Allen E. Thornton

Functional neuroimaging of working memory in schizophrenia: task performance as a moderating variable.

Functional neuroimaging studies in schizophrenia have demonstrated abnormal activation of dorsolateral prefrontal cortex (DLPFC) during working memory (WM) performance. However, findings of increased and decreased activity have been reported. The authors used meta-analysis to investigate whether diverging results arise as a function of differential WM task performance between patients and control participants. Results indicate that the magnitude of the group difference in WM performance is a moderator of DLPFC activation differences, and concepts such as hypo- or hyperfrontality do not universally characterize WM findings in schizophrenia. Thus, the variability in the WM activation findings between participants with schizophrenia and control participants reflects the specific conditions under which WM functions are evaluated, not just the WM construct per se.

The impact of atypical antipsychotic medications on long-term memory dysfunction in schizophrenia spectrum disorder: a quantitative review

This meta-analytic review examines the ef.cacy of antipsychotic medications in ameliorating schizophrenia-related long-term memory (LTM) impairments. Twenty-three studies were reviewed that compared schizophrenia spectrum patients treated (a) with atypical versus typical antipsychotic medications, or (b) with various atypical treatments. In 17 atypical versus typical trials aggregating 939 participants, superior overall (verbal and nonverbal) LTM was detected in patients assigned to atypical trials. However, this difference was small (effect size estimate (ES) 0.17; 95% Con.dence Interval (CI) 0.04 to 0.31) and speci.c to certain atypical treatments. Relative to typical antipsychotic trials, LTM superiority was marginally signi.cant for risperidone trials (ES 0.20; 95% CI 0.03 to 0.44) and signi.cant for olanzapine trials (ES 0.29; 95% CI 0.08 to 0.49). In contrast, clozapine trials did not produce a LTM advantage over typical trials (ES 0.06; 95% CI 0.35 to 0.23). Due to the lack of available studies, the effect of quetiapine was indeterminate. Direct comparison between atypical trials revealed a similar effect pattern. A marginally signi.cant superiority in overall LTM was detected for risperidone and olanzapine compared to clozapine (ES 0.28; 95% CI 0.04 to 0.59), which reached signi.cance for verbal LTM (ES 0.36; 95% CI 0.04 to 0.67). Finally, the bene.cial impact of antipsychotic medications emerged as a function of differences in the anticholinergic properties of the treatment arms being compared.

Cumulative concussion exposure in rugby players: Neurocognitive and symptomatic outcomes

A total of 111 rugby players underwent comprehensive testing to determine the impact of self-reported concussion exposure. Reliable estimates of concussion exposure were associated with an increase in postconcussion symptoms (PCS), but not diminished neurocognitive functioning. Importantly, the effects of concussion exposure on PCS varied as a function of player status. More specifically, extent of concussion exposure was associated with increased memory complaints and overall PCS endorsements in a dose-dependent manner for retired and older recreational players, but not for those who were younger and playing at more competitive levels. Future work should systematically evaluate the constituent participant factors that may influence differential concussion outcomes.

Cognitive-behavioral prevention of postconcussion syndrome in at-risk patients: a pilot randomized controlled trial.

Objective:To examine the tolerability and estimate the treatment effect of cognitive-behavioral therapy (CBT) delivered soon after mild traumatic brain injury to patients at risk for chronic postconcussion syndrome (PCS). Setting:Tertiary rehabilitation center. Participants:Twenty-eight patients with uncomplicated mild traumatic brain injury, determined to be at risk for chronic PCS based on a published algorithm that incorporates subacute postconcussion symptoms and maladaptive illness beliefs (recovery expectations and perceived consequences). They were enrolled within 6 weeks postinjury. Design:Open-label, parallel-group, randomized controlled trial, with masked outcome assessment 3 months after enrolment. Interventions were (1) treatment as usual (education, reassurance, and symptom management strategies) from an occupational therapist, or (2) treatment as usual plus CBT delivered by a psychologist. Main Measures:Rivermead Postconcussion Symptoms Questionnaire. Results:Four participants (2:2) withdrew. Treatment credibility and satisfaction ratings were high in the CBT group. Treatment effect sizes were moderate for postconcussion symptoms (Cohen d = 0.74) and moderate-large for most secondary outcome measures (Cohen d = 0.62-1.61). Fewer participants receiving CBT had a diagnosis of PCS at follow-up (54% vs 91%, P < .05). Conclusion:Our preliminary data suggest that CBT delivered soon after mild traumatic brain injury is well tolerated and may facilitate recovery in patients who are at risk for chronic PCS. A definitive clinical trial is warranted.

