Anxiety Disorders: Yonkers KA

Brawman-Mintzer O, Yonkers KA. · Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29406, USA. · CNS Spectr. · Pubmed #15303077 No free full text.

Abstract: Anxiety disorders are among the most prevalent psychiatric disorders in the general population, found nearly twice as often in women, and estimated to affect 26.9 million individuals in the United States alone. Anxiety disorders are associated with considerable chronicity, morbidity, and disability. Treatment of anxiety disorders includes pharmacologic and nonpharmacologic approaches. The first-line pharmacologic treatments currently include the use of serotonin reuptake inhibitors and selective serotonin reuptake inhibitors. However, despite the general success of the available treatments, no single anxiolytic appears to be effective for all patients suffering from anxiety. Low recovery rates have been reported in all anxiety disorders, underscoring the need for optimizing treatment for these disabling disorders. In recent years, there is increasing interest in the use of atypical neuroleptics in the treatment of anxiety disorders patients. This article discusses the emerging data on the use of these agents in the treatment of anxiety with a focus on treatment-refractory patients and on the implications for the treatment of women suffering from anxiety disorders.

Yonkers KA. · Reproductive Mood Disorders Program, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Suite 520, Dallas, TX 75235-9101, USA. · J Gend Specif Med. · Pubmed #11252853 No free full text.

Abstract: Women who suffer from severe dysphoric premenstrual complaints can now be accurately diagnosed. A diagnosis of premenstrual dysphoric disorder is best made by ruling out other psychiatric and general medical conditions and by collecting daily ratings of symptom expression across the menstrual cycle. Recent treatment findings support the use of (1) antidepressants that block the serotonin transporter, and (2) the benzodiazepine anxiolytic alprazolam. Medication administered only during the luteal phase of the cycle will result in substantial relief for patients suffering from severe premenstrual dysphoric disorder.

Howell HB, Brawman-Mintzer O, Monnier J, Yonkers KA. · Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. · Psychiatr Clin North Am. · Pubmed #11225506 No free full text.

Abstract: Women have a higher prevalence of GAD than do men. This ratio holds true in most clinical and general-population samples. Some variations exist, with evidence to suggest the strong impact of environment and life events. Women are sensitive to lifetime adversity and exacerbation of symptoms in conjunction with their menstrual cycle. Comorbidity is a crucial diagnostic factor when treating anyone with GAD, especially women. Most notably, high comorbidity with other anxiety disorders, MDD and alcohol-abuse disorder occurs for women. Overall, although the prevalence of women with GAD is greater than that of men with GAD, the course of illness and prognosis are not qualitatively different. Across varied methodology, data suggest gender-related differences in the metabolism and potentially in the effects and side effects of the various benzodiazepines and antidepressant psychopharmacologic treatments of GAD. Additional research is needed to better understand these differences.

Kessler RC, Gruber M, Hettema JM, Hwang I, Sampson N, Yonkers KA. · Department of Health Care Policy, Harvard Medical School, Boston, MA 02115, USA. · Psychol Med. · Pubmed #18047766 No free full text.

Abstract: BACKGROUND: Although generalized anxiety disorder (GAD) and major depressive episode (MDE) are known to be highly co-morbid, little prospective research has examined whether these two disorders predict the subsequent first onset or persistence of the other or the extent to which other predictors explain the time-lagged associations between GAD and MDE. METHOD: Data were analyzed from the nationally representative two-wave panel sample of 5001 respondents who participated in the 1990-1992 National Comorbidity Survey (NCS) and the 2001-2003 NCS follow-up survey. Both surveys assessed GAD and MDE. The baseline NCS also assessed three sets of risk factors that are considered here: childhood adversities, parental history of mental-substance disorders, and respondent personality. RESULTS: Baseline MDE significantly predicted subsequent GAD onset but not persistence. Baseline GAD significantly predicted subsequent MDE onset and persistence. The associations of each disorder with the subsequent onset of the other attenuated with time since onset of the temporally primary disorder, but remained significant for over a decade after this onset. The risk factors predicted onset more than persistence. Meaningful variation was found in the strength and consistency of associations between risk factors and the two disorders. Controls for risk factors did not substantially reduce the net cross-lagged associations of the disorders with each other. CONCLUSIONS: The existence of differences in risk factors for GAD and MDE argues against the view that the two disorders are merely different manifestations of a single underlying internalizing syndrome or that GAD is merely a prodrome, residual, or severity marker of MDE.

