New Book Alert: Panic Disorder: Neurobiological and Treatment Aspects

Posted on November 24, 2014 by Maurice Preter MD
Panic Disorder

Panic Disorder

Neurobiological and Treatment Aspects

Nardi, Antonio Egidio, Freire, Rafael Christophe R (Eds.)

2015, Approx. 300 p. 20 illus., 5 illus. in color.

Available Formats:

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approx. $189.00

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ISBN 978-3-319-12537-4

free shipping for individuals worldwide

Due: July 25, 2015

 

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  • All updated neurobiological aspects in just one book
  • Researchers from different countries working together
  • Psychopharmacological aspects based on research data described in a clear and practical way to clinicians
  • Neuroimaging and respiratory data
The book focuses on the neurobiological and treatment aspects of panic disorder. It describes the most recent research data and pharmacological therapeutic aspects of panic disorder. The biochemical, respiratory, imaging, and translational aspects will be together with diagnostic and pharmacological discussion. We have the collaboration of important and recognized researchers from various countries – Brazil, USA, Italy, Spain, United Kingdom, and Switzerland – all of them with a continuous and relevant work on anxiety disorders. “Panic Disorder: Neurobiological and Treatment Aspects” is intended to be a reference book for those who research or treat panic disorder and anxiety disorder patients.

Content Level » Professional/practitioner

Keywords » Diagnosis – Imaging – Neuropharmacology – Panic disorder – Treatment

Related subjects » Biomedical Sciences – Neuroscience – Psychiatry – Psychology

TABLE OF CONTENTS

1. Panic disorder respiratory subtype.- 2. A neural systems approach to the study of panic disorder.- 3. Benzodiazepines in panic disorder.- 4. Pharmacological treatment with  the Serotonin Selective Receptores inhibitors.- 5. The psychological development of panic disorder: implications for neurobiology and treatment.- 6. Panic Disorder, is it really a mental disorder? From body functions to the homeostatic brain.- 7. Panic disorder and personality disorders.- 8. Panic Disorder and general medical comorbidities.- 9. Repetitive transcranial magnetic stimulation to treat panic disorder.- 10. The hippocampus and Panic Disorder: evidence from animal and human studies.- 11. Circadian Rhythm in Panic Disorder.- 12. Myocardial Perfusion and Panic Disorder.- 13. Exercise in Panic Disorder: implications for maintenance, treatment and physical health.- 14. Pulmonary thromboembolism as a differential diagnosis of respiratory panic disorder.- 15. Panic disorder and cardiovascular death: what’s beneath?.- 16. Update on genetics of panic disorder.- 17. Panic and Self-consciousness.- 18. Lifelong opioidergic vulnerability through early life separation: A recent extension of the false suffocation alarm theory of panic disorder.

NEW BOOK ALERT

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Clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss.

Posted on November 21, 2014 by Maurice Preter MD
Obes Rev. 2014 Nov 17. doi: 10.1111/obr.12230. [Epub ahead of print]

Do ketogenic diets really suppress appetite? A systematic review and meta-analysis.

Abstract

Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.

© 2014 International Association for the Study of Obesity (IASO).

KEYWORDS:

Appetite; ketogenic diet; low carbohydrate; very-low-energy diet

Posted in dietary, Health, keto, News | Tagged , |

Autoimmune disease, inflammation and the brain

Posted on November 4, 2014 by Maurice Preter MD

Went to a fabulous lecture by  Dr. Souhel Najjar on autoimmune encephalitis this morning. As a reminder, bad relationships (including with one’s self-image etc.) can also cause/contribute to inflammatory burden.

Below is a well-informed and written piece on Anti-NMDA-receptor encephalitis (one of many), courtesy of Wikipedia.

