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1.  A Clinically Useful Social Anxiety Disorder Outcome Scale 
Comprehensive psychiatry  2013;54(7):758-765.
Increasingly, emphasis is being placed on measurement-based care to improve the quality of treatment. Although much of the focus has been on depression, measurement-based care may be particularly applicable to social anxiety disorder (SAD) given its high prevalence, high comorbidity with other disorders, and association with significant functional impairment. Many self-report scales for SAD currently exist, but these scales possess limitations related to length and/or accessibility that may serve as barriers to their use in monitoring outcome in routine clinical practice. Therefore, the aim of the current study was to develop and validate the Clinically Useful Social Anxiety Disorder Outcome Scale (CUSADOS), a self-report measure of SAD. The CUSADOS was designed to be reliable, valid, sensitive to change, brief, easy to score, and easily accessible, to facilitate its use in routine clinical settings. The psychometric properties of the CUSADOS were examined in 2,415 psychiatric outpatients who were presenting for treatment and had completed a semi-structured diagnostic interview. The CUSADOS demonstrated excellent internal consistency, and high item-total correlations and test-retest reliability. Within a sub-sample of 381 patients, the CUSADOS possessed good discriminant and convergent validity as it was more highly correlated with other measures of SAD than with other psychiatric disorders. Furthermore, scores were higher in outpatients with a current diagnosis of SAD compared to those without a SAD diagnosis. Preliminary support also was obtained for the sensitivity to change of the CUSADOS in a sample of 15 outpatients receiving treatment for comorbid SAD and depression. Results from this validation study in a large psychiatric sample show that the CUSADOS possesses good psychometric properties. Its brevity and ease of scoring also suggest that it is feasible to incorporate into routine clinical practice.
PMCID: PMC3740001  PMID: 23642634
2.  Prevalence of Attenuated Psychotic Symptoms and their Relationship with DSM-IV Diagnoses in a General Psychiatric Outpatient Clinic 
Attenuated psychosis syndrome (APS) is being proposed for DSM-5 for those impaired by subthreshold psychotic symptoms that are not better accounted for by another diagnosis and not meeting criteria for a psychotic disorder. The rationale is to identify patients who are at high risk for transition to a psychotic disorder in the near future. However, the potential impact of using this new diagnosis in routine clinical practice settings has not been carefully examined.
We investigated the prevalence rate of endorsing attenuated psychotic experiences (PEs) in a treatment-seeking psychiatric outpatient sample (n = 1,257) recruited from June 1997 to June 2002 to identify patients who could potentially meet criteria for APS. Patients completed a self-report measure of psychiatric symptoms and afterward were administered structured clinical interviews.
After excluding those with lifetime DSM-IV psychotic disorders, PEs remained highly prevalent in the sample (28% reported at least one current PE) and rates were similar across all major diagnostic categories. Only 1 patient (0.08%) reported PEs but did not meet criteria for another current DSM disorder; however, this individual endorsed other nonpsychotic symptoms of greater severity. PE endorsement was positively correlated with nearly all other nonpsychotic symptom domains and multivariate analysis showed that general clinical severity predicted endorsement of PEs (ps < .001).
We could not identify any patients likely meeting criteria for APS alone in our sample. PEs appear to be common in outpatients and represent nonspecific indicators of psychopathology. Diagnosing APS in the community could result in high rates of false positives or high rates of APS “comorbidity” with other nonpsychotic disorders, leading to the increased use of antipsychotic medications without clear need. Therefore, the clinical utility of adding APS to the diagnostic system remains highly questionable.
PMCID: PMC4036523  PMID: 23146173
psychosis; diagnosis; attenuated psychosis syndrome; DSM-5; routine clinical practice
3.  A comparison study of body dysmorphic disorder versus social phobia 
Psychiatry research  2012;205(1-2):109-116.
