Andrew G. M. Bulloch

Transplantation and functional integration of an identified respiratory interneuron in lymnaea stagnalis

The possibility that damaged neural circuitries can be repaired through grafting has raised questions regarding the cellular mechanisms required for functional integration of transplanted neurons. Invertebrate models offer the potential to examine such mechanisms at the resolution of single identified neurons within well-characterized neural networks. Here it is reported that a specific deficit in the respiratory behavior of a pulmonate mollusc, caused by the ablation of a solitary interneuron, can be restored by grafting an identical donor interneuron. The transplanted interneuron not only survives and extends neurites within the host nervous system, but under specific conditions forms synapses with appropriate target neurons and is physiologically integrated into the hosts circuitry, thereby restoring normal behavior.

Somatostatin enhances neurite outgrowth and electrical coupling of regenerating neurons inHelisoma

The present study tested the ability of 3 peptides (somatostatin, arginine-vasopressin (AVP) and arginine-vasotocin (AVT)) to enhance neurite outgrowth from regenerating Helisoma neurons. The buccal ganglia from Helisoma were incubated either short-term in saline or longer-term (2-5 days) in medium and the extent of neurite outgrowth (induced by nerve crush) by a buccal neuron (neuron 5) was determined. Neurite outgrowth was consistently enhanced by both somatostatin and its extended analog somatostatin, but was unaffected by either AVT or AVP. The enhanced outgrowth due to somatostatin was associated with stronger electrical synapse formation between the two neurons 5, this being attributable to lower coupling resistance rather than a change in non-junctional resistance. Both the enhancement of neurite outgrowth and the increased efficacy of electrical coupling due to somatostatin were prevented by a somatostatin inhibitor. An immunohistochemical survey produced evidence for neurons containing a somatostatin-like peptide in both the cerebral ganglia and the enteric nervous system of Helisoma. It is concluded that somatostatin can act neurotrophically in the nervous system.

Depression in epilepsy: A systematic review and meta-analysis

Objective: To estimate the prevalence of depression in persons with epilepsy (PWE) and the strength of association between these 2 conditions. Methods: The MEDLINE (1948–2012), EMBASE (1980–2012), and PsycINFO (1806–2012) databases, reference lists of retrieved articles, and conference abstracts were searched. Content experts were also consulted. Two independent reviewers screened abstracts and extracted data. For inclusion, studies were population-based, original research, and reported on epilepsy and depression. Estimates of depression prevalence among PWE and of the association between epilepsy and depression (estimated with reported odds ratios [ORs]) are provided. Results: Of 7,106 abstracts screened, 23 articles reported on 14 unique data sources. Nine studies reported on 29,891 PWE who had an overall prevalence of active (current or past-year) depression of 23.1% (95% confidence interval [CI] 20.6%–28.31%). Five of the 14 studies reported on 1,217,024 participants with an overall OR of active depression of 2.77 (95% CI 2.09–3.67) in PWE. For lifetime depression, 4 studies reported on 5,454 PWE, with an overall prevalence of 13.0% (95% CI 5.1–33.1), and 3 studies reported on 4,195 participants with an overall OR of 2.20 (95% CI 1.07–4.51) for PWE. Conclusions: Epilepsy was significantly associated with depression and depression was observed to be highly prevalent in PWE. These findings highlight the importance of proper identification and management of depression in PWE.

Nitric oxide synthase-immunoreactive cells in the CNS and periphery of Lymnaea

The presence and distribution of nitric oxide synthase (NOS) in the CNS and peripheral organs (buccal muscles, oesophagus, salivary glands, foot, mantle and pneumostome) of the pulmonate mollusc, Lymnaea stagnalis were studied using an antiserum developed against rat cerebellar NOS. NOS-immunopositive neurones in Lymnaea were localized predominantly in the buccal ganglia as well as in distinct areas of the cerebral and suboesophageal ganglia. NOS-immunoreactive terminals were also found on the somata of some central neurones. In the periphery, NOS-immunostaining was detected only in a few neurones in the pneumostome area and in the osphradial ganglion. In addition, approximately 100 NOS-immunopositive cells have been found in the salivary glands. Our data supports other recent reports indicating that NO may be a signal molecule in the CNS of molluscs.

Early evolutionary origin of the neurotrophin receptor family

Neurotrophins and their Trk receptors play a crucial role in the development and maintenance of the vertebrate nervous system, but to date no component of this signalling system has been found in invertebrates. We describe a molluscan Trk receptor, designated Ltrk, from the snail Lymnaea stagnalis. The full‐length sequence of Ltrk reveals most of the characteristics typical of Trk receptors, including highly conserved transmembrane and intracellular tyrosine kinase domains, and a typical extracellular domain of leucine‐rich motifs flanked by cysteine clusters. In addition, Ltrk has a unique N‐terminal extension and lacks immunoglobulin‐like domains. Ltrk is expressed during development in a stage‐specific manner, and also in the adult, where its expression is confined to the central nervous system and its associated endocrine tissues. Ltrk has the highest sequence identity with the TrkC mammalian receptor and, when exogenously expressed in fibroblasts or COS cells, binds human NT‐3, but not NGF or BDNF, with an affinity of 2.5 nM. These findings support an early evolutionary origin of the Trk family as neuronal receptor tyrosine kinases and suggest that Trk signalling mechanisms may be highly conserved between vertebrates and invertebrates.

