The pharmacology of bipolar disorder during pregnancy and breastfeeding

Treating bipolar disorder in women during reproduction presents a significant challenge to the physician. The pharmaceutical agents most commonly used for treating bipolar disorder have been associated with adverse effects when used during pregnancy and breastfeeding. Of particular concern has been the association of lithium with cardiac malformations, and the association of carbamazepine and valproate with neural tube defects including spina bifida. Toxicity in neonates has also been reported for the most commonly used mood-stabilising agents. Treatment options for mood stabilisation are either associated with risks of adverse advents, have been used less frequently and their associated risks are unknown, or may not provide effective prophylaxis against recurrences of bipolar episodes. However, strategies are available that minimise the risk to the fetus and infant whilst still providing effective prophylaxis against bipolar disorder in the mother. Ideally, a treatment regimen tailored to suit the individual should consider both mother and baby and should be planned prior to conception.     

Association of Depressive Symptoms with Hippocampal Volume in 1936 Adults

Hippocampal atrophy is reported in major depressive disorder (MDD). However, sample sizes were generally modest, and participant characteristics, including age, differed between studies. This study used a community sample to examine relationships between current depressive symptom severity and hippocampal volume across the adult lifespan. A total of 1936 adults with magnetic resonance images of the brain and Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) scores were included. Brain volumes were quantified using the FSL program. Multiple linear regressions were performed using left, right, and total hippocampal volume as criterion variables, and predictor variables of QIDS-SR total, total brain volume, age, gender, education, psychotropic medications, alcohol use, and race/ethnicity. Post hoc analyses were conducted in participants with QIDS-SR scores ⩾11 (moderate or greater depressive symptom severity) and <11, and older and younger adults. In the primary analysis (sample as a whole) QIDS-SR was inversely associated with total hippocampal volume (b=−0.044, p=0.032, (CI−0.019 to −0.001)) but not with left or right hippocampal volume evaluated individually. In participants with QIDS-SR scores of <11, hippocampal volumes were not associated with QIDS-SR scores. In those with QIDS-SR scores ⩾11 total, right, and left hippocampal volumes were modestly, but significantly, associated with QIDS-SR scores. The association between QIDS-SR scores and the hippocampal volume was much stronger in older persons. Findings suggest smaller hippocampal volumes among those with greater reported depressive symptom severity—an association that is strongest in people with at least moderate depressive symptom levels.     

Psychiatric aspects of chronic renal disease

Abstract

Recognition of the prevalence of mood disorders and increased availability of medication options have led to calls for treating bipolar disorders in the primary care setting. Second-generation antipsychotic medications (SGAs) were initially lauded for treating bipolar disorders because of their efficacy and perceived safety relative to first-generation antipsychotic medications. Metabolic syndrome is a constellation of risk factors for cardiovascular disease and type 2 diabetes mellitus, which may emerge when treating bipolar disorders with SGAs. We conducted a search of the research literature examining the association between different SGAs and metabolic syndrome. Based on our review, we offer guidelines for monitoring patient status regarding metabolic syndrome and for providing interventions to promote healthy diet and exercise.     

Treatment response to sleep,pain, and mood disturbance and their correlation with sleep disturbance in adult patients with moderate-to-severe primary restless legs syndrome: Pooled analyses from 3 trials of gabapentin enacarbil

Abstract

Introduction. This pooled analysis investigated the effects of gabapentin enacarbil (GEn) on clinical correlates of sleep disturbance in adults with moderate-to-severe primary restless legs syndrome (RLS) and no-to-moderate or severe-to-very severe baseline sleep disturbance.

Methods. Co-primary end-points were mean change from baseline to week 12 in International Restless Legs Scale (IRLS) total score and proportion of responders (‘much’/‘very much’ improved) on the investigator-rated Clinical Global Impression–Improvement (CGI-I) scale (week 12). Pain, mood, individual IRLS items, and safety were assessed.