Body dysmorphic disorder (BDD) shares many characteristics with social phobia (SP), including high levels of social anxiety and avoidance, but to our knowledge no studies have directly compared these disorders’ demographic and clinical features. Demographic and clinical features were compared in individuals with BDD (n=172), SP (n=644), and comorbid BDD/SP (n=125). SP participants had a significantly earlier age of onset and lower educational attainment than BDD participants. BDD participants were significantly less likely to ever be married than SP participants, had a greater likelihood of ever being psychiatrically hospitalized, and had significantly lower mean GAF scores than SP participants. The two groups had different comorbidity patterns, which included a greater likelihood for BDD participants to have comorbid obsessive-compulsive disorder (OCD) or an eating disorder, versus a greater likelihood for SP participants to have a comorbid non-OCD anxiety disorder. The comorbid BDD/SP group had significantly greater morbidity across several domains than the SP only group, but not the BDD only group. In summary, although BDD and SP were similar across many demographic and clinical features, they had important differences. Future studies are needed to confirm these findings and address similarities and differences between these disorders across a broader range of variables.
PMCID: PMC3552120  PMID: 22999105
body dysmorphic disorder; dysmorphophobia; comorbidity; social phobia; social anxiety disorder; phenomenology; anxiety disorders
4.  Diagnostic Orphans for Alcohol Use Disorders in a Treatment-Seeking Psychiatric Sample 
Drug and alcohol dependence  2008;96(0):187-191.
Individuals who endorse one or two of the DSM-IV criterion items for alcohol dependence but do not meet criteria for either alcohol abuse or dependence have been referred to in the literature as “diagnostic orphans.” The goal of the present study is to compare diagnostic orphans for alcohol use disorders (AUD) to patients with lifetime DSM-IV alcohol abuse, alcohol dependence, and those with no-AUD symptoms on a series of demographic, diagnostic, and clinical measures. Participants were treatment-seeking psychiatric outpatients (n = 1793; 61.5% women) who completed an in-depth, face-to-face diagnostic evaluation for DSM-IV axis I and axis II disorders. Results revealed that diagnostic orphans were younger, had a higher frequency of family history positive for alcoholism, and higher rates of cannabis dependence, as compared to the no-AUD symptoms group. Diagnostic orphans differed significantly from patients with alcohol abuse and dependence on a number of demographic, diagnostic, and clinical measures. Most notably, on a lifetime basis, diagnostic orphans were less likely to meet diagnostic criteria for various substance use disorders, as compared to individuals with alcohol abuse and dependence. Taken together, these results generally do not support combining diagnostic orphans to individuals with alcohol abuse.
PMCID: PMC3741088  PMID: 18430524
diagnostic orphans; alcohol; DSM-IV; alcohol use disorders
5.  Clinical correlates of desire for treatment for current alcohol dependence among patients with a primary psychiatric disorder 
Background & Objectives
Rates of treatment seeking for alcohol use disorders are notably low. In order to elucidate the clinical correlates of treatment seeking for alcoholism, this study compared patients with current alcohol dependence and a primary psychiatric diagnosis who endorsed a desire for alcoholism treatment to patients who refused treatment or who were unsure.
A total of 131 (54 females) psychiatric outpatients with current alcohol dependence completed an intake assessment at a large hospital-based psychiatric clinic and at the end of the intake were asked whether they would like to receive treatment for alcohol problems.
As compared to alcohol dependent patients who refused treatment for alcoholism or who were unsure (n = 46), patients who expressed a desire for treatment (n = 85) were older, more likely to be female, reported higher levels of social impairments, and were more likely to endorse the following alcohol dependence symptoms: (a) multiple unsuccessful efforts or persistent desire to stop or cut down on their drinking; and (b) drinking more than intended.
Approximately 35% of patients who met current DSM-IV criteria for alcohol dependence reported no interest (or were unsure) in alcoholism treatment despite being engaged in treatment-seeking for another psychiatric disorder.
Scientific Significance
These findings extend previous epidemiological studies documenting treatment seeking patterns for alcoholism by identifying clinical features associated with interest in treatment for this disorder among psychiatric outpatients.
PMCID: PMC3741090  PMID: 21219256
alcohol dependence; treatment; diagnosis; desire for treatment
6.  Diagnosing alcohol abuse in alcohol dependent individuals: diagnostic and clinical implications 
Addictive behaviors  2009;34(0):587-592.
