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A controlled family history study of childhood-onset depressive disorder.

BACKGROUND: We studied the family psychiatric history of 125 youths with childhood-onset depressive disorder (a portion of whom developed bipolar disorder) and 55 psychiatric controls with nonaffective disorder. METHODS: Probands were classified according to prospectively observed clinical course in childhood. Family psychiatric history was determined by interviewers blind to probands' diagnosis, with mothers typically informing about themselves and about remaining first- and a all second-degree adult relatives. RESULTS: Families of affectively ill juveniles had 5-fold greater odds of lifetime depressive disorder and 2-fold greater odds of recurrent unipolar depressive disorder than did families of psychiatric controls. The higher risk of depression was most evident in first-degree and female relatives. Mothers of affectively ill youths were younger at onset of depression than were mothers of controls. Alcoholism and substance use disorders were more prevalent in relatives of affectively ill probands than in controls and cosegregated with familial depression. However, other covariates were more important at predicting patterns of familial depression. Familial illness patterns also varied somewhat with proband characteristics. CONCLUSIONS: Child probands with affective disorder identify families enriched with affective disorder (even compared with families of psychiatric controls), suggesting that juvenile- and adult-onset forms of this condition share the same diathesis. Rates of affective illness in the families of depressed youngsters also are notably higher than population-based estimates. The findings therefore indicate that very-early-onset affective disorder is familial and that pedigrees ascertained through affectively ill children are good candidates for family and genetic studies.

Adolescent↗

Adolescent onset of the gender difference in lifetime rates of major depression: a theoretical model.

Prepubescent boys are, if anything, more likely than girls to be depressed. During adolescence, however, a dramatic shift occurs: between the ages of 11 and 13 years, this trend in depression rates is reversed. By 15 years of age, females are approximately twice as likely as males to have experienced an episode of depression, and this gender gap persists for the next 35 to 40 years. We offer a theoretical framework that addresses the timing of this phenomenon. First, we discuss the social and hormonal mechanisms that stimulate affiliative needs for females at puberty. Next, we describe how heightened affiliative need can interact with adolescent transition difficulties to create a depressogenic diathesis as at-risk females reach puberty. This gender-linked vulnerability explains why adolescent females are more likely than males to become depressed when faced with negative life events and, particularly, life events with interpersonal consequences.

Adolescent↗

Controlled, blindly rated, direct-interview family study of a prepubertal and early-adolescent bipolar I disorder phenotype: morbid risk, age at onset, and comorbidity.

CONTEXT: A key question is whether a prepubertal and early-adolescent bipolar I disorder phenotype (PEA-BP-I) is the same illness as adult BP-I. This question arises because of the greater severity, longer current episode duration, preponderance of mania, and high rates of ultradian rapid cycling and comorbid attention-deficit/hyperactivity disorder (ADHD) in PEA-BP-I. OBJECTIVES: To examine morbid risk (MR) of BP-I in first-degree relatives of PEA-BP-I, ADHD, and healthy control probands, as well as imprinting, sibling recurrence risk, and anticipation. DESIGN: Controlled, blind direct interview. There were no family psychopathology exclusions for any proband group. SETTING: University medical school research unit. PARTICIPANTS: First-degree relatives 6 years and older (n = 690) of 219 probands (95 with PEA-BP-I, 47 with ADHD, and 77 healthy controls). The PEA-BP-I and ADHD probands were obtained by consecutive new case ascertainment, and healthy controls were from a random survey; proband diagnoses were validated via 4-year prospective follow-up. The PEA-BP-I probands had a mean +/- SD age of 10.8 +/- 2.6 years. Main Outcome Measure Morbid risk. RESULTS: The MR of BP-I was higher in relatives of PEA-BP-I probands compared with ADHD or healthy controls (P<.001 for both); the MR in relatives of ADHD and healthy controls was similar. The MR of BP-I in relatives with ADHD was higher (P<.001) and age at onset of BP-I was younger in parents with ADHD than in those without (P<.001). The MR of BP-I in relatives with oppositional, conduct, or antisocial disorders was higher than in those without (P<.001). Anticipation was evidenced by a younger age at onset of BP-I in probands than in their parents (P<.001). No imprinting was found. CONCLUSIONS: Findings support that PEA-BP-I and adult BP-I are the same diathesis, 7 to 8x greater familiality in child vs adult BP-I, and family study validation of PEA-BP-I, including its differentiation from ADHD.

