Deborah A. Mancini

Calculated bioavailable testosterone levels and depression in middle-aged men

BACKGROUND The association between circulating total testosterone (TT) levels and depressive symptoms remains unclear. We sought to determine the relationship between physiologically active bioavailable testosterone (BT) and depressive symptoms in middle-aged men with and without major depressive disorder (MDD). METHODS We assessed and compared calculated BT levels in two groups of middle-aged men (40-65 years): untreated subjects meeting DSM-IV-TR-defined criteria for a major depressive episode as part of major depressive disorder (N=44) and a matched non-depressed control group (N=50). RESULTS Depressed men had lower mean BT levels (3.51+/-1.69 vs. 4.69+/-2.04 nmol/L; p=0.008) and TT levels (11.94+/-4.63 vs. 17.64+/-1.02 nmol/L; p<0.001) when compared to the control group. Biochemical hypogonadism (i.e., BT level< or =2.4 nmol/L or TT level< or =12.14 nmol/L) was also more prevalent in depressed men vs. non-depressed controls (34% vs. 6%, p<0.001; 61% vs. 14%, p<0.001, respectively). CONCLUSIONS Changes in physiologically active BT concentration may be a vulnerability factor for depressive symptoms in middle-aged depressed men.

The relationship between childhood abuse and suicidality in adult bipolar disorder

This study evaluates the effect of childhood sexual and physical abuse on suicidality in adults with bipolar disorder. We conducted a retrospective chart review of adult outpatients (N = 381) with DSM-IV-TR–defined bipolar disorder seeking evaluation and treatment at an academic specialty research program (i.e., Mood Disorders Pharmacology Unit, University Health Network, University of Toronto) between October 2002 and November 2005. Eighteen percent (n = 68) of adult patients with bipolar disorder had a recorded history of childhood abuse (p = 0.009). Sixty-three percent (n = 43) of bipolar patients with a history of childhood abuse reported lifetime suicidality (χ2 = 6.885, df = 1, p = 0.009). Logistic regression analysis indicated that Childhood abuse was a significant predictor of lifetime suicidality in adult bipolar patients (OR = 2.05, CI = 1.19–3.510). Childhood abuse is associated with suicidal ideation and suicide attempts in adults with bipolar disorder. Anamnestic inquiry regarding childhood maltreatment is salient to risk assessment, illness management planning, preventative strategies, and treatment interventions in bipolar disorder.

Hormone replacement therapy and antidepressant prescription patterns: a reciprocal relationship

Major depressive disorder is a prevalent and disabling condition.[1][1] The causes of mood disorders are heterogeneous, involving a complicated interplay of both psychosocial and biological variables.[2][2],[3][3] In an analysis of adult women, the psychosocial variables that predicted major

Antipsychotic-induced weight gain: Bipolar disorder and leptin

Novel antipsychotics impart substantial weight gain. Persons with bipolar disorder are frequently treated with these and other agents known to impart substantial weight gain. We sought to describe the influence of adjunctive risperidone and olanzapine on body weight, body mass index (BMI, kg/m2) and serum leptin levels over a prospective observation period of 6 months. Throughout the 6-month investigation, significant increases from baseline to end point in weight were noted with both agents; with significantly greater weight gain with olanzapine (t10 = 2.761, P = 0.023; t9 = 4.783, P = 0.001). Leptin levels were highly correlated with increases in weight and were significantly elevated from baseline at 4 months (r = 0.658, P < 0.05). Significant increases in weight and body mass index were apparent at 3 months (P < 0.05). The temporal association between weight increase and leptin changes does not support the notion that leptin is a primary promoter of antipsychotic-induced weight gain; however, a secondary perpetuating role cannot be ruled out.

Botulinum Toxin Use in Refractory Pain and Other Symptoms in Parkinsonism.

