August 22, 2011 Volume 6, Number 17 ����������� ���� TM
www.psychiatryweekly.com This Week in Psychiatry
In Session With: Andreas MeyerLindenberg, MD
The Urban Environment and Neural Social Stress Processing
Q: Why do urban environments affect the neural reaction to social stress? A: That’s something we can’t answer in our study, obviously, but we can speculate. We know from animal studies that the amygdala and especially the cingulate cortex are very responsive to stress in early brain development. We also know that the amygdala is implicated in the gene-environment interaction in carriers of genetic variants that can impair the ability to deal with environmental adversity. We know that social stressors have an impact on those circuits. A recent study found that the size of your social network is positively correlated to the volume of those brain areas. All this means that protective and risk factors of the social environment converge on this circuit, so our hypothesis is that the brain areas that are differentially active during social stress not only mediate the urbanicity effect, but that stress is also causal for the abnormal function of these regions in the first place. Reference: 1. Lederbogen F, Kirsch P, Haddad L, et al. City living and urban upbringing affect neural social stress processing in humans. Nature. 2011;474:498-501. Disclosure: Dr. Meyer-Lindenberg reports no affiliations with, or financial interests in, any organization that may pose a conflict of interest.
Taral R. Sharma, MD, MBA
How Many Veterans Use Available PTSD Treatment? A study in Psychiatric Services evaluated the adequacy of PTSD treatment utilized by US veterans through a specialty care program of the Department of Veterans Affairs. Nearly 900 veterans, including those who had served in Iraq and Afghanistan, visited the PTSD specialty clinic within 1 year of screening positive for PTSD. Thirty-three percent (n=286) of veterans who visited the clinic received adequate treatment. Veterans who had not served in Iraq or Afghanistan were more likely to receive minimally adequate treatment. Living in an urban area, visiting the clinic within one month of positive screening, and having psychiatric comorbidities, were predictors of receiving adequate treatment. p s . p s y c h i a t r yo n l i n e . o r g / c g i / c o n t e n t / abstract/62/8/943
Director, Central Institute of Mental Health, Mannheim, Chair of Psychiatry and Psychotherapy, University of Heidelberg/ Medical Faculty, Mannheim, Germany
Q: How can an urban environment affect the brain’s reaction to social stress? A: Epidemiological studies have shown strong associations between urban life and specific mental disorders. Urban upbringing has an at least 2-fold greater risk of schizophrenia. For current urban living, there is no strong evidence of a heightened schizophrenia risk, but there is consistent evidence of an ~30% increased risk for depression and anxiety disorders. The predominant hypothesis has always been that this may have to do with the urban social environment, specifically with social stress. In attempt to measure and define the neural systems that are differentially active during social stress, we conducted two experiments in which we exposed subjects to a social stressor as they underwent MRI scanning. We did that by inviting subjects to do arithmetic. We asked subjects to solve math problems, which we described as elementary school level. By using an adaptive computer software, we ensured that the exercise stress rate met a minimum threshold—if subjects solved a problem correctly, the problems would automatically become more difficult and be presented more quickly. A performance meter showed subjects that their results were among the poorest of anyone who had ever done the same test, and in intervals between tests, laboratory staff would criticize the subjects and urge them to try harder. This caused social evaluative stress, demonstrated by higher levels of cortisol and other stress markers. We found that, of the set of brain areas differentially active during social stress, one specific brain area was reactive to, or correlated with, a current urban environment: the amygdala. There was a stepwise increase in amygdala activity from rural to town to large city inhabitants. We also found that the perigenual anterior cingulate cortex showed activity specifically correlated to the years of urban upbringing. We wondered whether these specific brain activities were actually related to social stress, or whether they had to do with doing demanding cognitive tasks. We therefore accounted for urbanicity in a sample of ~80 people performing cognitive exercises without stress. In this third experiment, we found no correlation between urbanicity and any increased stress.
