Multiple Depressive Episodes Research Articles

Salivary α-amylase as a stress biomarker in mentally and physically disabled individuals during COVID-19 times.

Stress is faced by every individual in their day-to-day life activities. During pandemic, most people have experienced multiple episodes of depression, anxiety, and insomnia. Several medical and dental problems are reported with stress and the fastest and easiest way to study and investigate is through body fluids, mainly saliva. Hence, we aim to study salivary α amylase in disabled individuals and hypothesize that salivary α amylase could be a reliable stress biomarker in disabled individuals. Cross-sectional study was conducted including 200 individuals grouped into controls (100) and disabled individuals (100). Disabled individuals were further grouped into physically (50) and mentally (50) disabled. Stimulated and unstimulated saliva was collected from all the participants and were investigated for salivary α-amylase by direct substrate method. The enzyme activity was analyzed using a spectrophotometer and the obtained were analyzed statistically. Salivary α-amylase showed significant difference between controls and disabled group (p = 0.000). Salivary α-amylase was least in the mentally disabled group compared to physically disabled group. Age related comparison of salivary α-amylase was higher in physically disabled whereas gender related comparison showed females in physically disabled group to be more affected than controls. Saliva, the easy and most researched fluid, is rich in salivary α-amylase. Salivary α-amylase is a potential biomarker to assess stress. Further diagnostic studies are required to know the salivary changes and their influence on individual general health status.

Intravenous Reelin rescues despair-like behavior, Reelin cells in the dentate sub-granular zone, and spleen atrophy in the cyclic corticosterone model of recurring depressive episodes.

Novel antidepressants are predominantly evaluated preclinically in rodent models of chronic stress in which animals experience a single prolonged exposure to chronic stress prior to treatment. Rodent models of a single episode of chronic stress translate poorly to human depressive disorders, which are commonly marked by recurring depressive episodes. Intravenous administration of Reelin has previously been shown to resolve immobility in the forced swim test of rats exposed to a single prolonged exposure to chronic stress. To determine whether Reelin has antidepressant-like properties in a model of recurring depressive episodes, Long-Evans rats (N = 57) were exposed to multiple cycles of chronic stress and stress-free periods before the administration of a single injection of Reelin during the final cycle of chronic stress. The animals then performed in the forced swim test and open field test before the post-mortem evaluation of Reelin cell counts in the sub-granular zone of the dentate gyrus to determine the impact of treatment on hippocampal Reelin levels and spleen white pulp to evaluate the role of Reelin treatment in peripheral inflammation. The results show a single Reelin injection reversed elevated levels of immobility in the forced swim test in both male and female subjects exposed to the cyclic chronic stress model of recurring depressive episodes. Treatment with Reelin also restored Reelin-positive cell counts in the dentate gyrus sub-granular zone and reversed atrophy of spleen white pulp. The results shown here indicate that treatment with Reelin could effectively resolve alterations in forced swim test behavior caused by the cyclic corticosterone model of recurring depressive episodes and that Reelin homeostasis is important for regulating stress-related inflammation. Future preclinical antidepressant research should incorporate models of multiple depressive episodes to improve the translation of preclinical rodent research to human depressive disorders.

PSYCHOSOCIAL INTERVENTION FOR REDUCING RELAPSE AND IMPROVING TREATMENT ADHERENCE IN BIPOLAR AFFECTIVE DISORDER WITH POOR SOCIO-OCCUPATIONAL FUNCTIONING AND HIGH EXPRESSED EMOTION IN THE FAMILY: A CASE REPORT

