This study compared outpatients (n = 196) with PTSD versus PTSD + alcohol use disorders (AUD) on clinical measures. PTSD + AUD patients were more likely to meet criteria for Borderline and Antisocial Personality Disorders. Emotion dysregulation may help account for the relationship between PTSD and AUD.

Onset of social anxiety disorder (SAD) often precedes that of major depressive disorder (MDD) in patients with this comorbidity pattern. The current study examined the association between three SAD onset groups (childhood, adolescent, adulthood) and clinical characteristics of 412 psychiatric outpatients diagnosed with MDD and SAD based on a semi-structured diagnostic interview. Childhood and adolescent SAD onset groups were more likely to report an onset of MDD prior to age 18 and have made at least one prior suicide attempt compared to the adulthood onset group. The childhood SAD onset group also was more likely to have chronic MDD, poorer past social functioning, and an increased hazard of MDD onset compared to the adulthood onset group. Findings suggest that patients with an onset of SAD in childhood or adolescence may be particularly at risk for a more severe and chronic course of depressive illness.

Psychotic symptoms may occur in 15–64% of individuals with post-traumatic stress disorder, suggesting that the syndrome could be subtyped in a similar fashion to mood disorders. In our study of 1800 psychiatric out-patients who completed comprehensive diagnostic interviews, the lifetime prevalence of psychotic symptoms in people with PTSD was 17% (odds ratio (OR) = 3.48, 95% CI 2.32–5.21). However, after excluding people with comorbid conditions also known to be associated with psychotic symptoms this dropped to only 2.5% (OR) = 0.60, 95% CI 0.08–4.52). In contrast, rates of psychotic major depression did not change after excluding these same comorbidities. Our results do not support the official psychotic subtyping of PTSD.

Previous studies have shown that both bipolar disorder (BPD) and psychomotor agitation (PMA) are associated with substance dependence. These two findings have yet to be integrated, despite evidence that PMA is closely linked with the bipolar spectrum. Accordingly, the current study examined whether BPD and PMA had unique or overlapping associations with substance dependence disorders. Participants were 2300 individuals seeking outpatient psychiatric treatment. Before treatment, participants were assessed using structured clinical interviews, which yielded DSM-IV psychiatric diagnoses and clinical ratings of mood symptoms. Current PMA and lifetime BPD were present in 483 and 172 (Bipolar I, n = 71; Bipolar II, n = 101) participants, respectively. Current PMA and lifetime BPD each were associated with increased prevalence of lifetime nicotine, alcohol, and drug dependence (ORs ≥ 1.52, ps ≤ .0004). These associations remained significant when controlling for demographic characteristics and comorbid psychiatric disorders, except the link between agitation and alcohol dependence, which was reduced to a trend (p=.058). Although BPD and PMA were associated with each other, these two factors demonstrated unique, non-overlapping relationships to nicotine, alcohol, and drug dependence. Individuals with both PMA and BPD exhibited especially high rates of comorbid substance dependence. The present results replicate and extend previous findings documenting the relations of BPD and PMA to substance dependence. BPD and PMA may represent independent psychopathological correlates of substance dependence. Future research should explore the theoretical and clinical significance of these potentially distinct relations to substance dependence.

Background

Psychotic major depression (PMD) is a severe mental disorder characterized by high levels of illness severity, chronicity, impairment, and treatment resistance. However, most past research on PMD has been conducted in inpatient hospital samples, and relatively little is known about PMD patients presenting for treatment in the community specifically.

Methods

In this study, we examined the prevalence and clinical characteristics of PMD in a large sample (n = 2,500) of treatment-seeking outpatients who were administered structured clinical interviews by trained diagnosticians.