Rogal SS, Poschman K, Belanger K, Howell HB, Smith MV, Medina J, Yonkers KA. · Yale University Department of Psychiatry, USA. · J Affect Disord. · Pubmed #17291588 links to  free full text

Abstract: BACKGROUND: The purpose of this study was to determine the association between posttraumatic stress disorder (PTSD), diagnosed prospectively during pregnancy, and the risk of delivering a low birth weight (<2500 g) or preterm (<37 weeks gestational age) infant. METHODS: Pregnant women were recruited from obstetrics clinics and screened for major and minor depressive disorder, panic disorder, PTSD, and substance use. Current episodes of PTSD were diagnosed according to the MINI International Neuropsychiatric Interview, and pregnancy outcomes were abstracted from hospital records. RESULTS: Among the 1100 women included in analysis, 31 (3%) were in episode for PTSD during pregnancy. Substance use in pregnancy, panic disorder, major and minor depressive disorder, and prior preterm delivery were significantly associated with a diagnosis of PTSD. Preterm delivery was non-significantly higher in pregnant women with (16.1%) compared to those without (7.0%) PTSD (OR=2.82, 95% C.I. 0.95, 8.38). Low birth weight (LBW) was present in 6.5% of women and was not significantly associated with a diagnosis of PTSD in pregnancy after adjusting for potential confounders. However, LBW was significantly associated with minor depressive disorder (OR=1.82, 95% C.I. 1.01, 3.29). LIMITATIONS: There was a low prevalence of PTSD in this cohort, resulting in limited power. CONCLUSIONS: These data suggest a possible association between PTSD and preterm delivery. Coupled with the association found between LBW and a depressive disorder, these results support the utility of screening for mental health disorders in pregnancy.

Smith MV, Poschman K, Cavaleri MA, Howell HB, Yonkers KA. · Department of Psychiatry, Yale University, 142 Temple St., Suite 301, New Haven, CT 06510, USA. · Am J Psychiatry. · Pubmed #16648330 links to  free full text

Abstract: OBJECTIVE: The purpose of this study was to examine symptoms of posttraumatic stress disorder (PTSD) in a community sample of low-income pregnant women who met the DSM-IV diagnostic criteria for the disorder. METHOD: Pregnant women (N=948) were screened for trauma, PTSD, depression, and co-occurring illicit substance use. PTSD symptoms were compared in traumatized pregnant women and a sample of nonpregnant traumatized women from the National Comorbidity Survey. RESULTS: Suicidal thoughts and a high degree of psychiatric comorbidity were common in pregnant women with PTSD. Pregnant women were selectively and significantly less likely to endorse reexperiencing symptoms of PTSD (29.5%, N=82), compared to nonpregnant women (79.4%, N=464). CONCLUSIONS: PTSD in pregnancy was associated with comorbidity, poor health behaviors, and lower recall of memory-related PTSD symptoms. Further prospective study is needed.