Introduction: Bipolar affective disorder (BPAD) is a chronic psychiatric disorder with an admixture of frequent and recurrent episodes of mania, hypomania, depression, or mixed episodes. More than 1% of the world's population and at least 0.3% of the Indian population are affected by BPAD. We have chosen a case of BPAD with multiple episodes to study the impact of psychosocial intervention in the management of the illness of the affected person and family. The index client, a male, Presentation of the case: 32 years of age, visited the Institute of Psychiatry (IOP) with caregivers and was referred to the psychiatric social work department of the IOP on April 24, 2019, with symptoms of mania and psychosis. He had 7-years history of psychiatric illness, including multiple episodes of mania and depression, as well as frequent irregular medication; burden and conict, insufcient social support, poor communication and interaction patterns, poor coping and problem-solving skills in the family. Therapists imparted Interpersonal and Social Rhythm Therapy (IPSRT) and family-focused therapy to the client and family members. It was found that there Discussion: was a signicant difference between pre- and postpsychosocial interventions in the life and wellbeing of a person with BPAD and his family. Post intervention, client's level of social and occupational functioning was increased, high expressed emotion had been notably decreased, adaptive patterns had been improved, and cohesion in the family had been strengthened. The client and his family members learned to prevent development of future episodes. Conclusion: Psychiatric social work interventions have been a key area in the management of BPAD involving the family, which helps in maintaining a prolonged euthymic period and better treatment compliance.

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan.

Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research.

On Structural Racism and Mental Illness

On Structural Racism and Mental Illness

A primer on TMS with a focus on its use in treatment‐resistant depression

I recently met Ms. B — a woman in her forties with a history of multiple episodes of severe depression since her teenage years. She attempted suicide multiple times in the past and had multiple psychiatric admissions. She had trialed multiple anti‐depressants (and augmentation agents) and was referred for TMS treatment by her outpatient psychiatrist after another bout of depression leading to hopelessness and poor functioning at home. After doing treatment for 3 weeks, her affect started to change, her hygiene improved, she became hopeful, and wanted to do things such as sit by the lake, dip her toes in the water, and enjoy the sunshine. After completing treatment for 6 weeks, she was in remission. She told me “TMS is my lifesaver.” This was her second round of treatment in the last 3 years, and she was one of the 40%–60% of treatment‐resistant patients with depression who respond well to TMS.

An ongoing process of reconnection: A qualitative exploration of mindfulness-based cognitive therapy for adults in remission from depression.

Mindfulness-based cognitive therapy (MBCT) is an 8-week relapse-prevention intervention designed for people who have experienced multiple episodes of depression and remain vulnerable to relapse. Previous qualitative explorations of the effects of MBCT for people in remission from depression have suggested a number of themes regarding changes arising from participating in MBCT ranging from awareness, agency, perspective, group processes, self-related change, and new ways of understanding depression. We aimed to qualitatively explore how participants in remission from depression experienced MBCT both post-MBCT and during a follow-up period. In a preference-choice trial design, 35 participants took part in qualitative interviews and assessments post-MBCT and at three time points during a 12-month follow-up. Data were analysed using reflexive thematic analysis. Two overarching themes were developed as follows: (1) 'reconnection with experience, self, and others' and (2) 'acknowledging an ongoing process of change'. In theme one, sub-themes captured participants' experiences of increasing levels of awareness of their experience (e.g., thoughts, emotions, sensations, and present moment) from which they described changes in their relationship with experience describing increases in control, choice, acceptance, and calm. Participants described shifts towards reconnection with aspects of the self and relationships with others. In theme two, sub-themes reflected participants' conflict between avoidance and engagement in mindfulness practices, and the recognition of the gradual change following MBCT and long-term investment needed in mindfulness practices. Our findings have clinical implications in terms of facilitating MBCT and point to important themes around recognizing the ongoing process of reconnection with experiences, self, and others. Participants with histories of depression may have experienced disconnection and isolation from internal experiences (e.g., thoughts and emotions), self, and others; MBCT encourages a deliberate shift towards reconnection with these experiences. Practitioners could encourage more psychoeducation and discussions around depression during MBCT to encourage reflections on the process of reconnection. Practitioners should maintain an awareness of the ongoing, gradual processes of change and potential for conflict experienced during MBCT Practitioners could provide a stronger emphasis on building awareness of body sensations during MBCT, with suggestions provided in the discussion section.

Quantitative Electroencephalography in Patients With Depression and Epilepsy Spectrum Disorder and Its Correlation With Clinical Features of Depression.