Last edited 11 days ago by an anonymous user

Anti-NMDA receptor encephalitis

Anti-NMDA (N-methyl D-aspartate) receptor antibody encephalitis, also termed NMDA receptor antibody encephalitis, is an acute form of encephalitis which is potentially lethal but has high probability for recovery. It is caused by an autoimmunereaction primarily against the NR1 subunit of the NMDA receptor.[1] Different descriptions and syndromal designations for this disease existed in medical literature prior to 2007 but it was then that the disease was officially categorized and named by Dalmau and colleagues.[2]

Movement disorder relapses after herpes simplex virus 1 (HSV1) encephalitis have been hypothesized to be secondary to postviral autoimmunity. Recently, a proportion of patients with HSV1 encephalitis (HSE) were shown to produce autoantibodies against N-methyl-D-aspartate receptor (NMDAR).[3]

The condition is associated with tumours, mostly teratomas of the ovaries, and is thus considered a paraneoplastic syndrome. However, there are a substantial number of cases with no detectable tumour and in fact it is emerging that most cases do not have tumour.[4] This is an especially important point as the search for a tumour should not occupy attention when immune treatments are being planned.

 

Incidence and epidemiologyEdit

The overall incidence of the condition is unknown .[5] More recent figures produced by the California Encephalitis Project showed that the disease had a higher incidence than its individual viral counterparts in patients <30 years.[6] The largest cases series to date characterized 577 patients with anti-NMDA receptor encephalitis. The epidemiologic data were limited but this study provides the best approximation of disease distribution. This case series found that women are disproportionally affected, with 81% of cases reported as female. Disease onset is skewed towards children, with a median age of diagnosis of 21 years. Over a third of cases were children, while only 5% of cases were patients over the age of 45. This same review found showed that 394 out of 501 patients (79%) had a good outcome by 24 months.[7] 30 patients (6%) died and the rest were left with mild to severe deficits. This study also confirmed that patients with the condition are more likely to be of Asian or African origin.

Signs and symptomsEdit

Prior to the development of a symptom complex that is specific to anti-NMDA receptor encephalitis, patients may experience prodromal symptoms. These could include headaches, flu-like illness, or symptoms similar to an upper respiratory infection. These symptoms may be present for weeks or months prior to disease onset.[1] Beyond the prodromal symptoms the disease progresses at varying rates and patients may present with a variety of neurologic symptoms. During the initial stage of the disease symptoms vary slightly between children and adults- however behavior changes are a common first symptom within both groups. These changes often include increased agitation, paranoia, psychosis, and violent behaviors. Other common first manifestations include seizures and bizarre, often rhythmic, movements mostly of the lips and mouth but also including pedaling motions with legs or hand movements resembling playing a piano. Some other symptoms typical during the disease onset include impaired cognition, memory deficits, and speech problems (including aphasia or mutism).[7][8]

As the disease progresses the symptoms become medically urgent and often include autonomic dysfunction, hypoventilation, cerebellar ataxia, hemiparesis, loss of consciousness, or catatonia. During this acute phase most patients require care in an Intensive Care Unit to stabilize breathing, heart rate, and blood pressure. It is important to note one distinguishing characteristic of Anti-NMDA Receptor Encephalitis is the concurrent presence of many of the above listed symptoms. It is extremely unusual that patients have only one or two symptoms- the majority of patients experience at least four symptoms with many experiencing six or seven over the course of the disease.[7][8]

PathophysiologyEdit

The presence of antibodies in the serum and cerebrospinal fluid (CSF)

The condition is mediated by autoantibodies that target NMDA receptors in the brain. These are produced by cross reactivitywith NMDA receptors in the teratoma; these tumours contain many different cell types, including brain cells, and thus present a window in which a breakdown in immunological tolerance can occur. Other autoimmune mechanisms are suspected for patients that lack any form of neoplasm. Whilst the exact pathophysiology of the disease is still debated, empirical evaluation of the origin of anti-NMDA antibodies in the serum and the CSF leads to the consideration of two possible mechanisms.

These mechanisms may be informed by some simple observations. Firstly, serum NMDAR-antibodies are consistently found at higher concentrations than CSF antibodies, on average 10 fold higher.[9][10] This strongly suggests the antibody production is systemic rather than in the brain / CSF. When concentrations are normalised for total IgG, ‘intrathecal synthesis’ is detected. This implies that there is more NMDAR-antibody in the CSF than would be predicted given the expected quantities of total IgG.

