Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: Comparing vulnerability markers

Dept of Psychiatry & Behavioral Neuroscience, Wayne State University SOM, Detroit, MI 48301, USA.
Progress in Neuro-Psychopharmacology and Biological Psychiatry (Impact Factor: 3.69). 07/2011; 35(5):1349-54. DOI: 10.1016/j.pnpbp.2011.04.009
Source: PubMed


Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree.
Three groups (n=100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2s & 12s); sustained attention processing was assessed using the Continuous Performance Task-Identical Pairs version.
SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls.
These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP.

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Available from: Dhruman Goradia, Oct 02, 2015
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    • "Deficits in sustained attention deficits are widely implicated in several psychiatric disorders that are adolescent onset or the origins of which lie in adolescence. These include not only core attention-related disorders such as attention deficit hyperactivity disorder (6, 12), but also bipolar disorder (13) and schizophrenia (14). The evidence regarding schizophrenia and bipolar disorder is compelling as studies now suggest attention deficits serve as a prelude in adolescence to the emergence of these late adolescent or adult-onset phenotypes. "
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    ABSTRACT: Abnormalities in the brain's attention network may represent early identifiable neurobiological impairments in individuals at increased risk for schizophrenia or bipolar disorder. Here, we provide evidence of dysfunctional regional and network function in adolescents at higher genetic risk for schizophrenia or bipolar disorder [henceforth higher risk (HGR)]. During fMRI, participants engaged in a sustained attention task with variable demands. The task alternated between attention (120 s), visual control (passive viewing; 120 s), and rest (20 s) epochs. Low and high demand attention conditions were created using the rapid presentation of two- or three-digit numbers. Subjects were required to detect repeated presentation of numbers. We demonstrate that the recruitment of cortical and striatal regions are disordered in HGR: relative to typical controls (TC), HGR showed lower recruitment of the dorsal prefrontal cortex, but higher recruitment of the superior parietal cortex. This imbalance was more dramatic in the basal ganglia. There, a group by task demand interaction was observed, such that increased attention demand led to increased engagement in TC, but disengagement in HGR. These activation studies were complemented by network analyses using dynamic causal modeling. Competing model architectures were assessed across a network of cortical-striatal regions, distinguished at a second level using random-effects Bayesian model selection. In the winning architecture, HGR were characterized by significant reductions in coupling across both frontal-striatal and frontal-parietal pathways. The effective connectivity analyses indicate emergent network dysconnection, consistent with findings in patients with schizophrenia. Emergent patterns of regional dysfunction and dysconnection in cortical-striatal pathways may provide functional biological signatures in the adolescent risk-state for psychiatric illness.
    Frontiers in Psychiatry 05/2014; 5:50. DOI:10.3389/fpsyt.2014.00050
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    • "However, a number of studies using animal models of mania have observed increased levels of reactive oxygen species (ROS), a marker of mitochondrial dysfunction (Murphy, 2013). One study demonstrated increased lipid peroxidation, and a high number of free radical, superoxide in submitochondrial particles of the prefrontal cortex and hippocampus (Diwadkar et al., 2011). A second study showed that repeated amphetamine exposure, which induces manic symptomatology in animal models, increases levels of anti-oxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), in regional specific manner, in the prefrontal cortex, hippocampus and striatum (Glahn et al., 2007). "
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    ABSTRACT: Objectives Recent studies have pointed to neuroinflammation, oxidative stress and neurotrophic factors as key mediators in the pathophysiology of mood disorders. Little is however known about the cascade of biological episodes underlying the cognitive deficits observed during the acute and euthymic phases of bipolar disorder (BD). The aim of this review is to assess the potential association between cognitive impairment and biomarkers of inflammation, oxidative stress and neurotrophic activity in BD. Methods Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to November 2013, for human studies that collected both inflammatory markers and cognitive data in BD. Selected search terms were bipolar disorder, depression, mania, psychosis, inflammatory, cognitive and neurotrophic. Results Ten human studies satisfied the criteria for consideration. The findings showed that high levels of peripheral inflammatory-cytokine, oxidative stress and reduced brain derived neurotrophic factor (BDNF) levels were associated with poor cognitive performance. The BDNF val66met polymorphism is a potential vulnerability factor for cognitive impairment in BD. Conclusions Current data provide preliminary evidence of a link between the cognitive decline observed in BD and mechanisms of neuroinflammation and neuroprotection. The identification of BD specific inflammatory markers and polymorphisms in inflammatory response genes may be of assistance for therapeutic intervention.
    Journal of Psychiatric Research 05/2014; In press. DOI:10.1016/j.jpsychires.2014.04.017 · 3.96 Impact Factor
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    • "However , data examining infants of patients with bipolar disorder appear lacking. This study's goal was to compare behavioral and physiological measures among infants of mothers with bipolar disorder, major depressive disorder and psychiatrically healthy controls, specifically focusing on respiratory sinus arrhythmia (Diwadkar et al., 2011). Respiratory sinus arrhythmia (RSA) is a naturally occurring variation in heart rate that occurs in synchrony with respiration, reflecting the balance of sympathetic and parasympathetic regulation of heart rate (Berntson, Cacioppo, & Quigley, 1993; Berntson et al., 1997). "
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    ABSTRACT: The offspring of mothers with mood disorders may evidence increased behavioral problems as early as preschool; however, no study to date has examined psychophysiological characteristics during infancy, particularly among offspring of mothers diagnosed with bipolar disorder. Elucidating psychobiological mechanisms of risk early in development is critical to inform prevention and early intervention efforts. This study compared physiological and behavioral responsivity in 6-month-old infants (N = 329) of mothers with lifetime histories of bipolar disorder (BD, n = 44), major depressive disorder (MDD, n = 244), or no history of Axis I disorders (CTL, n = 41). Infant respiratory sinus arrhythmia (RSA) was measured in a laboratory stressor paradigm. Measures of infant affect and behavior during mother-infant interaction, current maternal depressive symptoms, and exposure to stressful life events were examined with respect to diagnostic group and RSA. Groups did not differ in baseline RSA or infant affect measures. However, during the stressor task, infants of mothers with BD evidenced increases in RSA, while infants of MDD and CTL mothers evidenced decreases in RSA. Though levels of postnatal stress and current levels of maternal depressive symptoms differed among groups, neither of these factors predicted infant psychophysiological responses. At 6 months of age, infants of mothers with BD show differences in psychophysiological regulation. These differences cannot be accounted for by perinatal outcome, current maternal depressive symptoms, or exposure to stressful life events, and thus may reflect endophenotypic markers of psychopathological risk.
    Journal of Child Psychology and Psychiatry 08/2013; 55(2). DOI:10.1111/jcpp.12130 · 6.46 Impact Factor
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