To determine the associations of epilepsy spectrum disorder (ESD) with brain insult and certain quantitative electroencephalographic (QEEG) and clinico-demographic parameters in patients with depression. 21 right-handed patients aged 18 to 50 years with the diagnosis of depression and ESD (scored ≥70 in Iowa Interview for Partial seizure-like symptoms) were compared with 21 patients with depression but without ESD (scored <70) and 21 normal subjects with <3 positive scores on the 12-Item General Health Questionnaire. Their QEEG parameters such as power spectrum and coherence of five frequency bands in 11 regions were compared. Patients with ESD had more minor traumatic brain injury along with more severe and multiple depressive episodes. Patients with ESD had significantly higher beta1 power over all regions on the left scalp than did normal subjects. Patients with ESD had significantly higher beta2 power over the left central region than did patients with no ESD and normal subjects. For patients with severe recurrent depression, clinicians should systematically check for episodic partial seizure-like phenomena, especially when QEEG shows electrical disorganisation in the left side in those with mild traumatic brain injury.

Volumetric brain differences in clinical depression in association with anxiety: a systematic review with meta-analysis

Structural differences associated with depression have not been confirmed in brain regions apart from the hippocampus. Comorbid anxiety has been inconsistently assessed, and may explain discrepancies in previous findings. We investigated the link between depression, comorbid anxiety and brain structure. We followed Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42018089286). We searched the Cochrane Library, MEDLINE, PsycInfo, PubMed and Scopus, from database inception to Sept. 13, 2018, for MRI case-control studies that reported brain volumes in healthy adults and adults with clinical depression. We summarized mean volumetric differences using meta-analyses, and we assessed demographics, depression factors and segmentation procedure as moderators using meta-regressions. We included 112 studies in the meta-analyses, assessing 4911 healthy participants and 5934 participants with depression (mean age 49.8 yr, 68.2% female). Volume effects were greater in late-onset depression and in multiple episodes of depression. Adults with depression and no comorbidity showed significantly lower volumes in the putamen, pallidum and thalamus, as well as significantly lower grey matter volume and intracranial volume; the largest effects were in the hippocampus (6.8%, p < 0.001). Adults with depression and comorbid anxiety showed significantly higher volumes in the amygdala (3.6%, p < 0.001). Comorbid anxiety lowered depression effects by 3% on average. Sex moderated reductions in intracranial volume. High heterogeneity in hippocampus effects could not be accounted for by any moderator. Data on symptom severity and medication were sparse, but other factors likely made significant contributions. Depression-related differences in brain structure were modulated by comorbid anxiety, chronicity of symptoms and onset of illness. Early diagnosis of anxiety symptomatology will prove crucial to ensuring effective, tailored treatments for improving long-term mental health and mitigating cognitive problems, given the effects in the hippocampus.

