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Background: There is evidence that exposure to social stress plays a crucial role in the onset and relapse of schizophrenia; however, the reaction of patients with schizophrenia spectrum disorder (SSD) to experimentally induced social stress is not yet fully understood., Method: Original research published between January 1993 and August 2015 was included in this systematic literature research. Social stress paradigms, reporting subjective responses to stress measures, plasma or saliva cortisol, or heart rate (HR) in patients with SSD were included. 1528 articles were screened, 11 papers (390 patients) were included., Results: Three main findings were attained concerning chronically ill patients: (1) overall similar subjective responses to stress ratings between SDD patients and controls, (2) no group differences in cortisol response to psychosocial stress and (3) an increase in HR after the stress exposure was seen in patients and controls. The study examining first-episode patients found higher subjective responses to stress and lower stress-induced cortisol levels., Conclusion: The results indicate that first-onset medication free patients may show differences in subjective responses to stress measures and cortisol release while chronically ill patients display no differences in subjective and cortisol response. This may be the correlate of a pathophysiological dysfunction of the hypothalamic-pituitary-adrenal axis prior or at the onset of SSD and a subsequent change in dysregulation during the course of the illness. Given the paucity of studies investigating psychosocial stress in SSD and the pathophysiological relevance of psychosocial stress for the illness, there is need for further research. (PROSPERO registration number: CRD42015026525)., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Major depression is a common, recurrent mental illness that affects millions of people worldwide. Recently, a unique fast neuroprotective and antidepressant treatment effect has been observed by ketamine, which acts via the glutamatergic system. Hence, a steady accumulation of evidence supporting a role for the excitatory amino acid neurotransmitter (EAA) glutamate in the treatment of depression has been observed in the last years. Emerging evidence indicates that N-methyl-D-aspartate (NMDA), group 1 metabotropic glutamate receptor antagonists and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) agonists have antidepressant properties. Indeed, treatment with NMDA receptor antagonists has shown the ability to sprout new synaptic connections and reverse stress-induced neuronal changes. Based on glutamatergic signaling, a number of therapeutic drugs might gain interest in the future. Several compounds such as ketamine, memantine, amantadine, tianeptine, pioglitazone, riluzole, lamotrigine, AZD6765, magnesium, zinc, guanosine, adenosine aniracetam, traxoprodil (CP-101,606), MK-0657, GLYX-13, NRX-1047, Ro25-6981, LY392098, LY341495, D-cycloserine, D-serine, dextromethorphan, sarcosine, scopolamine, pomaglumetad methionil, LY2140023, LY404039, MGS0039, MPEP, 1-aminocyclopropanecarboxylic acid, all of which target this system, have already been brought up, some of them recently. Drugs targeting the glutamatergic system might open up a promising new territory for the development of drugs to meet the needs of patients with major depression., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Schizophrenia spectrum disorders (SSD) constitute a group of psychiatric illnesses which frequently lead to persisting mental impairment. Although some patients show a clinical course with few episodes and good long-term outcome, the course of the disease is often chronic and unfavorable. Long-term treatment (LTT) of SSD pertains to the postacute stabilization period and the remission period following pharmacological and psychosocial therapy of an acute illness episode. This article provides an overview of treatment recommendations concerning long-term pharmacotherapy, dealing with side effects, treatment of non-response and therapy resistance and the treatment of psychiatric comorbidities. Furthermore, an overview of non-pharmacological treatment options is presented. An integrated therapeutic setting combining evidence-based pharmacotherapy, psychosocial interventions, and supportive therapies is recommended for optimal LTT of SSD. Considering the limited financial resources available in the healthcare system, one of the major challenges is to provide patients with access to the evidence-based treatment options available.

Objective: To determine pathologic regulations and potential compensatory mechanisms in the supraspinal locomotor network of patients with progressive supranuclear palsy (PSP) by investigation of brain activation during walking and correlation to gait performance., Methods: Twelve patients with PSP were scanned with [18F]-FDG-PET during walking and at rest as has been described earlier. Results were compared to age-matched healthy controls (n = 12)., Results: The major results were as follows. (1) At rest, the regional cerebral glucose metabolism (rCGM) in the supraspinal locomotor centers, i.e., the prefrontal cortex, the subthalamic nucleus, and the pedunculopontine/cuneiform nucleus complex, was reduced in PSP. (2) Severity of gait impairment, measured by gait velocity, step length, and progressive supranuclear palsy rating scales/gait, correlated with decrease of rCGM in the prefrontal cortex and subthalamic nucleus. (3) Accordingly, during walking functional activation of the prefrontal cortex, the subthalamic nucleus, the pedunculopontine/cuneiform nucleus complex, and the thalamus was reduced in patients with PSP compared to controls. (4) The precentral gyrus and the vermal cerebellum were activated more strongly during locomotion in PSP., Conclusions: Gait impairment in PSP is especially associated with dysfunction of the indirect, modulatory prefrontal-subthalamic-pedunculopontine loop of locomotor control. The direct, stereotyped locomotor loop from the primary motor cortex to the spinal cord with rhythmic cerebellar drive shows increased activity in PSP. The latter can be interpreted as an attempt of compensation, but may also contribute to a stereotyped gait pattern in PSP.

Objective: To determine how postural imbalance and falls are related to regional cerebral glucose metabolism (PET) and functional activation of the cerebral postural network (fMRI) in patients with progressive supranuclear palsy (PSP)., Methods: Sixteen patients with PSP, who had self-monitored their frequency of falls, underwent a standardized clinical assessment, posturographic measurement of balance during modified sensory input, and a resting [¹⁸F]FDG-PET. In addition, patients performed an fMRI paradigm using mental imagery of standing. Results were compared to healthy controls (n = 16)., Results: The frequency of falls/month in patients (range 1-40) correlated with total PSP rating score (r = 0.90). Total sway path in PSP significantly correlated with frequency of falls, especially during modulated sensory input (eyes open: r = 0.62, eyes closed: r = 0.67, eyes open/head extended: r = 0.84, eyes open/foam-padded platform: r = 0.87). Higher sway path values and frequency of falls were associated with decreased regional glucose metabolism (rCGM) in the thalamus (sway path: r = -0.80, falls: r = -0.64) and increased rCGM in the precentral gyrus (sway path: r = 0.79, falls: r = 0.64). Mental imagery of standing during fMRI revealed a reduced activation of the mesencephalic brainstem tegmentum and the thalamus in patients with postural imbalance and falls., Conclusions: The new and clinically relevant finding of this study is that imbalance and falls in PSP are closely associated with thalamic dysfunction. Deficits in thalamic postural control get most evident when balance is assessed during modified sensory input. The results are consistent with the hypothesis that reduced thalamic activation via the ascending brainstem projections may cause postural imbalance in PSP.