Bruce SE, Yonkers KA, Otto MW, Eisen JL, Weisberg RB, Pagano M, Shea MT, Keller MB. · Department of Psychiatry and Human Behavior, Brown University, RI 02906, USA. · Am J Psychiatry. · Pubmed #15930067 links to  free full text

Abstract: OBJECTIVE: The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder, generalized anxiety disorder, and social phobia. METHOD: Data were drawn from the Harvard/Brown Anxiety Disorders Research Program, a prospective, naturalistic, longitudinal, multicenter study of adults with a current or past history of anxiety disorders. Probabilities of recovery and recurrence were calculated by using standard survival analysis methods. Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence. RESULTS: Survival analyses revealed an overall chronic course for the majority of the anxiety disorders. Social phobia had the smallest probability of recovery after 12 years of follow-up. Moreover, patients who had prospectively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period. The overall clinical course was worsened by several comorbid psychiatric conditions, including major depression and alcohol and other substance use disorders, and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia. CONCLUSIONS: These data depict the anxiety disorders as insidious, with a chronic clinical course, low rates of recovery, and relatively high probabilities of recurrence. The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence. The findings add to the understanding of the nosology and treatment of these disorders.

Perkonigg A, Yonkers KA, Pfister H, Lieb R, Wittchen HU. · Technical University of Dresden, Institute of Clinical Psychology and Psychotherapy, Dresden, Germany. · J Clin Psychiatry. · Pubmed #15491233 No free full text.

Abstract: BACKGROUND: There is some evidence that the onset and course of premenstrual syndrome is related to stress; however, few studies have explored the role of traumatic events and post-traumatic stress disorder (PTSD) as risk factors for the development of premenstrual dysphoric disorder (PMDD). METHOD: A community cohort of 1488 women (aged 14-24 years at baseline) were prospectively and longitudinally evaluated up to 3 times over a period of about 42 months from 1995 to 1999. The DSM-IV version of the Munich-Composite International Diagnostic Interview was used to establish PMDD and PTSD diagnostic status; stressful life events and conditions were assessed with the Munich Events List and the Daily Hassles Scale. Prevalence and incidence of either threshold or subthreshold PMDD from baseline to the second follow-up were calculated. Risk factors, including prior comorbid mental disorders and traumatic events, were examined using logistic regression analysis. RESULTS: The incidence of threshold PMDD was 3.0%. The most powerful predictors were subthreshold PMDD at baseline (OR = 11.0, 95% CI = 4.7 to 25.9). Traumatic events greatly increased the odds of developing PMDD at follow-up (OR = 4.2, 95% CI = 1.2 to 12.0). Other predictors were a history of anxiety disorder (OR = 2.5, 95% CI = 1.1 to 5.5) and elevated daily hassles scores (OR = 1.6, 95% CI = 1.1 to 2.3). Both were also associated with the risk of developing subthreshold PMDD, although the association was less robust. CONCLUSIONS: Traumatic events and pre-existing anxiety disorders are risk factors for the development of PMDD. The underlying mechanisms are unknown, making further investigation necessary.

Smith MV, Rosenheck RA, Cavaleri MA, Howell HB, Poschman K, Yonkers KA. · Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USA. · Psychiatr Serv. · Pubmed #15067153 links to  free full text

Abstract: OBJECTIVE: This study assessed rates of detection and treatment of minor and major depressive disorder, panic disorder, and posttraumatic stress disorder among pregnant women receiving prenatal care at public-sector obstetric clinics. METHODS: Interviewers systematically screened 387 women attending prenatal visits. The screening process was initiated before each woman's examination. After the visit, patients were asked whether their clinician recognized a mood or anxiety disorder. Medical records were reviewed for documentation of psychiatric illness and treatment. RESULTS: Only 26 percent of patients who screened positive for a psychiatric illness were recognized as having a mood or anxiety disorder by their health care provider. Moreover, clinicians detected disorders among only 12 percent of patients who showed evidence of suicidal ideation. Women with panic disorder or a lifetime history of domestic violence were more likely to be identified as having a psychiatric illness by a health care provider at some point before or during pregnancy. All women who screened positive for panic disorder had received or were currently receiving mental health treatment outside the prenatal visit, whereas 26 percent of women who screened positive for major or minor depression had received or were currently receiving treatment outside the prenatal visit. CONCLUSIONS: Detection rates for depressive disorders in obstetric settings are lower than those for panic disorder and lower than those reported in other primary care settings. Consequently, a large proportion of pregnant women continue to suffer silently with depression throughout their pregnancy. Given that depressive disorders among perinatal women are highly prevalent and may have profound impact on infants and children, more work is needed to enhance detection and referral.

