Antipsychotic (AP) medications are the mainstay for the treatment of schizophrenia spectrum disorders (SSD), but their efficacy is unpredictable and widely variable. Substantial efforts have been made to identify prognostic biomarkers that can be used to guide optimal prescription strategies for individual patients. Striatal regions involved in salience and reward processing are disrupted as a result of both SSD and cannabis use, and research demonstrates that striatal circuitry may be integral to response to AP drugs.
View Article and Find Full Text PDFSecond-generation antipsychotic drugs (SGAs) are essential in the treatment of psychotic disorders, but are well-known for inducing substantial weight gain and obesity. Critically, weight gain may reduce life expectancy for up to 20-30 years in patients with psychotic disorders, and prognostic biomarkers are generally lacking. Even though other receptors are also implicated, the dorsal striatum, rich in dopamine D2 receptors, which are antagonized by antipsychotic medications, plays a key role in the human reward system and in appetite regulation, suggesting that altered dopamine activity in the striatal reward circuitry may be responsible for increased food craving and weight gain.
View Article and Find Full Text PDFAvolition, a decrease in the initiation and persistence of goal-directed behavior, is a critical determinant of disability in patients with schizophrenia. Recent studies have demonstrated that avolition can be modeled using reward-based, behavioral paradigms. These studies suggest that avolition represents a motivational deficit, accounted for by a diminished ability to anticipate pleasurable experiences.
View Article and Find Full Text PDFBackground: Altered striatal development contributes to core deficits in motor and inhibitory control, impulsivity, and inattention associated with attention-deficit/hyperactivity disorder and may likewise play a role in deficient reward processing and emotion regulation in psychosis and depression. The maturation of striatal connectivity has not been well characterized, particularly as it relates to clinical symptomatology.
Methods: Resting-state functional connectivity with striatal subdivisions was examined for 926 participants (8-22 years of age, 44% male) from the general population who had participated in two large cross-sectional studies.
Neuropsychopharmacology
February 2019
Postpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy (H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS.
View Article and Find Full Text PDFPatients with first-episode psychosis experience psychotic symptoms for a mean of up to 2 years prior to initiation of treatment, and long duration of untreated psychosis (DUP) is associated with poor clinical outcomes. Meanwhile, evidence compiled from numerous studies suggests that longer DUP is not associated with structural brain abnormalities. To date, few studies have examined the relationship between DUP and functional neuroimaging measures.
View Article and Find Full Text PDFCONTEXT Iatrogenic obesity caused by atypical antipsychotics increases the rate of death from all causes. Olanzapine is a commonly prescribed atypical antipsychotic medication that frequently causes weight gain. To our knowledge, the neural correlates of this weight gain have not been adequately studied in humans.
View Article and Find Full Text PDFBackground: Major depression (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive amygdala activity and under-recruitment of dorsolateral prefrontal cortex (DLPFC). The purpose of this study was to examine the effects of antidepressant treatment on anomalous neural activity in cognitive-control and emotion-processing circuitry.
View Article and Find Full Text PDFBackground: Major depression is characterized by a negativity bias: an enhanced responsiveness to, and memory for, affectively negative stimuli. However, it is not yet clear whether this bias represents 1) impaired top-down cognitive control over affective responses, potentially linked to deficits in dorsolateral prefrontal cortex function; or 2) enhanced bottom-up responses to affectively laden stimuli that dysregulate cognitive control mechanisms, potentially linked to deficits in amygdala and anterior cingulate function.
Methods: We used an attentional interference task using emotional distracters to test for top-down versus bottom-up dysfunction in the interaction of cognitive-control circuitry and emotion-processing circuitry.
Parkinson's disease has been associated with executive dysfunction, especially task-switching deficits. One factor contributing to task-switching costs is backward inhibition, as measured by less efficient performance when switching back to a task from which one has recently switched away. This alternating-switch cost is considered to be due to persisting inhibition of elements of the previous task set after a switch.
View Article and Find Full Text PDFJ Int Neuropsychol Soc
September 2003
Klinefelter syndrome (KS) is a sex chromosome abnormality associated with male infertility and mild cognitive deficits. Individuals with KS have been reported to have impaired verbal ability, as well as deficits in executive function. To further understand the nature of their deficits, we assessed specific elements of frontal lobe function such as working memory and relational reasoning.
View Article and Find Full Text PDFReasoning and problem solving depend on the ability to represent and integrate complex relationships among stimuli. For example, deciding whether an animal is dangerous requires integrating information about the type of animal, its size, its distance from oneself, and one's proximity to shelter. Relational complexity increases with the number of such interdependent elements that must be simultaneously considered to solve a problem.
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