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Biomedical subjects

John Hennen

Publications and source records attributed to John Hennen.

At least 19 recordsLinked to original sources
PubMed2007

Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders.

OBJECTIVE: Bipolar disorders are prevalent major illnesses with high rates of morbidity, comorbidity, disability, and mortality. A growing number of psychotropic drugs are used to treat bipolar disorder, often off-label and in untested, complex combinations. METHODS: To quantify utilization rates for psychotropic drug classes, this study used the 2002-2003 U.S. national MarketScan research databases to identify 7,760 persons with ICD-9 bipolar disorder subtypes. Survival analysis was used to estimate times until initial monotherapies were augmented, changed, or discontinued. RESULTS: The most commonly prescribed first drug class was antidepressants (50% of patients), followed by mood stabilizers (25%: anticonvulsants, 17%, and lithium, 8%), sedatives (15%), and antipsychotics (11%). At study midpoint only 44% of patients were receiving monotherapy. Those receiving monotherapy were ranked by initial drug prescribed and percentage of patients (bipolar I and bipolar II): antidepressants (55% and 65%), lithium (51% and 41%), antipsychotics (32% and 31%), anticonvulsants (28% and 29%), and sedatives (28%, 25%). Median time to adding another psychotropic was 2.5-times less than median time to changing the initial treatment (16.4 compared with 40.9 weeks), and stopping was rare. Median weeks until therapy was changed in any way for 25% of patients was as follows: lithium, 29 weeks; antidepressants, 13; anticonvulsants, 13; antipsychotics, 13; and sedatives, 9. CONCLUSIONS: Antidepressants were the first-choice agent twice as often as mood stabilizers. Lithium was sustained longer than monotherapy with other mood stabilizers. Time to augmentation was much shorter than time to change or discontinuation.

Adult↗
PubMed2006

A strategy for identifying phenotypic subtypes: concordance of symptom dimensions between sibling pairs who met screening criteria for a genetic linkage study of childhood-onset bipolar disorder using the Child Bipolar Questionnaire.

BACKGROUND: Specific symptom dimensions have been used to establish phenotypic subgroups in recent genetic studies of bipolar disorder. In preparation for a genetic linkage study of childhood-onset bipolar disorder (COBPD), we conducted an exploratory analysis of the concordance of prominent symptom dimensions between sibling pairs (N=260) who screened positive for COBPD. This report presents data on the potential usefulness of these dimensions in genotyping. METHOD: A principal components factor analysis was conducted on the symptoms of 2795 children who screened positive for COBPD on the Child Bipolar Questionnaire (CBQ). The resulting factors were used in a concordance analysis between 260 proband/sibling pairs and 260 proband/matched comparison pairs. RESULTS: Ten factors were extracted. The strongest concordance coefficients (rho) between probands and siblings, and the widest contrasts between proband/sibling vs. proband/comparison pairs, were for Factor 9 (Fear of harm), Factor 5 (Aggression), Factor 10 (Anxiety), Factor 4 (Sensory sensitivity), Factor 6 (Sleep-wake cycle disturbances), and Factor 2 (Attention/Executive function deficits). Based on factor loadings and multivariate analyses, CBQ items were selected for a "Core Index" subscale that had a robust concordance estimate in the sibpair group (rho=0.514, 95% CI 0.450-0.577) as compared to the proband-matched comparison group (rho=0.093, 95% CI 0.008 to 0.178). LIMITATIONS: Research diagnostic interviews (K-SADS P/L) were conducted to confirm bipolar diagnosis in only a subsample (N=100) of the children whose data were used for the concordance analysis. CONCLUSIONS: Our data suggest a profile of heritable clinical dimensions in addition to classic mood symptomatology in COBPD. These features may represent a more homogeneous phenotypic subtype of COBPD that may prove more useful for delineating the neurobiology and genetics of the disorder than standard diagnostic models.

Adolescent↗
PubMed2006

The child bipolar questionnaire: a dimensional approach to screening for pediatric bipolar disorder.