In DMS-IV, the diagnosis of alcohol abuse is precluded by the diagnosis of alcohol dependence. The goal of this study was to examine the diagnostic and clinical implications of diagnosing alcohol abuse among alcohol dependent individuals. Treatment-seeking psychiatric outpatients with a lifetime history of alcohol dependence (n = 544), some of whom (n = 45) did not meet lifetime criteria for alcohol abuse completed in-depth, face-to-face, semi-structured clinical assessments of DSM-IV axis I and axis II psychopathology. Alcohol dependent patients who did not meet criteria for alcohol abuse were significantly more likely to be female, have a later age of onset for alcohol dependence, have fewer dependence symptoms, and have a lower rate of positive family history for alcoholism, and were less likely to report a lifetime history of DSM-IV drug use disorders and PTSD. These findings suggest that diagnosing alcohol abuse among alcohol dependent patients may be clinically useful as an index of severity and higher likelihood of comorbid drug abuse and dependence. Future studies are needed to establish whether these differences are clinically significant in terms of the course of the disorder and response to treatment.
PMCID: PMC3741094  PMID: 19362427
DSM-IV; alcohol abuse; alcohol dependence; diagnosis; rule out; comorbidity
7.  The Factor Structure and Severity of DSM-IV Alcohol Abuse and Dependence Symptoms in Psychiatric Outpatients 
The goal of the present study was to examine the factor structure and estimated severity of alcohol use disorder (AUD) symptoms in a sample of treatment-seeking psychiatric outpatients. Participants (n = 1027, 51.2% women) met the screening criteria for the lifetime assessment of alcohol use disorders according to the Structured Clinical Interview for DSM-IV Disorders (SCID-I/P; First et al., 1995) and as a result completed an assessment of alcohol abuse and dependence symptoms. The average age of the sample was 36.6 (SD = 11.4) and 71% of participants met lifetime DSM-IV criteria for an alcohol use disorder. Exploratory factor analysis of the tetrachoric correlation matrix of alcohol abuse and dependence criteria revealed that a single factor best accounted for the data in this sample. Results of Rasch model analyses indicated that the severity ordering of the DSM-IV abuse and dependence symptoms was not consistent with the hierarchical structure suggested by the DSM-IV. Instead, abuse items were found to be spread across a full range of the AUD continuum and were not consistently in the lower ranges of severity. This study extends the literature by examining a treatment-seeking psychiatric outpatient sample and using a semi-structured diagnostic interview administered by mental health professionals. Methodological considerations and implications for the conceptualization of AUD are discussed.
PMCID: PMC3741100  PMID: 18612564
DSM-IV; alcohol abuse; alcohol dependence; factor structure; SCID; Rasch model
8.  Does Comorbid Posttraumatic Stress Disorder Affect the Severity and Course of Psychotic Major Depression? 
Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are commonly comorbid conditions that result in greater severity, chronicity, and impairment compared with either disorder alone. However, previous research has not systematically explored the potential effects of the psychotic subtyping of MDD and comorbid PTSD.
The sample consisted of psychiatric outpatients diagnosed with psychotic MDD with PTSD, psychotic MDD without PTSD, and nonpsychotic MDD with PTSD presenting for clinic intake. Clinical indices of severity, impairment, and history of illness were assessed by trained diagnosticians using the Structured Clinical Interview for DSM-IV supplemented by items from the Schedule for Affective Disorders and Schizophrenia.
In terms of current severity and impairment, the psychotic MDD with PTSD and psychotic MDD only groups were similar to each other, and both tended to be more severe than the nonpsychotic MDD with PTSD group. In terms of history of illness, the psychotic MDD with PTSD group tended to show greater severity and impairment relative to either the psychotic MDD only or nonpsychotic MDD with PTSD groups. Furthermore, the psychotic MDD with PTSD patients had an earlier time to depression onset than patients with either psychotic MDD alone or nonpsychotic MDD with PTSD, which appeared to contribute to the poorer history of illness demonstrated in the former group.
Future research should explore the possibility of a subtype of psychotic depression that is associated with PTSD, resulting in a poorer course of illness. The current findings highlight the need for pharmacological and psychotherapeutic approaches that can be better tailored to psychotic MDD patients with PTSD comorbidity.