The Hotel Study: Multimorbidity in a Community Sample Living in Marginal Housing

OBJECTIVEnThe health of people living in marginal housing is not well characterized, particularly from the perspective of multimorbid illness. The authors investigated this population in a community sample.nnnMETHODnA prospective community sample (N=293) of adults living in single-room occupancy hotels was followed for a median of 23.7 months. Assessment included psychiatric and neurological evaluation, multimodal MRI, and viral testing.nnnRESULTSnPrevious homelessness was described in 66.6% of participants. Fifteen deaths occurred during 552 person-years of follow-up. The standardized mortality ratio was 4.83 (95% CI=2.91-8.01). Substance dependence was ubiquitous (95.2%), with 61.7% injection drug use. Psychosis was the most common mental illness (47.4%). A neurological disorder was present in 45.8% of participants, with definite MRI findings in 28.0%. HIV serology was positive in 18.4% of participants, and hepatitis C virus serology in 70.3%. The median number of multimorbid illnesses (from a list of 12) was three. Burden of multimorbidity was significantly correlated with lower role functioning score. Comorbid addiction or physical illness significantly decreased the likelihood of treatment for psychosis but not the likelihood of treatment for opioid dependence or HIV disease. Participants who died during follow-up appeared to have profiles of multimorbidity similar to those of the overall sample.nnnCONCLUSIONSnThis marginally housed cohort had greater than expected mortality and high levels of multimorbidity with adverse associations with role function and likelihood of treatment for psychosis. These findings may guide the development of effective health care delivery in the setting of marginal housing.

Hippocampal volume and the brain-derived neurotrophic factor Val66Met polymorphism in first episode psychosis

INTRODUCTIONnSmall hippocampi and impaired memory are common in patients with psychosis and brain-derived neurotrophic factor (BDNF) plays a critical role in hippocampal neuroplasticity and memory. A common BDNF allele (Val66Met) has been the focus of numerous studies but results from the few BDNF-imaging studies are complex and contradictory. The objective of this study was to determine the association between Val66Met and hippocampal volume in patients with first episode psychosis. Secondary analyses explored age-related associations and the relationship between Val66Met and memory.nnnMETHODnHippocampal volume and BDNF genotyping were obtained for 58 patients with first-episode psychosis and 39 healthy volunteers. Patients were recruited from an early psychosis program serving a catchment-area population.nnnRESULTSnHippocampal volume was significantly smaller in patients than controls (F(1,92)=4.03, p<0.05) and there was a significant group-by-allele interaction (F(1,92)=3.99, p<0.05). Hippocampal volume was significantly smaller in patients than controls who were Val-homozygotes but no group differences were found for Met carriers. Findings were not affected by diagnosis, antipsychotic medication, or age, and there was no change in hippocampal volume during a one-year follow-up. Val-homozygous patients had worse immediate and delayed memory than their Met counterparts.nnnCONCLUSIONSnResults suggest the effects of the BDNF Val66Met allele may be different in patients with psychosis than in healthy adults. Hippocampal volume in patient and control Met allele carriers was very similar suggesting that illness-related factors have minimal influence in this group. In contrast, Val homozygosity was related to smaller hippocampi and poorer memory functioning only in patients with psychosis.

Antipsychotic medications: linking receptor antagonism to neuropsychological functioning in first episode psychosis.