BACKGROUND: The Child Bipolar Questionnaire (CBQ) is a rapid screener with a Core Index subscale of symptom dimensions frequently reported in childhood-onset bipolar disorder (BD) and scoring algorithms for DSM-IV BD, with and without attention-deficit/hyperactivity disorder (ADHD), and the proposed Narrow, Broad, and Core phenotypes. This report provides preliminary data on the reliability and validity of the CBQ. METHOD: Test-retest and inter-rater reliability of the CBQ were assessed. The ability of CBQ screening diagnoses and of the CBQ Core Index subscale to effectively predict diagnostic classification by structured interview was assessed using the K-SADS P/L. RESULTS: Preliminary test-retest data showed excellent reliability for both the CBQ total score (r = 0.82) and the Core Index subscale (r = 0.86). Preliminary validity data was also promising. CBQ screening algorithms performed with a specificity of 97% and a sensitivity of 76% in classifying subjects with K-SADS P/L diagnosis of BD vs. no BD. The Core Index subscale had excellent agreement with K-SADS P/L diagnosis (k = 0.84) in classifying BD, ADHD-only, and no diagnosis and demonstrated 100% sensitivity and 86% specificity in classifying BD vs. no BD. LIMITATIONS: This preliminary data is from a sample enriched with bipolar disorder cases. Further validation is needed with samples in which childhood-onset BD is rarer and diagnoses more diverse. CONCLUSIONS: The CBQ shows potential for rapid and economically feasible identification of possible childhood-onset BD cases as defined by DSM-IV criteria as well as by alternate disease phenotypes. Further validation studies will focus on inpatient and outpatient samples with a broader range of variability.

Adolescent↗
PubMed2006

Clinical outcome in patients with bipolar I disorder, obsessive compulsive disorder or both.

BACKGROUND: Bipolar disorder (BPD) is often comorbid with obsessive-compulsive (OCD) and other anxiety disorders, but the impact of such comorbidity on long-term outcome has not been evaluated systematically. METHODS: Extensive follow-up assessments were carried out at 4.3 years after index hospitalizations in a mixed BPD-OCD group (N=20) compared to matched groups with BPD (N=22) or OCD (N=20) alone. RESULTS: At follow-up, ratings of functional status were similar across groups. Rehospitalizations were similar among BPD-OCD and BPD subjects, but 2.9-times more frequent among comorbid than OCD patients. OCD symptoms averaged 150% more severe in OCD than comorbid subjects, and were not measured in BPD subjects. CONCLUSIONS: Despite potential sampling bias with previously hospitalized subjects, the findings suggest that comorbid BPD-OCD patients may be clinically more similar to BPD than OCD patients, and that BPD-OCD comorbidity may not negatively impact the long-term clinical outcome.

Adult↗
PubMed2006

An ongoing study of group treatment for men involved in problematic Internet-enabled sexual behavior.

Exponential advances have been made regarding computer/Internet technology in the past decade. This growth, in large part, can be attributed to greater access to, affordability of, and anonymity while on the computer. However, this progress has also produced negative psychological issues. Problematic Internet-enabled sexual behavior (IESB) has increasingly affected individuals' family relationships, work productivity, and academic success. This article is the first-known, empirically based outcome study regarding the effectiveness of group therapy treatment for men with problematic IESB. These closed-groups, which ran for 16 weeks, used a combination of Readiness to Change (RtC), Cognitive Behavioral Therapy (CBT), and Motivational Interviewing (MI) interventions. Five groups were analyzed for this paper (yielding a total N of 35), with the average member's age being 44.5 years old. Three different scales (the Orzack Time Intensity Survey, the BASIS-32, and the BDI) were used to track participants' progress across time. The results demonstrated that this group treatment intervention significantly increased members' quality of life and decreased the severity of their depressive symptoms. However, the protocol failed to reduce participants' inappropriate computer use. Regarding comorbidity, the results showed the following: members in the "anxiety" category responded best to the current treatment, those in the "mood" cluster responded relatively positively, and those in the "A-D/HD" category failed to respond significantly. It is clear from this report that more attention must be focused on the treatment of problematic IESB, as opposed to exploratory studies.

Cognitive Behavioral Therapy↗
PubMed2006

Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review.