Results

Of the patients diagnosed with major depression, 5.3% had psychotic features. PMD patients were more likely to be members of a racial/ethnic minority and to have lower educational attainment compared to those with nonpsychotic major depression. In addition, PMD patients were found to have greater current depression severity, suicidal ideation, and social and work impairment. These patients also were more likely to have histories of suicide attempts and psychiatric hospitalizations, to report an earlier age of illness onset, and to meet criteria for chronic depression. In terms of psychiatric comorbidity, PMD patients had higher rates of certain anxiety disorders as well as more somatoform and cluster A personality disorders.

Conclusions

Results indicated that PMD was present in a relatively small percentage of treatment-seeking outpatients but was associated with disproportionately high levels of severity and impairment. Similarities and differences between the current findings and those from past research are discussed, including clinical implications for the identification and treatment of PMD in routine practice settings.

Recent reports suggest bipolar disorder is not only under-diagnosed but may at times be over-diagnosed. Little is known about factors that increase the odds of such mistakes. The present work explores whether symptoms of borderline personality disorder increase the odds of a bipolar misdiagnosis. Psychiatric outpatients (N = 610) presenting for treatment were administered the Structured Clinical Interview for DSM-IV (SCID) and the Structured Interview for DSM-IV Personality for DSM-IV axis II disorders (SIDP-IV), as well as a questionnaire asking if they had ever been diagnosed with bipolar disorder by a mental health care professional. Eighty-two patients who reported having been previously diagnosed with bipolar disorder but who did not have it according to the SCID were compared to 528 patients who had never been diagnosed with bipolar disorder. Patients with borderline personality disorder had significantly greater odds of a previous bipolar misdiagnosis, but no specific borderline criteria was unique in predicting this outcome. Patients with borderline personality disorder, regardless of how they meet criteria, may be at increased risk of being misdiagnosed with bipolar disorder.

Background

Chronic Myeloid Leukemia (CML) is caused by the abnormal fusion protein BCR-ABL1, a constitutively active tyrosine kinase and product of the Philadelphia chromosome. Gleevec (Imatinib mesylate) is a selective inhibitor of this kinase. Treatment with this agent is known to result in hematologic, cytogenetic, and molecular responses. Patan hospital (Patan, Nepal) is one of the Gleevec International Patient Assistance Program (GIPAP) centers for patients with CML.

Methods

A total of 106 Philadelphia positive CML patients were enrolled in our center between Feb 2003 and Jun 2008, and 103 of them were eligible for cytogenetic and/or hematologic response analyses.

Results

Out of 103 patients, 27% patients underwent cytogenetic analysis. Imatinib induced major cytogenetic responses in 89% and complete hematologic responses in almost 100% of the patients with confirmed CML. After a mean follow up of 27 months, an estimated 90% of the patients on imatinib remained in hematologic remission and more than 90% of the patients are still alive. About 30% of patients developed some form of manageable myelosuppression. A few patients developed non-hematologic toxic side effects such as edema and hepatotoxicity.

Conclusions

Our study demonstrates that imatinib is safe to use in a developing country. Furthermore, we demonstrate that imatinib is very effective and induced long lasting responses in a high proportion of patients with Ph chromosome/BCR-ABL1 positive CML. Imatinib is well tolerated by our patients. The lack of cytogenetic analysis in the majority of our patients hindered our ability to detect inadequate responses to imatinib and adjust therapy appropriately.

The aim of this study was to elucidate the depression-nicotine dependence link by evaluating which specific depressive symptoms are uniquely associated with nicotine dependence in psychiatric outpatients. Participants were assessed using structured clinical interviews which yielded psychiatric diagnoses and clinical ratings on a wide variety of depressive symptoms. Depressive symptoms were compared across three groups: (1) patients with no history of nicotine dependence (NND; n=1015); (2) patients with past nicotine dependence in full remission for at least 2 months (PND; n=211); and (3) patients with current nicotine dependence (CND; n=342). Participants with CND evidenced elevations on certain typical-vegetative, melancholic, and dysphoric depressive symptoms as compared to patients with NND and (to a lesser extent) patients with PND. Group differences were most consistent for depressed mood, anhedonia, appetite/weight loss, psychomotor disturbance, fatigue, and insomnia. Differences were least apparent for atypical symptoms. The symptomatic profiles of PND and NND patients were virtually indistinguishable. Certain vegetative, melancholic and dysphoric depressive symptoms are closely associated with nicotine dependence and could play an important etiological role in depression-nicotine dependence comorbidity.