Case Report
Maternal Depression: Children’s Outcomes, From Illness to Remission
High-Schoolers More Likely to Access School Services for Mental Health Care
Myrna M. Weissman, PhD Professor of Epidemiology and Psychiatry, Columbia University College of Physicians and Surgeons, Mailman School of Public Health; Chief, Division of Epidemiology, New York State Psychiatric Institute
F
or women, the childbearing years coincide with the period of greatest risk for new-onset major depressive disorder (MDD); the usual age of onset ranges from 15–20 years of age. The heritability of depression is very well established, although exactly which environmental and physiological mechanisms—or which combination of them—can be said to account for its heritability has not been determined. Given that women have a higher prevalence rate of depression than men (4% vs. 2.7%), and the powerful influences mothers have on their offspring, it makes sense to evaluate the
months had an 8% increase in diagnoses. In a more recent report, children were assessed 1 year after the mother’s remission. To compare the effects of the mother’s time to remission, children were assessed for psychopathology every 3 months for 1 year, and were categorized by the mother’s remission status—early (0–3 months), late (3–12 months), and nonremitting. “If the mothers remitted early, say in the first 3 months, the kids remitted early,” says Dr. Weissman. “If the mothers remitted later, during the first year, the kids’ remission was later, too. The kids had the best outcome if the mother had an early remission, which was reflected not only in their psychiatric symptoms but also in their social functioning. We now know from other studies that improvement takes longer for social functioning than for the psychiatric symptoms. For the children whose mothers did not remit, there was also some increase in externalizing disorders.”
Remission of maternal depression was associated with an 11% decrease in the number of children’s affective disorder diagnoses. effect of maternal depression on the family and offspring. Dr. Myrna Weissman has conducted a multitude of studies on depression and families, including a 3-generation heritability study for psychiatric disorders, where a later 20-year followup report found a 2- to 3-fold greater risk of depression for the offspring of parents with depression. In 2006, Weissman and colleagues studied how children are affected by maternal depression specifically, and also how remission of maternal depression affects the children’s mood and affective well-being.
Offspring and Maternal Depression In a 2006 report that drew data from the STAR*D-Child study, Weissman and colleagues found that remission of maternal depression after 3 months of antidepressant treatment was associated with an 11% decrease in the number of children’s affective disorder diagnoses. In comparison, children whose mothers did not remit after 3
Dr. Weissman says that these findings have attracted the attention of clinicians in a number of other specialties—obstetricians, gynecologists, and pediatricians—partly because of the clear benefits for children when their mothers receive depression treatment, and partly because of the striking absence of additional, separate treatment for the children who remitted along with their mothers, what Dr. Weissman calls “a twofer.” “We observed that very few children in this study received any psychiatric treatment,” she says. “If a child was having symptoms we had an obligation to refer them to treatment, and in some cases their parents did take them for treatment. But psychiatric treatment for kids is not widely available, and we found that maternal remission was a more powerful predictor for children’s remission, so child treatment didn’t really affect the outcomes. We are certainly not saying that children should not get treatment, however; our study simply was not designed to report on
the nature of their treatment. The big issue here, clinically, is whether these mothers can be kept in remission and whether adequate treatment remains accessible to them, because depression is a recurrent illness.” Family structure was associated with children’s risk, as well. Mothers who were not either married or raising children with a live-in partner fared more poorly in terms of adequate response to antidepressant therapy. This was, in turn, reflected in their children’s mental health status. That is, single mothers remitted less frequently, and, when they did, their children also took longer to remit.
Conclusion “If we were to suppose what can be done to help ameliorate depression in kids, it would be to target single mothers with depression to provide them with consistent depression treatment,” says Dr. Weissman. “A lot is said about how psychiatry has few efficacious treatments. In point of fact, we have many efficacious treatments, imperfect as they may be. This type of criticism is probably misattributed at times because of the major problem, as I see it: treatments that are inaccessible, or only sporadically available, to many people who need them. It is clear that children benefit through childhood into adulthood when their mothers receive appropriate depression treatment. That should only heighten our vigilance when it comes to detecting depression in the context of the family structure.” Disclosure: Dr. Weissman has received funding from the NIMH, the National Institute on Drug Abuse, the National Alliance for Research on Schizophrenia and Depression, the Sackler Foundation, the Templeton Foundation, and the Interstitial Cystitis Association; and receives royalties from the Oxford University Press, Perseus Press, the American Psychiatric Association Press, and MultiHealth Systems.