OBJECTIVES: To update and extend comparisons of rates of suicides and suicide attempts among patients with major affective disorders with versus without long-term lithium treatment. METHODS: Broad searching yielded 45 studies providing rates of suicidal acts during lithium treatment, including 34 also providing rates without lithium treatment. We scored study quality, tested between-study variance, and examined suicidal rates on versus off lithium by meta-analytic methods to determine risk ratios (RRs) and 95% confidence intervals (CI). RESULTS: In 31 studies suitable for meta-analysis, involving a total of 85,229 person-years of risk-exposure, the overall risk of suicides and attempts was five times less among lithium-treated subjects than among those not treated with lithium (RR = 4.91, 95% CI 3.82-6.31, p < 0.0001). Similar effects were found with other meta-analytic methods, as well as for completed versus attempted suicide, and for bipolar versus major mood disorder patients. Studies with higher quality ratings, including randomized, controlled trials, involved shorter exposures with somewhat lesser lithium superiority. Omitting one very large study or those involving lithium-discontinuation had little effect on the results. The incidence-ratio of attempts-to-suicides increased 2.5 times with lithium-treatment, indicating reduced lethality of suicidal acts. There was no indication of bias toward reporting positive findings, nor were outcomes significantly influenced by publication-year or study size. CONCLUSIONS: Risks of completed and attempted suicide were consistently lower, by approximately 80%, during treatment of bipolar and other major affective disorder patients with lithium for an average of 18 months. These benefits were sustained in randomized as well as open clinical trials.

Bipolar Disorder↗
PubMed2006

Prediction of the 10-year course of borderline personality disorder.

OBJECTIVE: The purpose of this study was to determine the most clinically relevant baseline predictors of time to remission for patients with borderline personality disorder. METHOD: A total of 290 inpatients meeting criteria for both the Revised Diagnostic Interview for Borderlines and DSM-III-R for borderline personality disorder were assessed during their index admission with a series of semistructured interviews and self-report measures. Diagnostic status was reassessed at five contiguous 2-year time periods. Discrete survival analytic methods, which controlled for baseline severity of borderline psychopathology and time, were used to estimate hazard ratios. RESULTS: Eighty-eight percent of the patients with borderline personality disorder studied achieved remission. In terms of time to remission, 39.3% of the 242 patients who experienced a remission of their disorder first remitted by their 2-year follow-up, an additional 22.3% first remitted by their 4-year follow-up, an additional 21.9% by their 6-year follow-up, an additional 12.8% by their 8-year follow-up, and another 3.7% by their 10-year follow-up. Sixteen variables were found to be significant bivariate predictors of earlier time to remission. Seven of these remained significant in multivariate analyses: younger age, absence of childhood sexual abuse, no family history of substance use disorder, good vocational record, absence of an anxious cluster personality disorder, low neuroticism, and high agreeableness. CONCLUSIONS: The results of this study suggest that prediction of time to remission from borderline personality disorder is multifactorial in nature, involving factors that are routinely assessed in clinical practice and factors, particularly aspects of temperament, that are not.

Adult↗
PubMed2006

Reported childhood onset of self-mutilation among borderline patients.

The purpose of this study was to determine the percentage of borderline patients who first engaged in self-mutilation as children and to compare the parameters of their self-harm to those of borderline patients who first harmed themselves at an older age. Two hundred and ninety inpatients meeting both Revised Diagnostic Interview for Borderlines (DIB-R; Zanarini, Gunderson, Frankenburg, & Chauncey, 1989) and Diagnostic and Statistical Manual of Mental Disorders (3rd ed. ref.) (DSM-III-R; APA, 1987) criteria for borderline personality disorder were interviewed about their history of self-mutilation. Of the 91% with a history of self mutilation, 32.8% reported first harming themselves as children (12 years of age or younger), 30.2% as adolescents (13-17 years of age), and 37% as adults (18 or older). Using logistic regression analyses and controlling for baseline age, it was found that those with a childhood onset reported more episodes of self-harm, a longer duration of self-harm, and a greater number of methods of self-harm than either those with an adolescent or adult onset to their self-mutilation. The results of this study suggest that a sizable minority of borderline patients first engage in self-harm as children and that the course of their self-mutilation may be particularly malignant.

Adolescent↗
PubMed2006

Manual assisted cognitive treatment for deliberate self-harm in borderline personality disorder patients.