C-L Psychiatry Vital in Assessing Patients Before, After Bariatric Surgery

C-L Psychiatry Vital in Assessing Patients Before, After Bariatric Surgery

SA37 - NEUROINFLAMMATORY GENE EXPRESSION IN HIPPOCAMPUS IN MAJOR DEPRESSIVE DISORDER

Background Major Depressive Disorder (MDD) is a common psychiatric disease for which available medications are often not effective. Full remission from depression is achieved by less than 50 percent of patients using medications that mainly target serotonin or norepinephrine systems (Berton and Nestler, 2006; Rush et al., 2006). The economic burden of depression in the U.S., along with comorbid conditions, is estimated at over $170B and depressive disorders are the leading contributors to global burden of disease (Greenberg et al., 2015; Whiteford et al., 2013). The high prevalence of MDD and modest response to existing therapies compels efforts to better understand and treat the disorder. One promising avenue of research suggests that decreases in hippocampal volume with increasing duration of depression results from a decrease in neurogenesis or altered gene expression (Sheline et al., 1996, Cobb et al., 2013). Methods Tissue punches from the dentate gyrus were collected from 23 subjects (MDD, medication-free) and 23 demographically-matched normal controls. Of the 23 subjects with MDD, 17 died by suicide and 17 had multiple depressive episodes. High quality total RNA, RNA Quality Index > 6, was isolated and whole transcriptome paired-end shotgun sequencing was performed using an Illumina NextSeq. 500. For each sample, raw RNA-seq reads (adapter-trimmed fastq files) were aligned to the Ensembl GRCh38 human reference genome using GSNAP (Genomic Short-read-Nucleotide Alignment Program). Differential gene expression was determined using cuffdiff, and core biological processes, molecular networks, and pathways pathologically disrupted in MDD were identified using Ingenuity Pathway Analysis. Results For each sample, 37 to 112 million reads were obtained and 64 to 96% were mapped successfully to the human genome, with most samples mapping above 85%. ‘Cuffdiff’ analysis in the Tuxedo suite revealed 30 significant genes differentially expressed in all MDD compared to controls (Lumenogix™, FDR Discussion The key finding in the primary MDD dataset as well as in the subsets is the overrepresentation of neuroinflammation related genes. Inflammatory and neurogenesis-related (ERK/MAPK) signaling pathways were significantly altered in the hippocampal dentate gyrus in MDD, with cytokine signaling and inflammatory pathways preferentially altered in MDD-suicide vs. MDD-non-suicide. Together this suggests that neuroinflammation, mediated by microglia and astrocytes may play a crucial role in major depressive disorder. These findings suggest a novel approach by seeking targets for new treatment of MDD that includes anti-inflammatory and neuroprotective properties.

Migraine with visual aura associated with thicker visual cortex.

Until recent years it was believed that migraine with aura was a disorder causing intermittent neurological symptoms, with no impact on brain structure. However, recent MRI studies have reported increased cortical thickness of visual and somatosensory areas in patients with migraine with aura, suggesting that such structural alterations were either due to increased neuronal density in the areas involved, or a result of multiple episodes of cortical spreading depression as part of aura attacks. Subsequent studies have yielded conflicting results, possibly due to methodological reasons, e.g. small number of subjects. In this cross-sectional study, we recruited females aged 30-60 years from the nationwide Danish Twin Registry. Brain MRI of females with migraine with aura (patients), their co-twins, and unrelated migraine-free twins (controls) were performed at a single centre and assessed for cortical thickness in predefined cortical areas (V1, V2, V3A, MT, somatosensory cortex), blinded to headache diagnoses. The difference in cortical thickness between patients and controls adjusted for age, and other potential confounders was assessed. Comparisons of twin pairs discordant for migraine with aura were also performed. Comparisons were based on 166 patients, 30 co-twins, and 137 controls. Compared with controls, patients had a thicker cortex in areas V2 [adjusted mean difference 0.032 mm (95% confidence interval 0.003 to 0.061), V3A [adjusted mean difference 0.037 mm (95% confidence interval 0.008 to 0.067)], while differences in the remaining areas examined were not statistically significant [adjusted mean difference (95% confidence interval): V1 0.022 (-0.007 to 0.052); MT: 0.018 (-0.011 to 0.047); somatosensory cortex: 0.020 (-0.009 to 0.049)]. We found no association between the regions of interest and active migraine, or number of lifetime aura attacks. Migraine with aura discordant twin pairs (n = 30) only differed in mean thickness of V2 (0.039 mm, 95% CI 0.005 to 0.074). In conclusion, females with migraine with aura have a thicker cortex corresponding to visual areas and our results indicate this may be an inherent trait rather than a result of repeated aura attacks.

Lifetime Duration of Depressive Disorders in Patients With Type 2 Diabetes.