This study investigated the link between physical pain and non-medical prescription analgesic use (NMPAU), as well as the degree to which this association may vary by the presence of psychiatric and substance use disorders. Data were from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative, in-person probability sample of adults (n=43,093) aged 18 or older in the United States (2001–2002). Face-to-face interviews were used to gather information on past-year levels of physical pain (i.e., low, medium, high), in addition to DSM-IV classifications for mood, anxiety, substance use problems (i.e., abuse and/or dependence), and personality disorders. Within the analytic sample of those with valid data (n=42,734), the past-year rate of NMPAU was 1.8%, of which 20% met the DSM-IV criteria for abuse/dependence. Among past-year NMPAUs, 53% was incidental (e.g., less than monthly), but daily use was substantial (13% of NMPAUs). Accounting for our target confounding factors, pain was positively associated (p<.05) with an increased probability of non-disordered (i.e., no abuse and/or dependence) and disordered (i.e., abuse and/or dependence) NMPAU in the past year. Within each level of pain, the odds of past-year non-disordered and disordered NMPAU were significantly higher (p<.05) for those with disordered alcohol use compared with non-disordered users. This pattern was similar for illicit drugs, although marginally significant (p=.060) and specific to disordered NMPAU. In contrast, psychiatric disorders increased the probability of both types of NMPAU, but these associations did not differ by levels of pain. These findings suggest that pain is an independent risk factor for non-disordered and disordered NMPAU, yet its effects are substantially modified by patterns of substance use.

Evaluating whether certain subtypes of Major Depressive Disorder (MDD) are more strongly associated with Substance Use Disorders (SUDs) may help clarify reasons for MDD–SUD relations. Therefore, this study compared DSM-IV-defined non-atypical/non-melancholic depression (undifferentiated depression; n=365), atypical depression (n=117), melancholic depression (n=245), and atypical-melancholic depression (n=68) in the prevalence of current SUDs, while controlling for relevant demographic and clinical variables. Psychiatric outpatients with a current diagnosis of unipolar MDD were assessed using the Structured Clinical Interview for DSM-IV, supplemented by questions from the Schedule for Affective Disorders and Schizophrenia. Results showed that compared with patients with undifferentiated depression, melancholic patients had higher rates of current nicotine dependence (34% vs. 26%) and drug abuse/dependence (8% vs. 3%), Ps<0.05. These differences were explained by the association between specific melancholic features (marked psychomotor agitation and weight loss/decreased appetite) and nicotine and drug use disorders. Atypical depression, atypical-melancholic depression, and other subtype symptoms were not significantly associated with any SUDs. Although this study is limited by low prevalence of alcohol and drug use disorders, the present findings suggest that different symptomatic expressions of MDD differentially associate with some SUDs.

Background

Previous research suggests that patients with psychotic major depression (PMD) may differ from those with nonpsychotic major depression (NMD) not only in terms psychotic features, but also in their depressive symptom presentation. The present study contrasted the rates and severity of depressive symptoms in outpatients diagnosed with PMD versus NMD.

Method

The sample consisted of 1,112 patients diagnosed with major depression, of which 60 (5.3%) exhibited psychotic features. Depressive symptoms were assessed by trained diagnosticians at intake using the Structured Clinical Interview for DSM-IV and supplemented by severity items from the Schedule for Affective Disorders and Schizophrenia.