This study examines the efficacy of a short-term individual therapy, Manual Assisted Cognitive Treatment (MACT), which was developed to treat parasuicidal (suicidal or self-harming) patients. In this trial, MACT was modified to focus on deliberate self-harm (DSH) in patients with borderline personality disorder (BPD). Thirty BPD patients who were engaged in DSH while in ongoing treatments, i.e., treatment-as-usual (TAU), were randomly assigned to receive MACT (N = 15) or not. DSH and level of suicide ideation were assessed at the baseline, at completion of the MACT intervention, and six months later. Results indicated that MACT was associated with significantly less frequent DSH upon completion of the intervention and with significantly decreased DSH frequency and severity at the six months follow-up. Moreover, MACT's contribution to reducing DSH frequency and severity was greater than the contribution by the amount of concurrent treatments. In contrast, MACT did not affect the level of suicide ideation and time-to-repeat of DSH. In conclusion, MACT seems to be a promising intervention for DSH in patients with BPD. More definitive studies are needed.

Adult↗
PubMed2006

Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry.

The effects of type 1 diabetes and key metabolic variables on brain structure are not well understood. Sensitive methods of assessing brain structure, such as voxel-based morphometry (VBM), have not previously been used to investigate central nervous system changes in a diabetic population. Using VBM, we compared type 1 diabetic patients aged 25-40 years with disease duration of 15-25 years and minimal diabetes complications with an age-matched, nondiabetic control group. We investigated whether lower than expected gray matter densities were present, and if so, whether they were associated with glycemic control and history of severe hypoglycemic events. In comparison with control subjects, diabetic patients showed lower density of gray matter in several brain regions. Moreover, in the patient group, higher HbA(1c) levels and severe hypoglycemic events were associated with lower density of gray matter in brain regions responsible for language processing and memory. Our study represents the first comprehensive study of gray matter density changes in type 1 diabetes and suggests that persistent hyperglycemia and acute severe hypoglycemia have an impact on brain structure.

Adolescent↗
PubMed2005

Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment.

RATIONALE: There is evidence that prefrontal lobe GABA levels are low in cocaine-dependent (CD) individuals, and treatment with GABA agonists decreases cocaine self-administration. OBJECTIVES: The aim of the study is to measure changes in GABA levels in CD subjects at baseline and after 8 weeks of treatment with pramipexole, venlafaxine, or placebo. METHODS: CD subjects enrolled in a treatment trial for cocaine dependence were recruited for this proton (1H) magnetic resonance spectroscopy (MRS) study. GABA levels in the prefrontal lobe were measured before and after treatment. RESULTS: Mean percentage changes in GABA levels were as follows: pramipexole +17.0+/-28.0%, venlafaxine +13.0+/-11.0%, and placebo -2.1+/-19.5%. Pramipexole-treated subjects had significantly increased brain GABA levels compared to placebo (p=0.031). Venlafaxine treatment was nonsignificantly associated with increased GABA levels compared to placebo (p=0.16). The overall statistical model for the effect of drug treatment vs placebo on brain GABA levels, including adjustment for baseline levels, was highly significant (p=0.002). Despite significant changes in GABA levels, there were no significant differences in the number of urine samples positive for cocaine metabolites. CONCLUSIONS: This study demonstrates that 1H MRS can measure changes in GABA levels following pharmacologic treatment. The increase in GABA levels, although significant, is modest compared to other MRS studies of depression or epilepsy associated with clinical improvements. The failure to see larger increases in GABA levels and an associated reduction in cocaine consumption may reflect the relatively low doses of medication used.

Adult↗
PubMed2005

Obsessive fears about harm to self or others and overt aggressive behaviors in youth diagnosed with juvenile-onset bipolar disorder.