  1. Passive access involves the diffusion of antibodies from the blood across a pathologically disrupted blood-brain barrier(BBB).[11] This cellular filter, separating the central nervous system from the circulatory system, normally prevents larger molecules from entering the brain. A variety of reasons for such a collapse in integrity have been suggested, with the most likely answer being the effects of acute inflammation of the nervous system. Likewise, the involvement of corticotropin releasing hormone on mast cells in acute stress has been shown to facilitate BBB penetration.[12] However, it is also possible that the autonomic dysfunction manifested in many patients during the later phases of the condition aids antibody entry. For example, an increase in blood pressure would force larger proteins, such as antibodies, to extravasate into the CSF.
  2. Intrathecal production (production of antibodies in the intrathecal space) may also be a possible mechanism. Dalmau et al. demonstrated that 53 out of 58 patients with the condition had at least partially preserved BBBs, whilst having a high concentration of antibodies in the CSF. Furthermore cyclophosphamide and rituximab,[13] drugs used to eliminate dysfunctional immune cells, have been shown to be successful second line treatments in patients where first line immunotherapy has failed.[14] These destroy excess antibody producing cells in the thecal space, thus alleviating the symptoms.

A more sophisticated analysis of the processes involved in antibody presence in the CSF hint at a combination of these two mechanisms in tandem.

The binding of antibodies to NMDA receptors

Once the antibodies have entered the CSF, they bind to the NR1 subunit of the NMDA receptor. There are 3 possible methods in which neuronal damage occurs.

  1. A reduction in the density of NMDA receptors on the post synaptic knob,due to receptor internalisation once the antibody has bound. This is dependent on antibodies cross linking.[15]
  2. The direct antagonism of the NMDA receptor by the antibody, similar to the action of typical pharmacological blockers of the receptor, such as phencyclidine and ketamine.
  3. The recruitment of the complement cascade via the classical pathway (antibody-antigen interaction). Membrane attack complex (MAC) is one of the end products of this cascade[16] and can insert into neurons as a molecular barrel, allowing water to enter. The cell subsequently lyses. Notably, this mechanism is unlikely as it causes cell to die, which is inconsistent with current evidence.

Management and prognosisEdit

If patients are found to have a tumour, the long term prognosis is generally better and the chance of relapse is much lower. This is because the tumour can be removed surgically, thus eradicating the source of autoantibodies. In general, early diagnosis and aggressive treatment is believed to improve patient outcomes, but this remains impossible to know without data from randomized controlled trials.[7] Given that the majority of patients are initially seen by psychiatrists (not neurologists) due to the development of psychiatric symptoms, it is critical that all physicians (especially psychiatrists) consider anti-NMDA receptor encephalitis as a cause for acute psychosis in adolescents with no past neuropsychiatric history.

  • If a tumour is detected, its removal should occur in conjunction with first line immunotherapy . This involves steroids to suppress the immune system, intravenous immunoglobulins and plasmapheresis to physically remove autoantibodies. The study of 577 patients showed that over 4 weeks, about half the patients improved after receiving first line immunotherapy.
  • Second line immunotherapy includes rituximab, a monoclonal antibody that targets the CD20 receptor on the surface of B cells, thus destroying the self-reactive B cells. Cyclophosphamide, an alkylating agent that cross-links DNA and is used to treat both cancer and autoimmune diseases, has sometimes been proven to be useful when other therapies have failed.
  • Other medications, such as alemtuzumab remain experimental.[17]

In the mediaEdit

New York Post reporter Susannah Cahalan wrote a book called Brain on Fire: My Month of Madness about her experience with the disease.[18]

Dallas Cowboys defensive lineman Amobi Okoye spent 17 months battling Anti-NMDA receptor encephalitis. In addition to 3 months in a medically-induced coma, he experienced a 145-day memory gap and lost 78 pounds. He returned to practice on October 23, 2014.[19]