Results

PMD patients were more likely to endorse the presence of weight loss, insomnia, psychomotor agitation, indecisiveness, and suicidality compared to NMD patients. Furthermore, PMD patient showed higher levels of severity on several depressive symptoms, including depressed mood, appetite loss, insomnia, psychomotor disturbances (agitation and retardation), fatigue, worthlessness, guilt, cognitive disturbances (concentration and indecisiveness), hopelessness, and suicidal ideation. The presence of psychomotor disturbance, insomnia, indecisiveness, and suicidal ideation were predictive of diagnostic status even after controlling for the effects of demographic characteristics and other symptoms.

Conclusions

These findings are consistent with past research suggesting that PMD is characterized by a unique depressive symptom profile in addition to psychotic features and higher levels of overall depression severity. The identification of specific depressive symptoms in addition to delusions/hallucinations that can differentiate PMD versus NMD patients can aid in the early detection of the disorder. These investigations also provide insights into potential treatment targets for this high-risk population.

The ability of a diagnostic interview to identify all individuals with a particular psychiatric disorder depends, in part, on the performance of the interview’s initial screening questions. The Structured Clinical Interview for DSM-IV (SCID) is the most widely used research diagnostic interview, yet little research has examined the performance of the SCID screening questions. Because Social Anxiety Disorder (SAD) is one of the most frequent psychiatric disorders, we examined the performance of the SCID screening question in the SAD module to detect social fears and SAD. The incremental validity of a more comprehensive list of social fears was examined by determining how many patients were diagnosed with SAD in those who were originally missed by the SCID screening question. Five percent of those originally missed by the SCID screening question subsequently received a lifetime diagnosis of SAD, and there was a significant increase in the prevalence of social fears after patients were cued by the social fears list. The most commonly reported fears missed by the SCID screening question included speaking in a group, with sexually attractive others, and with authority figures. Results suggest that perhaps these fears could be added to the SCID screening question in order to capture individuals missed by the SCID screening question and to provide more comprehensive information for treatment purposes.

Background

The excess mortality associated with depressive disorders has been most often attributed to risks for suicide but diverse findings indicate that depressive disorders also increase risks for cardiovascular (CV) mortality. Among the possible mediators is the HPA-axis hyperactivity that characterizes many cases of relatively severe depressive disorder and severity is characteristic of psychotic depressive disorder.

Methods

The following describes a 17-year mortality follow-up of 54 patients with Research Diagnostic Criteria (RDC) psychotic major depression or schizoaffective, mainly affective, depression. All had baseline assessments that included a 1mg dexamethasone suppression test with post-dexamethasone samples at 8 a.m., 4 p.m. and 11 p.m.

Results

Regression analyses showed that both greater age and higher maximum post-dexamethasone cortisol concentrations predicted deaths due to cardiovascular (CV) causes (t = 4.01, p < .001 and t = 3.03, p = .004, respectively); the 11 p.m. cortisol concentration predicted death due to suicide (t = 2.05, p = 0.048). The 4 who died from CV disease had a mean (SD) post-dexamethasone cortisol concentration of 18.0 (6.0) μg/dl while the mean (SD) value for the remaining 50 patients was 7.6 (6.6) μg/dl (t = 3.03, df = 53, p = 0.004). Regression analyses showed the 11 p.m. post-dexamethasone value to be predictive of suicide (t = 2.05, p = 0.048).

Conclusions

Conclusions should be tentative because an earlier follow-up of a more heterogeneous, but larger, sample did not find a relationship between DST results and CV mortality, and because only 4 CV deaths occurred in the present study. HPA-axis hyperactivity is probably only one of a number of factors that link depressive disorder to CV mortality.

This study evaluated whether psychiatric outpatients with a past stimulant use disorder in full remission for ≥ 2 months (STIM+, n = 204) and those with no history of stimulant use disorder (STIM−, n = 2070) differed in the prevalence of current anhedonia and amotivation. Results showed that a significantly greater proportion of STIM+ participants reported anhedonia and amotivation than STIM− participants. The relation between stimulant use disorder history and anhedonia remained robust after controlling for other relevant clinical and demographic factors. These findings suggest that anhedonia may be a preexisting risk factor or protracted effect of stimulant misuse.