BACKGROUND: Obsessive fear-of-harm, either fear of doing harm or fear of harm coming to self, may be closely associated with aggressive behaviors in juvenile-onset bipolar disorder. METHODS: We analyzed parent-report data on the Yale-Brown Obsessive Compulsive Scale (YBOCS) and Overt Aggression Scale (OAS) for 1601 children/adolescents with a clinician-assigned diagnosis of bipolar disorder. The summing of 6 YBOCS items rated "often" or "very often or almost constant" yielded a biphasic distribution of scores. Median-split was used to define meaningful subgroups contrasting high vs. low "fear-of-harm", which were then compared on parent-reported severe injury to self and others and on parent-reported suicide threats. RESULTS: High fear-of-harm was strongly associated with parent-reported severe injury to self and others. For self-injury, the estimated risk ratio for high vs. low fear-of-harm subgroups was 2.68 (95% confidence interval 1.87-3.86), indicating greater than doubling of risk associated with high fear-of-harm. For severe injury to others, the estimated risk ratio was 7.97 (95% confidence interval 4.19-15.2), suggesting a nearly eight-fold increased risk associated with high fear-of-harm. High fear-of-harm subjects were reported to make serious suicide threats much more frequently than low fear-of-harm subjects (odds ratio, estimated by ordinal logistic regression modeling methods, was 2.42 (95% CI 2.00 to 2.92; z=9.12, p<0.001). LIMITATIONS: Child report data was not obtained; clinician diagnosis was not validated via research interview. CONCLUSIONS: Obsessive fears about harm to self or others in a sample of children with a clinician-assigned diagnosis of bipolar disorder were found to be positively related to increased behavioral aggression towards self and others, as well as to frequent suicide threats.

Adolescent↗
PubMed2005

Suicidal risk during treatment with clozapine: a meta-analysis.

OBJECTIVE: Suicide remains a major cause of premature mortality among patients with schizophrenia. Evidence of reduced suicidal risk with available psychiatric treatments is limited, but emerging data suggest such an effect of clozapine in chronically psychotic patients, leading us to compile the reported evidence. METHOD: We searched for published studies with contrasting rates of suicides or attempts by psychotic patients treated with clozapine vs. other agents. RESULTS: Among six such studies, random-effects meta-analysis indicated a substantially lower overall risk of suicidal behaviors with clozapine vs. other treatments (risk-ratio 3.3; 95% confidence interval [CI] 1.7-6.3; p<0.0001). For completed suicides, the risk ratio (RR) was 2.9 ([CI 1.5-5.7]; p=0.002). CONCLUSION: Long-term treatment with clozapine was associated with three-fold overall reduction of risk of suicidal behaviors. However, available findings are quantitatively inconsistent, well-designed studies remain rare, and the only randomized trial did not find reduced risk of completed suicide. Additional randomized comparisons among modern treatments for psychotic disorders are required to clarify their impact on mortality.

Antipsychotic Agents↗
PubMed2005

Use of combinations of antipsychotics: McLean Hospital inpatients, 2002.

BACKGROUND: The empirical use of combinations of antipsychotic agents appears to be increasing with little research support for the relative efficacy, safety or cost-effectiveness of this practice. Such treatment was evaluated in hospitalized psychiatric patients. METHODS: Samples of consecutive inpatients treated with > or = 2 ('polytherapy') vs 1 antipsychotic ('monotherapy') were matched on age, sex, diagnosis and admission clinical ratings, and these groups were compared on total daily chlorpromazine-equivalent doses, days in hospital, and changes in clinical ratings between admission and discharge. RESULTS: The study sample included 69 polytherapy and 115 well-matched monotherapy subjects. Despite matching for initial CGI and GAF ratings, polytherapy was associated with high PANSS subscale scores of positive symptoms among affective psychosis, and relatively greater PANSS subscale ratings of excitement-agitation among patients diagnosed with schizophrenia. Estimated clinical improvement during hospitalization was similar among poly- and monotherapy patients, but total daily CPZ-eq doses at discharge averaged twice-greater with polytherapy, and hospitalization lasted 1.5 times longer. CONCLUSIONS: Antipsychotic polytherapy as well as the types of agents combined may reflect clinician responses to particular symptom patterns. The value of specific combinations of antipsychotic agents and their comparison with monotherapies requires specific, prospective, randomized and well-controlled trials that consider matching on clinical characteristics and truly comparable doses across regimens.

Adult↗
PubMed2005

Factors associated with parent-reported suicide threats by children and adolescents with community-diagnosed bipolar disorder.

