Claudia B. Padula

Impact of Adolescent Alcohol and Drug Use on Neuropsychological Functioning in Young Adulthood: 10-Year Outcomes

Because of ongoing neuromaturation, youth with chronic alcohol/substance use disorders (AUD/SUD) are at risk for cognitive decrements during young adulthood. We prospectively examined cognition over 10 years based on AUD/SUD history. Youth (N = 51) with no AUD/SUD history (n = 14), persisting AUD/SUD (n = 18), or remitted AUD/SUD (n = 19) were followed over 10 years with neuropsychological assessments. Groups were compared at baseline and 10-year follow-up. Both AUD/SUD groups declined in visuospatial construction at year 10 (p = .001). Further, cumulative alcohol use (p < .01) and drug withdrawal (p < .05) predicted year-10 visuospatial function. Alcohol use predicted verbal learning/memory (p < .05), while stimulant use predicted visual learning/memory (p = .01). More recent substance use predicted poorer executive function (p < .05). In conclusion, heavy alcohol and other substance use from adolescence through young adulthood may produce cognitive disadvantages, including visuospatial and memory decline. Youth with heavy, chronic alcohol use and/or drug withdrawal symptoms may be at particular risk.

Gender effects on amygdala morphometry in adolescent marijuana users

Adolescent developments in limbic structures and the endogenous cannabinoid system suggest that teenagers may be more vulnerable to the negative consequences of marijuana use. This study examined the relationships between amygdala volume and internalizing symptoms in teenaged chronic marijuana users. Participants were 35 marijuana users and 47 controls ages 16-19 years. Exclusions included psychiatric (e.g., mood and anxiety) or neurologic disorders. Substance use, internalizing (anxiety/depression) symptoms and brain scans were collected after 28 days of monitored abstinence. Reliable raters manually traced amygdala and intracranial volumes on high-resolution magnetic resonance images. Female marijuana users had larger right amygdala volumes and more internalizing symptoms than female controls, after covarying head size, alcohol, nicotine and other substance use (p<0.05), while male users had similar volumes as male controls. For female controls and males, worse mood/anxiety was linked to smaller right amygdala volume (p<0.05), whereas more internalizing problems was associated with bigger right amygdala in female marijuana users. Gender interactions may reflect marijuana-related interruptions to sex-specific neuromaturational processes and staging. Subtle amygdala development abnormalities may underlie particular vulnerabilities to sub-diagnostic depression and anxiety in teenage female marijuana users.

Acute Ethanol Effects on Brain Activation in Low- and High-Level Responders to Alcohol

BACKGROUND A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk of alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. METHODS A total of 30 matched high- and low-LR pairs (N = 60 healthy young adults) were recruited from the University of California, San Diego, and administered a structured diagnostic interview and laboratory alcohol challenge followed by two functional magnetic resonance imaging (fMRI) sessions under placebo and alcohol conditions, in randomized order. Task performance and blood oxygen level-dependent response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task were examined across 120 fMRI sessions. RESULTS Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p < 0.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. CONCLUSIONS Alcohol had differential effects on brain activation for low- and high-LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR and identify brain regions that may be associated with the low LR response.

Serotonin transporter gene moderates associations between mood, memory and hippocampal volume

BACKGROUND The short (S) allele of the serotonin transporter gene (5-HTTLPR) is associated with reduced serotonin turnover compared to the long (L) allele in Caucasians. Few studies have examined its impact on memory and brain structure in healthy young adults. METHODS Participants included 51 healthy young adults (25 female; ages 18-25). Multiple regressions examined the independent contribution of 5-HTTLPR biomarker genotype and its interactions with gender and sub-clinical depressive symptoms on hippocampal volumes and memory. RESULTS The 5-HTTLPR genotype significantly interacted with gender in predicting larger left hippocampal volumes in S-carrying females and smaller hippocampal volumes in males (p<.03). Gender also moderated the impact of the 5-HTTLPR on neurocognition. In females, S allele carriers had poorer visual recall compared to L carriers (p<.05). A three-way interaction between 5-HTTLPR, gender, and depressive symptoms was also observed (p<.04). In females, larger left hippocampal volumes were associated with increased depressive symptoms while the opposite was seen in males. Finally, in male and female S carriers, increased depressive symptoms were marginally associated with poorer verbal memory (p<.09). CONCLUSIONS In females, the 5-HTTLPR S allele was associated with poorer memory performance, increased depressive symptoms and larger hippocampal volumes. In males, the S allele predicted smaller hippocampal volumes and increased depressive symptoms. The opposite morphometric patterns likely reflect gender differences in adolescent hippocampal development. Larger longitudinal studies are needed to examine whether the impact of 5-HTTLPR genotype on neurocognition across development differs according to extent of mood symptoms and gender.

Alcohol attenuates activation in the bilateral anterior insula during an emotional processing task: a pilot study.

AIMS Alcohol acutely reduces agitation and is widely used in social situations, but the neural substrates of emotion processing during its intoxication are not well understood. We examine whether alcohols social stress dampening effect may be via reduced activity in the cortical systems that subserve awareness of bodily sensations, and are associated with affective distress. METHODS Blood oxygen level-dependent activation was measured through 24 functional magnetic resonance imaging sessions in 12 healthy volunteers during an emotional face-processing task following ingestion of a moderate dose of alcohol and a placebo beverage. RESULTS Results revealed that bilateral anterior insula response to emotional faces was significantly attenuated following consumption of alcohol, when compared with placebo (clusters >1472 μl; corrected P < 0.05). CONCLUSION Attenuated response in the anterior insula after alcohol intake may explain some of the decreased interoceptive awareness described during intoxication.

