The Canadian Journal of Psychiatry

Major depressive disorder is the most common psychiatric disorder, worldwide, yet response and remission rates are still unsatisfactory. The identification of genetic predictors of antidepressant (AD) response could provide a promising opportunity to improve current AD efficacy through the personalization of treatment. The major steps and findings along this path are reviewed together with their clinical implications and limitations.

We systematically reviewed the literature through MEDLINE and Embase database searches, using any word combination of “antidepressant,” “gene,” “polymorphism,” “pharmacogenetics,” “genome-wide association study,” “GWAS,” “response,” and “adverse drug reactions.” Experimental works and reviews published until March 2012 were collected and compared.

Numerous genes pertaining to several functional systems were associated with AD response. The more robust findings were found for the following genes: solute carrier family 6 (neurotransmitter transporter), member 4; serotonin receptor 1A and 2A; brain-derived neurotrophic factor; and catechol-O-methyltransferase. Genome-wide association studies (GWASs) provided many top markers, even if none of them reached genome-wide significance.

AD pharmacogenetics have not produced any knowledge applicable to routine clinical practice yet, as results were mainly inconsistent across studies. Despite this, the rising awareness about methodological deficits of past studies could allow for the identication of more suitable strategies, such as the integration of the GWAS approach with the candidate gene approach, and innovative methodologies, such as pathway analysis and study of depressive endophenotypes.

During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors.

We reviewed studies on pharmacogenetics of AP response and adverse effects published on PubMed until early 2012. Owing to the high number of published studies, we focused our review on findings that have been replicated in independent studies or are supported by meta-analyses.

Most robust findings were reported for associations between polymorphisms of the cytochrome P450 system, the dopamine and the serotonin transmitter systems, and dosage, treatment response, and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These associations were either detected for specific medications or for classes of APs.

First promising and robust results show that pharmacogenetics bear promise for a widespread use in future clinical practice. This will likely be achieved by developing algorithms that will include many genetic variants. However, further investigation is warranted to replicate and validate previous findings, as well as to identify new genetic variants involved in AP response and for replication of existing findings.

Research is needed to clarify and improve our understanding of appropriateness and safety issues concerning antidepressant (AD) treatment. We explored the long-term trend in the dispensing of pediatric ADs using provincial, population-based data from Canada.

Data covering 22 ADs were drawn from the Saskatchewan Ministry of Health administrative data files in outpatient settings. The data were for 9 triennial years from 1983 to 2007, a 24-year period, for those aged 0 to 19 in the general population. Descriptive analyses were used.

In 1983, 5.9 per 1000 population aged 0 to 19 were dispensed at least 1 AD; this decreased to 5.1 per 1000 population in 1989, and then increased to 15.4 per 1000 population in 2007, with a slower increase after 2004. Both sexes were dispensed more ADs from 1989 onwards, with females being the heavier users. The rate of AD use increased significantly with age, and this trend became more pronounced after 1998. Family physicians were the major prescribers and their prescriptions significantly increased from 1989 to 2004 and decreased in 2007. The use of selective serotonin reuptake inhibitors (SSRIs) was the major reason for the increase. The number of AD scripts per patient also increased.

The growth in the prevalence of AD use among children and youth was largely caused by the use of SSRIs. The possibility of safety issues induced by AD use among children and adolescents, and different patterns of medication practice, suggest continuing education is warranted.

Adolescent mothers are at increased risk of mistreating their children. Intervening before they become pregnant would be an ideal primary prevention strategy. Our goal was to determine whether psychopathology, exposure to maltreatment, preparedness for child-bearing, substance use disorders (SUDs), IQ, race, and socioeconomic status were associated with the potential for child abuse in nonpregnant adolescent girls.

The Child Abuse Potential Inventory (CAPI) was administered to 195 nonpregnant girls (aged 15 to 16 years; 54% African American) recruited from the community. Psychiatric diagnoses from a structured interview were used to form 4 groups: conduct disorder (CD), internalizing disorders (INTs; that is, depressive disorder, anxiety disorder, or both), CD + INTs, or no disorder. Exposure to maltreatment was assessed with the Childhood Trauma Questionnaire, and the Childbearing Attitudes Questionnaire measured maternal readiness.

CAPI scores were positively correlated with all types of psychopathology, previous exposure to maltreatment, and negative attitudes toward child-bearing. IQ, SUDs, and demographic factors were not associated. Factors associated with child abuse potential interacted in complex ways, but the abuse potential of CD girls was high, regardless of other potentially protective factors.

Our study demonstrates that adolescent girls who have CD or INT are at higher risk of perpetrating physical child abuse when they have children. However, the core features of CD may put this group at a particularly high risk, even in the context of possible protective factors. Treatment providers should consider pre-pregnant counselling about healthy mothering behaviours to girls with CD.

Although there is some evidence that methamphetamine (MA) abuse may play a causative role in the development of schizophrenia, studies directly linking these 2 are rare.

In our study, the effect of MA abuse on the development of schizophrenia was investigated in 15 MA abusers who are offspring of patients with schizophrenia and 15 siblings of MA abusers without a history of drug abuse. Cognitive deficits and resting-state brain function were evaluated in all participants. Correlations between cognitive deficits and schizophrenia development were investigated.

Significantly more cognitive impairments were observed in MA abusers, compared with their siblings without a history of drug use. Significant abnormalities in regional homogeneity (ReHo) signals were observed in resting brain in MA abusers. Decreased ReHo was found to be distributed over the bilateral cingulate gyrus, right Brodmann area 24, and bilateral anterior cingulate cortex. Seven MA abusers were diagnosed with schizophrenia, while 1 control sibling was diagnosed with schizophrenia during the 5-year follow-up. The cognitive scores correlated with the development of schizophrenia in MA abusers.

Our study provides direct evidence for the causative role of MA use in the etiology of schizophrenia and highlights the role of MA-induced brain abnormalities in cognitive deficiency and development of schizophrenia.