Bipolar Disorder: Identity, Social Support, Religiosity and Spirituality. Can Religiosity/Spirituality be a Mood Balancing Factor? An Italian Case Report.

This paper presents a case study to support the hypothesis that religiosity and spirituality (R/S), as mood balancing factors, could facilitate the recovery process for patients suffering from bipolar disorder (BD) once they have been stabilized and are receiving appropriate support (e.g., in a residential rehabilitative center). After a succinct review of BD and R/S, the patient's medical history and rehabilitation pathway are described, with a particular focus on the role played by R/S. The authors found that in this case, once the patient was stabilized, R/S helped to consolidate her feelings of well-being, increasing her positive perception of social support services and ultimately her self-confidence.

New perspectives on techniques for the clinical psychiatrist: Brain stimulation, chronobiology and psychiatric brain imaging.

This review summarizes a scientific dialogue between representatives in non-pharmacological treatment options of affective disorders. Among the recently introduced somatic treatments for depression those with most evidenced efficacy will be discussed. The first part of this article presents current opinions about the clinical applications of transcranial magnetic stimulation in the treatment of depression. The second part explains the most relevant uses of chronobiology in mood disorders, while the last part deals with the main perspectives on brain imaging techniques in psychiatry. The aim was to bridge gaps between the research evidence and clinical decisions, and reach an agreement on several key points of chronobiological and brain stimulation techniques, as well as on relevant objectives for future research.

Depression and neurological disorders.

PURPOSE OF REVIEW: Clinical studies support a bidirectional link between depression and neurological diseases. Here we review the most recent findings supporting the hypothesis that major depression is a medical illness of the brain which can be elicited by neurological illnesses. RECENT FINDINGS: In the last year major improvements in brain-imaging techniques allowed correlations to be demonstrated between functional and structural brain abnormalities in specific brain areas (prefrontal cortex, hippocampus, cingulate gyrus) and the presence and severity of affective disorders, thus suggesting a neural basis for their onset and progression. Similar lesions, caused by neurological diseases, have been found to correlate with the presence of depression in neurological illnesses, but literature on the topic is still lacking. Depression in neurological disorders responds to the same treatments available for idiopathic major depression, but patients seem to have different sensitivities to side effects depending on their specific neurological syndrome. Most available data come from case reports and open trials. SUMMARY: 'Psychiatric' and 'neurologic' depression seem to share common abnormalities in specific brain areas, but sound brain-imaging studies of the neural correlates of depression in neurological disorders are still lacking. Available treatments are efficacious, but no clear-cut guidelines about the best drugs and dosages can be defined because double-blind placebo-controlled studies are still scarce.

Long-term response to lithium salts in bipolar illness is influenced by the glycogen synthase kinase 3-beta -50 T/C SNP.

The molecular mechanisms driving the biological clock in the suprachiasmatic nucleus of the hypothalamus may play a role in mood disorders. A single nucleotide polymorphism (SNP) (-50 T/C) falling into the effective promoter region (nt -171 to +29) of the gene coding for glycogen synthase kinase 3-beta (GSK3-beta) has been linked with different age at onset of bipolar illness and with different antidepressant effects of total sleep deprivation. GSK3-beta codes for an enzyme which is a target for the action of lithium and possibly of valproic acid. We studied the effect of this polymorphism on the therapeutic response to lithium salts of 88 bipolar type I patients. Data about recurrence rate of mood episodes were collected for at least 2 years before lithium and 2 years on lithium. Results showed that homozygotes for the wild variant did not change their recurrence index while carriers of the mutant allele improved, thus supporting the hypothesis that GSK is a target for the therapeutic action of lithium. Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, but caution ought to be taken in interpreting these preliminary results and future replication studies must be awaited because of the low frequency of the GSK3-beta*C/C genotype in the studied populations.

Combined total sleep deprivation and light therapy in the treatment of drug-resistant bipolar depression: acute response and long-term remission rates.

BACKGROUND: Drug resistance remains a persistent source of morbidity and mortality for patients with bipolar depression. A growing number of clinical studies support the usefulness of chronotherapeutic interventions, such as total sleep deprivation (TSD) and light therapy (LT), in the treatment of nonresistant bipolar depression. METHOD: To investigate the clinical usefulness of TSD plus LT in the treatment of drug-resistant bipolar depression, we treated 60 inpatients for 1 week with repeated TSD and LT combined with ongoing antidepressants and lithium salts. All patients had a DSM-IV diagnosis of bipolar I disorder. Drug resistance was rated according to Thase and Rush criteria. The pattern of relapses and recurrences was assessed during a prospective 9-month follow-up. Data were gathered from September 2002 to July 2004. RESULTS: A 2-way repeated-measures analysis of variance with changes in self-rated perceived mood scores as dependent variable and with time and group (history of drug resistance) as independent factors confirmed significant time-by-group interaction (p = .0339). A logistic regression on rates of achievement of response (50% reduction in Hamilton Rating Scale for Depression ratings) confirmed the significance of observed differences: overall, 70% (23/33) of nonresistant versus 44% (12/27) of drug-resistant patients achieved response (p = .045). A survival time analysis (Cox proportional hazards model) showed that history of drug resistance significantly influenced the pattern of relapses and recurrences, with 57% (13/23) of nonresistant responders and 17% (2/12) of drug-resistant responders being euthymic after 9 months (p = .0212). DISCUSSION: The combination of repeated TSD and LT in drug-resistant patients was useful in triggering an acute response. Further clinical research is needed to optimize this treatment option for drug-resistant patients in the long term.