BACKGROUND Parkinsons disease (PD) and other parkinsonian syndromes are chronic, progressive neurodegenerative diseases. With advancing disease, both motor and non-motor symptoms represent a considerable burden and symptom relief and quality of life improvement become the main goal of treatment. Botulinum toxins (BTX) are an effective treatment modality for many neurological conditions. METHODS To understand the potential usefulness of BTX in this population, we performed a retrospective chart review of all patients with a clinical diagnosis of idiopathic PD and atypical parkinsonism who received treatment with BTX injections in our center from 1995 to 2014 for a variety of symptoms. Response to BTX was assessed using a subjective Clinical Global Impression. RESULTS Records of 160 patients were reviewed. Probable idiopathic PD was the diagnosis in 117 patients (73.1%). The main indication for BTX treatment was pain (50.6% of cases). Other indications were the treatment of functional impairment resulting from dystonia (26.25%), sialorrhea (18.75%), freezing of gait, and camptocormia. Considering pain as indication, 81% of all patients with PD reported benefits after the first BTX injections. This benefit was maintained after the last recorded visit without significant difference in outcome compared with the first injection (p=0.067). Similar results were observed in patients with atypical parkinsonism. CONCLUSIONS Our results confirm the safety and efficacy of different uses of BTX in the symptomatic treatment of patients with parkinsonism even in advanced stages of the disease, and suggest BTX treatment could have a safe and useful role in the treatment of pain in this population.

Comparing Features of Bipolar Disorder to Major Depressive Disorder in a Tertiary Mood Disorders Clinic

BACKGROUND We sought to describe features that distinguish individuals with bipolar disorder from major depressive disorder. METHODS A retrospective chart review of adult outpatients (N = 1000) seeking evaluation and treatment was conducted at the Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto between October 2002 and November 2005 was conducted. Sociodemographic parameters, illness-characteristics and therapeutic interventions were evaluated and compared. RESULTS The MDPU referring diagnosis were major depressive disorder (52%), bipolar disorder (29%), and unspecified (19%). Of all individuals with a non-bipolar entry diagnosis (n = 699), 23% (n = 159) were subsequently diagnosed with bipolar disorder (p < 0.001); the majority of whom (n = 117, 74%) received a non-bipolar I disorder diagnosis [e.g. bipolar II disorder (n = 71); bipolar NOS disorder (n = 46) (p < 0.001)]. Higher rates of unemployment/disability, previous depressive episodes, psychiatric hospitalization, comorbid hypertension, and lifetime substance use disorders, as well as an earlier age of illness-onset were more frequently endorsed by individuals with a diagnosis of bipolar disorder. Fifteen percent of individuals who were newly-diagnosed with bipolar disorder reported a history of antidepressant-associated mania. CONCLUSIONS The majority of individuals with a newly-diagnosed bipolar disorder at this tertiary center have a non-bipolar I disorder (i.e., bipolar spectrum). Several indices of illness severity differentiate individuals with bipolar disorder from major depressive disorder.

Botulinum Toxin Type A for Pain in Advanced Parkinson’s Disease

Background and Objective Pain is a frequent symptom in Parkinsons disease (PD), and the therapeutic alternatives are scarce. The goal of this trial was to measure the effects of botulinum toxin type A (BTXA) in the treatment of limb pain in advanced PD. Methods A randomized double-blind crossover versus placebo study of BTXA for limb pain in advanced Parkinsons disease was conducted. Subjects received individualized BTXA/placebo dosing per pain distribution in limbs. The primary outcome was a measure of change in global pain on a numeric rating scale (NRS) at 4 and 12 weeks postinjection and on a visual analogue scale 12 weeks after treatment. Secondary outcomes included the percentage of responders, physician-rated clinical global impressions, MDS-UPDRS and PDQ-39 scores, and adverse events. Results A total of 12 subjects completed the trial. Treatment with BTXA (average dose=241.66 U) produced a significant reduction in NRS score 4 weeks after the injections (-1.75 points, range from -3 to 7, p=0.033). However, there was no significant difference compared to placebo (p=0.70). Participants with dystonic pain showed a greater reduction in NRS score after 4 weeks when treated with BTXA (2.66 points vs. 0.75 for placebo). There were no significant differences for any of the secondary outcomes or significant adverse events. Conclusions Targeted BTXA injections were safe in patients with limb pain and advanced PD; however, the present study failed to show a significant effect when compared to placebo. Further studies may be focused on evaluating the effect of BTXA particularly in dystonic pain.