See alsoEdit

ReferencesEdit

  1. Dalmau, Josep; Gleichman, Amy J; Hughes, Ethan G; Rossi, Jeffrey E; Peng, Xiaoyu; Lai, Meizan; Dessain, Scott K; Rosenfeld, Myrna R; Balice-Gordon, Rita; Lynch, David R (2008). “Anti-NMDA-receptor encephalitis: Case series and analysis of the effects of antibodies”. The Lancet Neurology 7 (12): 1091–8. doi:10.1016/S1474-4422(08)70224-2.PMC 2607118. PMID 18851928.
  2. Dalmau, Josep; Tüzün, Erdem; Wu, Hai-yan; Masjuan, Jaime; Rossi, Jeffrey E.; Voloschin, Alfredo; Baehring, Joachim M.; Shimazaki, Haruo; Koide, Reiji; King, Dale; Mason, Warren; Sansing, Lauren H.; Dichter, Marc A.; Rosenfeld, Myrna R.; Lynch, David R. (2007). “Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma”.Annals of Neurology 61 (1): 25–36. doi:10.1002/ana.21050. PMC 2430743. PMID 17262855.
  3. Mohammad, S. S., Sinclair, K., Pillai, S., Merheb, V., Aumann, T. D., Gill, D., Dale, R. C. and Brilot, F. (2014). “Herpes simplex encephalitis relapse with chorea is associated with autoantibodies to N-Methyl-D-aspartate receptor or dopamine-2 receptor.”. Mov. Disord. 29: 117–122. doi:10.1002/mds.25623.
  4. Irani SR, Bera K, Waters P, Zuliani L, Maxwell S, Zandi MS, Friese MA, Galea I, Kullmann DM, Beeson D, Lang B, Bien CG, Vincent A. Brain. 2010 Jun;133(6):1655-67. doi: 10.1093/brain/awq113. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes.
  5. Pruss, H.; Dalmau, J.; Harms, L.; Höltje, M.; Ahnert-Hilger, G.; Borowski, K.; Stoecker, W.; Wandinger, K. P. (2010). “Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin”. Neurology 75 (19): 1735–9.doi:10.1212/WNL.0b013e3181fc2a06. PMID 21060097.
  6. Gable, M. S.; Sheriff, H.; Dalmau, J.; Tilley, D. H.; Glaser, C. A. (2012). “The Frequency of Autoimmune N-Methyl-D-Aspartate Receptor Encephalitis Surpasses That of Individual Viral Etiologies in Young Individuals Enrolled in the California Encephalitis Project”. Clinical Infectious Diseases 54 (7): 899–904. doi:10.1093/cid/cir1038. PMC 3297648.PMID 22281844.
  7. Titulaer, Maarten J; McCracken, Lindsey; Gabilondo, Iñigo; Armangué, Thaís; Glaser, Carol; Iizuka, Takahiro; Honig, Lawrence S; Benseler, Susanne M; Kawachi, Izumi; Martinez-Hernandez, Eugenia; Aguilar, Esther; Gresa-Arribas, Núria; Ryan-Florance, Nicole; Torrents, Abiguei; Saiz, Albert; Rosenfeld, Myrna R; Balice-Gordon, Rita; Graus, Francesc; Dalmau, Josep (2013). “Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: An observational cohort study”. The Lancet Neurology 12 (2): 157–65. doi:10.1016/S1474-4422(12)70310-1. PMC 3563251.PMID 23290630.
  8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158385/
  9. Irani SR, Bera K, Waters P, Zuliani L, Maxwell S, Zandi MS, Friese MA, Galea I, Kullmann DM, Beeson D, Lang B, Bien CG, Vincent A. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain. 2010 Jun;133(6):1655-67. doi:10.1093/brain/awq113
  10. Clin Chim Acta. 2013 Jun 5;421:1-6. doi: 10.1016/j.cca.2013.02.010. Epub 2013 Feb 27. Anti-NMDA-receptor antibody encephalitis: performance evaluation and laboratory experience with the anti-NMDA-receptor IgG assay. Suh-Lailam BB1, Haven TR, Copple SS, Knapp D, Jaskowski TD, Tebo AE.
  11. Moscato, Emilia H.; Jain, Ankit; Peng, Xiaoyu; Hughes, Ethan G (2010). “Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: Insights from molecular, cellular and synaptic studies”.doi:10.1111/j.1460-9568.2010.07349.x.
  12. Rabchevsky, Alexander G.; Degos, Jean-Denis; Dreyfus, Patrick A. (1999). “Peripheral injections of Freund’s adjuvant in mice provoke leakage of serum proteins through the blood–brain barrier without inducing reactive gliosis”. Brain Research832 (1–2): 84–96. doi:10.1016/S0006-8993(99)01479-1. PMID 10375654.
  13. BritishNational Formulary. 2012. http://www.bnf.org/bnf/index.htm[verification needed]
  14. Florance, Nicole R.; Davis, Rebecca L.; Lam, Christopher; Szperka, Christina; Zhou, Lei; Ahmad, Saba; Campen, Cynthia J.; Moss, Heather; Peter, Nadja; Gleichman, Amy J.; Glaser, Carol A.; Lynch, David R.; Rosenfeld, Myrna R.; Dalmau, Josep (2009). “Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents”. Annals of Neurology 66(1): 11–8. doi:10.1002/ana.21756. PMC 2826225. PMID 19670433.
  15. Hughes, E. G.; Peng, X.; Gleichman, A. J.; Lai, M.; Zhou, L.; Tsou, R.; Parsons, T. D.; Lynch, D. R.; Dalmau, J.; Balice-Gordon, R. J. (2010). “Cellular and Synaptic Mechanisms of Anti-NMDA Receptor Encephalitis”. Journal of Neuroscience30 (17): 5866–75. doi:10.1523/JNEUROSCI.0167-10.2010. PMC 2868315. PMID 20427647.
  16. AbbasA et al. 2010. Cellular and Molecular Immunology. (6th ed.)[page needed]
  17. Liba, Zuzana; Sebronova, Vera; Komarek, Vladimir; Sediva, Anna; Sedlacek, Petr (2013). “Prevalence and treatment of anti-NMDA receptor encephalitis”. The Lancet Neurology 12 (5): 424. doi:10.1016/S1474-4422(13)70070-X.PMID 23602155.
  18. “A YoungReporter Chronicles Her ‘Brain On Fire'”. Fresh Air. WHYY; NPR. November 14, 2012. Retrieved September 20, 2013.
  19. Whitmire, Keith. “Cowboys’ Okoye returns to practice after battling rare brain disease”. www.foxsports.com. FOX Sports Southwest. Retrieved 24 October 2014.