Sleep architecture in adolescent marijuana and alcohol users during acute and extended abstinence.

This study examined sleep changes following cessation of marijuana and alcohol use during late adolescence. Twenty-nine heavy marijuana and alcohol users and 20 matched controls were studied during a 28-day monitored abstinence period. Sleep was examined as a function of prior substance use during Nights 1-2 and Nights 27-28. On Night 2, percent rapid eye movement sleep was predicted by past month alcohol use, whereas percent slow wave sleep was predicted by marijuana intake. By Night 28, neither alcohol nor marijuana use predicted any sleep architecture measure. However, on Night 28, indices of period limb movements (PLMs) in sleep were predicted by marijuana and alcohol intake. Results indicate that in adolescents: (1) cessation of heavy marijuana and alcohol use may influence sleep; (2) most sleep abnormalities abate within several weeks of abstinence; and (3) PLMs may increase following abstinence.

Impact of Type 2 Diabetes and Postmenopausal Hormone Therapy on Incidence of Cognitive Impairment in Older Women

OBJECTIVE In older women, higher levels of estrogen may exacerbate the increased risk for cognitive impairment conveyed by diabetes. We examined whether the effect of postmenopausal hormone therapy (HT) on cognitive impairment incidence differs depending on type 2 diabetes. RESEARCH DESIGN AND METHODS The Women’s Health Initiative (WHI) randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/day medroxyprogesterone acetate) or matching placebo for an average of 4.7–5.9 years. A total of 7,233 women, aged 65–80 years, were classified according to type 2 diabetes status and followed for probable dementia and cognitive impairment (mild cognitive impairment or dementia). RESULTS Through a maximum of 18 years of follow-up, women with diabetes had increased risk of probable dementia (hazard ratio [HR] 1.54 [95% CI 1.16–2.06]) and cognitive impairment (HR 1.83 [1.50–2.23]). The combination of diabetes and random assignment to HT increased their risk of dementia (HR 2.12 [1.47–3.06]) and cognitive impairment (HR 2.20 [1.70–2.87]) compared with women without these conditions, interaction P = 0.09 and P = 0.08. These interactions appeared to be limited to women assigned to unopposed conjugated equine estrogens. CONCLUSIONS These analyses provide additional support to a prior report that higher levels of estrogen may exacerbate risks that type 2 diabetes poses for cognitive function in older women. The role estrogen plays in suppressing non–glucose-based energy sources in the brain may explain this interaction.

Cannabis use patterns and motives: A comparison of younger, middle-aged, and older medical cannabis dispensary patients

INTRODUCTION Medical cannabis is increasingly being used for a variety of health conditions as more states implement legislation permitting medical use of cannabis. Little is known about medical cannabis use patterns and motives among adults across the lifespan. METHODS The present study examined data collected at a medical cannabis dispensary in San Francisco, California. Participants included 217 medical cannabis patients who were grouped into age-defined cohorts (younger: 18-30, middle-aged: 31-50, and older: 51-72). The age groups were compared on several measures of cannabis use, motives and medical conditions using one-way ANOVAs, chi-square tests and linear regression analyses. RESULTS All three age groups had similar frequency of cannabis use over the past month; however, the quantity of cannabis used and rates of problematic cannabis use were higher among younger users relative to middle-aged and older adults. The association between age and problematic cannabis use was moderated by age of regular use initiation such that earlier age of regular cannabis use onset was associated with more problematic use in the younger users, but not among older users. Middle-aged adults were more likely to report using medical cannabis for insomnia, while older adults were more likely to use medical cannabis for chronic medical problems such as cancer, glaucoma and HIV/AIDS. Younger participants reported cannabis use when bored at a greater rate than middle-aged and older adults. CONCLUSIONS Findings suggest that there is an age-related risk for problematic cannabis use among medical cannabis users, such that younger users should be monitored for cannabis use patterns that may lead to deleterious consequences.

Cognition and competency restoration: using the RBANS to predict length of stay for patients deemed incompetent to stand trial.

Intact cognition is a foundational component of one’s ability to be competent to stand trial. Given the cost of assessing and treating incompetence, it is recommended that clinicians develop efficient methods to identify individuals who are most likely to require intensive competence-related treatment interventions. This study sought to ascertain whether a brief cognitive screening instrument, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), could predict the length of stay required to restore trial competency among 288 forensic psychiatric inpatients undergoing competency restoration treatment. Results indicated that incompetent defendants who were older or demonstrated poorer overall RBANS performance required longer hospitalizations to be deemed restored to trial competence. Interestingly, incompetent defendants scoring in the 51–60 range on the RBANS Total Scale Index were almost three times more likely to require hospitalization beyond the average length of stay. Findings support the use of the RBANS to identify individuals early in the treatment process who may require and benefit from intensive restoration treatment.

The association between an inflammatory diet and global cognitive function and incident dementia in older women: The Women's Health Initiative Memory Study

The Mediterranean and Dietary Approaches to Stop Hypertension diets have been associated with lower dementia risk. We evaluated dietary inflammatory potential in relation to mild cognitive impairment (MCI)/dementia risk.