Results. The modified intent-to-treat population was 671 adults randomized to GEn 600 mg (n = 161), GEn 1200 mg (n = 266), or placebo (n = 244). GEn significantly improved least squares mean change in IRLS total score from baseline versus placebo for no-to-moderate (GEn 600 mg,? 12.3; 1200 mg, ? 11.3; placebo, ? 7.7) and severe-to-very severe (? 16.6; ? 17.0; ? 12.7) groups (all P < 0.01). Significantly more GEn-treated patients (both doses) were CGI-I responders (week 12) versus placebo in both sleep subgroups (all P < 0.01). GEn substantially improved mood and pain scores for both sleep subgroups versus placebo. The most frequent treatment-emergent adverse events were somnolence and dizziness.

Conclusion. GEn (600 mg and 1200 mg) was effective and well tolerated in adults with moderate-to-severe primary RLS regardless of baseline sleep disturbance level.     

Low Level Exposure to Carbon Monoxide and Driving Performance

Subjects were exposed to low levels (700 ppm) of carbon monoxide (CO) until carboxyhemoglobin (COHb) levels of 6%, 11%, and 17% were reached, and they were then tested as to their ability to perform both selected driving-related laboratory tests of visual response and control reactions and over-the-road vehicle driving. These test results were then compared with those on the same subjects taken under control conditions without exposure to CO.

The overall pattern of results indicates that a 6% COHb level had no effect on driving ability, and that COHb levels of 11 % and 17% did not appear to seriously affect the ability to drive motor vehicles, as measured by the tests administered in this study. However, certain statistically significant differences were found in some of the tests that suggest some decrement in performance as a result of CO exposure.     

A Three-Generational Study of Risk Factors for Childhood Externalizing Behavior among African Americans and Puerto Ricans

This is the first prospective study to examine the precursors of child externalizing behavior across three generations of African Americans and Puerto Ricans. Participants comprised a community cohort of male and female African Americans and Puerto Ricans (N = 366, [`(X)] \overline{X} age = 29.4 years), who are part of an ongoing study of drug use and problem behaviors, and who had a child. Data were collected at four time waves, spanning the participants’ adolescence to adulthood. Questionnaires were initially self-administered in schools in East Harlem, NY, USA (time 1). Subsequently, structured interviews were conducted by trained interviewers (times 2 and 3), and self-administered via mail (time 4). The independent variables consisted of the participants’ prospective reports of their (a) relationships with their parents during adolescence, (b) depressive mood and drug use (adolescence to adulthood), (c) relationship with their oldest child between the ages of 6–13, and (d) perceptions of neighborhood crime and deterioration (in adulthood). The dependent variable was externalizing behavior in the participant’s oldest child ([`(X)] \overline{X} age = 9.6 years; SD = 2.0). Structural equation modeling showed that the parent–child relationship during participants’ adolescence was linked with the participants’ depressive mood and drug use which, in turn, were associated with the participants’ relationship with their own child, as well as with neighborhood crime and deterioration when participants were adults. The participants’ depressive mood, and relationship with their own child, as well as neighborhood crime and deterioration, each had a direct pathway to externalizing behavior in the participant’s child. Findings suggest that intervention programs and public policy should address parental attributes, neighborhood factors, and, especially, parenting skills, to reduce risk factors for the intergenerational transmission of externalizing behavior.     

Alterations of Host Defence System after Sleep Deprivation are followed by Impaired Mood and Psychosocial Functioning

In healthy humans, sleep deprivation (SD) has consistently been demonstrated to impair different parameters of the host defence system and of psychosocial functioning. However, the individual timing of these alterations and their possible association have remained unknown so far. We therefore investigated functional measures of the individual host defence system as well as of subjective well-being and psychosocial performance in 10 healthy male adults before and after SD, as well as after recovery sleep. In detail, we examined the number of leukocytes, granulocytes, monocytes, lymphocytes, B cells, T cells, T helper and cytotoxic T cells, natural killer (NK) cells as well as the interleukin-1β (IL-1β) release from platelets after serotonin (5-HT) stimulation. Mood and psychosocial performance (excitement, energy, ability to work and timidity) were measured by visual analogue scales. Taken together, SD induced a deterioration of both mood and ability to work, which was most prominent in the evening after SD, while the maximal alterations of the host defence system could be found twelve hours earlier, i.e., already in the morning following SD. Our findings therefore suggest an SD-induced alteration of these psychoimmune response patterns in healthy humans preceding deterioration of mood and psychosocial functioning.