OBJECTIVEDepression in patients with type 2 diabetes (T2D) is associated with long-term complications, disability, and early mortality. No studies have systematically examined the length of episodes and remission in adults with major depressive disorder (MDD) and T2D. This study examined the course of depressive disorders in patients with T2D and MDD.RESEARCH DESIGN AND METHODSParticipants (N = 50) enrolled in a behavioral intervention for adults with T2D and MDD were interviewed using the Structured Clinical Interview for DSM-IV-TR to assess history of depressive disorders at baseline (lifetime history), postintervention, and 3-month follow-up. Onset and remission dates were recorded for all Axis I depressive disorders from birth to final interview.RESULTSAverage number of MDD episodes was 1.8 with a mean duration of 23.4 months (SD 31.9; range 0.5–231.3). Over the life course, mean exposure to MDD was 43.1 months (SD 46.5; range 0.5–231.3). Kaplan-Meier survival curve analysis indicated median episode duration decreased with subsequent episodes (14 months, first episode; 9 months, second episode; P < 0.002). In patients with multiple depressive episodes, recovery time was shorter with each subsequent episode (P = 0.002). No differences in length of episode or remission were observed based on chronology of T2D diagnosis.CONCLUSIONSThe overall exposure to depression in this sample of adults with T2D represents a substantial period of time that can contribute to negative medical and psychiatric outcomes. Recurrent episodes decrease in duration as do recovery periods, resulting in a waxing and waning pattern. Findings from this study underscore the need to effectively diagnose and treat depression in patients with T2D to minimize risk of future depressive episodes.

Cognitive reactivity, self-depressed associations, and the recurrence of depression

BackgroundMixed evidence exists regarding the role of cognitive reactivity (CR; cognitive responsivity to a negative mood) as a risk factor for recurrences of depression. One explanation for the mixed evidence may lie in the number of previous depressive episodes. Heightened CR may be especially relevant as a risk factor for the development of multiple depressive episodes and less so for a single depressive episode. In addition, it is theoretically plausible but not yet tested that the relationship between CR and number of episodes is moderated by the strength of automatic depression-related self-associations. AimTo investigate (i) the strength of CR in remitted depressed individuals with a history of a single vs. multiple episodes, and (ii) the potentially moderating role of automatic negative self-associations in the relationship between the number of episodes and CR. MethodCross-sectional analysis of data obtained in a cohort study (Study 1) and during baseline assessments in two clinical trials (Study 2). Study 1 used data from the Netherlands Study of Depression and Anxiety (NESDA) and compared never-depressed participants (n=901) with remitted participants with either a single (n=336) or at least 2 previous episodes (n=273). Study 2 included only remitted participants with at least two previous episodes (n=273). The Leiden Index of Depression Sensitivity Revised (LEIDS-R) was used to index CR and an Implicit Association Test (IAT) to measure implicit self-associations. ResultsIn Study 1, remitted depressed participants with multiple episodes had significantly higher CR than those with a single or no previous episode. The remitted individuals with multiple episodes of Study 2 had even higher CR scores than those of Study 1. Within the group of individuals with multiple episodes, CR was not heightened as a function of the number of episodes, even if individual differences in automatic negative self-associations were taken into account. LimitationsThe study employed a cross-sectional design, which precludes a firm conclusion with regard to the direction of this relationship. ConclusionsThe findings are consistent with the view that high CR puts people at risk for recurrent depression and is less relevant for the development of an incidental depressive episode. This suggests that CR is an important target for interventions that aim to prevent the recurrence of depression.

The prospective association between obesity and major depression in the general population: does single or recurrent episode matter?

