Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry

Freud began his career as a neurologist studying the anatomy and physiology of the nervous system, but it was his later work in psychology that would secure his place in history. This paper draws attention to consistencies between physiological processes identified by modern clinical research and psychological processes described by Freud, with a special emphasis on his famous paper on depression entitled 'Mourning and melancholia'. Inspired by neuroimaging findings in depression and deep brain stimulation for treatment resistant depression, some preliminary physiological correlates are proposed for a number of key psychoanalytic processes. Specifically, activation of the subgenual cingulate is discussed in relation to repression and the default mode network is discussed in relation to the ego. If these correlates are found to be reliable, this may have implications for the manner in which psychoanalysis is viewed by the wider psychological and psychiatric communities

Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder

Background: Manic-depression or bipolar disorder (BD) is a multi-faceted illness with an inevitably complex treatment. Methods: This article summarizes the current status of our knowledge and practice of its treatment. Results: It is widely accepted that lithium is moderately useful during all phases of bipolar illness and it might possess a specific effectiveness on suicidal prevention. Both first and second generation antipsychotics are widely used and the FDA has approved olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole for the treatment of acute mania. These could also be useful in the treatment of bipolar depression, but only limited data exists so far to support the use of quetiapine monotherapy or the olanzapine-fluoxetine combination. Some, but not all, anticonvulsants possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be effective in the treatment of depression but not mania. Antidepressant use is controversial. Guidelines suggest their cautious use in combination with an antimanic agent, because they are supposed to induce switching to mania or hypomania, mixed episodes and rapid cycling. Conclusion: The first-line psychosocial intervention in BD is psychoeducation, followed by cognitive-behavioral therapy. Other treatment options include Electroconvulsive therapy and transcranial magnetic stimulation. There is a gap between the evidence base, which comes mostly from monotherapy trials, and clinical practice, where complex treatment regimens are the rule

Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

OBJECTIVE: Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines. The authors looked for the features associated with risk of recurrence. METHOD: The authors examined prospective data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study for up to 24 months. For those who were symptomatic at study entry but subsequently achieved recovery, time to recurrence of mania, hypomania, mixed state, or a depressive episode was examined with Cox regression. RESULTS: Of 1,469 participants symptomatic at study entry, 858 (58.4%) subsequently achieved recovery. During up to 2 years of follow-up, 416 (48.5%) of these individuals experienced recurrences, with more than twice as many developing depressive episodes (298, 34.7%) as those who developed manic, hypomanic, or mixed episodes (118, 13.8%). The time until 25% of the individuals experienced a depressive episode was 21.4 weeks and until 25% experienced a manic/hypomanic/mixed episode was 85.0 weeks. Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence. Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic, hypomanic, or mixed episode recurrence. CONCLUSIONS: Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery. Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence

Linkage disequilibrium mapping of the chromosome 6q21-22.31 bipolar I disorder susceptibility locus.

We previously reported genome-wide significant evidence for linkage between chromosome 6q and bipolar I disorder (BPI) by performing a meta-analysis of original genotype data from 11 genome scan linkage studies. We now present follow-up linkage disequilibrium mapping of the linked region utilizing 3,047 single nucleotide polymorphism (SNP) markers in a case-control sample (N = 530 cases, 534 controls) and family-based sample (N = 256 nuclear families, 1,301 individuals). The strongest single SNP result (rs6938431, P = 6.72 x 10(-5)) was observed in the case-control sample, near the solute carrier family 22, member 16 gene (SLC22A16). In a replication study, we genotyped 151 SNPs in an independent sample (N = 622 cases, 1,181 controls) and observed further evidence of association between variants at SLC22A16 and BPI. Although consistent evidence of association with any single variant was not seen across samples, SNP-wise and gene-based test results in the three samples provided convergent evidence for association with SLC22A16, a carnitine transporter, implicating this gene as a novel candidate for BPI risk. Further studies in larger samples are warranted to clarify which, if any, genes in the 6q region confer risk for bipolar disorder

Serotonin gene polymorphisms and bipolar I disorder: focus on the serotonin transporter.

The pathogenesis of bipolar disorder may involve, at least in part, aberrations in serotonergic neurotransmission. Hence, serotonergic genes are attractive targets for association studies of bipolar disorder. We have reviewed the literature in this field. It is difficult to synthesize results as only one polymorphism per gene was typically investigated in relatively small samples. Nevertheless, suggestive associations are available for the 5HT2A receptor and the serotonin transporter genes. With the availability of extensive polymorphism data and high throughput genotyping techniques, comprehensive evaluation of these genes using adequately powered samples is warranted. We also report on our investigations of the serotonin transporter, SLC6A4 (17q11.1-q12). An insertion/deletion polymorphism (5HTTLPR) in the promoter region of this gene has been investigated intensively. However, the results have been inconsistent. We reasoned that other polymorphism/s may contribute to the associations and the inconsistencies may be due to variations in linkage disequilibrium (LD) patterns between samples. Therefore, we conducted LD analyses, as well as association and linkage using 12 polymorphisms, including 5HTTLPR. We evaluated two samples. The first sample consisted of 135 US Caucasian nuclear families having a proband with bipolar I disorder (BDI, DSM IV criteria) and available parents. For case-control analyses, the patients from these families were compared with cord blood samples from local Caucasian live births (n = 182). Our second, independent sample was recruited through the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD, 545 cases, 548 controls). No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do not support association between SLC6A4 and BDI families. Further studies using sub-groups of BDI are worthwhile