External linksEdit

 

 

 

 

 

Posted in Aging, dietary, epigenetics, Events, Fifth Avenue Concierge Medicine, Health, keto, News, Psychiatry/Neurology | Tagged , , , , , , , , , , , , |

Low male sex hormones (“Low T”), heart attack risk, and social status

Posted on October 31, 2014 by Maurice Preter MD

There has recently been more buzz around low male sex hormones/”low-T” and heart attack/stroke risk. Not usually mentioned is the fact that “T” (testosterone) is a social hormone (most hormones are). Low social status lowers “T”. Injecting/supplementing T  without proper attention to the psychology of the situation may make things worse.

Here are some more abstracts on the subject:

Atherosclerosis. 2010 May;210(1):232-6. doi: 10.1016/j.atherosclerosis.2009.10.037. Epub 2009 Nov 13.

Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors.

Abstract

OBJECTIVE:

Recent epidemiological studies have found that testosterone deficiency is associated with higher mortality largely due to cardiovascular (CV) disease in community-dwelling older men. We investigated whether a low plasma testosterone level could predict cardiovascular events in middle-aged Japanese men with coronary risk factors.

METHODS:

One hundred and seventy-one male outpatients (30-69 years old, mean+/-SD=48+/-13 years) who had any coronary risk factor (hypertension, diabetes, dyslipidemia, smoking, and obesity) without a previous history of CV disease were followed up. At baseline, the subjects underwent examination of coronary riskfactors, measurement of flow-mediated dilation (FMD) of the brachial artery as an indicator of vascular endothelial function and assays of plasma total testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol and cortisol.

RESULTS:

During the mean follow-up period of 77 months, a total of 20 CV events occurred. Kaplan-Meier survival analysis by tertile of plasma hormone levels revealed that the subjects with the lowest testosterone tertile were more likely to develop CV events than those with the highest tertile (P<0.01 by log-rank test). Cox proportional hazards models showed that the subjects with the lowest tertile of plasma testosterone (<14.2 nmol/L) had an approximately 4-fold higher CV event risk compared to those with the higher testosterone tertiles after adjustment for coronary risk factors including medication and FMD (unadjusted hazard ratio, 3.61; 95% CI, 1.47-8.86: multivariate-adjusted hazard ratio, 4.61; 95% CI, 1.02-21.04). Multivariate analysis did not show any significant association of DHEA-S, estradiol or cortisol with CV events.

