Aberrant parasympathetic reactivity to acute psychosocial stress in male patients with schizophrenia spectrum disorders.

Autonomic dysfunction represents a core domain of the pathophysiology of schizophrenia spectrum disorders (SCZ), with aberrant physiologic arousal underlying maladaptive social and cognitive behaviors. Antagonistic parasympathetic and sympathetic systems support autonomic flexibility to appropriately regulate arousal and respond to environmental challenges, which can be modeled using physiologic measures. SCZ patients consistently show heightened basal stress, however, their parasympathetic reactivity to an acute psychosocial stressor is poorly understood. Heart period (HP-arousal), respiratory sinus arrhythmia (RSA-parasympathetic vagal activity), and their relationship were measured in SCZ patients (n = 19) and healthy controls (n = 20) at baseline and during psychosocial stress exposure. Parasympathetic vagal control of arousal, reflected in RSA-HP coupling, was assessed for the first time in SCZ. Patients demonstrated blunted physiologic reactivity (less change in heart period and respiratory sinus arrhythmia), a unique increase in respiratory sinus arrhythmia relative to baseline during recovery, and elevated arousal was associated with poor cognitive performance and greater positive symptoms. Arousal regulation was tightly controlled by parasympathetic activity in controls only, indicated by a strong association between changes in heart period and respiratory sinus arrhythmia. Results are the first to demonstrate maladaptive, inefficient parasympathetic arousal regulation (RSA-HP decoupling) in reaction to psychosocial stress in SCZ, representing an autonomic profile incompatible with appropriate social and emotional functioning.

Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect.

Maternal behavior (MB) is a complex response to infant cues, orchestrated by postpartum neurophysiology. Although mesolimbic dopamine contributes toward MB, little is known about real-time dopamine fluctuations during the postpartum period. Thus, we used fast-scan cyclic voltammetry to measure individual dopamine transients in the nucleus accumbens of early postpartum rats and compared them with dopamine transients in virgins and in postpartum females exposed to cocaine during pregnancy, which is known to disrupt MB. We hypothesized that dopamine transients are normally enhanced postpartum and support MB. In anesthetized rats, electrically evoked dopamine release was larger and clearance was faster in postpartum females than in virgins and gestational cocaine exposure blocked the change in clearance. In awake rats, control mothers showed more dopamine transients than cocaine-exposed mothers during MB. Salient pup-produced stimuli may contribute toward differences in maternal phasic dopamine by evoking dopamine transients; supporting the feasibility of this hypothesis, urine composition (glucose, ketones, and leukocytes) differed between unexposed and cocaine-exposed infants. These data, resulting from the novel application of fast-scan cyclic voltammetry to models of MB, support the hypothesis that phasic dopamine signaling is enhanced postpartum. Future studies with additional controls can delineate which aspects of gestational cocaine reduce dopamine clearance and transient frequency.

Electrophysiological Correlates of Aberrant Motivated Attention and Salience Processing in Unaffected Relatives of Schizophrenia Patients.

Patients with schizophrenia (SCZ) exhibit debilitating deficits in attention and affective processing, which are often resistant to treatment and associated with poor functional outcomes. Impaired orientation to task-relevant target information has been indexed by diminished P3b event-related potentials in patients, as well as their unaffected first-degree relatives, suggesting that P3b may be a vulnerability marker for schizophrenia. Despite intact affective valence processing, patients are unable to employ cognitive change strategies to reduce electrophysiological responses to aversive stimuli. Less is known about the attentional processing of emotionally salient task-irrelevant information in patients and unaffected first-degree relatives. The goal of the present study was to examine the neural correlates of salience processing, as indexed by the late positive potential (LPP), during the processing of emotionally salient distractor stimuli in 31 patients with SCZ, 28 first-degree relatives, and 47 control participants using an oddball paradigm. Results indicated that despite intact novelty detection (P3a), both SCZ and first-degree relatives demonstrated deficiencies in attentional processing, reflected in attenuated target-P3b, and aberrant motivated attention, with reduced early-LPP amplitudes for aversive stimuli relative to controls. First-degree relatives revealed a unique enhancement of the late-LPP response, possibly underlying an exaggerated evaluation of salient information and a compensatory engagement of neural circuitry. Furthermore, reduced early-LPP and target-P3b amplitudes were associated with enhanced symptom severity. These findings suggest that, in addition to P3b, LPP may be useful for monitoring clinical state. Future studies will explore the value of P3 and LPP responses as vulnerability markers for early detection and prediction of psychopathology.