Secondary negative symptoms — A review of mechanisms, assessment and treatment

Kirschner, Matthias; Alemán, André; Kaiser, Stefan

doi:10.1016/j.schres.2016.05.003

Cited by 149 publications

(160 citation statements)

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“…When interpreting the results of the present study, it is therefore important to take into account the concept of secondary negative symptoms: Whereas primary negative symptoms are defined by being inherent to the disorder, secondary negative symptoms are thought to have different underlying sources such as depressive symptoms, productive psychotic features or medication (Kirkpatrick, 2014, Kirschner et al , 2017). Our data clearly show that in euthymic patients with bipolar disorder motivational negative symptoms are at least in part secondary to sub-syndromal depressive symptoms.…”

Section: Discussionmentioning

confidence: 99%

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Kirschner

Cathomas

Manoliu

et al. 2019

Preprint

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BackgroundBipolar disorder I (BD-I) is defined by episodes of mania, depression, and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood.MethodsWe first assessed the severity of negative symptoms in 25 euthymic BD-I patients compared to 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral and dorsal striatal activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS.ResultsIn BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant ventral and dorsal striatal activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole brain analyses revealed reduced extra-striatal activation in BD-I patients compared to HC and an association between reduced activation of the inferior frontal gyrus and apathy.ConclusionThis study found that in BD-I patients apathy is present to an extent comparable to schizophrenia, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

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Section: Discussionmentioning

confidence: 99%

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Kirschner

Cathomas

Manoliu

et al. 2019

Preprint

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“…apathy) and anhedonia are common to both [66]. The association of apathy-anhedonia to both depression and negative symptoms indicates similarities in underlying CNS functions [67].…”

Section: Early Clinical or Demographic Predictors Of Apathy Developmementioning

confidence: 96%

Trajectory and early predictors of apathy development in first-episode psychosis and healthy controls: a 10-year follow-up study

Lyngstad

Gardsjord

Engen

et al. 2020

Eur Arch Psychiatry Clin Neurosci

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Apathy is prevalent in first-episode psychosis (FEP) and associated with reduced global functioning. Investigations of the trajectory of apathy and its early predictors are needed to develop new treatment interventions. We here measured the levels of apathy over the first 10 years of treatment in FEP and in healthy controls (HC). We recruited 198 HC and 198 FEP participants. We measured apathy with the Apathy Evaluation Scale, self-report version, psychotic symptoms with the Positive and Negative Syndrome Scale, depression with the Calgary Depression Scale for Schizophrenia, functioning with the Global Assessment of Functioning Scale, and also estimated the duration of untreated psychosis (DUP). The longitudinal development of apathy and its predictors were explored using linear mixed models analyses. Associations to functioning at 10 years were investigated using multiple hierarchical linear regression analyses. In HC, mean apathy levels were low and stable. In FEP, apathy levels decreased significantly during the first year of treatment, followed by long-term stability. High individual levels of apathy at baseline were associated with higher apathy levels during the follow-up. Long DUP and high baseline levels of depression predicted higher apathy levels at follow-ups. The effect of DUP was persistent, while the effect of baseline depression decreased over time. At 10 years, apathy was statistically significantly associated with reduced functioning. The early phase of the disorder may be critical to the development of apathy in FEP.

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“…These findings show that the two-syndrome framework differentiating "negative from positive symptoms" [2] is not accurate because PHEM (psychosis, hostility, excitation, mannerism) and negative symptoms belong to one and the same dimension [1]. Moreover, previous theories suggesting that affective symptoms are differently associated with positive versus negative symptoms [3,4] should be revised because all symptoms of both dimensions load highly on an overarching "generalized psychopathology dimension", which comprises two inter-related PHEMN and DAPS subdimensions. In addition, negative, affective and physio-somatic symptoms of schizophrenia are strongly predicted by impairments in semantic and episodic memory as measured with Consortium to Establish a Registry for Alzheimer's disease (CERAD) tests [1,5,6].…”

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confidence: 96%

A new schizophrenia model: immune activation is associated with induction of the tryptophan catabolite pathway and increased eotaxin levels which together determine memory impairments and schizophrenia symptom dimensions

Sirivichayakul

Kanchanatawan

Thika

et al. 2018

Preprint

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Abstract.Objective Recently, we reported that stable-phase schizophrenia is characterized by two interrelated symptom dimensions: PHEMN (psychotic, hostility, excitation, mannerism and negative symptoms); and DAPS (depressive, anxiety and physio-somatic symptoms) and that Major Conclusions. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/393173 doi: bioRxiv preprint first posted online Aug. 16, 2018; 3 Current findings indicate that in schizophrenia, immune activation may underpin activation of indoleamine-2,3-dioxygenase and kynurenine monooxygenase, while impairments in episodic and semantic memory may be caused by the neurotoxic effects of TRYCATs and eotaxin. The combined effects of immune activation, eotaxin and memory defects determine to a large extent PHEMN/DAPS symptoms and the MNP phenotype. These findings indicate that schizophrenia phenomenology is largely mediated by multiple neuro-immune pathways and that immune activation, increased production of eotaxin and neurotoxic TRYCATs (picolinic acid, xanthurenic acid and 3-HO-kynurenine) are new drug targets in schizophrenia and MNP.

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Secondary negative symptoms — A review of mechanisms, assessment and treatment

Cited by 149 publications

References 142 publications

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Trajectory and early predictors of apathy development in first-episode psychosis and healthy controls: a 10-year follow-up study

A new schizophrenia model: immune activation is associated with induction of the tryptophan catabolite pathway and increased eotaxin levels which together determine memory impairments and schizophrenia symptom dimensions

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