Adolescent↗

Primary duodenal tumors: a diagnostic and therapeutic dilemma.

The case records of ten patients with benign, three with endocrine, and 19 with malignant duodenal tumors were reviewed. Patients with benign tumors had episodes of bleeding that were recurrent in a number of cases. The endocrine tumors were all gastrinomas; patients had ulcer diathesis associated with the Zollinger-Ellison syndrome. All malignant tumors were symptomatic, with chronic gastrointestinal blood loss or duodenal obstruction. All benign tumors were demonstrated preoperatively, but only ten of 19 malignant tumors were confirmed preoperatively. The data suggest that duodenal tumors masquerade as more common diseases and as a result, their diagnosis and treatment are delayed inordinately. Awareness of this problem is encouraged, and a more aggressive diagnostic effort in selected patients, including fiberoptic endoscopy, is suggested.

Adult↗

Dextran 40-induced coagulopathy confused with von Willebrand disease.

In a patient who had undergone reconstructive surgery on the subclavian artery and was treated postoperatively with aspirin and dextran 40, a bleeding diathesis developed within 24 hours. This was at first thought to be von Willebrand disease, since the bleeding time was longer than ten minutes; the factor VIII level, 28%; and the activated partial thromboplastin time, 50 seconds (normal 30 to 38). The patient's defect responded to discontinuance of the low-molecular-weight, dextran and aspirin therapy and administration of a cryoprecipitate. Later studies of the coagulation mechanism up to two and one-half months were entirely normal. The postoperative defect therefore was assumed to have been the result of the administration of dextran and aspirin. It is possible that in a similar future case, discontinuance of dextran infusion and administration of a single bolus of 12 bags of cryoprecipitate may be adequate treatment.

Blood Coagulation Disorders↗

Renal failure in ascites secondary to hepatic, renal, and pancreatic disease. Treatment with a LeVeen peritoneovenous shunt.

Renal failure occurs in ascites of diverse causes. Functional renal failure (the hepatorenal syndrome) in cirrhotic patients is usually progressive and rapidly fatal. Insertion of a LeVeen shunt significantly reduces weight, as well as abdominal girth, and improves preoperative urine flow (488 vs 2,318 ml/24 hr; P less than .001) and natriuresis (12 +/- 15 vs 45 +/- 33 mEq/liter; P less than .003). The shunt should not be inserted in patients with alcoholic hepatitis (bilirubin level greater than 8 mg/100 ml). Ascitic fluid should be discarded at the time of surgery in patients with impaired cardiac function, a bleeding diathesis, and when liver function is more severely deranged.

Acute Kidney Injury↗

Hemobilia after percutaneous transhepatic biliary drainage.

Hemobilia after the inception of percutaneous transhepatic biliary drainage (PTBD) has been reported as an uncommon, but sometimes fatal, complication. We examined the incidence, pathogenesis, and management of hemobilia in 94 patients who received PTBD. There were seven cases (7.4%) with transient and six (6.4%) with severe hemobilia; one patient (1.1%) of the latter group died. There was no correlation between hemobilia and hemostatic or hepatic insufficiency. Angiography during PTBD was performed in 47 patients, and abnormalities restricted to arterial changes were noted in nine (19.1%). All but one patient with hemobilia showed angiographic abnormalities. Our findings indicate that hemobilia occurs more often than has been suspected and that it is usually due to intrahepatic vessel injury rather than to hemorrhagic diathesis or hepatic insufficiency. The primary management of hemobilia consists of maintaining continuous patency of the drainage catheter.