BackgroundObesity and major depressive disorder (MDD) are important public health problems. MDD is a heterogeneous disorder and the direction of its association with obesity remains unclear. Evidence grows that recurrent MDD (MDD-R) differs in etiology and prognosis from single episode MDD (MDD-S), which could affect associations with obesity. However, evidence on this differential effect is lacking. The aim of this study was to examine the direction of the association between obesity and MDD, single or recurrent episode.MethodsA longitudinal study was performed in a cohort of 1094 participants of the PREVEND study, on whom data were collected at baseline and at an average 2-year follow-up. MDD-S and MDD-R were assessed by the Composite International Diagnostic Interview (CIDI 2.1). Obesity was defined as Body Mass Index ≥ 30 kg/m2. Binary logistic regression analyses were conducted to examine whether obesity predicts MDD-S/MDD-R or vice versa, adjusted for potential confounders.ResultsProspective analyses showed that BMI at baseline was associated with the onset of MDD-R (Odds ratio, OR = 1.32; 95% confidence interval, 95%CI: 1.11; 1.57) during 2-year follow-up, but not with the onset of MDD-S (OR = 0.98; 95%CI: 0.89; 1.07). Obesity at baseline was not associated with the onset of MDD-S during follow-up (OR = 0.75; 95%CI: 0.25; 2.30), but associated with the onset of MDD-R during follow-up (OR = 11.63; 95%CI: 1.05; 128.60). Neither MDD-S nor MDD-R were associated with the development of obesity during 2-year follow-up (OR = 1.67, 95%CI: 0.64; 4.29 and OR = 2.32, 95%CI: 0.82; 6.58, respectively).ConclusionsOur findings add to the available evidence that obesity might specifically be associated with the onset of multiple episodes of major depression (MDD-R). Although the reverse association was not found, MDD-R tends to be also associated with subsequent development of obesity, but larger studies are needed to fully assess this issue. The heterogeneity of MDD should be considered when examining the effect of obesity on MDD.

The effects of recurrent episodes of depression on startle responses

Prior work suggests that major depression is associated with abnormal startle blink responses; however, only chronic or recurrent depression appears to be associated with this effect. The current study tested this hypothesis directly by examining whether recurrent major depression accounted for the anomalous startle seen in major depression using a sample of 515 female twins from the Minnesota Twin Family Study. Blink responses recorded at the age of 20 were examined in relation to number of episodes of depression prospectively assessed from ages 11 to 20. Results showed that only subjects who had experienced multiple episodes of depression showed abnormal startle responses. Subjects who had experienced just one episode of depression in their lifetime did not differ from controls. This lends additional support to the idea that recurrent depression may have a different etiological basis than nonrecurrent depression.

Recovery From Multiple Episodes of Bipolar I Depression

To describe the duration of bipolar I major and minor depressive episodes and factors associated with time to recovery. As part of the National Institute of Mental Health Collaborative Depression Study, 219 participants with bipolar I disorder based on Research Diagnostic Criteria analogs to DSM-IV-TR criteria were recruited at 5 academic medical centers from 1978 to 1981 and followed for up to 25 years with the Longitudinal Interval Follow-Up Evaluation. The probability of recovery over time from depressive episodes, the primary outcome measure, was examined with mixed-effects grouped-time survival models. The median duration of major depressive episodes was 14 weeks, and over 70% of participants recovered within 12 months of episode onset. The median duration of minor depressive episodes was 8 weeks, and approximately 90% of participants recovered within 6 months of onset of the episode. Aggregated data demonstrated similar durations of the first 3 major depressive episodes. However, for each participant with multiple episodes of major depression or minor depression, the duration of each episode was not consistent (intraclass correlation coefficient = 0.07 and 0.25 for major and minor depression, respectively). The total number of years in episode over follow-up with major plus minor depression prior to onset of a major depressive episode was significantly associated with a decreased probability of recovery from that episode; with each additional year, the likelihood of recovery was reduced by 7% (hazard ratio = 0.93; 95% CI, 0.89-0.98; P = .002). Bipolar I major depression generally lasts longer than minor depression, and the duration of multiple episodes within an individual varies. However, the probability of recovery over time from an episode of major depression appears to decline with each successive episode.