CONCLUSIONS:

A low plasma testosterone level is associated with CV events in middle-aged Japanese men, independent of coronary risk factors and endothelial function. This is the first report to show the relationship between endogenous testosterone and CV events in Asian population.

Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

PMID:

 19963216

[PubMed – indexed for MEDLINE]

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2.
Am J Epidemiol. 2001 Jan 1;153(1):79-89.

Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study.

Abstract

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been characterized as “protective” against ischemic heart disease (IHD), especially in men, on the basis of sparse epidemiologic evidence. The authors used data from the Massachusetts Male Aging Study, a random sample prospective study of 1,709 men aged 40-70 years at baseline, to test whether serum levels of DHEA or DHEAS couldpredict incident IHD over a 9-year interval. At baseline (1987-1989) and follow-up (1995-1997), an interviewer-phlebotomist visited each subject in his home to obtain comprehensive health information, body measurements, and blood samples for hormone and lipid analysis. Incident IHD between baseline and follow-up was ascertained from hospital records and death registries, supplemented by self-report and evidence of medication. In the analysis sample of 1,167 men, those with serum DHEAS in the lowest quartile at baseline (<1.6 microg/ml) were significantly more likely to incur IHD by follow-up (adjusted odds ratio = 1.60, 95 percent confidence interval: 1.07, 2.39; p = 0.02), independently of a comprehensive set of known risk factors including age, obesity, diabetes, hypertension, smoking, serum lipids, alcohol intake, and physical activity. Low serum DHEA was similarly predictive. These results confirm prior evidence that low DHEA and DHEAS can predict IHD in men.

PMID:

 11159150

[PubMed – indexed for MEDLINE]

Free full text

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3.
Ann Epidemiol. 1992 Sep;2(5):675-82.

Lower endogenous androgens predict central adiposity in men.

Abstract

Central adiposity, sometimes described as male pattern fat distribution, is adversely related to cardiovascularrisk and mortality independent of other measures of obesity. In a cohort of 511 men aged 30 to 79 years in 1972 to 1974, levels of androstenedione, testosterone, and sex hormone-binding globulin measured at baseline were inversely related to subsequent central adiposity, estimated 12 years later using the waist-hip circumference ratio. The observed differences in waist-hip ratio between top and bottom tertiles of these hormones and sex hormone-binding globulin were similar to mean waist-hip ratio differences between men with stroke or ischemic heart disease and those without in another prospective study. These findings, consistent with studies suggesting that testosterone seems to mobilize the abdominal depot on males, suggest that “male pattern” fat distribution may be a misleading description for central adiposity, at least, in men. Degree of maleness as indicated by total androgen levels is, in fact, negatively associated with central adiposity. However, the role of sex hormone-binding globulin in regulating androgenic activity warrants further investigation.

PMID:

 1342319

[PubMed – indexed for MEDLINE]

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Association of Childhood Adversities and Early-Onset Mental Disorders With Adult-Onset Chronic Physical Conditions

Posted on October 20, 2014 by Maurice Preter MD

Important paper on childhood adversities an adult-age chronic medical conditions, published just before our study on endogenous opioid dysregulation after early childhood adversity in psychiatrically and physically “healthy” adults.

 

Archives of General Psychiatry

Original Article | Aug 2011

Association of Childhood Adversities and Early-Onset Mental Disorders With Adult-Onset Chronic Physical Conditions

Kate M. Scott, PhD; Michael Von Korff, ScD; Matthias C. Angermeyer, MD, PhD; Corina Benjet, PhD; Ronny Bruffaerts, PhD; Giovanni de Girolamo, MD; Josep Maria Haro, MD, MPH, PhD; Jean-Pierre Lépine, MD; Johan Ormel, PhD; José Posada-Villa, MD; Hisateru Tachimori, PhD; Ronald C. Kessler, PhD
Arch Gen Psychiatry. 2011;68(8):838-844. doi:10.1001/archgenpsychiatry.2011.77.
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Context The physical health consequences of childhood psychosocial adversities may be as substantial as the mental health consequences, but whether this is the case remains unclear because much prior research has involved unrepresentative samples and a selective focus on particular adversities or physical outcomes. The association between early-onset mental disorders and subsequent poor physical health in adulthood has not been investigated.