Yonkers KA, Bruce SE, Dyck IR, Keller MB. · Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06510, USA. · Depress Anxiety. · Pubmed #12768651 No free full text.

Abstract: Anxiety disorders are chronic illnesses that occur more often in women than men. Previously, we found a significant sex difference in the 5-year clinical course of uncomplicated panic disorder that was attributable to a doubling of the illness relapse rate in women compared to men. However, we have not detected a sex difference in the clinical course of panic with agoraphobia, generalized anxiety disorder (GAD), or social phobia (SP), which are conditions generally thought to be more chronic than uncomplicated panic disorder. Given that a longer follow-up period may be required to detect differences in clinical course for more enduring illnesses, we conducted further analyses on this same cohort after a more protracted interval of observation to determine whether sex differences would emerge or be sustained. Data were analyzed from the Harvard/Brown Anxiety Research Program (HARP), a naturalistic, longitudinal study that repeatedly assessed patients at 6 to 12 month intervals over the course of 8 years. Data regarding remission and relapse status were collected from 558 patients and treatment was observed but not prescribed. Cumulative remission rates were equivalent among men and women with all diagnoses. Patients who experienced remission were more likely to improve during the first 2 years of study. Women with GAD continued remitting late into the observation period and experienced fewer overall remission events by 8 years. However, the difference in course failed to reach statistical significance. Relapse rates for women were comparable to those for men who suffered from panic disorder with agoraphobia, GAD, and SP. Again, initial relapse events were more likely to occur within the first 2 years of observation. However, relapse events for uncomplicated panic in women were less restricted to the first 2 years of observation and by 8 years, the relapse rates for uncomplicated panic was 3-fold higher in women compared with men. Anxiety disorders are chronic in the majority of men and women, although uncomplicated panic is characterized by frequent remission and relapse events. Short interval follow-up shows sex differences in the remission and relapse rates for some but not all anxiety disorders. These findings suggest important differences in the clinical course among the various anxiety disorders and support nosological distinctions among the various types of anxiety. It may be that sex differences in the clinical course of anxiety disorders hold prognostic implications for patients with these illnesses.

Yonkers KA, Dyck IR, Keller MB. · Department of Psychiatry, Yale University School of Medicine, 142 Temple Street, New Haven, CT 06510, USA. · Psychiatr Serv. · Pubmed #11331798 links to  free full text

Abstract: OBJECTIVE: Social phobia is a chronic disorder with a higher prevalence among women than men. Data from an eight-year longitudinal study were analyzed to investigate the course of social phobia and to explore potential sex differences in the course and characteristics of the illness. METHODS: Data were analyzed from the Harvard/Brown Anxiety Research Program, a naturalistic, observational study begun in 1989 in which patients with social phobia are assessed every six to 12 months. Treatment was observed but not prescribed by the program personnel. Data on comorbidity, remission, and health-related quality of life were collected for 176 patients with social phobia. RESULTS: Only 38 percent of women and 32 percent of men experienced a complete remission during the eight-year study period, a difference that was not significant. A larger proportion of women than men had the generalized form of social phobia, although the difference was not significant. Women were more likely to have concurrent agoraphobia, and men had a higher rate of comorbid substance use disorders. Social phobia had a more chronic course among women who had low Global Assessment of Functioning scores and a history of suicide attempts at baseline than among men who had these characteristics. Health-related quality of life was similar for both men and women, except that women were slightly but significantly more impaired in household functioning. CONCLUSIONS: The chronicity of social phobia was striking for both men and women. Although remission rates did not differ significantly between men and women, clinicians should be alert to the fact that women with poor baseline functioning and a history of suicide attempts have the greatest chronicity of illness.

