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This study aims to summarize the current state of knowledge regarding approaches to treatment-resistant depression in pregnancy and the postpartum period and to develop algorithms for ante- and postnatal management in cases of refractory major depression. PubMed, Scopus, Google Scholar, and the Cochrane Library databases were searched without temporal restriction. Search terms included pregnancy and depression, perinatal depression, postnatal depression, treatment resistance and depression, antipsychotics and pregnancy, antidepressants and pregnancy, and mood stabilizers and pregnancy. Abstracts were reviewed for relevance, and further articles were obtained from bibliographic citations. There is a significant subpopulation of patients in pregnancy and postpartum whose depressive symptoms do not respond to first-line treatments. No research studies have focused specifically on this population. Data extracted from studies on women with depressive symptoms in pregnancy suggest that in the absence of evidence on which to base clinical decisions, many are receiving combinations of psychotherapeutic medications that have not been specifically studied for use in pregnancy. Antidepressant use in pregnancy is well studied, but studies specifically addressing the case of the patient who does not respond to first-line treatments are absent. Research in this area is urgently needed. The authors review a number of possible therapeutic approaches to treatment-resistant depression in pregnancy and the postpartum period. [ABSTRACT FROM AUTHOR]

Abstract: To test the possibility that chronic mild stress (CMS) might be unreliable in producing its often-intended outcome (i.e., decreased preference for sucrose, hypothesized to represent depression-relevant anhedonia) because it is typically applied to “normal” rats, a CMS procedure was applied to rats that may possess genetic susceptibility to affective disorders, having had been selectively-bred to show behavior indicative of such disorders. These rat lines were: Hyperactive (HYPER) rats, which show characteristics of bipolar disorder, Swim-test Susceptible (SUS) and Swim-test Resistant (RES) rats, being susceptible or resistant to effects of stress in the swim test, Swim High-active (SwHi) and Swim Low-active (SwLo) rats, which innately show high or low activity in the swim test. These selectively-bred lines were compared to normal, non-selectively bred (NS) rats. During CMS, HYPER rats, both females and males, as well as RES and SwHi rats, showed reduced consumption of a palatable 2% sucrose solution, and reduced preference for sucrose (vs. water) in comparison to non-stressed rats (no CMS) of the same lines. In contrast, CMS produced no decrease in sucrose consumption or in preference for sucrose in normal NS rats, and actually a caused a slight increase in sucrose consumption and preference in male NS rats. Other measures that indicate depression – food intake and motor activity in the home cage – were also assessed. SwLo and SwHi showed greater sensitivity to having their home-cage ambulatory activity reduced by CMS than did NS rats, but no other such differences relative to NS rats were seen for these other measures; thus, changes in sucrose intake or preference could not be explained by a change in caloric intake. These results suggest that the genetic attributes of animals can influence the outcome of CMS, and that the application of CMS to normal, non-selected rats may account, at least in part, for the unreliability of CMS in decreasing consumption of palatable substances and decreasing preference for such substances. [Copyright &y& Elsevier]

Although a strong co-morbidity exists clinically between epilepsy and depression, the cause of this co-morbidity remains unknown, and a valid animal model is crucial for the identification of underlying mechanisms and the development of a screening tool for novel therapies. Although some rodent models of epilepsy have been reported to display behaviors relevant to affective disorders, the seizure susceptibility of animals prone to depression-like behavior has not been characterized. Toward this end, we assessed several forms of seizure sensitivity and epileptogenesis in rats selectively bred for vulnerability (Swim Lo-Active; SwLo) or resilience (Swim High-Active; SwHi) to depression-like phenotypes. The SwLo rats exhibit decreased motor activity in a swim test and other depression-like phenotypes, whereas the SwHi rats display increased motor activity in a swim test. SwLo rats exhibited a decreased latency to limbic motor seizures following acute pilocarpine administration in the absence of differences in pilocarpine pharmacokinetics, and also had a decreased threshold to tonic seizures induced by electroshock. Approximately half of the SwLo rats, but none of the SwHi rats, had spontaneous limbic motor seizures 5 weeks following pilocarpine-induced status epilepticus. While the number of stimulations required to achieve full amygdala and hippocampal electrical kindling were similar in the two rat lines, SwLo rats had a lower final hippocampal kindling threshold and more wet dog shakes during both amygdala and hippocampal kindling. Combined, these results indicate that SwLo rats are a model of epilepsy and depression co-morbidity that can be used for investigating underlying neurobiological and genetic mechanisms and screening novel therapeutics. [ABSTRACT FROM AUTHOR]

