This is a selective review that provides the context for the study of perinatal affective disorder mechanisms and outlines directions for future research. We integrate existing literature along neural networks of interest for affective disorders and maternal caregiving: (i) the salience/fear network; (ii) the executive network; (iii) the reward/social attachment network; and (iv) the default mode network. Extant salience/fear network research reveals disparate responses and corticolimbic coupling to various stimuli based upon a predominantly depressive versus anxious (post-traumatic stress disorder) clinical phenotype. Executive network and default mode connectivity abnormalities have been described in postpartum depression (PPD), although studies are very limited in these domains. Reward/social attachment studies confirm a robust ventral striatal response to infant stimuli, including cry and happy infant faces, which is diminished in depressed, insecurely attached and substance-using mothers. The adverse parenting experiences received and the attachment insecurity of current mothers are factors that are associated with a diminution in infant stimulus-related neural activity similar to that in PPD, and raise the need for additional studies that integrate mood and attachment concepts in larger study samples. Several studies examining functional connectivity in resting state and emotional activation functional magnetic resonance imaging paradigms have revealed attenuated corticolimbic connectivity, which remains an important outcome that requires dissection with increasing precision to better define neural treatment targets. Methodological progress is expected in the coming years in terms of refining clinical phenotypes of interest and experimental paradigms, as well as enlarging samples to facilitate the examination of multiple constructs. Functional imaging promises to determine neural mechanisms underlying maternal psychopathology and impaired caregiving, such that earlier and more precise detection of abnormalities will be possible. Ultimately, the discovery of such mechanisms will promote the refinement of treatment approaches toward maternal affective disturbance, parenting behaviours and the augmentation of parenting resiliency.

Background There is well-known heterogeneity in affective mechanisms in depression that may extend to positive affect. We used data-driven parsing of neural connectivity to reveal subgroups present across depressed and healthy individuals during positive processing, informing targets for mechanistic intervention. Methods 92 individuals (68 depressed patients, 24 never-depressed controls) completed a sustained positive mood induction during fMRI. Directed functional connectivity paths within a depression-relevant network were characterized using Group Iterative Multiple Model Estimation, a method shown to accurately recover the direction and presence of connectivity paths in individual participants. During model-selection, individuals were clustered using community detection on neural connectivity estimates. Subgroups were externally tested across multiple levels of analysis. Results Two connectivity-based subgroups emerged: Subgroup A, characterized by weaker connectivity overall, and Subgroup B, exhibiting hyperconnectivity (relative to Subgroup A), particularly among ventral affective regions. Subgroup predicted diagnostic status (Subgroup B contained 81% of patients;50% of controls;χ2=8.6,p=.003) and default mode network connectivity during a separate resting state task. Among patients, Subgroup B members had higher self-reported symptoms, lower sustained positive mood during the induction, and higher negative bias on a reaction time task. Symptom-based depression subgroups did not predict these external variables. Conclusions Neural connectivity-based categorization travels with diagnostic category and is clinically predictive, but not clinically deterministic. Both patients and controls showed heterogeneous, and overlapping, profiles. The larger, and more severely affected patient subgroup was characterized by ventrally-driven hyperconnectivity during positive processing. Data-driven parsing suggests heterogeneous substrates of depression, and possible resilience in controls in spite of biological overlap.

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Background This study was conducted to test whether non-normative socialization mediates the association between transmissible risk measured in childhood and cannabis use disorder manifested by young adulthood, and whether the sequence of drug use initiation (“gateway”, i.e., consuming legal drugs before cannabis, or the reverse) increases accuracy of prediction of cannabis use disorder. Methods Sons of fathers with or without substance use disorders (SUD) related to illicit drugs were tracked from 10–12 to 22 years of age to model the association between transmissible risk for SUD, socialization (peer deviance), order of drug use initiation (“gateway” or reverse sequence), and development of cannabis use disorder. Path analysis was used to evaluate relationships among the variables. Results Non-normative socialization mediates the association between transmissible risk measured during childhood and cannabis use disorder manifest by young adulthood. The sequence of drug use initiation did not contribute additional explanatory information to the model. Conclusions The order of drug use initiation does not play a substantial role in the etiology of cannabis use disorder.

Background Research has shown involvement of hormones of the hypothalamic pituitary adrenal (HPA) axis and hypothalamic pituitary gonadal (HPG) axis in the regulation of behaviors that also contribute to SUD risk and its intergenerational transmission. Neighborhood environment has also been shown to relate to hormones of these two neuroendocrine systems and behaviors associated with SUD liability. Accordingly, it was hypothesized that 1) parental SUD severity and neighborhood quality correlate with activity of the HPG axis (testosterone level) and HPA axis (cortisol stability), and 2) transmissible risk during childhood mediates these hormone variables on development of SUD measured in adulthood. Method Transmissible risk for SUD measured by the Transmissible Liability Index (TLI; Vanyukov et al., 2009) along with saliva cortisol and plasma testosterone were prospectively measured in boys at ages 10-12 and 16. Neighborhood quality was measured using a composite score encompassing indicators of residential instability and economic disadvantage. SUD was assessed at age 22. Results Neither hormone variable cross-sectionally correlated with transmissible risk measured at ages 10-12 and 16. However, the TLI at age 10-12 predicted testosterone level and cortisol stability at age 16. Moreover, testosterone level, correlated with cortisol stability at age 16, predicted SUD at age 22. Conclusion HPA and HPG axes activity do not underlie variation in TLI, however, high transmissible risk in childhood predicts neuroendocrine system activity presaging development of SUD.