Lormetazepam in depressive insomnia: new evidence of phase-response effects of benzodiazepines.

Benzodiazepines can shift the phase of circadian rhythms in mammalian species, but few data are available on their phase-response effects in humans, and on possible links between timing of administration and hypnotic efficacy. Using a placebo-controlled, cross-over design, we evaluated the hypnotic effect of lormetazepam 0.03 mg/kg and placebo in 38 inpatients who were affected by a major depressive episode. Patients were divided into three groups, receiving treatment at 18.00 h, 20.00 h or 22.00 h, respectively. Sleep and psychiatric symptoms were evaluated with self-administered scales and a sleep diary. The results demonstrate that active treatment significantly improved insomnia independent of the severity of depression, which remained unchanged. Timing of treatment influenced changes in timing of sleep observed with active treatment. Although sleep duration was equally improved in all treatment groups, patients who received treatment at 20.00 h showed an acute advance of sleep onset, with no changes in morning awakening. Patients who received treatment at 22.00 h showed an acute delay in morning awakening, with no changes of sleep onset. Finally, patients who received treatment at 18.00 h showed a non-significant trend in the same direction. These effects reverted with cross-over return to placebo. The perceived degree of improvement of insomnia was proportional to the advance in timing of sleep onset obtained with treatment. Our results suggest that the effects of lormetazepam on the subjective sleep of patients affected by a major depressive episode depend upon the timing of administration, and that improvement in subjective sleep is related to advance of sleep onset, and not to delay of morning awakening.

A single nucleotide polymorphism in glycogen synthase kinase 3-beta promoter gene influences onset of illness in patients affected by bipolar disorder.

Genetic studies in medicine exploited age of onset as a criterion to delineate subgroups of illness. Bipolar patients stratified with this criterion were shown to share clinical characteristics and patterns of inheritance of illness. The molecular mechanisms driving the biological clock in the suprachiasmatic nucleus of the hypothalamus may play a role in mood disorders. A single nucleotide polymorphism (SNP) (-50 T/C) falling into the effective promoter region (nt -171 to +29) of the gene coding for glycogen synthase kinase 3-beta (GSK3-beta) has been identified. GSK3-beta codes for an enzyme which is a target for the action of lithium and which is also known to regulate circadian rhythms in Drosophila. We studied the effect of this polymorphism on the age at onset of bipolar disorder type I. A homogeneous sample of 185 Italian patients affected by bipolar disorder was genotyped. Age at onset was retrospectively ascertained with best estimation procedures. No association was detected between GSK3-beta -50 T/C SNP and the presence of bipolar illness. Homozygotes for the wild variant (T/T) showed an earlier age at onset than carriers of the mutant allele (F=5.53, d.f.=2,182, P=0.0047). Results warrant interest for the variants of genes pertaining to the molecular clock as possible endophenotypes of bipolar disorder, but caution ought to be taken in interpreting these preliminary results and future replication studies must be awaited.

Antidepressant effects of light therapy combined with sleep deprivation are influenced by a functional polymorphism within the promoter of the serotonin transporter gene.

BACKGROUND: A functional polymorphism within the promoter of the serotonin transporter has been shown to influence the antidepressant response to serotonergic drug treatments and to total sleep deprivation (TSD). The short-term relapse that follows acute response to TSD has been successfully prevented by combining TSD with light therapy. The mechanism of action of this combined treatment is unknown. METHODS: We tested the hypothesis that allelic variation of the serotonin transporter (5-HTT) linked polymorphic region (5-HTTLPR) could influence the response to the combination of light therapy and TSD. Twenty-two bipolar depressed inpatients were administered a night of TSD combined with 30 min light therapy given during the TSD night and in the morning after recovery sleep. 5-HTTLPR was genotyped using polymerase chain reaction techniques. Changes in perceived mood were rated on a visual analog scale. RESULTS: Light therapy sustained the effect of TSD. The effect was more marked in homozygotes for the long variant of 5-HTTLPR than in heterozygotes and homozygotes for the short variant. CONCLUSIONS: The influence of 5-HTTLPR on response to the combination of TSD and light therapy is similar to that observed on response to TSD and serotonergic drug treatments.

Morning light treatment hastens the antidepressant effect of citalopram: a placebo-controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors are effective in approximately 70% of patients with a major depressive episode, but therapeutic changes usually require 2 weeks of administration to become clinically relevant. Adjunct light therapy has been proposed to hasten the effects of drug treatment. The purpose of the present study was to evaluate the effect of morning light therapy or placebo combined with citalopram in the treatment of patients affected by a major depressive episode without psychotic features. METHOD: Thirty inpatients (DSM-IV major depressive disorder [N = 21] and bipolar disorder [N = 9]) were treated with citalopram, 40 mg, and randomized in a 3:2 manner to receive 30 minutes of 400 lux green light treatment in the morning or placebo (exposure to a deactivated negative ion generator) during the first 2 weeks of drug treatment. Timing of light therapy was individually defined to obtain a 2-hour phase advance to morning light. Outcome was measured with the Hamilton Rating Scale for Depression and the Zung Self-Rating Depression Scale every week, and with a Visual Analogue Scale 3 times a day during the first week. RESULTS: All outcome measures showed significantly (p <.05) better mood improvement in light-treated patients, resulting in faster responses to antidepressant treatment. CONCLUSION: The combination of citalopram and light treatment was more effective than citalopram and placebo in the treatment of major depression. With an optimized timing of administration, low-intensity light treatment significantly hastened and potentiated the effect of citalopram, thus providing the clinical psychiatrists with an augmenting strategy that was found effective and devoid of side effects.