BACKGROUND IVF, using donor oocytes, has become increasingly common. The donation procedure carries psychiatric risks, including depression, anxiety and rarely, psychosis, and this risk increases when there is a past history of psychiatric illness. We report on the psychiatric status, at intake assessment, of a group of candidate oocyte donors. METHODS The authors reviewed clinical records of 63 women continuously presenting to a University medical center for psychiatric evaluation as part of the screening process for oocyte donation. A board certified psychiatrist administered a structured clinical interview to candidate donors, and self-report measures were obtained from 28 women. RESULTS There was a significant discrepancy between psychiatric history of depression and current mood status, as measured by both clinical interview and psychometric self-report data. Nearly one-quarter of candidate donors (22%) reported a history of major depressive disorder; however, all candidate donors denied current mood disturbance on clinical interview, and mean Beck depression inventory and profile of mood states scores were lower than expected compared with psychometric norms (P < 0.0005), epidemiological data and the recurrent nature of depressive disorders. CONCLUSIONS Candidate donors may minimize psychiatric symptoms. Given the potential for ovarian stimulation protocols to induce or exacerbate mood symptoms, and the moderate heritability of mood disorders, careful evaluation of candidate donor affective disorder history is recommended. This evaluation should focus on sensitivity to mood destabilization during times of hormonal change. Measures that examine whether a candidate donor may have a tendency to present herself in an overly favorable manner, and/or a tendency to minimize symptoms, are recommended. [ABSTRACT FROM AUTHOR]

The article provides information on the biological effects of estrogen and progesterone and their use to treat mood disorders in women. It states that both hormones have neurotrophic properties that regulate cortical blood flow and affects the central nervous system. It discusses the use of progestin and transdermal 17ß-estradiol in hormone replacement therapy and combined oral contraceptives as treatment for premenstrual dysphoric disorder, unipolar depression, bipolar disorder and mood disorders in perimenopause and postmenopause.

Abstract: This paper reviews progress made in testing the idea that depression-related behavioral changes can arise from hyperactivity of locus coeruleus (LC) neurons which consequently inhibits activity of mesocorticolimbic dopamine neurons in the ventral tegmentum (VTA) via release of galanin from terminals on LC axons in VTA. Results from pre-clinical testing are described, including the most recent findings indicating that, in an animal model that shows long-lasting symptoms of depression, recovery to normal activity in the home cage is accelerated by infusion of a galanin receptor antagonist, galantide (M15), into VTA. Data are also described suggesting that all effective antidepressant treatments decrease activity of LC neurons. [Copyright &y& Elsevier]

Summary: This study assessed effects of a CRF1 receptor antagonist, R121919, on the behavior of rats that have been selectively bred to exhibit very high or very low activity in a swim test. Following treatment with R121919 (10mg/kg, s.c.) or vehicle, several types of behavior were examined including: (1) spontaneous ambulatory activity in a novel environment, (2) swim-test activity, (3), and responses in an elevated plus maze. The most pronounced effects were observed in the swim test. Although R121919 had little effect on the swim-test behavior of normal, non-selected rats, Swim High-active rats (SwHi), characterized by being very active and exhibiting pronounced struggling behavior in the swim test, showed increased activity (more struggling) after R121919; in contrast, Swim Low-active (SwLo) rats, characterized by being very inactive and exhibiting pronounced floating behavior in the swim test, showed decreased activity (more floating) after R121919. This effect was observed in both male and female rats. No differences between strains or the effects of R121919 were observed for spontaneous ambulation or in the elevated plus maze test. [Copyright &y& Elsevier]

Abstract: The bidirectional comorbidity between epilepsy and depression is associated with severe challenges for treatment efficacy and safety, often resulting in poor prognosis and outcome for the patient. We showed previously that rats selectively bred for depression-like behaviors (SwLo rats) also have increased limbic seizure susceptibility compared with their depression-resistant counterparts (SwHi rats). In this study, we examined the therapeutic efficacy of voluntary exercise in our animal model of epilepsy and depression comorbidity. We found that chronic wheel running significantly increased both struggling duration in the forced swim test and latency to pilocarpine-induced limbic motor seizure in SwLo rats but not in SwHi rats. The antidepressant and anticonvulsant effects of exercise were associated with an increase in galanin mRNA specifically in the locus coeruleus of SwLo rats. These results demonstrate the beneficial effects of exercise in a rodent model of epilepsy and depression comorbidity and suggest a potential role for galanin. [Copyright &y& Elsevier]

Abstract: Depression and psychostimulant addiction are co-morbid conditions; depression is a significant risk factor for psychostimulant abuse, and the rate of depression in drug addicts is higher than in the general population. Despite the prevalence of this comorbidity, there are few animal models examining psychostimulant abuse behaviors in depression. We have shown previously that while rats selectively bred for depression-like phenotypes (SwLo) have blunted mesolimbic dopamine (DA) signaling and locomotor responses to dopaminergic drugs, they voluntarily administer excessive amounts of psychostimulants compared to normal or depression-resistant (SwHi) rats in oral consumption paradigms. To determine whether this increased drug intake by depression-sensitive rats extends to operant self-administration, we assessed fixed ratio-1, progressive ratio, extinction, and reinstatement responding for cocaine and amphetamine in SwLo and SwHi rats. Contrary to the oral consumption results, we found that the SwHi rats generally responded more for both cocaine and amphetamine than the SwLo rats in several instances, most notably in the progressive ratio and reinstatement tests. Food-primed reinstatement of food seeking was also elevated in SwHi rats. These results provide further insight into the neurobiology of depression and addiction comorbidity and caution that oral and operant psychostimulant self-administration paradigms can yield different, and this case, opposite results. [Copyright &y& Elsevier]