Prescribing antidepressants for depression: time to be dimensional and inclusive

The article by Middleton and Moncrieff questions the role of antidepressants in treating depression on both philosophical and practical grounds; namely that depression isn''t a brain disease to be treated by a drug and that antidepressants are ineffective except as placebos. We argue that their stance is unhelpful and factually incorrect and that a more dimensional and integrative approach is needed in order to be able to best tailor treatment to individual needs. This involves a personalised assessment of the likely benefits and risks of both psychological and drug approaches when recommending treatment for someone with depression.     

Returning to tricyclic antidepressants for depression during childbearing: clinical and dosing challenges

Managing depression and anxiety during pregnancy and the postpartum period is challenging. Both pharmacological treatment and the lack thereof can pose threats to a fetus. SSRIs are the drugs of choice for use during pregnancy, but there is considerable evidence for the safety and efficacy of older antidepressants during pregnancy as well. This study highlights a single case of the use of the tricyclic nortriptyline during pregnancy and postpartum. The subject involved had an unexpectedly high ratio of serum level to drug dose during the postpartum period. We monitored the subject for a significantly greater portion of the postpartum period than has been done in previous studies, and explored medical and lifestyle changes that could account for the level-to-dose ratios we observed. Differences in smoking patterns, coupled with the patient’s status as a genetic poor metabolizer, were the most likely explanations.     

Tricyclic antidepressants and tryptophan in unipolar depression.

Depressed patients (unipolar) were given one of the following combinations in an attempt to test aspects of the 'amine hypothesis' and to find a preferential therapy: (1) clomipramine; (2) clomipramine and tryptophan; (3) desipramine and clomipramine, and (4) desipramine and tryptophan. Treatment (2) should have given optimal potentiation of 5-HT neurones and (3) and (4) should have acted similarly on both serotoninergic and adrenergic pathways. In no group was there any evidence of accelerated recovery, indicating that the process of conversion to normal mood may be more complex than suggested by most versions of the amine hypothesis.     

Maternal depression and anxiety are associated with altered gene expression in the human placenta without modification by antidepressant use: implications for fetal programming

We sought to determine if maternal depression, anxiety, and/or treatment with selective serotonin reuptake inhibitors (SSRIs) affect placental human serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) gene expression. Relative mRNA expression was compared among placental samples (n = 164) from healthy women, women with untreated depression and/or anxiety symptoms during pregnancy, and women who used SSRIs. SLC6A4 expression was significantly increased in placentas from women with untreated mood disorders and from women treated with SSRIs, compared to controls. SLC6A2 and 11β-HSD2 expression was increased in noncontrol groups, though the differences were not significant. SLC6A4, SLC6A2, and 11β-HSD2 expression levels were positively correlated. The finding that maternal depression/anxiety affects gene expression of placental SLC6A4 suggests a possible mechanism for the effect(s) of maternal mood on fetal neurodevelopmental programming. SSRI treatment does not further alter the elevated SLC6A4 expression levels observed with exposure to maternal depression or anxiety.     

Evolution and depression: issues and implications

Depression is well recognized to be rooted in the down-regulation of positive affect systems. This paper reviews some of the social and non-social theories that seek to explain the potential adaptive advantages of being able to tone down positive affect, and how dysfunctions in such affect control can occur in some contexts. Common to most evolutionary theories of depression is the view that loss of control over aversive events and/or major resources/rewards exert downward pressure on positive affect. Social theories, however, suggest that it is loss of control over the social environment that is particularly depressogenic. Two evolutionary theories (the attachment-loss, and the defeat-loss theories) are briefly reviewed and their interaction considered. It is suggested that phenotypes for toning down positive affect, in the face of loss of control, may become more severe in the context of socially hostile, unsupportive and/or excessively competitive environments. The paper briefly considers how human competencies for self-evaluation in relation to others, rumination, self-criticism, and modern social contexts can accentuate dysfunctional expressions of affect regulation.     

Selective gene expression in regions of primate neocortex: implications for cortical specialization

The neocortex, which is characteristic of mammals, has evolved to play important roles in cognitive and perceptual functions. The localization of different functions in different regions of the neocortex was well established within the last century. Studies on the formation of the neocortex have advanced at the molecular level, thus clarifying the mechanisms that control neural or glial cell differentiation and sensory projections. However, mechanisms that underlie cortical area specialization remain unsolved. To address this problem, our approach has been to isolate and characterize the genes that are selectively expressed in particular subsets of neocortical areas in primates; these areas are most distinctive among mammals. By differential display and restriction landmark cDNA scanning (RLCS) methods, we have identified two major classes of genes that are specifically expressed in the adult macaque monkey neocortical areas: one is expressed in the primary sensory areas, particularly, in the primary visual cortex (V1) and the other is expressed in the association areas. The genes that show these specific expression patterns are limited to only several gene families among our large-scale screening. In this review, I first describe the isolation and characterization of these genes, along with another class of genes specifically expressed in motor areas. Then, I discuss their functional significance in the primate neocortex. Finally, I discuss the implication of these gene expression patterns in neocortical specialization in primates and possible future research directions.     

Age and recognition of depression: implications for a cohort effect in major depression

Studies relying on subjects' retrospective reports have recently been interpreted as indicating that individuals born since World War II are at increased risk for a diagnosis of lifetime major depression. Examining the validity of this 'cohort effect' is essential, given the potential importance of such a phenomenon for research and policy. Among a number of artefactual explanations for the cohort effect is the possibility that older individuals are less likely to recognize depression as a mental disorder, and hence are less likely to remember depressive episodes as such, or to report these episodes in interviews on mental health. To test whether age was related to the recognition of major depression as a mental problem, we analysed responses from 152 randomly selected community residents on whether a vignette describing DSM-III major depression represented a psychological or emotional problem. Older respondents were much less likely to characterize major depression this way, even controlling for other factors. Such an age effect may provide a partial explanation for the apparent cohort effect, although the issue is complex and further research is needed.