Table 1.

Psychiatric disorders in multiple sclerosis

Psychiatric disorders	Prevalence	Etiological considerations	Clinical features	Treatment
Depression	25-50%	Structural changes:	Most common symptoms: irritability, discouragement, memory and concentration problems, fatigue, insomnia and poor appetite	1st line: SSRI
	2 to 5 times higher than GP	• Higher lesion load in the left arcuate fasciculus, prefrontal cortex, anterior temporal lobe and parietal lobe		2nd line: SNRI, TCA, Mirtazapine CBT: mild to moderate depression
		• Shape variations of hippo campus;	Symptom overlap: fatigue, insomnia and cognitive dysfunction	ECT: last resort treatment
		• Changes in the cortico-striatal-pallido-thalamic loop	Suicidality:
		Neuroendocrine changes:	• Prevalence:
		• HPA axis dysfunction	- Suicidal ideation: 2.3 to 14 times higher than GP
		MS treatment:	- Suicide rate: 1.8-15.1%
		• INFβ: controversial issue	- Suicide risk: higher in the first 5 years after diagnosis; 50% of all suicides
		Psychosocial factors:	• Predictors: depression, social isolation and alcohol abuse
		• Coping mechanisms:
		- Cognitive reframing: lower levels of depression
		- Escape-avoidance and emotional respite: higher levels of depression
Anxiety disorders	Anxiety disorders: 13-31.7%; 3 times higher than GP	Structural: atrophy in the superior and middle gyri of the right frontal lobe	Symptom overlap between MS somatic manifestations and anxiety symptoms	1st line: SSRI and CBT
				Alternative: SNRI
	Anxiety symptoms: 26% to 63.4%	MS specific: injection anxiety	Anxiety and depression:
			• Increased physical complaints
			• Social dysfunction
			• Alcohol consumption
			• Suicidal ideation
			Precipitant of relapse in MS patients
Bipolar disorder	5.8%	Structural: plaques in the temporal horn areas; periventricular white matter, corpus callosum, subcortical “white matter”, frontal and temporal lobes and right cerebellar peduncle	BD symptoms throughout the evolution of the illness: impulsivity; emotional lability may occur during exacerbations	Treatment of mania: mood stabilizers, antipsychotics and benzodiazepines
		Therapy: steroid therapy		Steroid-induced mania: lithium prophylaxis and reduction of steroid doses
Psychotic disorders	Psychotic symptoms: 2 to 3 times higher than GP	Structural: medial temporal lobe; lesions in the periventricular white matter	Hallucinations and delusions (mostly paranoid), irritability/agitation, sleep disturbance, grandiosity, blunted affect, and rare symptoms like catatonia and transient catalepsy	Antipsychotics: clozapine, risperidone, ziprasidone, low-dose chlorpromazine
	Psychosis: 0.41-7.46%	Genetic: genetic markers of immune activation		Prophylactic use of lithium alongside corticosteroid therapy
	Schizophrenia: 0-7.4%	Therapy: corticosteroids; INFβ
Personality disorders	2.6%	Structural: orbital-frontal-subcortical circuits; cingular-anterior-subcortical circuits	More neurotic features and less empathic, agreeable and conscientious	Palliative medication and behavior modification strategies
Substance misuse	Alcohol: 3.96–18.2%		Alcohol: potentiate mild cognitive deficit; decreased alcohol tolerance; aggravated neurological symptoms	Psychoeducational measures
	Drug abuse: 2.5–7.4%		Cannabis use for symptom control
Affect abnormalities	Pseudobulbar affect: 10%	Disconnection syndrome: loss of brainstem inhibition in a putative control center on crying and laughter	Alteration of affect not representing an underlying emotion, such as pathological crying/laughter	SSRI
				Dextromethorphan+quinidine

GP: general population, HPA: hypothalamus-pituitary-adrenal, INFβ: interferon-beta, SSRI: selective serotonine reuptake inhibitors, SNRI: serotonine and norepinephrine reuptake inhibitors, TCA: tricyclic antidepressants, CBT: cognitive behavioral therapy, ECT: eletroconvulsivetherapy