Adult↗

Embolization of bleeding esophageal varices via umbilical vein. An alternative approach.

Embolization of bleeding esophageal varices via the umbilical vein can be used as an alternative technique to percutaneous transhepatic coronary vein occlusion (PTCVO). Both techniques can stop acute bleeding from esophageal varices and allow the cirrhotic patient with portal hypertension to be prepared for an elective rather than an emergency shunt. Embolization via the umbilical vein can be performed with a patient under local anesthesia, can be effective when other methods fail, and can be done safely in the presence of both ascites and a bleeding diathesis, which are two contraindications to PTCVO.

Acute Disease↗

Preoperative disseminated intravascular coagulation associated with aortic aneurysms. A prospective study of 76 cases.

A prospective study of 76 preoperative patients with aortic aneurysms was undertaken to determine the true incidence of associated disseminated intravascular coagulation (DIC). Although 39% of the patients showed a notable elevation of the fibrin split products level, only three had thrombocytopenia and a clinical bleeding diathesis, as well. Thus, clinically overt DIC occurred preoperatively in only 4% of the patients. All three patients had extensive aneurysms that involved the thoracoabdominal aorta. Preoperative fibrinogen levels in this series tended to be high-normal or elevated and were not good indicators of underlying excessive fibrinolysis. Hemostatic abnormalities, such as ecchymoses and petechiae, may be the key to the clinical diagnosis of DIC in preoperative patients with aortic aneurysms.

Aged↗

A foregut carcinoid tumor causing Zollinger-Ellison syndrome.

A patient had severe peptic ulcer disease complicated by gastric outlet obstruction and choledochoduodenal fistula. Serum gastrin levels were elevated preoperatively to 340 ng/L. A 1.5-cm histologically benign carcinoid tumor of the antrum of the stomach was found at surgery, and surgical resection of the tumor resulted in normalization of serum gastrin levels and amelioration of the peptic acid diathesis. The patient remains asymptomatic at one year. Immunohistochemical staining demonstrated that the carcinoid indeed contained gastrin along with chromogranin, cholecystokinin, and neuron-specific enolase. This is a case of Zollinger-Ellison syndrome caused by a benign foregut carcinoid (gastric carcinoid-gastrinoma).

Aged↗

Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood.

CONTEXT: Evidence suggests that early adverse experiences play a preeminent role in development of mood and anxiety disorders and that corticotropin-releasing factor (CRF) systems may mediate this association. OBJECTIVE: To determine whether early-life stress results in a persistent sensitization of the hypothalamic-pituitary-adrenal axis to mild stress in adulthood, thereby contributing to vulnerability to psychopathological conditions. DESIGN AND SETTING: Prospective controlled study conducted from May 1997 to July 1999 at the General Clinical Research Center of Emory University Hospital, Atlanta, Ga. PARTICIPANTS: Forty-nine healthy women aged 18 to 45 years with regular menses, with no history of mania or psychosis, with no active substance abuse or eating disorder within 6 months, and who were free of hormonal and psychotropic medications were recruited into 4 study groups (n = 12 with no history of childhood abuse or psychiatric disorder [controls]; n = 13 with diagnosis of current major depression who were sexually or physically abused as children; n = 14 without current major depression who were sexually or physically abused as children; and n = 10 with diagnosis of current major depression and no history of childhood abuse). MAIN OUTCOME MEASURES: Adrenocorticotropic hormone (ACTH) and cortisol levels and heart rate responses to a standardized psychosocial laboratory stressor compared among the 4 study groups. RESULTS: Women with a history of childhood abuse exhibited increased pituitary-adrenal and autonomic responses to stress compared with controls. This effect was particularly robust in women with current symptoms of depression and anxiety. Women with a history of childhood abuse and a current major depression diagnosis exhibited a more than 6-fold greater ACTH response to stress than age-matched controls (net peak of 9.0 pmol/L [41.0 pg/mL]; 95% confidence interval [CI], 4.7-13.3 pmol/L [21.6-60. 4 pg/mL]; vs net peak of 1.4 pmol/L [6.19 pg/mL]; 95% CI, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% CI, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001). CONCLUSIONS: Our findings suggest that hypothalamic-pituitary-adrenal axis and autonomic nervous system hyperreactivity, presumably due to CRF hypersecretion, is a persistent consequence of childhood abuse that may contribute to the diathesis for adulthood psychopathological conditions. Furthermore, these results imply a role for CRF receptor antagonists in the prevention and treatment of psychopathological conditions related to early-life stress. JAMA. 2000;284:592-597