Over the last decade rapid progress has been made in the study of ethanol-related traits including alcohol abuse and dependence, and behavioral responses to ethanol in both humans and animal models. To collect, curate, integrate these results so as to make them easily accessible and interpretable for researchers, we developed ERGR, a comprehensive ethanol-related gene resource. We collected and curated more than 30 large-scale data sets including linkage, association and microarray gene expression from the literature and 21 mouse QTLs from public databases. At present, the ERGR deposits ethanol-related information of ∼7000 genes from five organisms: human (3311), mouse (2129), rat (679), fly (614) and worm (228). ERGR provides gene annotations and orthologs, detailed gene study information (e.g. fold changes of gene expression, P-values), and both the text and BLAST searches. Moreover, ERGR has data integration tools such as for data union and intersection, and candidate gene selection based on evidence in multiple datasets or organisms. The ERGR database is evolving with new data releases. More functions will also be added. ERGR has a user-friendly web interface with browse and search functions at multiple levels. It is freely available at http://bioinfo.vipbg.vcu.edu/ERGR/.

Murine typhus was diagnosed by PCR in 50 (7%) of 756 adults with febrile illness seeking treatment at Patan Hospital in Kathmandu, Nepal. Of patients with murine typhus, 64% were women, 86% were residents of Kathmandu, and 90% were unwell during the winter. No characteristics clearly distinguished typhus patients from those with blood culture–positive enteric fever.

Background

Although previous research has examined comorbidity in principal Social Anxiety Disorder (SAD), few studies have examined the disorders for which those with comorbid SAD seek treatment. Further, studies have shown that depressive disorders often are associated with SAD, but few have examined the clinical characteristics of patients with this particular comorbidity.

Method

The current study examined the prevalence of various principal Axis I disorders in 577 individuals diagnosed with comorbid SAD.

Results

Consistent with previous research, Major Depressive Disorder (MDD) was the most frequent principal diagnosis in patients with comorbid SAD. Those with principal MDD and comorbid SAD (MDD-SAD) were compared to those with MDD without SAD (MDD) on demographic and clinical characteristics. Patients with MDD-SAD versus those with MDD were more severe in terms of social functioning, duration of depressive episode, suicidal ideation, time out of work, presence of current alcohol abuse/dependence, and age of onset of MDD. Social functioning, duration of episode, suicidal ideation, and age of onset of MDD remained significant even after controlling for additional comorbid disorders.

Conclusions

Findings suggest the need for future research to determine how treatments could be adapted for this commonly occurring comorbidity.

Background

Significant research has looked at the psychosocial impairment associated with bipolar I disorder and major depressive disorder. Far less is known about the impact of bipolar II disorder. The present study assessed the social and work impairment associated with bipolar II disorder and whether these are more or less severe than those associated with bipolar I disorder or major depressive disorder.

Methods

Psychiatric outpatients with bipolar II disorder (n = 89), bipolar I disorder (n = 45) and major depressive disorder (n = 1,251) were assessed cross-sectionally by highly trained raters using semi-structured interviews. Participants were in a major depressive episode. Groups were compared on a series of indicators of psychosocial functioning.

Results

Bipolar I and II disorder were associated with greater absenteeism from work due to psychopathology compared to major depressive disorder. The bipolar disorders also had higher rates of hospitalization and suicide attempts. Bipolar II disorder had fewer hospitalization than bipolar I disorder which may have led to slightly less severe work impairment. Both conditions had similar rates of serious suicide attempts.

Limitations

The study was cross-sectional and retrospective. Furthermore, the sample consisted of outpatients seeking treatment, limiting generalizability to other settings.

Conclusion

Bipolar II disorder is associated with serious work impairment and a high number of serious suicide attempts. The level of impairment is more similar than it is different from that associated with bipolar I disorder. Clinicians would be mistaken to presume that the “softer” bipolar spectrum, specifically bipolar II disorder, is less impairing than bipolar I disorder.