Potential Mechanisms of Action of Lithium in Bipolar Disorder

Lithium has been used for over half a century for the treatment of bipolar disorder as the archetypal mood stabilizer, and has a wealth of empirical evidence supporting its efficacy in this role. Despite this, the specific mechanisms by which lithium exerts its mood-stabilizing effects are not well understood. Given the inherently complex nature of the pathophysiology of bipolar disorder, this paper aims to capture what is known about the actions of lithium ranging from macroscopic changes in mood, cognition and brain structure, to its effects at the microscopic level on neurotransmission and intracellular and molecular pathways. A comprehensive literature search of databases including MEDLINE, EMBASE and PsycINFO was conducted using relevant keywords and the findings from the literature were then reviewed and synthesized. Numerous studies report that lithium is effective in the treatment of acute mania and for the long-term maintenance of mood and prophylaxis; in comparison, evidence for its efficacy in depression is modest. However, lithium possesses unique anti-suicidal properties that set it apart from other agents. With respect to cognition, studies suggest that lithium may reduce cognitive decline in patients; however, these findings require further investigation using both neuropsychological and functional neuroimaging probes. Interestingly, lithium appears to preserve or increase the volume of brain structures involved in emotional regulation such as the prefrontal cortex, hippocampus and amygdala, possibly reflecting its neuroprotective effects. At a neuronal level, lithium reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission; however, these broad effects are underpinned by complex neurotransmitter systems that strive to achieve homeostasis by way of compensatory changes. For example, at an intracellular and molecular level, lithium targets second-messenger systems that further modulate neurotransmission. For instance, the effects of lithium on the adenyl cyclase and phospho-inositide pathways, as well as protein kinase C, may serve to dampen excessive excitatory neurotransmission. In addition to these many putative mechanisms, it has also been proposed that the neuroprotective effects of lithium are key to its therapeutic actions. In this regard, lithium has been shown to reduce the oxidative stress that occurs with multiple episodes of mania and depression. Further, it increases protective proteins such as brain-derived neurotrophic factor and B-cell lymphoma 2, and reduces apoptotic processes through inhibition of glycogen synthase kinase 3 and autophagy. Overall, it is clear that the processes which underpin the therapeutic actions of lithium are sophisticated and most likely inter-related.

Risk factors for onset of multiple or long major depressive episodes versus single and short episodes

Major depressive disorder may vary according to number and duration of episodes. It is unclear whether risk factors for onset of multiple or long episodes of depression (MDE) differ from risk factors for the onset of single and short ones. Data were used from a cohort study of 5,256 GP attendees without major depressive disorder at baseline, who were followed up three times (predictD). The numbers and duration of MDE were noted and categorized into no episodes, single and short (≤3months), and multiple or long (>3months) episodes at follow-up. Log-binomial regression models were used to calculate relative risks between the groups for 18 risk factors examined at baseline. 165 persons (3%) had a single and short MDE and 328 (6%) had multiple or long MDE at follow-up. Lower education, anxiety, problems at work and financial strain significantly increased the risk of multiple or long MDE when compared to single and short MDE. Younger people were at reduced risk of multiple or long MDE. Our findings suggest that several risk factors can be identified that may help to predict onset of different types of MDE. These factors are easy to assess and may be used in the prevention of depression.

Residual memory dysfunction in recurrent major depressive disorder—A longitudinal study from Juntendo University Mood Disorder Project

Depression may increase the risk of developing Alzheimer's disease. Large cohort studies have shown that recurrent depression is associated with a risk of developing dementia. Other studies have documented smaller hippocampal volume in patients with recurrent depression. It is speculative that a greater risk of developing dementia may result from a higher number of previous depressive episodes. This study compared patients with recurrent and single-episode depression in the remitted stage, and healthy controls to elucidate the impact of the number of depressive episodes on memory. Logical memory and visual reproduction subtests of the Wechsler Memory Scale-Revised were given to 68 patients with major depressive disorder (MDD) (30 patients with a single episode and residual 38 patients with recurrent multiple episodes) and 57 healthy controls. The patients with MDD received memory assessment at the time of initial remission and at the follow-up period 3 years after remission. At the time of initial remission, scores of both logical memory and visual reproduction subtests were significantly lower in both patient groups compared with healthy controls. At follow-up, memory dysfunction of the single-episode group disappeared, whereas scores in the recurrent group remained significantly lower than those of the single-episode group and controls. All patients in the present study were on antidepressant medications. Patients with recurrent MDD with multiple depressive episodes showed residual memory dysfunction even after 3 years of remission. Persistence of memory deficits in the recurrent depression may be a risk factor for developing dementia.