Objective To investigate whether childhood adversities and early-onset mental disorders are independently associated with increased risk of a range of adult-onset chronic physical conditions in culturally diverse samples spanning the full adult age range.

Design Cross-sectional community surveys of adults in 10 countries.

Setting General population.

Participants Adults (ie, aged≥18 years; N = 18 303), with diagnostic assessment and determination of age at onset of DSM-IV mental disorders, assessment of childhood familial adversities, and age of diagnosis or onset of chronic physical conditions.

Main Outcome Measures Risk (ie, hazard ratios) of adult-onset (ie, at age >20 years) heart disease, asthma, diabetes mellitus, arthritis, chronic spinal pain, and chronic headache as a function of specific childhood adversities and early-onset (ie, at age<21 years) DSM-IV depressive and anxiety disorders, with mutual adjustment.

Results A history of 3 or more childhood adversities was independently associated with onset of all 6 physical conditions (hazard ratios, 1.44 to 2.19). Controlling for current mental disorder made little difference to these associations. Early-onset mental disorders were independently associated with onset of 5 physical conditions (hazard ratios, 1.43 to 1.66).

Conclusions These results are consistent with the hypothesis that childhood adversities and early-onset mental disorders have independent, broad-spectrum effects that increase the risk of diverse chronic physical conditions in later life. They require confirmation in a prospectively designed study. The long course of these associations has theoretical and research implications.

The deleterious mental health consequences of childhood psychosocial adversities, such as abuse and neglect, have been well documented.1 Although less extensively researched, childhood adversities have been hypothesized to increase the risk of adult onset of a spectrum of chronic physical diseases.2,3 A recent meta-analysis4 of the effects of child abuse on medical outcomes in adulthood reached that exact conclusion, finding that the increased risk of selected adverse physical health outcomes was comparable to that observed for poor mental health outcomes. However, the evidence base for the association of child maltreatment with subsequent physical health has significant limitations, which include lack of control for the potentially biasing effects of current mental disorder on recall of childhood adversities, a predominant focus on a single adversity (ie, sexual abuse), and a lack of sample diversity in terms of race/ethnicity (ie, mostly white), age (ie, mostly young adults), and sex (ie, mostly female). The relatively young age of current prospective cohorts with childhood maltreatment data is a particular limitation because it greatly restricts the range of disease outcomes studied and truncates the full expression of disease risk, potentially biasing findings toward the null.

In prior research that has considered the influence of the early psychosocial environment on later physical health, mental disorders have generally been out of the frame of consideration, which may be an important oversight. It is possible that early-onset mental disorders may function as a type of endogenous psychosocial stressor, associated with later poor physical health not only through risky health behaviors but also through direct biological mechanisms. Mental disorders have been hypothesized to contribute to allostatic load,5 a chronic imbalance in the hormonal and neurotransmitter mediators of the stress response6 that has been linked to a range of adverse metabolic, cardiovascular, immune, and cognitive effects.7,8 Research suggests that the stressors that occur early in life have the most potential to contribute to allostatic load through dysregulation of the hypothalamic-pituitary-adrenal axis.9– 11 This finding generates a hypothesis that associations might exist between early-onset mental disorders and chronic physical conditions in adulthood. Although associations between depression and anxiety measured in midlife and the subsequent onset of heart disease and other chronic conditions are well established,12,13 the associations between diagnosed early-onset mental disorders and adult-onset physical conditions have not been studied previously, to our knowledge. The span of time during which mental-physical sequential associations may be developing has important implications for the understanding of mechanisms and the planning of interventions.