PMCID: PMC3671375  PMID: 20021993
major depression; posttraumatic stress disorder; psychosis; comorbidity; psychiatric outpatients; onset of illness
9.  The Relationship between Childhood Trauma History and the Psychotic Subtype of Major Depression 
Acta psychiatrica Scandinavica  2009;121(6):462-470.
Increasing evidence exists linking childhood trauma and primary psychotic disorders, but there is little research on patients with primary affective disorders with psychotic features.
The sample consisted of adult outpatients diagnosed with Major Depressive Disorder (MDD) at clinic intake using a structured clinical interview. Patients with MDD with (n = 32) versus without psychotic features (n = 591) were compared as to their rates of different types of childhood trauma.
Psychotic MDD patients were significantly more likely to report histories of physical (OR = 2.81) or sexual abuse (OR = 2.75) compared with nonpsychotic MDD patients. These relationships remained after controlling for baseline differences. Within the subsample with comorbid posttraumatic stress disorder, patients with psychotic MDD were significantly more likely to report childhood physical abuse (OR = 3.20).
Results support and extend previous research by demonstrating that the relationship between childhood trauma and psychosis is found across diagnostic groups.
PMCID: PMC3671385  PMID: 19764926
major depression; childhood trauma; psychosis; posttraumatic stress disorder
10.  The relationship between borderline personality disorder and bipolar disorder 
It is clinically important to recognize both bipolar disorder and borderline personality disorder (BPD) in patients seeking treatment for depression, and it is important to distinguish between the two. Research considering whether BPD should be considered part of a bipolar spectrum reaches differing conclusions. We reviewed the most studied question on the relationship between BPD and bipolar disorder: their diagnostic concordance. Across studies, approximately 10% of patients with BPD had bipolar I disorder and another 10% had bipolar II disorder. Likewise, approximately 20% of bipolar II patients were diagnosed with BPD, though only 10% of bipolar I patients were diagnosed with BPD. While the comorbidity rates are substantial, each disorder is nontheless diagnosed in the absence of the other in the vast majority of cases (80% to 90%). In studies examining personality disorders broadly, other personality disorders were more commonly diagnosed in bipolar patients than was BPD. Likewise, the converse is also true: other axis I disorders such as major depression, substance abuse, and post-traumatic stress disorder are also more commonly diagnosed in patients with BPD than is bipolar disorder. These findings challenge the notion that BPD is part of the bipolar spectrum.
PMCID: PMC3811087  PMID: 24174890
bipolar disorder; borderline personality disorder; bipolar spectrum
11.  Targeted Deletion of the Metastasis-Associated Phosphatase Ptp4a3 (PRL-3) Suppresses Murine Colon Cancer 
PLoS ONE  2013;8(3):e58300.
Ptp4a3 (commonly known as PRL-3) is an enigmatic member of the Ptp4a family of prenylated protein tyrosine phosphatases that are highly expressed in many human cancers. Despite strong correlations with tumor metastasis and poor patient prognosis, there is very limited understanding of this gene family's role in malignancy. Therefore, we created a gene-targeted murine knockout model for Ptp4a3, the most widely studied Ptp4a family member. Mice deficient for Ptp4a3 were grossly normal. Fewer homozygous-null males were observed at weaning, however, and they maintained a decreased body mass. Although Ptp4a3 is normally associated with late-stage cancer and metastasis, we observed increased Ptp4a3 expression in the colon of wildtype mice immediately following treatment with the carcinogen azoxymethane. To investigate the role of Ptp4a3 in malignancy, we used the most commonly studied murine colitis-associated colon cancer model. Wildtype mice treated with azoxymethane and dextran sodium sulfate developed approximately 7–10 tumors per mouse in the distal colon. The resulting tumor tissue had 4-fold more Ptp4a3 mRNA relative to normal colon epithelium and increased PTP4A3 protein. Ptp4a3-null mice developed 50% fewer colon tumors than wildtype mice after exposure to azoxymethane and dextran sodium sulfate. Tumors from the Ptp4a3-null mice had elevated levels of both IGF1Rβ and c-MYC compared to tumors replete with Ptp4a3, suggesting an enhanced cell signaling pathway engagement in the absence of the phosphatase. These results provide the first definitive evidence implicating Ptp4a3 in colon tumorigenesis and highlight the potential value of the phosphatase as a therapeutic target for early stage malignant disease.