CRNF, a Molluscan Neurotrophic Factor That Interacts with the p75 Neurotrophin Receptor

A 13.1-kilodalton protein, cysteine-rich neurotrophic factor (CRNF), was purified from the mollusk Lymnaea stagnalis by use of a binding assay on the p75 neurotrophin receptor. CRNF bound to p75 with nanomolar affinity but was not similar in sequence to neurotrophins or any other known gene product. CRNF messenger RNA expression was highest in adult foot subepithelial cells; in the central nervous system, expression was regulated by lesion. The factor evoked neurite outgrowth and modulated calcium currents in pedal motor neurons. Thus, CRNF may be involved in target-derived trophic support for motor neurons and could represent the prototype of another family of p75 ligands.

Descriptive Epidemiology of Major Depressive Disorder in Canada in 2012

Objective: The epidemiology of major depressive disorder (MDD) was first described in the Canadian national population in 2002. Updated information is now available from a 2012 survey: the Canadian Community Health Study—Mental Health (CCHS-MH). Method: The CCHS-MH employed an adaptation of the World Health Organization World Mental Health Composite International Diagnostic Interview and had a sample of n = 25 113. Demographic variables, treatment, comorbidities, suicidal ideation, and perceived stigma were assessed. The analysis estimated adjusted and unadjusted frequencies and prevalence ratios. All estimates incorporated analysis methods to account for complex survey design effects. Results: The past-year prevalence of MDD was 3.9% (95% CI 3.5% to 4.2%). Prevalence was higher in women and in younger age groups. Among respondents with past-year MDD, 63.1% had sought treatment and 33.1% were taking an antidepressant (AD); 4.8% had past-year alcohol abuse and 4.5% had alcohol dependence. Among respondents with past-year MDD, the prevalence of cannabis abuse was 2.5% and that of dependence was 2.9%. For drugs other than cannabis, the prevalence of abuse was 2.3% and dependence was 2.9%. Generalized anxiety disorder was present in 24.9%. Suicide attempts were reported by 6.6% of respondents with past-year MDD. Among respondents accessing treatment, 37.5% perceived that others held negative opinions about them or treated them unfairly because of their disorder. Conclusions: MDD is a common, burdensome, and stigmatized condition in Canada. Seeking help from professionals was reported at a higher frequency than in prior Canadian studies, but there has been no increase in AD use among Canadians with MDD.

ALCOHOL CONSUMPTION AND MAJOR DEPRESSION IN THE GENERAL POPULATION: THE CRITICAL IMPORTANCE OF DEPENDENCE

Substance use disorders and major depressive episodes (MDEs) often co‐occur. Alcohol consumption may contribute to the aetiology of depressive episodes and/or vice versa. In Canada, the National Population Health Survey (NPHS) evaluated several aspects of alcohol use and MDE in a large population cohort over 12 years of follow‐up. We evaluated the incidence of MDE in relation to different patterns of alcohol use, and examined the incidence of alcohol misuse in respondents with and without MDE.

Cigarette smoking, stages of change, and major depression in the Canadian population.

Objective: To describe the 12-month prevalence of major depression in relation to smoking status, nicotine dependence levels, commitment to quit, attempts to quit, and maintenance of smoking cessation in the Canadian general population. Method: Data from Public Use Microdata File of the Canadian Community Health Survey: Health and Well-Being were used. The Composite International Diagnostic Interview—Short Form (CIDI-SF) for major depression was used to assess depressive disorder status. The survey also included a smoking module. There were 49 249 respondents assessed by the CIDI-SF, of whom 10 236 were administered the smoking module. Analyses used appropriate measures to deal with survey design effects. Result: The prevalence of major depression was highest in current smokers, followed by ever smokers, former smokers, and was lowest in the never smokers. This pattern persisted after stratification for age and sex. For quitting, the prevalence of major depression was highest among people who tried to quit, followed by those who considered quitting, those who quit in the past year, and lowest among those who maintained their smoking cessation status for longer than 1 year. The prevalence of depression among those with a high nicotine dependence level, as assessed by the Fagerstrom Tolerance Questionnaire, was about twice that of people with a low nicotine dependence level. Conclusion: The strikingly high prevalence of major depression among current smokers who are young, trying to quit, and with high nicotine dependence levels in the general population indicates that further longitudinal exploration of this topic is urgently needed.

Predictors of the Longitudinal Course of Major Depression in a Canadian Population Sample

Objective: Most psychiatric epidemiologic studies have used cross-sectional methods, resulting in a lack of information about the longitudinal course of depressive disorders. The objective of our study was to describe the longitudinal epidemiology of major depressive episodes (MDEs) in a Canadian sample using data from the National Population Health Survey (NPHS). Methods: The NPHS started data collection in 1994 and has evaluated past-year MDE using repeat interviews of the same cohort every 2 years since then. In our study, we examined the number of weeks depressed during years when MDEs occurred, the proportion of respondents having MDEs at consecutive cycles, and MDE counts during follow-up. Results: A sizable proportion of MDEs were brief: about one-half of respondents with past-year MDE reported 8 or fewer weeks of depression during that year. Less than 10% reported that they were depressed for the entire year. However, a larger proportion (19.1%) fulfilled criteria for MDE on consecutive interview cycles, suggesting either persistence or rapid recurrence. The mean number of detected MDEs among those with at least 1 detected MDE up to 2006 was 2. Positive family history, evidence of comorbidity, negative cognitive style, stress, pain, and smoking were associated with a more negative course. Conclusions: The longitudinal course of MDE in the general population is heterogeneous, including a mixture of brief and more protracted MDEs. Many risk factors for MDE are also associated with a negative course, exceptions being (younger) age and sex. These epidemiologic observations may assist with identification of patients requiring more intensive management in clinical practice.