SUMMARYA decline in mitochondrial respiration represents the root cause of a large number of inborn errors of metabolism. It is also associated with common age-associated diseases and the aging process. To gain insight into the systemic, biochemical consequences of respiratory chain dysfunction, we performed a case-control, prospective metabolic profiling study in a genetically homogenous cohort of patients with Leigh syndrome French Canadian variant, a mitochondrial respiratory chain disease due to loss-of-function mutations in LRPPRC. We discovered 45 plasma and urinary analytes discriminating patients from controls, including classic markers of mitochondrial metabolic dysfunction (lactate and acylcarnitines), as well as unexpected markers of cardiometabolic risk (insulin and adiponectin), amino acid catabolism linked to NADH status (α-hydroxybutyrate), and NAD+ biosynthesis (kynurenine and 3-hydroxyanthranilic acid). Our study identifies systemic, metabolic pathway derangements that can lie downstream of primary mitochondrial lesions, with implications for understanding how the organelle contributes to rare and common diseases.

Objective: To weight the potential of promotion, prevention, and treatment programs to help establish priorities in multipronged suicide prevention strategies. Methods:Psychological autopsy methods served to collect information on consecutive suicides over 14 months in New Brunswick (n = 102). A panel of researchers, clinicians, provincial planners, and consumers reviewed the cases and applied a systematic needs assessment procedure to establish interventions and services received, unmet needs at the individual level, and programmatic and systemic shortcomings.Results: More than two-thirds of the individuals suffered from a depressive disorder and a similar proportion from substance (essentially alcohol) abuse or dependence; one-half also presented a personality disorder. In the last year, more than one-half had been in contact with a mental health services specialist, but less than 5% had contact with addiction services, though one-third had previous contact in their lifetime. In one-third of the cases, service gaps called for greater coordination and integration of mental health specialists and addiction services within the health care system. In one-half of the cases, system needs were found to be unmet for public awareness efforts aimed at encouraging individuals to consult health and social services professionals, and in terms of training efforts geared to improving detection, treatment, and referral for mental illness, substance-related problems, and suicidal behaviour by primary medical, social, and specialist services. Conclusion:This study supports multipronged suicide prevention strategies that should include integrated public promotion, professional development campaigns, and better program coordination. Authorities in New Brunswick have opted to favour the latter strategy component, whose development and application must be evaluated to determine its impact on suicide rates. Can J Psychiatry 2008;53(10):671-678Clinical Implications · Psychiatric services should actively collaborate with addiction services in the case management of difficult comorbid cases. · Assertive approach protocols should be in place for the case management of difficult-to-engage comorbid cases with suicidal behaviour seen at hospital emergency services. · Primary medical, social, school, and police services should receive more support by specialist psychiatric and addiction services in detecting, treating, and referring individuals with mental and substance-related disorders. Limitations· The new components of the comprehensive needs assessment method were not tested for reliability by another set of raters. · In the end, systematic needs assessments remain hypotheses to be tested. · No control group was used.

The life calendar approach presented here in suicide research adds to the identification of life events, distal and recent, previously associated with suicide. It also quantifies the burden of adversity over the life course, defining two distinct profiles that could benefit from distinct targeted preventive intervention.