PMCID: PMC3610886  PMID: 23555575
12.  Posttraumatic stress disorder with and without alcohol use disorders: Diagnostic and clinical correlates in a psychiatric sample 
Psychiatry research  2009;170(2-3):278-281.
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.
PMCID: PMC3418967  PMID: 19900714
PTSD; alcohol use disorders; personality disorders
13.  Age of Onset of Social Anxiety Disorder in Depressed Outpatients 
Journal of anxiety disorders  2010;25(1):131-137.
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.
PMCID: PMC3006477  PMID: 20832989
social phobia; major depression; comorbidity; severity; impairment
14.  Evaluation of evidence for the psychotic subtyping of post-traumatic stress disorder 
The British Journal of Psychiatry  2010;197(4):326-327.
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.
PMCID: PMC2948047  PMID: 20884957
15.  The relative roles of bipolar disorder and psychomotor agitation in substance dependence 
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.
PMCID: PMC3150706  PMID: 20565163
Depression and anxiety  2009;26(1):54-64.
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.
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.
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.
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.
PMCID: PMC3111977  PMID: 18781658
major depression; psychotic depression; hallucinations; delusions; outpatient psychiatry
17.  Borderline Personality Disorder and the Misdiagnosis of Bipolar Disorder 
Journal of psychiatric research  2009;44(6):405-408.
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.
PMCID: PMC2849890  PMID: 19889426
18.  Patan hospital experience in treating philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia patients with gleevec (imatinib mesylate); the first generation specific tyrosine kinase inhibitor 
BMC Blood Disorders  2010;10:8.
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.
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.
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.
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.
PMCID: PMC3017013  PMID: 21138592
19.  Refining the Depression-Nicotine Dependence Link: Patterns of Depressive Symptoms in Psychiatric Outpatients with Current, Past, and No History of Nicotine Dependence 
Addictive behaviors  2008;34(3):297-303.
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.
PMCID: PMC2648971  PMID: 19062199
Depression; Nicotine Dependence; Depressive Symptoms; Melancholic Depression; Vegetative Symptoms; Psychiatric Patients
20.  Physical Pain, Common Psychiatric and Substance Use Disorders, and the Non-Medical Use of Prescription Analgesics in the United States 
Drug and alcohol dependence  2008;100(1-2):63-70.
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.
PMCID: PMC2647685  PMID: 19010611
Prescription drug abuse; opioids; pain reliever; psychiatric disorders; substance use disorders
21.  Associations between depression subtypes and substance use disorders 
Psychiatry research  2008;161(1):43-50.
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.
PMCID: PMC2650805  PMID: 18789540
Major depressive disorder; Melancholic depression; Atypical depression; Substance use disorders; Nicotine dependence; Psychomotor agitation; Decreased appetite
22.  Depressive Symptom Profiles and Severity Patterns in Outpatients with Psychotic versus Nonpsychotic Major Depression 
Comprehensive psychiatry  2008;49(5):421-429.
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.
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.
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.
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.
PMCID: PMC2601715  PMID: 18702928
23.  Screening for Social Fears and Social Anxiety Disorder in Psychiatric Outpatients 
Comprehensive psychiatry  2008;49(4):399-406.
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.
PMCID: PMC2526545  PMID: 18555062
Social Anxiety Disorder; social fears; assessment; SCID
24.  HPA-Axis Hyperactivity and Mortality in Psychotic Depressive Disorder: Preliminary Findings 
Psychoneuroendocrinology  2008;33(5):654-658.
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.
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.
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 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.
PMCID: PMC2435490  PMID: 18378097
25.  Anhedonia and Amotivation in Psychiatric Outpatients with Fully Remitted Stimulant Use Disorder 
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.
PMCID: PMC2650808  PMID: 18463999

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