The authors tested whether deficits in perceived social support predicted subsequent increases in depression and whether depression predicted subsequent decreases in social support with longitudinal data from adolescent girls (N = 496). Deficits in parental support but not peer support predicted future increases in depressive symptoms and onset of major depression. In contrast, initial depressive symptoms and major depression predicted future decreases in peer support but not parental support. Results are consistent with the theory that support decreases the risk for depression but suggest that this effect may be specific to parental support during early adolescence. Results are also consonant with the claim that depression promotes support erosion but imply that this effect may only occur with peer support during this period.

Cycle frequency, length, and vaginal cytology were measured longitudinally in three cohorts of singly housed virgin mice staggered across a 3-year interval. The age profiles of these parameters were qualitatively similar, but quantitatively different, among cohorts. Cycle frequency was initially low (Phase I), due to prolonged cycles and late-starting cycles, and did not peak (Phase II) until mice were 3-5 months old. Phase II lasted for 7-10 months, depending on the cohort. Thereafter cycle frequency declined steadily (Phase III). The average age of cessation of cyclicity varied among cohorts, occurring between 13 and 16 months of age. Age changes in cycle length paralleled those of cycle frequency. During Phase II, median cycle length was less than 5 days and variance was lowest. During Phases I and III, variance was about twofold greater and median cycle length was greater than 5 days. Although median cycle length remained stable for several months during Phase II, the peak period of 4-day cycles was much shorter. In all cohorts, 4-day cycles did not peak until 7-8 months of age and began to decline by 9 months. The decrease in 4-day cycles was associated with a progressive lengthening of cycles-first from 4 to 5 days, then to longer cycles. The fraction of cycles with extended cornification (greater than 2 days) increased with advancing age from less than 0.35 during the initial period of cycle lengthening to a maximum of 0.60. The observation that the initial phase o cycle prolongation was not usually associated with extended cornification is consistent with earlier evidence that this period is characterized by a delayed, rather than prolonged, preovulatory rise of estradiol. However, the increased fraction of prolonged cycles with extended cornification at later ages suggests that the preovulatory elevation of estradiol may ultimately be prolonged.

Alcohol dependence is characterized by tolerance, physical dependence, and craving. The neuroadaptations underlying these effects of chronic alcohol abuse are likely due to altered gene expression. Previous gene expression studies using human post-mortem brain demonstrated that several gene families were altered by alcohol abuse. However, most of these changes in gene expression were small. It is not clear if gene expression profiles have sufficient power to discriminate control from alcoholic individuals and how consistent gene expression changes are when a relatively large sample size is examined. In the present study, microarray analysis (B47 000 elements) was performed on the superior frontal cortex of 27 individual human cases (14 well characterized alcoholics and 13 matched controls). A partial least squares statistical procedure was applied to identify genes with altered expression levels in alcoholics. We found that genes involved in myelination, ubiquitination, apoptosis, cell adhesion, neurogenesis, and neural disease showed altered expression levels. Importantly, genes involved in neurodegenerative diseases such as Alzheimer's disease were significantly altered suggesting a link between alcoholism and other neurodegenerative conditions. A total of 27 genes identified in this study were previously shown to be changed by alcohol abuse in previous studies of human post-mortem brain. These results revealed a consistent re-programming of gene expression in alcohol abusers that reliably discriminates alcoholic from non-alcoholic individuals.

Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (post-natal day 28–42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive-ratio responding for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of a subgroup of regions (hippocampus, thalamus, dorsal striatum, neocortex and hypothalamus) were significantly different in AIE exposed adults compared to litter-matched control rats. Taken together, these findings demonstrate that binge-like exposure to alcohol during early to middle adolescence results in deficits in PFC-mediated behavioral control in adulthood.