mechanism behind the serotonin dysregulation in suicidal adolescents requires further investigation.

Sher L. · Division of Neuroscience, Department of Psychiatry, Columbia University, 1051 Riverside Drive, Suite 2917 Box 42, New York, NY 10032, United States. · Med Hypotheses. · Pubmed #15922089 No free full text.

Abstract: Post-traumatic stress disorder (PTSD) is frequently comorbid with depression. A number of studies have been conducted to compare individuals suffering from comorbid PTSD and depression with individuals suffering from PTSD alone or depression alone. Comorbidity of PTSD and depression is associated with more severe symptoms as well as higher levels of disability compared to individuals with PTSD alone. A severity of overall symptoms is three to fivefold greater in subjects with comorbid PTSD and depression compared to those with PTSD alone. The comorbid group is five times more likely to manifest functional impairment compared to those diagnosed with PTSD alone. Patients with comorbid PTSD and depression have higher depression, impulsivity, and hostility scores and are significantly more likely to make a suicide attempt compared to subjects with depression alone. Depressed subjects with comorbid PTSD tend towards earlier age of first hospitalization and a higher number of hospitalizations compared to depressed individuals without comorbid PTSD. Lower affinity of alpha-2 adrenoreceptors and higher plasma tyrosine availability to the brain are associated with comorbid PTSD and depression, but not with PTSD alone. Individuals with comorbid PTSD and depression do not exhibit the classic rapid eye movement sleep architectural modifications associated with depression, despite the fact that several other psychophysiological indices of dysphoria are detectable in their sleep. In fenfluramine challenge studies, depressed patients with comorbid PTSD have lower plasma cortisol compared to depressed patients without comorbid PTSD. Cortisol levels increase with age and the number of previous major depressive episodes is a predictor of the cortisol response to fenfluramine administration in depressed patients without PTSD, but not in depressed patients with comorbid PTSD. Depressed subjects with comorbid PTSD have higher cerebrospinal fluid homovanillic acid levels compared with depressed subjects without comorbid PTSD. Thus, studies suggest that patients suffering from comorbid PTSD and depression differ clinically and biologically from individuals with PTSD alone or depression alone. It is possible that some or all individuals diagnosed with comorbid PTSD and depression have a separate psychobiological condition that can be termed "post-traumatic mood disorder". Future clinical and neurobiological studies may not only advance our understanding of the role of environmental and genetic factors in the etiology and pathogenesis of stress-related disorders, but also be useful in refining conceptions of stress-related disorders themselves and possible approaches to the treatment of these conditions.

Sher L, Oquendo MA, Li S, Burke AK, Grunebaum MF, Zalsman G, Huang YY, Mann JJ. · Division of Neuroscience, Department of Psychiatry, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Suite 2917, Box 42, New York, NY 10032, USA. · Eur Neuropsychopharmacol. · Pubmed #15695066 No free full text.

Abstract: Major depression and posttraumatic stress disorder (PTSD) are often comorbid, resulting in more impairment compared than with either diagnosis alone. Both major depression and PTSD are thought to be associated with monoamine transmitter abnormalities. This study compared clinical features and cerebrospinal fluid (CSF) monoamine metabolites in drug-free depressed subjects with a current major depressive episode (MDE) without comorbid PTSD, subjects with a current MDE and comorbid PTSD, and healthy volunteers. Depressed subjects with comorbid PTSD had higher CSF homovanillic acid (HVA) levels compared with depressed subjects without comorbid PTSD or healthy volunteers. Higher HVA was present after adjustment for sex, lifetime aggression severity and depression scores, alcoholism, tobacco smoking, comorbid cluster B personality disorder, reported childhood abuse, and psychosis. We found no group difference in CSF 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels. Higher dopaminergic activity may contribute to alterations in memory and other cognitive functions, anhedonia, and hypervigilance observed in PTSD.

Sher L, Oquendo MA, Galfalvy HC, Cooper TB, Mann JJ. · Division of Neuroscience, Department of Psychiatry, Columbia University, 1051 Riverside Drive, Suite 2917, Box 42, New York, NY 10032, USA. · J Affect Disord. · Pubmed #15465576 No free full text.