Adrenocorticotropic Hormone↗

Suicide in teenagers: assessment, management, and prevention.

Adolescents who kill themselves invariably have an underlying psychiatric disorder. Biological markers are not yet clinically useful for identifying adolescents at risk, and there is a paucity of research data on the effectiveness of behavioral intervention for suicidal teenagers. A case of a 16-year-old scholar and athlete is presented to illustrate how multiple risk factors and a family diathesis often go undetected, resulting in tragic consequences. Psychiatric, familial, genetic, and social risk factors of adolescent suicide are reviewed, and the efficacy of lithium and antidepressant pharmacotherapy in reducing suicide rates is discussed. The importance of screening adolescent patients for depression is emphasized. Although teenage suicide is rare and hard to predict, identifying and treating adolescents at risk is essential to further reduce teenage suicide.

Adolescent↗

Hemorrhagic fever viruses as biological weapons: medical and public health management.

OBJECTIVE: To develop consensus-based recommendations for measures to be taken by medical and public health professionals if hemorrhagic fever viruses (HFVs) are used as biological weapons against a civilian population. PARTICIPANTS: The Working Group on Civilian Biodefense included 26 representatives from academic medical centers, public health, military services, governmental agencies, and other emergency management institutions. EVIDENCE: MEDLINE was searched from January 1966 to January 2002. Retrieved references, relevant material published prior to 1966, and additional sources identified by participants were reviewed. CONSENSUS PROCESS: Three formal drafts of the statement that synthesized information obtained in the evidence-gathering process were reviewed by the working group. Each draft incorporated comments and judgments of the members. All members approved the final draft. CONCLUSIONS: Weapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock. The mode of transmission and clinical course would vary depending on the specific pathogen. Diagnosis may be delayed given clinicians' unfamiliarity with these diseases, heterogeneous clinical presentation within an infected cohort, and lack of widely available diagnostic tests. Initiation of ribavirin therapy in the early phases of illness may be useful in treatment of some of these viruses, although extensive experience is lacking. There are no licensed vaccines to treat the diseases caused by HFVs.

Aerosols↗

Marshall-Stickler phenotype associated with von Willebrand disease.

We report on 6 individuals from three different kindreds with Marshall-Stickler (MS) phenotype, with characteristic orofacial abnormalities, arthropathy, deafness, and eye findings, all of whom were discovered to have a mild bleeding diathesis and coagulation-study findings consistent with mild von Willebrand disease (vWD). MS syndrome has been linked in some cases to the type II procollagen gene (COL2A1) on chromosome 12q, and to the collagen XI gene (COL11A2) on chromosome 6. The von Willebrand factor (vWF) is encoded by a 180-Kb gene located on the short arm of chromosome 12. This is the first reported association of these two disorders.

Adolescent↗

Twin studies in schizophrenia with special emphasis on concordance figures.