Mentors found the intensive, brief group mentorship model to be a powerful, time-efficient, and enjoyable approach to mentoring, increasing trainees' exposure to child and adolescent psychiatry. Although group composition, schedule coordination, and logistics warrant closer scrutiny, these positive perceptions bode well for mentor recruitment and retention and for using a similar program in other settings.

A large proportion of the adult population consumes substances that have abuse potential, spanning alcohol, tobacco, illegal drugs, over-the-counter medications, and prescribed psychotropic drugs. These substances have the potential to cause addiction and disease. By age 28, almost 90% of the U.S. population have ingested some kind of beverage alcohol, and 80% have experienced at least one episode of intoxication ( Johnston, O ' Malley, Bachman, & Schulenberg, 2009 ). Signifi cantly, almost 60% have used an illegal drug, illustrating that the motivation for consumption frequently surmounts prohibition against illegal behavior. Approximately 10.3% of the population that uses drugs (13.8% of men, 7.1% of women) qualify for a diagnosis of substance use disorder (SUD) at some time during their lifetime ( Compton, Thomas, Stinson, & Grant, 2007 ). The cost exacted from society by substance use and SUD is enormous consequent to treatment and frequently associated chronic medical disorders (e.g., HIV, cirrhosis, chronic obstructive pulmonary disease), acute infectious diseases (e.g., sexually transmitted diseases), physical and neurological disability caused by traumatic injury (e.g., car and industrial accidents), crime, unemployment, poverty, homelessness, and psychiatric illness. Preventing SUD and these diverse associated outcomes is accordingly a high priority. Effective prevention of SUD, however, is contingent on comprehensively understanding etiology.The peak prevalence of past-year alcohol and cannabis use disorders is before age 21 ( Substance Abuse and Mental Health Services Administration, 2004 ), that is, within 5 years of completing pubertal maturation, cognitive development, and physical growth. Brain maturation, still ongoing, is not completed until approximately age 26 ( National Research Council and Institute of Medicine, 2009 ). Accordingly, a developmental framework is essential for elucidating the etiology of SUD and for designing effective prevention strategies.As we discuss in this chapter, suboptimal acquisition of psychological self-regulation during ontogeny, resulting largely from frontal cortex dysfunction, is the cardinal characteristic predisposing children and adolescents to SUD by early adulthood. Sometimes referred to as Type 2 ( Cloninger, Bohman, & Sigvardson, 1981 ), this variant of SUD develops within a context of defi cient or deviant socialization ( Tarter, 1982 ). In many individuals, however, SUD manifests later in adulthood subsequent to normative socialization. In this situation, individuals engage in substance use in an attempt to relieve psychological dysregulation caused by exogenous or endogenous stressors. This variant of SUD, sometimes referred to as Type 1 ( Cloninger et al., 1981 ), has less genetic loading and greater environmental infl uence on etiology than the Type 2 variant and tends to be less severe. These two variants of SUD have also been labeled essential and reactive to denote the relative salience of developmental processes and acute life stressors in SUD...

Background Psychological items discriminating children of fathers diagnosed with an illicit drug-related substance use disorder and normal controls are indicators of a unidimensional construct termed transmissible liability index (TLI) (Vanyukov et al., 2009). TLI is a highly heritable (Vanyukov et al., 2009; Hicks, Iacono, McGue, 2012) and valid (Vanyukov et al., 2009; Hicks et al., 2012; Kirisci et al., 2013a) measure of childhood liability to substance use disorders (SUD). Aims This longitudinal study determined whether TLI has incremental validity for predicting SUD beyond commonly measured psychological indicators of risk. Methods TLI and measures of executive cognitive capacity, emotion dysregulation and externalizing disturbance were administered to boys at ages 10–12 and 16. SUD outcome determined at age 22 was assessed as (1) any SUD, (2) the number of drug-specific SUDs, and (3) SUD severity. Results TLI predicted SUD beyond the contribution of measures of emotion dysregulation, executive cognitive capacity and externalizing disturbance. The association of emotion dysregulation and externalizing behavior at age 10–12 and 16 with SUD at age 22 was also reduced to non-significance after controlling for transmissible risk measured by TLI. Conclusions TLI’s incremental validity beyond these latter indicators of risk points to its utility for identifying vulnerable youths requiring intervention.