Abstract: BACKGROUND: Post-traumatic stress disorder (PTSD) and major depression are frequently comorbid. Age and major depression are associated with higher cortisol levels and dexamethasone resistance, whereas PTSD is associated with lower cortisol and dexamethasone supersensitivity. Therefore, we examined the effect of age on the hypothalamic-pituitary-adrenal (HPA) system in depressed patients with and without PTSD. METHODS: Thirty-one depressed patients without PTSD, 12 depressed patients with PTSD, and 23 healthy volunteers were studied on 2 days. Subjects received single-blind placebo on day 1 and fenfluramine on day 2. Cortisol levels were drawn before challenge and for 5 h thereafter. RESULTS: Cortisol levels increase with age in depressed patients without PTSD but not in depressed patients with PTSD or in healthy volunteers. Number of previous major depressive episodes was a predictor of the cortisol response to fenfluramine administration in depressed patients without PTSD. CONCLUSIONS: The results of our study highlight the importance of considering age in psychobiology. Further research is needed to fully delineate the role of age in abnormalities of the HPA axis found in major depression and PTSD.

Wehr TA, Duncan WC, Sher L, Aeschbach D, Schwartz PJ, Turner EH, Postolache TT, Rosenthal NE. · Section o Biological Rhythms, Mood and Anxiety Disorders Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1390, USA. · Arch Gen Psychiatry. · Pubmed #11735838 links to  free full text

Abstract: BACKGROUND: In animals, the circadian pacemaker regulates seasonal changes in behavior by transmitting a signal of day length to other sites in the organism. The signal is expressed reciprocally in the duration of nocturnal melatonin secretion, which is longer in winter than in summer. We investigated whether such a signal could mediate the effects of change of season on patients with seasonal affective disorder. METHODS: The duration of melatonin secretion in constant dim light was measured in winter and in summer in 55 patients and 55 matched healthy volunteers. Levels of melatonin were measured in plasma samples that were obtained every 30 minutes for 24 hours in each season. RESULTS: Patients and volunteers responded differently to change of season. In patients, the duration of the nocturnal period of active melatonin secretion was longer in winter than in summer (9.0 +/- 1.3 vs 8.4 +/- 1.3 hours; P=.001) but in healthy volunteers there was no change (9.0 +/- 1.6 vs 8.9 +/- 1.2 hours; P=.5). CONCLUSIONS: The results show that patients with seasonal affective disorder generate a biological signal of change of season that is absent in healthy volunteers and that is similar to the signal that mammals use to regulate seasonal changes in their behavior. While not proving causality, this finding is consistent with the hypothesis that neural circuits that mediate the effects of seasonal changes in day length on mammalian behavior mediate effects of season and light treatment on seasonal affective disorder.

Sher L. · Rockville, MD, USA. · Med Hypotheses. · Pubmed #11421635 No free full text.

Abstract: The author suggests that biological abnormalities related to the development of anxiety disorders can be classified as real or relative. Individuals with 'real abnormalities' are not able to function under any circumstances, including the circumstances that are natural for humans. Persons with 'relative abnormalities' can function under the natural circumstances, but are not able to function in situations that are unnatural for humans. Unnatural situations include being in elevators, flying airplanes, driving cars, etc. The author suggests that all humans can be classified into four groups: 1. Individuals with excellent 'adaptational reserve' never develop anxiety disorders; 2. Individuals with good adaptational reserve develop anxiety disorders only if they are subjected to extremely stressful, unusual situations (e.g. being a hostage); 3. Individuals with moderate adaptational reserve develop anxiety disorders if they are exposed to unnatural situations. They have 'relative abnormalities'; 4. Individuals with poor adaptational reserve develop anxiety disorders in situations that are natural for humans. They have 'real abnormalities'.

Sher L. · No affiliation provided · Med Hypotheses. · Pubmed #10532702 No free full text.

Abstract: Psychological factors affect the condition of both healthy and sick people. Acute and chronic stress, depression, anxiety, maladaptive personality traits, and other behavioral disorders cause the diseases of the heart and blood vessels. The same psychological factors suppress the immune system and promote infection. Recent studies have demonstrated that infections can play an important role in the development of coronary artery disease. The author suggests that the immune system may mediate the harmful effects of certain psychological factors on the cardiovascular system.

Sher L. · No affiliation provided · Psychiatry Clin Neurosci. · Pubmed #19335403 No free full text.

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Sher L. · No affiliation provided · Med Hypotheses. · Pubmed #18829181 No free full text.

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Sher L. · No affiliation provided · Aust N Z J Psychiatry. · Pubmed #18788132 No free full text.

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