Twin studies in schizophrenia have been reviewed with special emphasis on concordance rates in population-based investigations. Sources of error have been discussed with particular focus on sampling. The pair-wise concordance rates in schizophrenia are 30-40% in MZ and 5-10% in DZ, with somewhat higher rates for proband concordance. The findings from twin studies support the diathesis stress model in schizophrenia, and it is argued that the polygenic model gives the best explanation for the empirical findings.

Computational Biology↗

Acquired hypoprothrombinemia: effects of danazol treatment.

The lupus anticoagulant may be accompanied by an acquired factor II deficiency and bleeding. We report on a patient with a lupus anticoagulant and factor II (Fll) deficiency responsive to Danazol. Acquired hypoprothrombinemia (FII) with the lupus anticoagulant (LA) may be accompanied by a hemorrhagic diathesis. A 64-year-old male with discoid lupus erythematosis bled after an intestinal polypectomy. His FII level was 18%, and his FII antigen level was 20%. Danazol (D) (600 mg per day) administration was associated with a rise in FII activity and antigen to 50% within 10 days. The patient underwent abdominal surgery. We studied the effect(s) of D on the FII level and on other coagulation factors in this patient. The patient's plasma FII antigen had a single precipitin arc compared to the two peaks of normal plasma on counterimmunoelectrophoresis with Ca++. The samples pre- and during D therapy had the same positively charged arc as normal samples, although they were quantitatively different. Neuraminidase treatment demonstrated a decrease in the positively charged migration of normal and the patient's FII antigen. Affinity chromatography of normal and patient plasma on a Sepharose protein A column revealed FII antigen present in the patient's bound fraction. The relative percentages of bound FII before and during D treatment were similar. During D therapy, levels of FIX and X rose 50-100%, and protein C rose 20-25%, while free protein S did not change. D is an effective therapy for acquired FII deficiency associated with LA. D does not affect the binding of Ig to FII, but D raises FII levels by increasing synthesis of the FII protein.

Blood Loss, Surgical↗

Successful treatment of acquired factor VIII inhibitors with cyclosporin.

The treatment of Factor VIII inhibitors remains controversial and no standard therapy exists. We describe in this report two consecutive patients with this inhibitor that responded to cyclosporin. Clinical improvement of the bleeding diathesis, a return to normal of the PTT, a decrease in the level of the inhibitor, and a return to normal of the factor VIII level followed use of this drug. We believe that cyclosporin is effective in the treatment of factor VIII inhibitors and deserves further investigation.

Adult↗

Successful treatment of transient acquired factor X deficiency by plasmapheresis with concomitant intravenous immunoglobulin and steroid therapy.

Two patients with no history of previous bleeding diatheses presented with active bleeding from multiple body sites, declining hemoglobin levels, and markedly prolonged prothrombin times (PT) and activated partial thromboplastin times (aPTT) with incomplete correction on PT mix assays. Both patients demonstrated a severe deficiency of factor X (F.X) (<1%; reference range 60-150%). F.X levels and bleeding were refractory to multiple transfusions of fresh frozen plasma (FFP) in both patients. In contrast, daily therapeutic plasma exchange (PLEX) with concomitant administration of intravenous immunoglobulin (IV IgG) and steroids produced a rapid increase in F.X levels with cessation of bleeding, followed by stabilization and normalization of F.X levels and progressive correction of coagulation times. Neither patient has demonstrated a recurrence of the bleeding tendency following discontinuation of steroid therapy. These patients had transient acquired F.X deficiency, a rare coagulopathy, which can result in a lethal bleeding diathesis. An IgG inhibitor that selectively inhibited F.X activation in Russell's viper venom or tissue factor/F.VIIa assays was demonstrated in one patient's pretreatment plasma. Previous treatment of hemorrhage in transient acquired F.X deficiency has been prothrombin complex and/or activated clotting concentrates, which can be associated with transient hypercoagulable states. This is the first reported use of PLEX in transient acquired F.X deficiency. PLEX is safe, efficacious, and rapidly restores hemostasis in this rare acquired bleeding disorder.

Adult↗