Objective

To assess the efficacy of gatifloxacin versus cefixime in the treatment of uncomplicated culture positive enteric fever.

Design

A randomized, open-label, active control trial with two parallel arms.

Setting

Emergency Room and Outpatient Clinics in Patan Hospital, Lagankhel, Lalitpur, Nepal.

Participants

Patients with clinically diagnosed uncomplicated enteric fever meeting the inclusion criteria.

Interventions

Patients were allocated to receive one of two drugs, Gatifloxacin or Cefixime. The dosages used were Gatifloxacin 10 mg/kg, given once daily for 7 days, or Cefixime 20 mg/kg/day given in two divided doses for 7 days.

Outcome Measures

The primary outcome measure was fever clearance time. The secondary outcome measure was overall treatment failure (acute treatment failure and relapse).

Results

Randomization was carried out in 390 patients before enrollment was suspended on the advice of the independent data safety monitoring board due to significant differences in both primary and secondary outcome measures in the two arms and the attainment of a priori defined endpoints. Median (95% confidence interval) fever clearance times were 92 hours (84–114 hours) for gatifloxacin recipients and 138 hours (105–164 hours) for cefixime-treated patients (Hazard Ratio[95%CI] = 2.171 [1.545–3.051], p<0.0001). 19 out of 70 (27%) patients who completed the 7 day trial had acute clinical failure in the cefixime group as compared to 1 out of 88 patients (1%) in gatifloxacin group(Odds Ratio [95%CI] = 0.031 [0.004 – 0.237], p<0.001). Overall treatment failure patients (relapsed patients plus acute treatment failure patients plus death) numbered 29. They were determined to be (95% confidence interval) 37.6 % (27.14%–50.2%) in the cefixime group and 3.5% (2.2%–11.5%) in the gatifloxacin group (HR[95%CI] = 0.084 [0.025–0.280], p<0.0001). There was one death in the cefixime group.

Conclusions

Based on this study, gatifloxacin is a better treatment for uncomplicated enteric fever as compared to cefixime.

Trial Registration

Current Controlled Trials ISRCTN75784880

Objective To determine, in one low income country (Nepal), which characteristics of medical students are associated with graduate doctors staying to practise in the country or in its rural areas.

Design Observational cohort study.

Setting Medical college registry, with internet, phone, and personal follow-up of graduates.

Participants 710 graduate doctors from the first 22 classes (1983-2004) of Nepal’s first medical college, the Institute of Medicine.

Main outcome measures Career practice location (foreign or in Nepal; in or outside of the capital city Kathmandu) compared with certain pre-graduation characteristics of medical student.

Results 710 (97.7%) of the 727 graduates were located: 193 (27.2%) were working in Nepal in districts outside the capital city Kathmandu, 261 (36.8%) were working in Kathmandu, and 256 (36.1%) were working in foreign countries. Of 256 working abroad, 188 (73%) were in the United States. Students from later graduating classes were more likely to be working in foreign countries. Those with pre-medical education as paramedics were twice as likely to be working in Nepal and 3.5 times as likely to be in rural Nepal, compared with students with a college science background. Students who were academically in the lower third of their medical school class were twice as likely to be working in rural Nepal as those from the upper third. In a regression analysis adjusting for all variables, paramedical background (odds ratio 4.4, 95% confidence interval 1.7 to 11.6) was independently associated with a doctor remaining in Nepal. Rural birthplace (odds ratio 3.8, 1.3 to 11.5) and older age at matriculation (1.1, 1.0 to 1.2) were each independently associated with a doctor working in rural Nepal.

Conclusions A cluster of medical students’ characteristics, including paramedical background, rural birthplace, and lower academic rank, was associated with a doctor remaining in Nepal and with working outside the capital city of Kathmandu. Policy makers in medical education who are committed to producing doctors for underserved areas of their country could use this evidence to revise their entrance criteria for medical school.