To determine how many high-schoolers are at risk for mental disorders, and what proportion of at-risk subjects seek school- and community-based services, the authors of a Journal of the American Academy of Child & Adolescent Psychiatry study screened 4,509 ninth-grade students. Twenty percent of students were identified as being at risk, of whom 73.6% were not receiving any treatment. More students received referrals to school services (74%) than services in the community (57.3%); school services had a higher rate of successful access (80.2%) than community-based services (41.9%). www.jaacap.com/article/S0890-8567(11)004461/abstract
Resident in Psychiatry, Carilion Clinic Virginia Tech-Carilion School of Medicine Psychiatry Residency Program, Roanoke, VA
Olanzapine Prolongs Clozapine-Induced Neutropenia In Otherwise Healthy Male
Case Description Mr. Z is a white male, 54-years-old, who was admitted to an acute inpatient psychiatric unit for disruptive and aggressive behavior at an assisted living facility. He has a psychiatric history significant for chronic remitting schizoaffective disorder, and a medical history of diabetes mellitus II, hypothyroidism, hyperlipidemia, hepatitis C, and peptic ulcer disease, with no history of reported blood disease. The patient has been tried on multiple antipsychotics, including quetiapine, aripiprazole, haloperidol, risperdal, and ziprasidone with limited success. He has also been tried on combined therapy of atypical and typical antipsychotics with multiple mood stabilizers, including valproic acid, oxcarbazepine, carbamazepine, and lithium carbonate, with little success and with no significant change in absolute neutrophil count (ANC). Upon admission, the patient was started on clozapine 25 mg/twice daily, which was titrated up to 150 mg/twice daily with good symptom control. The patient’s ANC dropped significantly on day 45, and clozapine was discontinued. A hematology consult recommended peripheral blood smear and FLOW studies to rule out non-pharmacological causes of a sudden drop in ANC. On day 48 of hospitalization, the patient was given a second trial of clozapine 25 mg/twice daily, which was discontinued within 1 week because of a critical drop in ANC. Clozapine was replaced with olanzapine 10 mg at bedtime to target psychotic symptoms. Patient’s ANC dropped further, requiring stopping olanzapine. Risperdal up to 3 mg/twice daily was started to target symptoms of psychosis and mania, with good control of symptoms. On day 150, patient’s white blood cell count (WBC) came back to 7.31 and ANC was 38.4% (Table).
Table. DAY
Depression and Binge Drinking in Older Adults Using data from the National Social Life, Health, and Aging Project, a International Journal of Geriatric Psychiatry study evaluated the role of gender and depression in alcohol use of older adults (aged 57–85 years) in the community (n=2,924). Binge drinking was defined as ≥4 drinks/day for men and ≥3/ day for women. Twelve percent of men, and 8% of women, were identified as binge drinkers. Although there were profound differences in social and health status between men and women, the frequency and extent of drinking habits were correlated to depression rating scores only in men. The authors suggest that these older men may use alcohol to cope with depression, and that heavy alcohol use may increase their social isolation. o n l i n e l i b r a r y. w i l e y. c o m / d o i / 1 0 . 1 0 0 2 / gps.2616/abstract
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1 30 45 48 55 57 64 66 90 150
MEDICATION(S) No clozapine/olanzapine Clozapine 300 mg/day Clozapine discontinued Clozapine restarted Clozapine discontinued Olanzapine 10 mg QHS Olanzapine discontinued No clozapine/olanzapine No clozapine/olanzapine No clozapine/olanzapine
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CRITICAL
31.4 28.4 26.6 23.5 CRITICAL
30.4 36 38.4
Upon baseline mental status exam, the patient displayed no abnormal movements and no psychomotor agitation or retardation. There was poverty of speech quality with some perseveration. Thought process was somewhat concrete, and thought content was devoid of suicidal or homicidal ideations—intent or plan. Insight was limited and judgment was poor. Impulse control was mostly preserved at most times. Some paranoia was present, but no obsessions, compulsions, ruminations, or fixed delusional systems were noted. Baseline examination was significant for Mini-Mental State Examination score of 25/30 and clock-drawing test score of 1/8. Significant labs included thrombocytopenia, requiring change of patient’s valproic acid dosage (normal limits returned upon discontinuation of valproic acid). Patient had no significant recent history of substance abuse.
Conclusion This report raises practical concerns about the hematological safety profile of olanzapine during the phase immediately following discontinuation of clozapine. This report also suggests the need to consider antipsychotics other than olanzapine in patients with clozapine-induced neutropenia to avoid a further drop in ANC.
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ANC (%) 50.7
WBC=white blood cell count; ANC=absolute neutrophil count Source: the author
Disclosure: Dr. Sharma reports no affiliations with, or financial interests in, any organization that may pose a conflict of interest. Psychiatry Weekly is published by Psychiatry Weekly, LLC. Copyright© 2011. Psychiatry WeeklyTM is a trademark of Psychiatry Weekly, LLC. Reproduction without written permission from the publisher is prohibited. Printed in the United States. Offices: 80 Broad Street, 22nd Floor. New York, NY 10004. E-mail:
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WBC 9.68 7.63 6.16 7.46 5.36 7.06 4.79 5.83 7.56 7.31
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