We further suggest the need to investigate the independent associations of childhood adversities and mental disorders with subsequent physical health. Childhood adversities are associated with mental and physical health outcomes and so may confound sequential associations between mental health and subsequent physical health.14 Moreover, current mental disorders may bias recall of childhood adversities15 and so may potentially inflate associations between childhood adversities and physical conditions in retrospective studies (ie, most studies rely on retrospective recall of childhood adversities, such as abuse and neglect).

In this study using data from 10 countries participating in the World Health Organization (WHO) World Mental Health (WMH) Surveys initiative, we sought to answer the following question: Are childhood adversities and early-onset mental disorders independently associated with increased risk of adult-onset chronic physical conditions in nationally representative, culturally diverse survey samples of men and women spanning the full adult age range? We also assessed the associations between childhood adversities and physical health outcomes after controlling for current mental disorder. Although the surveys are cross-sectional, they collected information on the age at onset of mental disorders and age at onset or diagnosis of chronic physical conditions, which allowed the use of survival analyses examining predictive associations.

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ARTICLE INFORMATION

Correspondence: Kate M. Scott, PhD, Department of Psychological Medicine, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, New Zealand (kate.scott@otago.ac.nz).

Submitted for Publication: September 13, 2010; final revision received January 24, 2011; accepted February 22, 2011.

Financial Disclosure: Dr Von Korff is principal investigator of work funded by a grant from Johnson& Johnson Inc to Group Health Research Institute. Dr Kessler has consulted for GlaxoSmithKline Inc, Kaiser Permanente, Pfizer Inc, sanofi-aventis, Shire Pharmaceuticals, and Wyeth-Ayerst; has served on advisory boards for Eli Lilly and Company and Wyeth-Ayerst; and has had research support for his epidemiologic studies from Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Johnson& Johnson Pharmaceuticals, Ortho-McNeil Pharmaceuticals Inc, Pfizer Inc, and sanofi-aventis.

Funding/Support: The World Health Organization World Mental Health Surveys initiative is supported by grant R01 MH070884 from the National Institute of Mental Health; contract HHSN271200700030C from the Mental Health Burden Study; the John D. and Catherine T. MacArthur Foundation; the Pfizer Foundation; grants R13-MH066849, R01-MH069864, and R01 DA016558 from the US Public Health Service; grant R03-TW006481 from the Fogarty International Center; the Pan American Health Organization; Eli Lilly and Company; Ortho-McNeil Pharmaceutical; GlaxoSmithKline; and Bristol-Myers Squibb. The Colombian National Study of Mental Health is supported by the Ministry of Social Protection, with supplemental support from the Saldarriaga Concha Foundation. The European surveys were funded by contracts QLG5-1999-01042 and SANCO 2004123 from the European Commission; the Piedmont Region, Italy; grant FIS 00/0028 from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain; grant SAF 2000-158-CE from the Ministerio de Ciencia y Tecnología, Spain; Departament de Salut, Generalitat de Catalunya, Spain; grants CIBER CB06/02/0046 and RETICS RD06/0011 REM-TAP from the Instituto de Salud Carlos III; and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. The World Mental Health Japan Survey is supported by the Research on Psychiatric and Neurological Diseases and Mental Health grants H13-SHOGAI-023, H14-TOKUBETSU-026, and H16-KOKORO-013 from the Japan Ministry of Health, Labour, and Welfare. The Mexican National Comorbidity Survey is supported by grant INPRFMDIES 4280 from the National Institute of Psychiatry Ramon de la Fuente and by grant CONACyT-G30544-H from the National Council on Science and Technology, with supplemental support from the PanAmerican Health Organization. The US National Comorbidity Survey Replication is supported by grant U01-MH60220 from the National Institute of Mental Health, with supplemental support from the National Institute of Drug Abuse, the Substance Abuse and Mental Health Services Administration, grant 044708 from the Robert Wood Johnson Foundation, and the John W. Alden Trust. A complete list of all within-country and cross-national WMH publications can be found athttp://www.hcp.med.harvard.edu/wmh/.

Role of the Sponsors: The funders had no input into the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

Disclaimer: The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of the sponsoring organizations, agencies, or governments.

Additional Contributions: We thank the staff of the World Mental Health Data Collection and Data Analysis Coordination Centers for assistance with instrumentation, fieldwork, and consultation regarding data analysis.

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