Yonkers KA, Dyck IR, Warshaw M, Keller MB. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, USA. · Br J Psychiatry. · Pubmed #10974960 links to  free full text

Abstract: BACKGROUND: Cross-sectional data show that generalised anxiety disorder (GAD) is a chronic condition with episodes lasting much longer than the six-month minimum required by DSM-III-R and DSM-IV. Although GAD is chronic, little is known about factors influencing illness duration. AIMS: To investigate variables that influence the clinical course of GAD. METHOD: A total of 167 patients with GAD participated in the Harvard-Brown Anxiety Research Program. Patients were assessed at intake and re-examined at six- to twelve-month intervals for five years. Kaplan-Meier curves were constructed to assess the likelihood of remission. Regression analysis was used to investigate factors predicting full or partial remission. RESULTS: The rate of remission was 0.38 after five years. Diminished likelihood of remission was associated with low overall life satisfaction, poor spousal or family relationships, a concurrent cluster B or C personality disorder and a low global assessment score. CONCLUSIONS: Full or partial remissions were less likely to occur in patients with poor relationships and personality disorders. These patients should be given more intensive and possibly multi-modal therapy.

Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, Gelenberg AJ, Ryan CE, Hess AL, Harrison W, Davis SM, Keller MB. · Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0710, USA. · J Affect Disord. · Pubmed #10940442 No free full text.

Abstract: BACKGROUND: While the sex difference in prevalence rates of unipolar depression is well established, few studies have examined gender differences in clinical features of depression. Even less is known about gender differences in chronic forms of depression. METHODS: 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were administered an extensive battery of clinician-rated and self-report measures. RESULTS: Women were less likely to be married and had a younger age at onset and greater family history of affective disorder compared to men. Symptom profile was similar in men and women, with the exception of more sleep changes, psychomotor retardation and anxiety/somatization in women. Women reported greater severity of illness and were more likely to have received previous treatment for depression with medications and/or psychotherapy. Greater functional impairment was noted by women in the area of marital adjustment, while men showed more work impairment. LIMITATIONS: Since our population consisted of patients enrolling in a clinical trial, study exclusion criteria may have affected gender-related differences found. CONCLUSIONS: Chronicity of depression appears to affect women more seriously than men, as manifested by an earlier age of onset, greater family history of affective disorders, greater symptom reporting, poorer social adjustment and poorer quality of life. These findings represent the largest study to date of gender differences in a population with chronic depressive conditions.

Yonkers KA, O'Brien PM, Eriksson E. · Department of Psychiatry, Yale School of Medicine, CT 06510, USA. · Lancet. · Pubmed #18395582 No free full text.

Abstract: Most women of reproductive age have some physical discomfort or dysphoria in the weeks before menstruation. Symptoms are often mild, but can be severe enough to substantially affect daily activities. About 5-8% of women thus suffer from severe premenstrual syndrome (PMS); most of these women also meet criteria for premenstrual dysphoric disorder (PMDD). Mood and behavioural symptoms, including irritability, tension, depressed mood, tearfulness, and mood swings, are the most distressing, but somatic complaints, such as breast tenderness and bloating, can also be problematic. We outline theories for the underlying causes of severe PMS, and describe two main methods of treating it: one targeting the hypothalamus-pituitary-ovary axis, and the other targeting brain serotonergic synapses. Fluctuations in gonadal hormone levels trigger the symptoms, and thus interventions that abolish ovarian cyclicity, including long-acting analogues of gonadotropin-releasing hormone (GnRH) or oestradiol (administered as patches or implants), effectively reduce the symptoms, as can some oral contraceptives. The effectiveness of serotonin reuptake inhibitors, taken throughout the cycle or during luteal phases only, is also well established.