BACKGROUND: It has recently been suggested that indicators of suicidality in youth may differ for different diagnostic groups []. Aggression, impulsivity and risk-taking behaviors may be strong indicators of suicidality in children and adolescents with symptoms of bipolar disorder. METHODS: Parents completed the Child Bipolar Questionnaire (CBQ) via a secure, Internet-based data acquisition system. In multivariate modeling analyses, with age and sex as covariates, CBQ items that were most closely correlated with parent-reported suicide threat were identified. The strength of this multifactor association was then examined among subjects reported to have a community diagnosis of bipolar disorder compared to those who did not. RESULTS: In order of strength of association, the CBQ items most closely correlated with parent-reported suicide threat were: hallucinations, cursing/foul language, low energy/withdrawal, imagery-gore/violence, destroys property, poor self-esteem, excessive risk-taking, and excessive anxiety/worry. Of these 8 CBQ items, 3 (low energy, poor self-esteem, and anxiety/worry) have a dysphoric orientation, but the items with the strongest associations are related to psychosis, aggression and impulsivity. The association of the 8 CBQ items with suicidal threats was found to be much stronger in subjects with a reported prior or current bipolar diagnosis, compared with all other subjects. LIMITATIONS: Child report data is not available. Parent report data has not yet been validated by research diagnostic interview. CONCLUSIONS: The presence of aggression and impulsivity are importantly related to suicidal threats independently of the risk associated with dysphoria in children and adolescents who have been assigned a diagnosis of bipolar disorder or exhibit some symptoms of the disorder. This may have implications for treatment with antidepressant medication when the diagnosis of bipolar disorder may be present.

Adolescent↗
PubMed2005

A comparison of brain and serum pharmacokinetics of R-fluoxetine and racemic fluoxetine: A 19-F MRS study.

Racemic fluoxetine consists of R- and S-fluoxetine, which are metabolized to R- and S-norfluoxetine, respectively. This study was designed to compare brain levels achieved with R-fluoxetine to those achieved with racemic fluoxetine in healthy subjects using fluorine-19 (19-F) magnetic resonance spectroscopy (MRS). In all, 13 healthy volunteers received study drug for 5 weeks using a dosing schedule designed to achieve steady state for 20 mg/day racemic fluoxetine, 80 mg/day R-fluoxetine, or 120 mg/day R-fluoxetine. The resulting brain drug levels were measured using 19-F MRS. At 5 weeks, the racemate, 80 and 120 mg/day R-fluoxetine groups had mean brain levels of 25.5, 34.9, and 41.4 microM, respectively. In the serum, R-norfluoxetine, which is thought to be an inactive metabolite, accounted for 17, 71, and 63% of the fluoxetine/norfluoxetine concentration, respectively. When the relative proportion of active to total species in serum are taken into account, the data suggest that doses of R-fluoxetine greater than 120 mg/day would be needed to achieve brain levels of active drug comparable to 20 mg/day of racemate. The 120 mg/day R-fluoxetine group experienced a mean increase in QTc interval of 44 ms, with one individual having an increase of 89 ms, which suggests that higher doses may not be tolerable. While these data support the use of MRS to aid in defining the therapeutic dose range for drug development, they also highlight the need for additional studies with concurrent animal models to establish the validity of using serum drug/metabolite ratios to interpret MRS determined brain drug levels.

Brain↗
PubMed2005

Adult experiences of abuse reported by borderline patients and Axis II comparison subjects over six years of prospective follow-up.

The main objective of this study was to assess the rates of adult experiences of verbal, emotional, physical, and sexual abuse reported by borderline patients and Axis II comparison subjects during 6 years of prospective follow-up. A semistructured interview was administered to 290 borderline patients and 72 Axis II comparison subjects during their index admission. A follow-up analogue to this interview was administered at three contiguous 2-year follow-up periods. Over 94% of surviving patients were re-interviewed at all three follow-up waves. The rates of all four forms of reported abuse declined significantly over time for all subjects considered together. However, each of these types of abuse was reported by a significantly higher percentage of borderline patients than Axis II comparison subjects. When the presence of these forms of abuse was used to predict time to remission, all but sexual abuse were strongly associated with the failure to achieve symptomatic remission from borderline personality disorder. Taken together, the results of this study suggest that the rates of adult abuse reported by borderline patients decline significantly with time but remain relatively high. They also suggest that adult experiences of abuse are strongly associated with a failure to remit from borderline personality disorder.

Adolescent↗