Antipsychotic medications can contribute to neurocognitive and motor impairments, but specific links to individualized pharmacological treatment regimens are unclear. In 68 participants with stabilized first-episode psychosis (FEP), we investigated the links between neuropsychological functions and an established anticholinergic potency index and a new D(2) antagonist potency index developed in our lab. Each participants psychiatric medication regimen was converted into estimated receptor antagonist loads based upon specific medication dosage(s) and reported in vitro brain muscarinic cholinergic and D(2) receptor antagonism. In addition to the global neuropsychological impairments of FEP participants, the findings supported the hypothesized links between receptor antagonist loads and specific deficits. Higher anticholinergic load was associated with poorer delayed verbal memory but was not related to motor functioning. In contrast, higher D(2) load was associated with poorer motor functioning but not verbal memory. These selective antagonist load associations explained 19% of the variance in motor functioning and 17% of the variance in delayed verbal memory. Evidently, some of the neuropsychological impairments found in persons with FEP are selectively related to the specific pharmacodynamics and the dosing of their medication regimens. Moreover, these effects can be readily estimated from practical and inexpensive indices.

The ecological validity of everyday cognition in hospitalized patients with serious mental illness

In 47 tertiary inpatients with schizophrenia or schizoaffective disorder, we report on the extent to which everyday cognition (EC), as represented by tasks utilizing naturalistic stimuli or commonly encountered problems, accounts for variation in daily functioning. Patients underwent interview-based measures of psychiatric symptoms, nurses observations of functioning, and measures of EC and traditional cognition (TC). Our results indicate that EC accounts for “real-world” functioning above that of TC and psychiatric symptoms. This observation supports the utility of incorporating salient measures that rely upon common experience and accumulated knowledge structure into existent test batteries.

The impact of monetary reward on memory in schizophrenia spectrum disorder.

The impact of monetary reward on verbal working memory (vWM) and verbal long-term memory (vLTM) was evaluated in 50 patients with schizophrenia spectrum disorders and 52 matched healthy participants. This research was motivated by the observations that negative symptoms in schizophrenia are associated with reduced drive and that patients with these symptoms exhibit greater mnemonic impairments. Reward-related gains were evaluated across two levels of vWM load on the n-back task and across three aspects of vLTM derived from the California Verbal Learning Test-II (i.e., learning, total immediate recall, and retention). Although healthy individuals benefited from reward at a high vWM load level, schizophrenia patients exhibited no reward-related improvements in vWM. In contrast, improvement in vLTM retention was induced by reward for both patients and controls. Finally, symptomatic and pharmacology treatment factors were associated with reward-related gains in persons with schizophrenia. In conclusion, contingent monetary rewards delivered during vWM and vLTM enhanced specific aspects of memory. The influence was relatively small and dependent on the specific neurocognitive operation examined, the mental health status of the participants, and for patients, their particular symptoms and pharmacological treatments.

Age Differences in Hindsight Bias: The Role of Episodic Memory and Inhibition

Background/Study Context: After learning an event’s outcome, people’s recollection of their former prediction of that event shifts towards the actual outcome. This hindsight bias (HB) phenomenon tends to be stronger in older compared with younger adults; however, it is unclear whether age-related changes in other cognitive abilities mediate this relationship. Methods: Sixty-four younger adults (Mage = 20.1; range = 18–25) and 60 community-dwelling older adults (Mage = 72.5; range = 65–87) completed a memory design HB task. Two aspects of HB, its occurrence and magnitude, were examined. Multiple regression and mediation analyses were conducted to determine whether episodic memory and inhibition mediate age differences in the occurrence and magnitude of HB. Results: Older adults exhibited a greater occurrence and magnitude of HB as compared with younger adults. The present findings revealed that episodic memory and inhibition mediated age-related increases in HB occurrence. Conversely, neither cognitive ability mediated age-related increases in HB magnitude. Conclusion: Older adults’ susceptibility to the occurrence of HB is partly due to age-related declines in episodic memory and inhibition. Conversely, age differences in the magnitude of HB appear to be independent of episodic memory and inhibition. These findings have important implications for understanding the mechanisms by which susceptibility to HB changes across the adult life span.